Bionics - James Geddes

Bionics
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Contents
Articles
Introduction
1
Bionics
1
Cyborg
7
Brain
14
Neuron
34
Key People
48
Kevin Warwick
48
Ivan Pavlov
57
Tipu Aziz
60
Eduard Hitzig
63
Gustav Fritsch
64
Miguel Nicolelis
65
José Manuel Rodriguez Delgado
67
Aimee Mullins
69
Conditions
72
Parkinson's disease
72
Epilepsy
87
Obsessive–compulsive disorder
Procedures
102
117
Deep brain stimulation
117
Brain implant
123
Krukenberg procedure
128
Neuroprosthetics
131
Cardiopulmonary bypass
143
Artificial pacemaker
147
Electroencephalography
159
Cochlear implant
172
Magnetic resonance imaging
188
Long-term video-EEG monitoring
207
Brain–computer interface
207
Artificial limb
219
X-ray computed tomography
227
Preimplantation genetic diagnosis
242
Multielectrode array
253
Surrounding Areas
259
Bioethics
259
Transhumanism
265
References
Article Sources and Contributors
283
Image Sources, Licenses and Contributors
290
Article Licenses
License
293
1
Introduction
Bionics
Bionics (also known as biomimicry, biomimetics, bio-inspiration, biognosis, and close to bionical creativity
engineering) is the application of biological methods and systems found in nature to the study and design of
engineering systems and modern technology. The word bionic was coined by Jack E. Steele in 1958, possibly
originating from the Greek word βίον, bíon, pronounced [bi:on] ("bee-on"), meaning 'unit of life' and the suffix -ic,
meaning 'like' or 'in the manner of', hence 'like life'. Some dictionaries, however, explain the word as being formed
from biology + electronics.
The transfer of technology between lifeforms and manufactures is, according to proponents of bionic technology,
desirable because evolutionary pressure typically forces living organisms, including fauna and flora, to become
highly optimized and efficient. A classical example is the development of dirt- and water-repellent paint (coating)
from the observation that the surface of the lotus flower plant is practically unsticky for anything (the lotus effect).
The term "biomimetic" is preferred when reference is made to chemical reactions. In that domain, biomimetic
chemistry refers to reactions that, in nature, involve biological macromolecules (for example, enzymes or nucleic
acids) whose chemistry can be replicated using much smaller molecules in vitro.
Examples of bionics in engineering include the hulls of boats imitating the thick skin of dolphins; sonar, radar, and
medical ultrasound imaging imitating the echolocation of bats.
In the field of computer science, the study of bionics has produced artificial neurons, artificial neural networks [1] ,
and swarm intelligence. Evolutionary computation was also motivated by bionics ideas but it took the idea further by
simulating evolution in silico and producing well-optimized solutions that had never appeared in nature.
It is estimated by Julian Vincent, professor of biomimetics at the University of Bath in the UK, that "at present there
is only a 10% overlap between biology and technology in terms of the mechanisms used".
History
The name biomimetics was coined by Otto Schmitt in the 1950s. The term bionics was coined by Jack E. Steele in
1958 while working at the Aeronautics Division House at Wright-Patterson Air Force Base in Dayton, Ohio.
However, terms like biomimicry or biomimetics are more preferred in the technology world in efforts to avoid
confusion between the medical term bionics. Coincidentally, Martin Caidin used the word for his 1972 novel
Cyborg, which inspired the series The Six Million Dollar Man. Caidin was a long-time aviation industry writer
before turning to fiction full time.
Bionics
Methods
Often, the study of bionics emphasizes implementing a function found in nature rather than just imitating biological
structures. For example, in computer science, cybernetics tries to model the feedback and control mechanisms that
are inherent in intelligent behavior, while artificial intelligence tries to model the intelligent function regardless of
the particular way it can be achieved.
The conscious copying of examples and mechanisms from natural organisms and ecologies is a form of applied
case-based reasoning, treating nature itself as a database of solutions that already work. Proponents argue that the
selective pressure placed on all natural life forms minimizes and removes failures.
Although almost all engineering could be said to be a form of biomimicry, the modern origins of this field are
usually attributed to Buckminster Fuller and its later codification as a house or field of study to Janine Benyus.
Roughly, we can distinguish three biological levels in the fauna or flora, after which technology can be modeled:
• Mimicking natural methods of manufacture
• Imitating mechanisms found in nature (velcro)
• Studying organizational principles from the social behaviour of organisms, such as the flocking behaviour of
birds, optimization of ant foraging and bee foraging, and the swarm intelligence (SI)-based behaviour of a school
of fish.
Examples
• Velcro is the most famous example of biomimetics. In 1948, the Swiss engineer George de Mestral was cleaning
his dog of burrs picked up on a walk when he realized how the hooks of the burrs clung to the fur.
• Cat's eye reflectors were invented by Percy Shaw in 1935 after studying the mechanism of cat eyes. He had found
that cats had a system of reflecting cells, known as tapetum lucidum, which was capable of reflecting the tiniest
bit of light.
• Leonardo da Vinci's flying machines and ships are early examples of drawing from nature in engineering.
• Resilin is a replacement for rubber that has been created by studying the material also found in anthropods.
• Julian Vincent drew from the study of pinecones when he developed in 2004 "smart" clothing that adapts to
changing temperatures. "I wanted a nonliving system which would respond to changes in moisture by changing
shape", he said. "There are several such systems in plants, but most are very small — the pinecone is the largest
and therefore the easiest to work on". Pinecones respond to higher humidity by opening their scales (to disperse
their seeds). The "smart" fabric does the same thing, opening up when the wearer is warm and sweating, and
shutting tight when cold.
• "Morphing aircraft wings" that change shape according to the speed and duration of flight were designed in 2004
by biomimetic scientists from Penn State University. The morphing wings were inspired by different bird species
that have differently shaped wings according to the speed at which they fly. In order to change the shape and
underlying structure of the aircraft wings, the researchers needed to make the overlying skin also be able to
change, which their design does by covering the wings with fish-inspired scales that could slide over each other.
In some respects this is a refinement of the swing-wing design.
2
Bionics
• Some paints and roof tiles have been engineered to be
self-cleaning by copying the mechanism from the Nelumbo
lotus.[2]
• Nanostructures and physical mechanisms that produce the
shining color of butterfly wings were reproduced in silico by
Greg Parker, professor of Electronics and Computer Science at
the University of Southampton and research student Luca
Plattner in the field of photonics, which is electronics using
photons as the information carrier instead of electrons.
Lotus leaf surface, rendered: microscopic view
• Cholesteric liquid crystals (CLCs) are the thin-film material
often used to fabricate fish tank thermometers or mood rings,
that change color with temperature changes. They change color because their molecules are arranged in a helical
or chiral arrangement and with temperature the pitch of that helical structure changes, reflecting different
wavelengths of light. Chiral Photonics, Inc. has abstracted the self-assembled structure of the organic CLCs to
produce analogous optical devices using tiny lengths of inorganic, twisted glass fiber.
• The wing structure of the blue morpho butterfly was studied and the way it reflects light was mimicked to create
an RFID tag that can be read through water and on metal[3] .
• Neuromorphic chips, silicon retinae or cochleae, has wiring that is modelled after real neural networks. S.a.:
connectivity.
• Synthetic or "robotic" vegetation, which aids in conservation and restoration,[4] are machines designed to mimic
many of the functions of living vegetation.
• Medical adhesives involving glue and tiny nano-hairs are being developed based on the physical structures found
in the feet of geckos.
• Computer viruses also show troubling similarities with biological viruses in their way to curb program-oriented
information towards self-reproduction and dissemination.
• The cooling system of the Eastgate Centre building, in Harare was modeled after a termite mound to achieve very
efficient passive cooling.
• Through the field of bionics, new aircraft designs with far greater agility and other advantages may be created.
This has been described by Geoff Spedding and Anders Hedenström in an article in Journal of Experimental
Biology. Similar statements were also made by John Videler and Eize Stamhuis in their book Avian Flight [5] and
in the article they present in Science about LEV's [6] . John Videler and Eize Stamhuis have since worked out
real-life improvements to airplane wings, using bionics research. This research in bionics may also be used to
create more efficient helicopters or miniature UAVs. This latter was stated by Bret Tobalske in an article in
Science about Hummingbirds [7] . Bret Tobalske has thus now started work on creating these miniature UAVs
which may be used for espionage. UC Berkeley as well as ESA have finally also been working in a similar
direction and created the Robofly [8] (a miniature UAV)and the Entomopter (a UAV which can walk, crawl and
fly).[9]
3
Bionics
Specific uses of the term
In medicine
Bionics is a term which refers to the flow of concepts from biology to engineering and vice versa. Hence, there are
two slightly different points of view regarding the meaning of the word.
In medicine, bionics means the replacement or enhancement of organs or other body parts by mechanical versions.
Bionic implants differ from mere prostheses by mimicking the original function very closely, or even surpassing it.
Bionics' German equivalent, Bionik, always adheres to the broader meaning, in that it tries to develop engineering
solutions from biological models. This approach is motivated by the fact that biological solutions will usually be
optimized by evolutionary forces.
While the technologies that make bionic implants possible are still in a very early stage, a few bionic items already
exist, the best known being the cochlear implant, a device for deaf people. By 2004 fully functional artificial hearts
were developed. Significant further progress is expected to take place with the advent of nanotechnologies. A well
known example of a proposed nanodevice is a respirocyte, an artificial red cell, designed (though not built yet) by
Robert Freitas.
Kwabena Boahen from Ghana was a professor in the Department of Bioengineering at the University of
Pennsylvania. During his eight years at Penn, he developed a silicon retina that was able to process images in the
same manner as a living retina. He confirmed the results by comparing the electrical signals from his silicon retina to
the electrical signals produced by a salamander eye while the two retinas were looking at the same image.
The Nichi-In group working on bimomimicking scaffolds in tissue engineering, stem cells and regenerative medicine
have given a detailed classification on biomimetics in medicine[10] .
Politics
A political form of biomimicry is bioregional democracy, wherein political borders conform to natural ecoregions
rather than human cultures or the outcomes of prior conflicts.
Critics of these approaches often argue that ecological selection itself is a poor model of minimizing manufacturing
complexity or conflict, and that the free market relies on conscious cooperation, agreement, and standards as much
as on efficiency – more analogous to sexual selection. Charles Darwin himself contended that both were balanced in
natural selection – although his contemporaries often avoided frank talk about sex, or any suggestion that free
market success was based on persuasion, not value.
Advocates, especially in the anti-globalization movement, argue that the mating-like processes of standardization,
financing and marketing, are already examples of runaway evolution – rendering a system that appeals to the
consumer but which is inefficient at use of energy and raw materials. Biomimicry, they argue, is an effective strategy
to restore basic efficiency.
Biomimicry is also the second principle of Natural Capitalism.
Other uses
Business biomimetics is the latest development in the application of biomimetics. Specifically it applies principles
and practice from biological systems to business strategy, process, organisation design and strategic thinking. It has
been successfully used by a range of industries in FMCG, defence, central government, packaging and business
services. Based on the work by Phil Richardson at the University of Bath[11] the approach was launched at the
House of Lords in May 2009.
In a more specific meaning, it is a creativity technique that tries to use biological prototypes to get ideas for
engineering solutions. This approach is motivated by the fact that biological organisms and their organs have been
well optimized by evolution. In chemistry, a biomimetic synthesis is a man-made chemical synthesis inspired by
4
Bionics
5
biochemical processes.
Another, more recent meaning of the term bionics refers to merging organism and machine. This approach results in
a hybrid system combining biological and engineering parts, which can also be referred as a cybernetic organism
(cyborg). Practical realization of this was demonstrated in Kevin Warwick's implant experiments bringing about
ultrasound input via his own nervous system.
See also
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Biomechatronics
Biomedical engineering
Biophysics
Cyborg
History of technology
Implant
Machine
Prosthesis
The Six Million Dollar Man
The Bionic Woman
• List of environment topics
• List of important publications in bionics
Compare with:
• Biotechnology
Sources
summary on the use of biomimetics in business [12]
European Space Agency [13] – Advanced Concepts Team Biomimetics Website
Biomimicry Institute [14]
Biomimicry: Innovation Inspired by Nature. 1997. Janine Benyus.
Biomimicry for Optimization, Control, and Automation, Springer-Verlag, London, UK, 2005, Kevin M. Passino
Ideas Stolen Right From Nature [15] (Wired Magazine)
Bionics and Engineering: The Relevance of Biology to Engineering, presented at Society of Women Engineers
Convention, Seattle, WA, 1983, Jill E. Steele
• Bionics: Nature as a Model. 1993. PRO FUTURA Verlag GmbH, München, Umweltstiftung WWF Deutschland
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External links
• BioParadigm ACCESS – Consolidates information on available biomimetic IP for product designers, engineers
and material scientists worldwide [16]
• Biomimetic Architecture [17]
• Biologize your business using biomimetics to develop strategic thinking and process [18]
• Bionic Eyes In Development [19]
• Festo Bionic Learning Network [20]
• Technology And The Quality Of Life: Part One—A Vision Of The Future [21]
• Boxfish – DaimlerChrysler [22]
• Center for Integration of Medicine and Innovative Technology developing nano-hair bionics [23]
• Bionics2Space: Bionics & Space System Design [24]
• Biomimicry Institute [14]
Bionics
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6
Biomimicry Guild [25]
LiveScience on Biomimetic armour [26]
An overview of biomimetics/biomimicry at the Science Creative Quarterly [27]
Rehabilitation Institute of Chicago's Neuro-Controlled Bionic Arm [28].
Neural Interface bionic Arm [29]
Biomimetics Network for Industrial Sustainability (BIONIS) [30]
FurTech outdoor clothing using feather and fur technology. [31]
Article on Bionics for the Disabled [32]
Bionics Research Group, Institute of Biomedical Engineering, Imperial College London [33]
Competence Network Biomimetics [34]
Biomimetic Autonomous Underwater Vehicles, AUVAC.org [35]
References
[1]
[2]
[3]
[4]
http:/ / www. duke. edu/ ~jme17/ Joshua_E. _Mendoza-Elias/ Research_Interests. html#Neuroscience_-_Neural_Plasticity_in
Nelumbo lotus inspiration for self-cleaning paint (http:/ / www. treehugger. com/ files/ 2005/ 09/ sto_lotusan_bio. php)
RFID Through Water and on Metal with 99.9% Reliability (Episode 015) (http:/ / www. rfidradio. com/ ?p=26), RFID Radio
Woodley, M. A. (2005). "Synthetic Vegetation: An Ecosystem Prosthesis", Int. J. Environ. Sci. Tech, 2:4, 395–398. (http:/ / www. ceers. org/
ijest/ issues/ abstract_result. asp?ID=204014)
[5] Avian Flight book (http:/ / www. amazon. com/ dp/ 0199299927)
[6] Videler, Stamhuis and Povel LEV-article in Science-magazine (http:/ / www. sciencemag. org/ cgi/ content/ abstract/ 306/ 5703/ 1960)
[7] Bret Tobalske's Hummingbird-research (https:/ / depts. washington. edu/ nwst/ issues/ index. php?issueID=fall_2005& storyID=742)
[8] Robofly UAV (http:/ / journalism. berkeley. edu/ projects/ mm/ spingarnkoff/ flyorama/ robofly. html)
[9] ESA's biomimetics program (http:/ / www. esa. int/ gsp/ ACT/ biomimetics/ index. htm)
[10] Nichi-In classification of biomimetics in medicine (http:/ / www. ncrm. org/ biomimetics. htm)
[11] http:/ / www. bath. ac. uk/ mech-eng/ biomimetics/
[12] http:/ / www. thoughtcrew. net/ index-4. html
[13] http:/ / www. esa. int/ gsp/ ACT/ bio/ index. htm
[14] http:/ / www. biomimicryinstitute. org
[15] http:/ / www. wired. com/ news/ technology/ 0,1282,65642,00. html?tw=wn_story_top5
[16] http:/ / www. biomimeticsregistry. net
[17] http:/ / www. biomimetic-architecture. com
[18] http:/ / www. biologize. com
[19] http:/ / www. amdsupport. ca/ articles/ 79/ 1/ Bionic-Eyes-Under-Development/ Page1. html
[20] http:/ / www. festo. com/ bionic
[21] http:/ / www. ccnmag. com/ story. php?id=197
[22] http:/ / www. daimlerchrysler. com/ dccom/ 0,,0-5-7154-1-503504-1-0-0-503518-0-0-8-10736-0-0-0-0-0-0-0,00. html
[23] http:/ / www. cimit. org
[24] http:/ / www. bionics2space. org/
[25] http:/ / www. biomimicryguild. com
[26] http:/ / www. livescience. com/ technology/ 050118_abalone_armor. html
[27] http:/ / www. scq. ubc. ca/ ?p=321
[28] http:/ / www. ric. org/ about/ news/ pr_display. php?id=319
[29] http:/ / www. sigmorobot. com/ technology/ news/ toast_bionic_man. htm
[30] http:/ / www. biomimetics. org. uk
[31] http:/ / furtech. typepad. com/ feather_and_fur_technolog
[32] http:/ / www. lfymag. com/ admin/ issuepdf/ bionics. pdf
[33] http:/ / www. imperial. ac. uk/ biomedeng/ research/ bionics
[34] http:/ / www. kompetenznetz-biomimetik. de/ index. php?lang=en
[35] http:/ / auvac. org/ resources/ search/ capabilities. php?biomimetic=y& submit
Cyborg
7
Cyborg
Part of the series on
Cyborgs
Cyborgology
Bionics / Biomimicry
Biomedical engineering
Brain-computer interface
Cybernetics
Distributed cognition
Genetic engineering
Human ecosystem
Human enhancement
Intelligence amplification
Theory
Cyborg theory
Postgenderism
Centers
Cyberpunk
Cyberspace
Politics
Cognitive liberty
Cyberpunk
Cyborg feminism
Crypto-anarchism
Extropianism
Morphological freedom
Singularitarianism
Transhumanism
A cyborg is a cybernetic organism (i.e. an organism that has both artificial and natural systems). The term was
coined in 1960 when Manfred Clynes and Nathan Kline used it in an article about the advantages of self-regulating
human-machine systems in outer space.[1] D. S. Halacy's Cyborg: Evolution of the Superman in 1965 featured an
introduction which spoke of a "new frontier" that was "not merely space, but more profoundly the relationship
between 'inner space' to 'outer space' -a bridge...between mind and matter."[2] The cyborg is often seen today merely
as an organism that has enhanced abilities due to technology,[3] but this perhaps oversimplifies the category of
feedback.
Fictional cyborgs are portrayed as a synthesis of organic and synthetic parts, and frequently pose the question of
difference between human and machine as one concerned with morality, free will, and empathy. Fictional cyborgs
may be represented as visibly mechanical (e.g. the Cybermen in the Doctor Who franchise or The Borg from Star
Trek); or as almost indistinguishable from humans (e.g. the "Human" Cylons from the re-imagining of Battlestar
Galactica). The 1970s television series The Six Million Dollar Man featured one of the most famous fictional
cyborgs. Cyborgs in fiction often play up a human contempt for over-dependence on technology, particularly when
used for war, and when used in ways that seem to threaten free will. Cyborgs are also often portrayed with physical
or mental abilities far exceeding a human counterpart (military forms may have inbuilt weapons, among other
things).
Real (as opposed to fictional) cyborgs are more frequently people who use cybernetic technology to repair or
overcome the physical and mental constraints of their bodies. While cyborgs are commonly thought of as mammals,
Cyborg
8
they can be any kind of organism.
Overview
According to some definitions of the term, the metaphysical and physical attachments humanity has with even the
most basic technologies have already made them cyborgs.[4] In a typical example, a human fitted with a heart
pacemaker or an insulin pump (if the person has diabetes) might be considered a cyborg, since these mechanical
parts enhance the body's "natural" mechanisms through synthetic feedback mechanisms. Some theorists cite such
modifications as contact lenses, hearing aids, or intraocular lenses as examples of fitting humans with technology to
enhance their biological capabilities; however, these modifications are no more cybernetic than would be a pen or a
wooden leg. Cochlear implants that combine mechanical modification with any kind of feedback response are more
accurately cyborg enhancements.
The term is also used to address human-technology mixtures in the abstract. This includes artifacts that may not
popularly be considered technology; for example, pen and paper, and speech and language. Augmented with these
technologies, and connected in communication with people in other times and places, a person becomes capable of
much more than they were before. This is like computers, which gain power by using Internet protocols to connect
with other computers. Cybernetic technologies include highways, pipes, electrical wiring, buildings, electrical plants,
libraries, and other infrastructure that we hardly notice, but which are critical parts of the cybernetics that we work
within.
Bruce Sterling in his universe of Shaper/Mechanist suggested an idea of alternative cyborg called Lobster, which is
made not by using internal implants, but by using an external shell (e.g. a Powered Exoskeleton).[5] Unlike human
cyborgs that appear human externally while being synthetic internally, a Lobster looks inhuman externally but
contains a human internally. The computer game Deus Ex: Invisible War prominently featured cyborgs called Omar,
where "Omar" is a Russian translation of the word "Lobster" (since the Omar are of Russian origin in the game).
History
The concept of a man-machine mixture was widespread in science fiction before World War II. As early as 1843,
Edgar Allan Poe described a man with extensive prostheses in the short story "The Man That Was Used Up". In
1908, Jean de la Hire introduced Nyctalope (perhaps the first true superhero was also the first literary cyborg) in the
novel L'Homme Qui Peut Vivre Dans L'eau (The Man Who Can Live in Water). Edmond Hamilton presented space
explorers with a mixture of organic and machine parts in his novel The Comet Doom in 1928. He later featured the
talking, living brain of an old scientist, Simon Wright, floating around in a transparent case, in all the adventures of
his famous hero, Captain Future. In the short story "No Woman Born" in 1944, C. L. Moore wrote of Deirdre, a
dancer, whose body was burned completely and whose brain was placed in a faceless but beautiful and supple
mechanical body.
One of the earliest uses of the term was by Manfred E. Clynes and Nathan S. Kline in 1960 to refer to their
conception of an enhanced human being who could survive in extraterrestrial environments:
For the exogenously extended organizational complex functioning as an integrated homeostatic system
unconsciously, we propose the term ‘Cyborg'. Manfred E. Clynes and Nathan S. Kline[6]
Their concept was the outcome of thinking about the need for an intimate relationship between human and machine
as the new frontier of space exploration was beginning to take place. A designer of physiological instrumentation
and electronic data-processing systems, Clynes was the chief research scientist in the Dynamic Simulation
Laboratory at Rockland State Hospital in New York.
However this may not have been the earliest use. Five months earlier The New York Times had printed:
A cyborg is essentially a man-machine system in which the control mechanisms of the human portion are
modified externally by drugs or regulatory devices so that the being can live in an environment different from
Cyborg
9
the normal one. [7]
A book titled Cyborg: Digital Destiny and Human Possibility in the Age of the Wearable computer was published by
Doubleday in 2001. Some of the ideas in the book were incorporated into the 35mm motion picture film Cyberman.
Individual cyborgs
Generally, the term "cyborg" is used to refer to a man or woman with bionic, or robotic, implants.
In current prosthetic applications, the C-Leg system developed by Otto Bock HealthCare is used to replace a human
leg that has been amputated because of injury or illness. The use of sensors in the artificial C-Leg aids in walking
significantly by attempting to replicate the user's natural gait, as it would be prior to amputation.[8] Prostheses like
the C-Leg and the more advanced iLimb are considered by some to be the first real steps towards the next generation
of real-world cyborg applications. Additionally cochlear implants and magnetic implants which provide people with
a sense that they would not otherwise have had can additionally be thought of as creating cyborgs.
In 2002, under the heading Project Cyborg, a British scientist, Kevin Warwick, had an array of 100 electrodes fired
in to his nervous system in order to link his nervous system into the Internet. With this in place he successfully
carried out a series of experiments including extending his nervous system over the Internet to control a robotic
hand, a loudspeaker and amplifier. This is a form of extended sensory input and the first direct electronic
communication between the nervous systems of two humans.[9]
In 2004, under the heading Bridging the Island of the Colourblind Project, a British and completely colorblind artist,
Neil Harbisson, had an eyeborg installed on his head in order to hear colors[10] . His prosthetic device was included
within his passport photograph as confirmation of its permanent and embedded cyborg status.[11]
Social cyborgs
More broadly, the full term "cybernetic organism" is used to describe larger networks of communication and
control. For example, cities, networks of roads, networks of software, corporations, markets, governments, and the
collection of these things together. A corporation can be considered as an artificial intelligence that makes use of
replaceable human components to function. People at all ranks can be considered replaceable agents of their
functionally intelligent government institutions, whether such a view is desirable or not.
Cyborg proliferation in society
In medicine
In medicine, there are two important and different types of cyborgs: these are the restorative and the enhanced.
Restorative technologies “restore lost function, organs, and limbs”.[12] The key aspect of restorative cyborgization is
the repair of broken or missing processes to revert to a healthy or average level of function. There is no enhancement
to the original faculties and processes that were lost.
On the contrary, the enhanced cyborg “follows a principle, and it is the principle of optimal performance:
maximising output (the information or modifications obtained) and minimising input (the energy expended in the
process) ”.[13] Thus, the enhanced cyborg intends to exceed normal processes or even gain new functions that were
not originally present.
Although prostheses in general supplement lost or damaged body parts with the integration of a mechanical artifice,
bionic implants in medicine allow model organs or body parts to mimic the original function more closely. Michael
Chorost wrote a memoir of his experience with cochlear implants, or bionic ear, titled "Rebuilt: How Becoming Part
Computer Made Me More Human." [14] Jesse Sullivan became one of the first people to operate a fully robotic limb
through a nerve-muscle graft, enabling him a complex range of motions beyond that of previous prosthetics. [15] By
2004, a fully functioning artificial heart was developed. [16] The continued technological development of bionic and
Cyborg
nanotechnologies begins to raise the question of enhancement, and of the future possibilities for cyborgs which
surpass the original functionality of the biological model. The ethics and desirability of "enhancement prosthetics"
have been debated; their proponents include the transhumanist movement, with its belief that new technologies can
assist the human race in developing beyond its present, normative limitations such as aging and disease, as well as
other, more general incapacities, such as limitations on speed, strength, endurance, and intelligence. Opponents of
the concept describe what they believe to be biases which propel the development and acceptance of such
technologies; namely, a bias towards functionality and efficiency that may compel assent to a view of human people
which de-emphasizes as defining characteristics actual manifestations of humanity and personhood, in favor of
definition in terms of upgrades, versions, and utility.[17]
A brain-computer interface, or BCI, provides a direct path of communication from the brain to an external device,
effectively creating a cyborg. Research of Invasive BCIs, which utilize electrodes implanted directly into the grey
matter of the brain, has focused on restoring damaged eye sight in the blind and providing functionality to paralyzed
people, most notably those with severe cases, such as Locked-In syndrome. This technology could enable people
who are missing a limb or are in a wheelchair the power to control the devices that aide them through neural signals
sent from the brain implants directly to computers or the devices. It is possible that this technology will also
eventually be used with healthy people also. [18]
Retinal implants are another form of cyborgization in medicine. The theory behind retinal stimulation to restore
vision to people suffering from retinitis pigmentosa and vision loss due to aging (conditions in which people have an
abnormally low amount of ganglion cells) is that the retinal implant and electrical stimulation would act as a
substitute for the missing ganglion cells (cells which connect the eye to the brain.)
While work to perfect this technology is still being done, there have already been major advances in the use of
electronic stimulation of the retina to allow the eye to sense patterns of light. A specialized camera is worn by the
subject , such as on the frames of their glasses, which converts the image into a pattern of electrical stimulation. A
chip located in the user’s eye would then electrically stimulate the retina with this pattern by exciting certain nerve
endings which transmit the image to the optic centers of the brain and the image would then appear to the user. If
technological advances proceed as planned this technology may be used by thousands of blind people and restore
vision to most of them.
A similar process has been created to aide people who have lost their vocal cords. This experimental device would
do away with previously used robotic sounding voice simulators. The transmission of sound would start with a
surgery to redirect the nerve that controls the voice and sound production to a muscle in the neck, where a nearby
sensor would be able to pick up its electrical signals. The signals would then move to a processor which would
control the timing and pitch of a voice simulator. That simulator would then vibrate producing a multitonal sound
which could be shaped into words by the mouth. [19]
In the military
Military organizations' research has recently focused on the utilization of cyborg animals for inter-species
relationships for the purposes of a supposed tactical advantage. DARPA has announced its interest in developing
"cyborg insects" to transmit data from sensors implanted into the insect during the pupal stage. The insect's motion
would be controlled from a MEMS, or Micro-Electro-Mechanical System, and would conceivably surveil an
environment and detect explosives or gas.[20] Similarly, DARPA is developing a neural implant to remotely control
the movement of sharks. The shark's unique senses would be exploited to provide data feedback in relation to enemy
ship movement and underwater explosives.[21]
In 2009 at the Institute of Electrical and Electronics Engineers (IEEE) Micro-electronic mechanical systems
(MEMS) conference in Italy, researchers demonstrated the “first wireless flying-insect cyborg.” [22] Engineers at the
University of California at Berkeley pioneered the design of a “remote controlled beetle,” funded by the Defense
Advanced Research Projects Agency (DARPA).Videographic evidence of this can be viewed here [23].
10
Cyborg
The success of the Beetle Borg has sparked an onslaught of research and the creation of a program called Hybird
Insect MEMS or HI-MEMS. The goal for HI-MEMS, according to DARPA’s Microsystems Technology Office, is to
develop “tightly coupled machine-insect interfaces by placing micro-mechanical systems inside the insects during the
early stages of metamorphosis. [24]
Eventually researchers plan to develop HI-MEMS for dragonflies, moths, beetles, bees, sharks, rats, and even
pigeons.[25] “The intimate control of insects with embedded microsystems will enable insect cyborgs, which could
carry one or more sensors, such as a microphone or a gas sensor, to relay back information gathered from the target
destination.” [26]
For the HI-MEMS cybernetic bug to be considered a success, it must fly 100 meters from a starting point, guided via
computer into a controlled landing within 5 meters of a specific end point. Once landed, the cybernetic bug must
remain in place. [27]
In sports
The cyborgization of sports has come to the forefront of the national consciousness in recent years. Through the
media, America has been exposed to the subject both with the BALCO scandal and the accusations of blood doping
at the Tour de France levied against Lance Armstrong and Floyd Landis. But, there is more to the subject; steroids,
blood doping, prosthesis, body modification, and maybe in the future, genetic modification are all topics that should
be included within cyborgs in sports.
As of now, prosthetic legs and feet are not advanced enough to give the athlete the edge, and people with these
prosthetics are allowed to compete, possibly only because they are not actually competitive in the Ironman event
among other such -athlons. Prosthesis in track and field, however, is a budding issue. Prosthetic legs and feet may
soon be better than their human counterparts. Some prosthetic legs and feet allow for runners to adjust the length of
their stride which could potentially improve run times and in time actually allow a runner with prosthetic legs to be
the fastest in the world. One model used for replacing a leg lost at the knee has actually improved runners' marathon
times by as much as 30 minutes. The leg is shaped out of a long, flat piece of metal that extends backwards then
curves under itself forming a U shape. This functions as a spring, allowing for runners to be propelled forward by
just placing their weight on the limb. This is the only form that allows the wearer to sprint.
In art
The concept of the cyborg is often associated with science fiction. However, many artists have tried to create public
awareness of cybernetic organisms; these can range from paintings to installations. Some artists who create such
works are Neil Harbisson,[28] Isa Gordon, Motohiko Odani, Nick Lampert, Patricia Piccinini[29] , Jenifer
Gonzalez,[30] Simbiotica and Oron Catts,[31] Iñigo Manglano-Ovalle,[32] Steve Mann, Orlan and Stelarc.[33] H.R.
Giger
Machines are becoming more ubiquitous in the artistic process itself, with computerized drawing pads replacing pen
and paper, and drum machines becoming nearly as popular as human drummers. This is perhaps most notable in
generative art and music. Composers such as Brian Eno have developed and utilized software which can build entire
musical scores from a few basic mathematical parameters.[34]
11
Cyborg
12
In popular culture
Cyborgs have become a well-known part of science fiction literature and other media. Examples of fictional
biologically based cyborgs include Robocop, Replicants, Star Trek's Borg and Star Wars' Darth Vader. Mechanically
based cyborgs include Cylons, and Terminators.
Further reading
• Balsamo, Anne. Technologies of the Gendered Body: Reading Cyborg Women. Durham: Duke University Press,
1996.
• Caidin, Martin. Cyborg; A Novel. New York: Arbor House, 1972.
• Clark, Andy. Natural-Born Cyborgs. Oxford: Oxford University Press, 2004.
• Crittenden, Chris. "Self-Deselection: Technopsychotic Annihilation via Cyborg." Ethics & the Environment 7.2
(Autumn 2002): 127-152.
• Franchi , Stefano, and Güven Güzeldere, eds. Mechanical Bodies, Computational Minds: Artificial Intelligence
from Automata to Cyborgs. MIT Press, 2005.
• Flanagan, Mary, and Austin Booth, eds. Reload: Rethinking Women + Cyberculture. Cambridge, Mass.: MIT
Press, 2002.
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Gray, Chris Hables. Cyborg Citizen: Politics in the Posthuman Age. Routledge & Kegan Paul, 2001.
Gray, Chris Hables, ed. The Cyborg Handbook. New York: Routledge, 1995.
Grenville, Bruce, ed. The Uncanny: Experiments in Cyborg Culture. Arsenal Pulp Press, 2002.
Halacy, D. S. Cyborg: Evolution of the Superman. New York: Harper & Row, 1965.
Halberstam, Judith, and Ira Livingston. Posthuman Bodies. Bloomington: Indiana University Press, 1995.
Haraway, Donna. Simians, Cyborgs, and Women; The Reinvention of Nature. New York: Routledge, 1990.
Klugman, Craig. "From Cyborg Fiction to Medical Reality." Literature and Medicine 20.1 (Spring 2001): 39-54.
Kurzweil, Ray. The Singularity Is Near: When Humans Transcend Biology. Viking, 2005.
Mann, Steve. "Telematic Tubs against Terror: Bathing in the Immersive Interactive Media of the Post-Cyborg
Age." Leonardo 37.5 (October 2004): 372-373.
Mann, Steve, and Hal Niedzviecki. Cyborg: digital destiny and human possibility in the age of the wearable
computer Doubleday, 2001. ISBN 0-385-65825-7 (A paperback version also exists, ISBN 0-385-65826-5).
Masamune Shirow, Ghost in the Shell. Endnotes, 1991. Kodansha ISBN 4-7700-2919-5.
Mertz, David. "Cyborgs" [35]. International Encyclopedia of Communications. Blackwell 2008.
ISBN 0195049942. Retrieved 2008-10-28.
Mitchell, William. Me++: The Cyborg Self and the Networked City. Cambridge, Mass.: MIT Press, 2003.
Muri, Allison. The Enlightenment Cyborg: A History of Communications and Control in the Human Machine,
1660–1830. Toronto: University of Toronto Press, 2006.
Muri, Allison. Of Shit and the Soul: Tropes of Cybernetic Disembodiment [36]. Body & Society 9.3 (2003):
73–92.
Nishime, LeiLani. "The Mulatto Cyborg: Imagining a Multiracial Future." Cinema Journal 44.2 (Winter 2005),
34-49.
The Oxford English dictionary. 2nd ed. edited by J.A. Simpson and E.S.C. Weiner. Oxford: Clarendon Press;
Oxford and New York: Oxford University Press, 1989. Vol 4 p. 188.
Rorvik, David M. As Man Becomes Machine: the Evolution of the Cyborg. Garden City, N.Y.: Doubleday, 1971.
Rushing, Janice Hocker, and Thomas S. Frentz. Projecting the Shadow: The Cyborg Hero in American Film.
Chicago: University of Chicago Press, 1995.
• Smith, Marquard, and Joanne Morra, eds. The Prosthetic Impulse: From a Posthuman Present to a Biocultural
Future. MIT Press, 2005.
Cyborg
• The science fiction handbook for readers and writers. By George S. Elrick. Chicago: Chicago Review Press,
1978, p. 77.
• The science fiction encyclopaedia. General editor, Peter Nicholls, associate editor, John Clute, technical editor,
Carolyn Eardley, contributing editors, Malcolm Edwards, Brian Stableford. 1st ed. Garden City, N.Y.:
Doubleday, 1979, p. 151.
• Warwick, Kevin. I,Cyborg, University of Illinois Press, 2004.
• Yoshito Ikada, Bio Materials: an approach to Artificial Organs
References
[1] " Cyborgs and Space (http:/ / www. scribd. com/ doc/ 2962194/ Cyborgs-and-Space-Clynes-Kline?autodown=pdf)," in Astronautics
(September 1960), by Manfred E. Clynes and Nathan S. Kline.
[2] D. S. Halacy, Cyborg: Evolution of the Superman (New York: Harper and Row Publishers, 1965), 7.
[3] Technology as extension of human functional architecture (http:/ / www. lucifer. com/ ~sasha/ articles/ techuman. html) by Alexander
Chislenko
[4] A Cyborg Manifesto: Science, Technology, and Socialist-Feminism in the Late Twentieth Century (http:/ / www. stanford. edu/ dept/ HPS/
Haraway/ CyborgManifesto. html) by Donna Haraway
[5] Sterling, Bruce. Schismatrix. Arbor House. 1985.
[6] Manfred E. Clynes, and Nathan S. Kline, (1960) "Cyborgs and space," Astronautics, September, pp. 26-27 and 74-75; reprinted in Gray,
Mentor, and Figueroa-Sarriera, eds., The Cyborg Handbook, New York: Routledge, 1995, pp. 29-34. (hardback: ISBN 0-415-90848-5;
paperback: ISBN 0-415-90849-3)
[7] OED On-line (http:/ / www. oed. com/ bbcwordhunt/ cyborg. html)
[8] Otto Bock HealthCare : a global leader in healthcare products | Otto Bock (http:/ / www. ottobockus. com/ PRODUCTS/
LOWER_LIMB_PROSTHETICS/ cleg_technology. asp)
[9] Warwick, K, Gasson, M, Hutt, B, Goodhew, I, Kyberd, P, Schulzrinne, H and Wu, X: “Thought Communication and Control: A First Step
using Radiotelegraphy”, IEE Proceedings on Communications, 151(3), pp.185-189, 2004
[10] Alfredo M. Ronchi: Eculture: Cultural Content in the Digital Age. Springer (New York, 2009). p.319 ISBN 978-3-540-75273-8
[11] Andy Miah, Emma Rich: The Medicalization of Cyberspace Routledge (New York, 2008) p.130 (Hardcover:ISBN 978-0-415-37622-8
Papercover: ISBN 978-0-415-39364-5)
[12] Gray, Chris Hables, ed. The Cyborg Handbook. New York: Routledge, 1995
[13] Lyotard, Jean François: The postmodern condition: A report on knowledge. Minneapolis: University of Minnesota Press, 1984
[14] Chorost, Michael. "The Naked Ear." Technology Review 111.1 (2008): 72-74. Academic Search Complete. EBSCO. Web. 8 Mar. 2010.
[15] Murray, Chuck. "Re-wiring the Body." Design News 60.15 (2005): 67-72. Academic Search Complete. EBSCO. Web. 8 Mar. 2010.
[16] Haddad, Michel, et al. "Improved Early Survival with the Total Artificial Heart." Artificial Organs 28.2 (2004): 161-165. Academic Search
Complete. EBSCO. Web. 8 Mar. 2010.
[17] Marsen, Sky. "Becoming More Than Human: Technology and the Post-Human Condition Introduction." Journal of Evolution & Technology
19.1 (2008): 1-5. Academic Search Complete. EBSCO. Web. 9 Mar. 2010.
[18] Baker, Sherry. "RISE OF THE CYBORGS." Discover 29.10 (2008): 50-57. Academic Search Complete. EBSCO. Web. 8 Mar. 2010.
[19] Thurston, Bonnie. "Was blind, but now I see." 11. Christian Century Foundation, 2007. Academic Search Complete. EBSCO. Web. 8 Mar.
2010.
[20] Washington Times - Military seeks to develop 'insect cyborgs' (http:/ / www. washingtontimes. com/ national/ 20060313-120147-9229r.
htm)
[21] Military Plans Cyborg Sharks | LiveScience (http:/ / www. livescience. com/ technology/ 060307_shark_implant. html)
[22] Ornes, Stephen. "THE PENTAGON'S BEETLE BORGS." Discover 30.5 (2009): 14. Academic Search Complete. EBSCO. Web. 1 Mar.
2010.
[23] http:/ / www. youtube. com/ watch?v=_i-_1QdY2Zc& feature=related
[24] Judy, Jack, Phd. "Hybrid Insect MEMS (HI-MEMS)." HI-MEMS - Programs - Microsystem Technology Office. DARPA, Web. 5 Mar
2010. <http://www.darpa.mil/mto/programs/himems/index.html#content>.
[25] Guizzo, Eric. "Moth Pupa + MEMS Chip = Remote Controlled Cyborg Insect." Automan. IEEE Spectrum, 17 Feb 2009. Web. 1 Mar 2010.
<http://spectrum.ieee.org/automaton/robotics/robotics-software/moth_pupa_mems_chip_remote_controlled_cyborg_insect>.
[26] Judy, Jack, Phd. "Hybrid Insect MEMS (HI-MEMS)." HI-MEMS - Programs - Microsystem Technology Office. DARPA, Web. 5 Mar
2010. <http://www.darpa.mil/mto/programs/himems/index.html#content>.
[27] Guizzo, Eric. "Moth Pupa + MEMS Chip = Remote Controlled Cyborg Insect." Automan. IEEE Spectrum, 17 Feb 2009. Web. 1 Mar 2010.
<http://spectrum.ieee.org/automaton/robotics/robotics-software/moth_pupa_mems_chip_remote_controlled_cyborg_insect>.
[28] Neil Harbisson personal website (http:/ / www. harbisson. com/ )
[29] Patricia Piccinini personal website (http:/ / patriciapiccinini. net/ )
[30] Gray, C.H.: The Cyborg Handbook. Routledge, 1995.
13
Cyborg
14
[31] Simbiotica personal website (http:/ / www. symbiotica. uwa. edu. au/ )
[32] Iñigo Manglano-Ovalle Guggenheim Museum page (http:/ / www. guggenheim. org/ exhibitions/ past_exhibitions/ moving_pictures/
highlights_15a. html)
[33] Zylinska, J: The Cyborg Experiments. Continuum, 2002.
[34] Generative Music - Brian Eno - In Motion Magazine (http:/ / www. inmotionmagazine. com/ eno1. html)
[35] http:/ / gnosis. cx/ publish/ mertz/ Cyborgs. pdf
[36] http:/ / headlesschicken. ca/ archive/ Shit& Soul. pdf
Brain
The brain is the center of the nervous system in all
vertebrate, and most invertebrate, animals.[1] Some
primitive animals such as jellyfish and starfish have a
decentralized nervous system without a brain, while
sponges lack any nervous system at all. In vertebrates,
the brain is located in the head, protected by the skull
and close to the primary sensory apparatus of vision,
hearing, balance, taste, and smell.
Brains can be extremely complex. The cerebral cortex
of the human brain contains roughly 15–33 billion
neurons, perhaps more, depending on gender and
age,[2] linked with up to 10,000 synaptic connections
each. Each cubic millimeter of cerebral cortex contains
roughly one billion synapses.[3] These neurons
communicate with one another by means of long
protoplasmic fibers called axons, which carry trains of
signal pulses called action potentials to distant parts of
the brain or body and target them to specific recipient
cells.
A chimpanzee brain
The brain controls the other organ systems of the body,
either by activating muscles or by causing secretion of
chemicals such as hormones. This centralized control allows rapid and coordinated responses to changes in the
environment. Some basic types of responsiveness are possible without a brain: even single-celled organisms may be
capable of extracting information from the environment and acting in response to it.[4] Sponges, which lack a central
nervous system, are capable of coordinated body contractions and even locomotion.[5] In vertebrates, the spinal cord
by itself contains neural circuitry capable of generating reflex responses as well as simple motor patterns such as
swimming or walking.[6] However, sophisticated control of behavior on the basis of complex sensory input requires
the information-integrating capabilities of a centralized brain.
Despite rapid scientific progress, much about how brains work remains a mystery. The operations of individual
neurons and synapses are now understood in considerable detail, but the way they cooperate in ensembles of
thousands or millions has been very difficult to decipher. Methods of observation such as EEG recording and
functional brain imaging tell us that brain operations are highly organized, while single unit recording can resolve
the activity of single neurons, but how individual cells give rise to complex operations is unknown.[7]
Brain
15
Macroscopic structure
The brain is the most complex biological structure known,[8] and comparing the brains of different species on the
basis of appearance is often difficult. Nevertheless, there are common principles of brain architecture that apply
across a wide range of species. These are revealed mainly by three approaches. The evolutionary approach means
comparing brain structures of different species, and using the principle that features found in all branches that have
descended from a given ancient form were probably present in the ancestor as well. The developmental approach
means examining how the form of the brain changes during the progression from embryonic to adult stages. The
genetic approach means analyzing gene expression in various parts of the brain across a range of species. Each
approach complements and informs the other two.
Bilateria
With the exception of a few primitive forms such as sponges and
jellyfish, all living animals are bilateria, meaning animals with a
bilaterally symmetric body shape (that is, left and right sides that are
approximate mirror images of each other).[9]
Nervous system of a bilaterian animal, in the
All bilateria are thought to have descended from a common ancestor
form of a nerve cord with segmental
that appeared early in the Cambrian period, 550–600 million years
enlargements, and a "brain" at the front
ago.[9] This ancestor had the shape of a simple tube worm with a
segmented body, and at an abstract level, that worm-shape continues to be reflected in the body and nervous system
plans of all modern bilateria, including humans.[10] The fundamental bilateral body form is a tube with a hollow gut
cavity running from mouth to anus, and a nerve cord with an enlargement (a "ganglion") for each body segment,
with an especially large ganglion at the front, called the "brain".
Invertebrates
For invertebrates (e.g., insects, molluscs, worms, etc.) the components
of the brain differ so greatly from the vertebrate pattern that it is hard
to make meaningful comparisons except on the basis of genetics. Two
groups of invertebrates have notably complex brains: arthropods
(insects, crustaceans, arachnids, and others), and cephalopods
(octopuses, squids, and similar molluscs).[11] The brains of arthropods
and cephalopods arise from twin parallel nerve cords that extend
through the body of the animal. Arthropods have a central brain with
three divisions and large optical lobes behind each eye for visual
processing.[11] Cephalopods have the largest brains of any
invertebrates. The brain of the octopus in particular is highly
developed, comparable in complexity to the brains of some vertebrates.
Drosophila
There are a few invertebrates whose brains have been studied intensively. The large sea slug Aplysia was chosen by
Nobel Prize-winning neurophysiologist Eric Kandel, because of the simplicity and accessibility of its nervous
system, as a model for studying the cellular basis of learning and memory, and subjected to hundreds of
experiments.[12] The most thoroughly studied invertebrate brains, however, belong to the fruit fly Drosophila and the
tiny roundworm Caenorhabditis elegans (C. elegans).
Because of the large array of techniques available for studying their genetics, fruit flies have been a natural subject
for studying the role of genes in brain development.[13] Remarkably, many aspects of Drosophila neurogenetics have
turned out to be relevant to humans. The first biological clock genes, for example, were identified by examining
Drosophila mutants that showed disrupted daily activity cycles.[14] A search in the genomes of vertebrates turned up
Brain
a set of analogous genes, which were found to play similar roles in the mouse biological clock—and therefore almost
certainly in the human biological clock as well.[15]
Like Drosophila, the nematode worm C. elegans has been studied largely because of its importance in genetics.[16]
In the early 1970s, Sydney Brenner chose it as a model system for studying the way that genes control development.
One of the advantages of working with this worm is that the body plan is very stereotyped: the nervous system of the
hermaphrodite morph contains exactly 302 neurons, always in the same places, making identical synaptic
connections in every worm.[17] In a heroic project, Brenner's team sliced worms into thousands of ultrathin sections
and photographed every section under an electron microscope, then visually matched fibers from section to section,
in order to map out every neuron and synapse in the entire body.[18] Nothing approaching this level of detail is
available for any other organism, and the information has been used to enable a multitude of studies that would not
have been possible without it.
Vertebrates
The brains of vertebrates are made of very soft tissue, with a texture
that has been compared to Jello.[19] Living brain tissue is pinkish on
the outside and mostly white on the inside, with subtle variations in
color. Vertebrate brains are surrounded by a system of connective
tissue membranes called meninges that separate the skull from the
brain.[20] This three-layered covering is composed of (from the outside
in) the dura mater ("hard mother"), arachnoid mater ("spidery
mother"), and pia mater ("soft mother"). The arachnoid and pia are
physically connected and thus often considered as a single layer, the
pia-arachnoid. Below the arachnoid is the subarachnoid space which
contains cerebrospinal fluid (CSF), which circulates in the narrow
spaces between cells and through cavities called ventricles, and serves
The brain of a shark
to nourish, support, and protect the brain tissue. Blood vessels enter the
central nervous system through the perivascular space above the pia
mater. The cells in the blood vessel walls are joined tightly, forming the blood-brain barrier which protects the brain
from toxins that might enter through the blood.
The first vertebrates appeared over 500 million years ago (mya), during the Cambrian period, and may have
somewhat resembled the modern hagfish in form.[21] Sharks appeared about 450 mya, amphibians about 400 mya,
reptiles about 350 mya, and mammals about 200 mya. No modern species should be described as more "primitive"
than others, since all have an equally long evolutionary history, but the brains of modern hagfishes, lampreys, sharks,
amphibians, reptiles, and mammals show a gradient of size and complexity that roughly follows the evolutionary
sequence.[22] All of these brains contain the same set of basic anatomical components, but many are rudimentary in
hagfishes, whereas in mammals the foremost parts are greatly elaborated and expanded.
All vertebrate brains share a common underlying form, which can most easily be appreciated by examining how they
develop.[23] The first appearance of the nervous system is as a thin strip of tissue running along the back of the
embryo. This strip thickens and then folds up to form a hollow tube. The front end of the tube develops into the
brain. In its earliest form, the brain appears as three swellings, which eventually become the forebrain, midbrain, and
hindbrain. In many classes of vertebrates these three parts remain similar in size in the adult, but in mammals the
forebrain becomes much larger than the other parts, and the midbrain quite small.
The relationship between brain size, body size and other variables has been studied across a wide range of vertebrate
species. Brain size increases with body size but not proportionally. Averaging across all orders of mammals, it
follows a power law, with an exponent of about 0.75.[24] This formula applies to the average brain of mammals but
each family departs from it, reflecting their sophistication of behavior.[25] For example, primates have brains 5 to 10
16
Brain
17
times as large as the formula predicts. Predators tend to have larger brains. When the mammalian brain increases in
size, not all parts increase at the same rate. The larger the brain of a species, the greater the fraction taken up by the
cortex.[26]
Vertebrate brain regions
Neuroanatomists usually consider the brain to consist of six main regions: the telencephalon (cerebral hemispheres),
diencephalon (thalamus and hypothalamus), mesencephalon (midbrain), cerebellum, pons, and medulla
oblongata.[27] Each of these areas in turn has a complex internal structure. Some areas, such as the cortex and
cerebellum, consist of layers, folded or convoluted to fit within the available space. Other areas consist of clusters of
many small nuclei. If fine distinctions are made on the basis of neural structure, chemistry, and connectivity,
thousands of distinguishable areas can be identified within the vertebrate brain.
Some branches of vertebrate evolution have led to substantial changes in brain shape, especially in the forebrain. The
brain of a shark shows the basic components in a straightforward way, but in teleost fishes (the great majority of
modern species), the forebrain has become "everted", like a sock turned inside out. In birds, also, there are major
changes in shape.[28] One of the main structures in the avian forebrain, the dorsal ventricular ridge, was long thought
to correspond to the basal ganglia of mammals, but is now thought to be more closely related to the neocortex.[29]
Several brain areas have maintained their identities across the whole
range of vertebrates, from hagfishes to humans.[1] Here is a list of some
of the most important areas, along with a very brief description of their
functions as currently understood (but note that the functions of most
of them are still disputed to some degree):
• The medulla, along with the spinal cord, contains many small nuclei
involved in a wide variety of sensory and motor functions.[30]
• The hypothalamus is a small region at the base of the forebrain,
whose complexity and importance belies its size. It is composed of
numerous small nuclei, each with distinct connections and distinct
neurochemistry. The hypothalamus is the central control station for
sleep/wake cycles, control of eating and drinking, control of
hormone release, and many other critical biological functions.[31]
• Like the hypothalamus, the thalamus is a collection of nuclei with
diverse functions. Some of them are involved in relaying
information to and from the cerebral hemispheres. Others are
Main anatomical regions of the vertebrate brain
involved in motivation. The subthalamic area (zona incerta) seems
to contain action-generating systems for several types of "consummatory" behaviors, including eating, drinking,
defecation, and copulation.[32]
• The cerebellum modulates the outputs of other brain systems to make them more precise. Removal of the
cerebellum does not prevent an animal from doing anything in particular, but it makes actions hesitant and
clumsy. This precision is not built-in, but learned by trial and error. Learning how to ride a bicycle is an example
of a type of neural plasticity that may take place largely within the cerebellum.[33]
• The tectum, often called "optic tectum", allows actions to be directed toward points in space. In mammals it is
called the "superior colliculus", and its best studied function is to direct eye movements. It also directs reaching
movements, though. It gets strong visual inputs, but also inputs from other senses that are useful in directing
actions, such as auditory input in owls, input from the thermosensitive pit organs in snakes, etc. In some fishes,
such as lampreys, it is the largest part of the brain.[34]
• The pallium is a layer of gray matter that lies on the surface of the forebrain. In reptiles and mammals it is called
cortex instead. The pallium is involved in multiple functions, including olfaction and spatial memory. In
Brain
mammals, where it comes to dominate the brain, it subsumes functions from many subcortical areas.[35]
• The hippocampus, strictly speaking, is found only in mammals. However, the area it derives from, the medial
pallium, has counterparts in all vertebrates. There is evidence that this part of the brain is involved in spatial
memory and navigation in fishes, birds, reptiles, and mammals.[36]
• The basal ganglia are a group of interconnected structures in the forebrain, of which our understanding has
increased enormously over the last few years. The primary function of the basal ganglia seems to be action
selection. They send inhibitory signals to all parts of the brain that can generate actions, and in the right
circumstances can release the inhbition, so that the action-generating systems are able to execute their actions.
Rewards and punishments exert their most important neural effects within the basal ganglia.[37]
• The olfactory bulb is a special structure that processes olfactory sensory signals, and sends its output to the
olfactory part of the pallium. It is a major brain component in many vertebrates, but much reduced in primates.[38]
Mammals
The cerebral cortex is the part of the brain that most strongly distinguishes mammals from other vertebrates,
primates from other mammals, and humans from other primates. The hindbrain and midbrain of mammals are
generally similar to those of other vertebrates, but dramatic differences appear in the forebrain, which is not only
greatly enlarged, but also altered in structure.[39] In non-mammalian vertebrates, the surface of the cerebrum is lined
with a comparatively simple layered structure called the pallium.[40] In mammals, the pallium evolves into a
complex 6-layered structure called neocortex or isocortex. In primates, the neocortex is greatly enlarged, especially
the part called the frontal lobes. In humans, this enlargement of the frontal lobes is taken to an extreme, and other
parts of the cortex also become quite large and complex. Also the hippocampus of mammals has a distinctive
structure.
Unfortunately, the evolutionary history of these mammalian features, especially the 6-layered cortex, is difficult to
trace.[41] This is largely because of a missing link problem. The ancestors of mammals, called synapsids, split off
from the ancestors of modern reptiles and birds about 350 million years ago. However, the most recent branching
that has left living results within the mammals was the split between monotremes (the platypus and echidna),
marsupials (opossum, kangaroo, etc.) and placentals (most living mammals), which took place about 120 million
years ago. The brains of monotremes and marsupials are distinctive from those of placentals in some ways, but they
have fully mammalian cortical and hippocampal structures. Thus, these structures must have evolved between 350
and 120 million years ago, a period that has left no evidence except fossils, which do not preserve tissue as soft as
brain.
Primates, including humans
The primate brain contains the same structures as the brains of other mammals, but is considerably larger in
proportion to body size.[26] Most of the enlargement comes from a massive expansion of the cortex, focusing
especially on the parts subserving vision and forethought.[42] The visual processing network of primates is very
complex, including at least 30 distinguishable areas, with a bewildering web of interconnections. Taking all of these
together, visual processing makes use of about half of the brain. The other part of the brain that is greatly enlarged is
the prefrontal cortex, whose functions are difficult to summarize succinctly, but relate to planning, working memory,
motivation, attention, and executive control.
18
Brain
19
Microscopic structure
Structure of a typical neuron
Neuron
Dendrite
Soma
Axon
Nucleus
Node of
Ranvier
Axon terminal
Schwann cell
Myelin sheath
The brain is composed of two broad classes of cells: neurons and glia.[43] These two types are equally numerous in
the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex.[44] Glia come in
several types, which perform a number of critical functions, including structural support, metabolic support,
insulation, and guidance of development.
The property that makes neurons so important is that, unlike glia, they are capable of sending signals to each other
over long distances.[45] They send these signals by means of an axon, a thin protoplasmic fiber that extends from the
cell body and projects, usually with numerous branches, to other areas, sometimes nearby, sometimes in distant parts
of the brain or body. The extent of an axon can be extraordinary: to take an example, if a pyramidal cell of the
neocortex were magnified so that its cell body became the size of a human, its axon, equally magnified, would
become a cable a few centimeters in diameter, extending farther than a kilometer. These axons transmit signals in the
form of electrochemical pulses called action potentials, lasting less than a thousandth of a second and traveling along
the axon at speeds of 1–100 meters per second. Some neurons emit action potentials constantly, at rates of 10–100
per second, usually in irregular temporal patterns; other neurons are quiet most of the time, but occasionally emit a
burst of action potentials.
Axons transmit signals to other neurons, or to non-neuronal cells, by means of specialized junctions called
synapses.[46] A single axon may make as many as several thousand synaptic connections. When an action potential,
traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The
neurotransmitter binds to receptor molecules in the membrane of the target cell. Some types of neuronal receptors
are excitatory, meaning that they increase the rate of action potentials in the target cell; other receptors are inhibitory,
meaning that they decrease the rate of action potentials; others have complex modulatory effects.
Brain
Axons actually fill most of the space in the brain.[47] Often large groups of them are bundled together in what are
called nerve fiber tracts. Many axons are wrapped in thick sheaths of a fatty substance called myelin, which serves to
greatly increase the speed of action potential propagation. Myelin is white, so parts of the brain filled exclusively
with nerve fibers appear as white matter, in contrast to the gray matter that marks areas with high densities of neuron
cell bodies. The total length of myelinated axons in an average adult human brain is well over 100000 kilometres
(62000 mi) .[48]
Development
The brain does not simply grow; rather, it develops in an intricately
orchestrated sequence of stages.[49] Many neurons are created in
special zones that contain stem cells, and then migrate through the
tissue to reach their ultimate locations.[50] In the cortex, for example,
the first stage of development is the formation of a "scaffold" by a
special group of glial cells, called radial glia, which send fibers
vertically across the cortex. New cortical neurons are created at the
bottom of the cortex, and then "climb" along the radial fibers until they
reach the layers they are destined to occupy in the adult.
In vertebrates, the early stages of neural development are similar for all
This diagram depicts the main subdivisions of the
species.[49] As the embryo transforms from a round blob of cells into a
embryonic vertebrate brain. These regions will
later differentiate into forebrain, midbrain and
wormlike structure, a narrow strip of ectoderm running along the
hindbrain structures.
midline of the back is induced to become the neural plate, the precursor
of the nervous system. The neural plate invaginates to form the neural
groove, and then the folds that line the groove merge to enclose the neural tube, a hollow cord of cells with a
fluid-filled ventricle at the center. At the front end, the ventricles and cord swell to form three vesicles that are the
precursors of the forebrain, midbrain, and hindbrain.[49] At the next stage, the forebrain splits into two vesicles called
the telencephalon (which will contain the cerebral cortex, basal ganglia, and related structures) and the diencephalon
(which will contain the thalamus and hypothalamus). At about the same time, the hindbrain splits into the
metencephalon (which will contain the cerebellum and pons) and the myelencephalon (which will contain the
medulla oblongata). Each of these areas contains proliferative zones at which neurons and glia cells are generated;
the resulting cells then migrate, sometimes for long distances, to their final positions.
Once a neuron is in place, it begins to extend dendrites and an axon into the area around it.[51] Axons, because they
commonly extend a great distance from the cell body and need to make contact with specific targets, grow in a
particularly complex way. The tip of a growing axon consists of a blob of protoplasm called a "growth cone",
studded with chemical receptors. These receptors sense the local environment, causing the growth cone to be
attracted or repelled by various cellular elements, and thus to be pulled in a particular direction at each point along its
path. The result of this pathfinding process is that the growth cone navigates through the brain until it reaches its
destination area, where other chemical cues cause it to begin generating synapses. Taking the entire brain into
account, many thousands of genes give rise to proteins that influence axonal pathfinding.
The synaptic network that finally emerges is only partly determined by genes, though. In many parts of the brain,
axons initially "overgrow", and then are "pruned" by mechanisms that depend on neural activity.[52] In the projection
from the eye to the midbrain, for example, the structure in the adult contains a very precise mapping, connecting
each point on the surface of the retina to a corresponding point in a midbrain layer. In the first stages of
development, each axon from the retina is guided to the right general vicinity in the midbrain by chemical cues, but
then branches very profusely and makes initial contact with a wide swath of midbrain neurons. The retina, before
birth, contains special mechanisms that cause it to generate waves of activity that originate spontaneously at some
20
Brain
point and then propagate slowly across the retinal layer.[53] These waves are useful because they cause neighboring
neurons to be active at the same time: that is, they produce a neural activity pattern that contains information about
the spatial arrangement of the neurons. This information is exploited in the midbrain by a mechanism that causes
synapses to weaken, and eventually vanish, if activity in an axon is not followed by activity of the target cell. The
result of this sophisticated process is a gradual tuning and tightening of the map, leaving it finally in its precise adult
form.
Similar things happen in other brain areas: an initial synaptic matrix is generated as a result of genetically
determined chemical guidance, but then gradually refined by activity-dependent mechanisms, partly driven by
internal dynamics, partly by external sensory inputs. In some cases, as with the retina-midbrain system, activity
patterns depend on mechanisms that operate only in the developing brain, and apparently exist solely for the purpose
of guiding development.[53]
In humans and many other mammals, new neurons are created mainly before birth, and the infant brain actually
contains substantially more neurons than the adult brain.[54] There are, however, a few areas where new neurons
continue to be generated throughout life. The two areas for which this is well established are the olfactory bulb,
which is involved in the sense of smell, and the dentate gyrus of the hippocampus, where there is evidence that the
new neurons play a role in storing newly acquired memories. With these exceptions, however, the set of neurons that
is present in early childhood is the set that is present for life. Glial cells are different, however; as with most types of
cells in the body, these are generated throughout the lifespan.
Although the pool of neurons is largely in place by birth, the axonal connections continue to develop for a long time
afterward. In humans, full myelination is not completed until adolescence.[55]
There has long been debate about whether the qualities of mind, personality, and intelligence can mainly be
attributed to heredity or to upbringing; the nature versus nurture debate.[56] This is not just a philosophical question:
it has great practical relevance to parents and educators. Although many details remain to be settled, neuroscience
clearly shows that both factors are essential. Genes determine the general form of the brain, and genes determine
how the brain reacts to experience. Experience, however, is required to refine the matrix of synaptic connections. In
some respects it is mainly a matter of presence or absence of experience during critical periods of development.[57]
In other respects, the quantity and quality of experience may be more relevant: for example, there is substantial
evidence that animals raised in enriched environments have thicker cortices, indicating a higher density of synaptic
connections, than animals whose levels of stimulation are restricted.[58]
Functions
From an organismic perspective, the primary function of a brain is to control the actions of an animal.[59] To do this,
it extracts enough relevant information from sense organs to refine actions. Sensory signals may stimulate an
immediate response as when the olfactory system of a deer detects the odor of a wolf; they may modulate an ongoing
pattern of activity as in the effect of light-dark cycles on an organism's sleep-wake behavior; or their information
may be stored in case of future relevance. The brain manages its complex task by orchestrating functional
subsystems, which can be categorized in a number of ways: anatomically, chemically, and functionally.
Functional subsystems
The most straightforward way to categorize the parts of the brain is anatomically, but there are also several ways to
subdivide it functionally. One of the most important of these is on the basis of the chemical neurotransmitters used
by neurons to communicate with each other. Another is in terms of the way a brain area contributes to information
processing: sensory areas bring information into the brain and reformat it; motor signals send information out of the
brain to control muscles and glands; arousal systems modulate the activity of the brain according to time of day and
other factors.
21
Brain
Neurotransmitter systems
With few exceptions, each neuron in the brain consistently releases the same chemical neurotransmitter, or
combination of neurotransmitters, at all of the synaptic connections it makes with other neurons; this rule is known
as Dale's principle.[60] Thus, a neuron can be characterized by the neurotransmitters it releases. The two
neurotransmitters that appear most frequently are glutamate, which is almost always excitatory, and
gamma-aminobutyric acid (GABA), which is almost always inhibitory. Neurons using these transmitters can be
found in nearly every part of the brain, making up a large percentage of the brain's pool of synapses.[61]
Nevertheless, the great majority of psychoactive drugs exert their effects by altering neurotransmitter systems not
directly involving glutamatergic or GABAergic transmission.[62] Drugs such as caffeine, nicotine, heroin, cocaine,
Prozac, Thorazine, etc., act on other neurotransmitters. Many of these other transmitters come from neurons that are
localized in particular parts of the brain. Serotonin, for example—the primary target of antidepressant drugs and
many dietary aids—comes exclusively from a small brainstem area called the Raphe nuclei. Norepinephrine, which
is involved in arousal, comes exclusively from a nearby small area called the locus ceruleus. Histamine, as a
neurotransmitter, comes from a tiny part of the hypothalamus called the tuberomammilary nucleus (histamine also
has non-CNS functions, but the neurotransmitter function is what causes antihistamines to have sedative effects).
Other neurotransmitters such as acetylcholine and dopamine have multiple sources in the brain, but are not as
ubiquitously distributed as glutamate and GABA.
Sensory systems
One of the primary functions of a brain is to extract biologically relevant information from sensory inputs.[63] Even
in the human brain, sensory processes go well beyond the classical five senses of sight, sound, taste, touch, and
smell: our brains are provided with information about temperature, balance, limb position, and the chemical
composition of the bloodstream, among other things. All of these modalities are detected by specialized sensors that
project signals into the brain. In other animals, additional senses may be present, such as the infrared heat-sensors in
the pit organs of snakes; or the "standard" senses may be used in nonstandard ways, as in the auditory "sonar" of
bats. Here are a few principles that apply to most sensory systems, using the auditory system for specific examples.
Each sensory system begins with specialized "sensory receptor" cells. These are neurons, but unlike most neurons,
they are not controlled by synaptic input from other neurons: instead they are activated by membrane-bound
receptors that are sensitive to some physical modality, such as light, temperature, or physical stretching. The axons
of sensory receptor cells travel into the spinal cord or brain. For the sense of hearing, the receptors are located in the
inner ear, on the cochlea, and are activated by vibration.[64]
For most senses, there is a "primary nucleus" or set of nuclei, located in the brainstem, that gathers signals from the
sensory receptor cells. For the sense of hearing, these are the cochlear nuclei.[64] In many cases, there are secondary
subcortical areas that extract special information of some sort. For the sense of hearing, the superior olivary area and
inferior colliculus are involved in comparing the signals from the two ears to extract information about the direction
of the sound source, among other functions.[64] Each sensory system also has a special part of the thalamus dedicated
to it, which serves as a relay to the cortex. For the sense of hearing, this is the medial geniculate nucleus.[64]
For each sensory system, there is a "primary" cortical area that receives direct input from the thalamic relay area. For
the auditory system this is the primary auditory cortex, located in the upper part of the temporal lobe.[64] There are
also usually a set of "higher level" cortical sensory areas, which analyze the sensory input in specific ways. For the
auditory system, there are areas that analyze sound quality, rhythm, and temporal patterns of change, among other
features.[64] Finally, there are multimodal areas that combine inputs from different sensory modalities, for example
auditory and visual. At this point, the signals have reached parts of the brain that are best described as integrative
rather than specifically sensory.[64]
All of these rules have exceptions. For example, the sense of touch (which is actually a set of at least half-a-dozen
distinct mechanical senses), the sensory inputs terminate mainly in the spinal cord, on neurons that then project to
22
Brain
the brainstem.[65] For the sense of smell, there is no relay in the thalamus; instead the signals go directly from the
primary brain area—the olfactory bulb—to the cortex.[66]
Motor systems
Motor systems are areas of the brain that are more or less directly involved in producing body movements, that is, in
activating muscles. With the exception of the muscles that control the eye, all of the voluntary muscles[67] in the
body are directly innervated by motor neurons in the spinal cord, which therefore are the final common path for the
movement-generating system.[68] Spinal motor neurons are controlled both by neural circuits intrinsic to the spinal
cord, and by inputs that descend from the brain. The intrinsic spinal circuits implement many reflex responses, and
also contain pattern generators for rhythmic movements such as walking or swimming.[69] The descending
connections from the brain allow for more sophisticated control.
The brain contains a number of areas that project directly to the spinal cord.[70] At the lowest level are motor areas in
the medulla and pons. At a higher level are areas in the midbrain, such as the red nucleus, which is responsible for
coordinating movements of the arms and legs. At a higher level yet is the primary motor cortex, a strip of tissue
located at the posterior edge of the frontal lobe. The primary motor cortex sends projections to the subcortical motor
areas, but also sends a massive projection directly to the spinal cord, via the so-called pyramidal tract. This direct
corticospinal projection allows for precise voluntary control of the fine details of movements. Other "secondary"
motor-related brain areas do not project directly to the spinal cord, but instead act on the cortical or subcortical
primary motor areas. Among the most important secondary areas are the premotor cortex, basal ganglia, and
cerebellum:
• The premotor cortex (which is actually a large complex of areas) adjoins the primary motor cortex, and projects to
it. Whereas elements of the primary motor cortex map to specific body areas, elements of the premotor cortex are
often involved in coordinated movements of multiple body parts.[71]
• The basal ganglia are a set of structures in the base of the forebrain that project to many other motor-related
areas.[72] Their function has been difficult to understand, but one of the most popular theories currently is that
they play a key role in action selection.[73] Most of the time they restrain actions by sending constant inhibitory
signals to action-generating systems, but in the right circumstances, they release this inhibition and therefore
allow their targets to take control of behavior.
• The cerebellum is a very distinctive structure attached to the back of the brain.[33] It does not control or originate
behaviors, but instead generates corrective signals to make movements more precise. People with cerebellar
damage are not paralyzed in any way, but their body movements become erratic and uncoordinated.
In addition to all of the above, the brain and spinal cord contain extensive circuitry to control the autonomic nervous
system, which works by secreting hormones and by modulating the "smooth" muscles of the gut.[74] The autonomic
nervous system affects heart rate, digestion, respiration rate, salivation, perspiration, urination, and sexual
arousal—but most of its functions are not under direct voluntary control.
Arousal systems
Perhaps the most obvious aspect of the behavior of any animal is the daily cycle between sleeping and waking.
Arousal and alertness are also modulated on a finer time scale, though, by an extensive network of brain areas.[75]
A key component of the arousal system is the suprachiasmatic nucleus (SCN), a tiny part of the hypothalamus
located directly above the point at which the optic nerves from the two eyes cross.[76] The SCN contains the body's
central biological clock. Neurons there show activity levels that rise and fall with a period of about 24 hours,
circadian rhythms: these activity fluctuations are driven by rhythmic changes in expression of a set of "clock genes".
The SCN continues to keep time even if it is excised from the brain and placed in a dish of warm nutrient solution,
but it ordinarily receives input from the optic nerves, through the retinohypothalamic tract (RHT), that allow daily
light-dark cycles to calibrate the clock.
23
Brain
24
The SCN projects to a set of areas in the hypothalamus, brainstem, and midbrain that are involved in implementing
sleep-wake cycles. An important component of the system is the so-called reticular formation, a group of
neuron-clusters scattered diffusely through the core of the lower brain.[75] Reticular neurons send signals to the
thalamus, which in turn sends activity-level-controlling signals to every part of the cortex. Damage to the reticular
formation can produce a permanent state of coma.
Sleep involves great changes in brain activity.[77] Until the 1950s it was generally believed that the brain essentially
shuts off during sleep[78] , but this is now known to be far from true: activity continues, but patterns become very
different. In fact, there are two types of sleep, REM sleep (with dreaming) and NREM (non-REM, usually without
dreaming) sleep, which repeat in slightly varying patterns throughout a sleep episode. Three broad types of distinct
brain activity patterns can be measured: REM, light NREM and deep NREM. During deep NREM sleep, also called
slow wave sleep, activity in the cortex takes the form of large synchronized waves, where in the waking state it is
noisy and desynchronized. Levels of the neurotransmitters norepinephrine and serotonin drop during slow wave
sleep, and fall almost to zero during REM sleep; levels of acetylcholine show the reverse pattern.
Brain energy consumption
Although the human brain represents only 2% of the body weight, it
receives 15% of the cardiac output, 20% of total body oxygen
consumption, and 25% of total body glucose utilization.[79] The need
to limit body weight in order, for example, to fly, has led to selection
for a reduction of brain size in some species, such as bats.[80] The brain
mostly utilizes glucose for energy, and deprivation of glucose, as can
happen in hypoglycemia, can result in loss of consciousness. The
energy consumption of the brain does not vary greatly over time, but
active regions of the cortex consume somewhat more energy than
inactive regions: this fact forms the basis for the functional brain
imaging methods PET and fMRI.[81] These are nuclear medicine
imaging techniques which produce a three-dimensional image of
metabolic activity.
PET Image of the human brain showing energy
consumption
Brain and mind
Understanding the relationship between the brain and the mind is a challenging problem both philosophically and
scientifically.[82] The most straightforward scientific evidence that there is a strong relationship between the physical
brain matter and the mind is the impact physical alterations to the brain have on the mind, such as with traumatic
brain injury and psychoactive drug use.[83]
The mind-body problem is one of the central issues in the history of philosophy,[84] which asks us to consider if the
brain and the mind are identical, partially distinct, or related in some unknown way. There are three major schools of
thought concerning the answer: dualism, materialism, and idealism. Dualism holds that the mind exists
independently of the brain;[85] materialism holds that mental phenomena are identical to neuronal phenomena;[86]
and idealism holds that only mental phenomena exist.[86]
In addition to the philosophical questions, the relationship between mind and brain involves a high number of
scientific questions, including understanding the relationship between mental activity and brain activity, the exact
mechanisms by which drugs influence cognition, and the neural correlates of consciousness.
Through most of history many philosophers found it inconceivable that cognition could be implemented by a
physical substance such as brain tissue (that is neurons and synapses).[87] Philosophers such as Patricia Churchland
posit that the drug-mind interaction is indicative of an intimate connection between the brain and the mind, not that
Brain
the two are the same entity.[88] Descartes, who thought extensively about mind-brain relationships, found it possible
to explain reflexes and other simple behaviors in mechanistic terms, although he did not believe that complex
thought, and language in particular, could be explained by reference to the physical brain alone.[89]
Research
The field of neuroscience encompasses all approaches that seek to understand the brain and the rest of the nervous
system.[90] Psychology seeks to understand mind and behavior, and neurology is the medical discipline that
diagnoses and treats pathologies of the nervous system. The brain is also the most important organ studied in
psychiatry, the branch of medicine that works to study, prevent, and treat mental disorders.[91] Cognitive science
seeks to unify neuroscience and psychology with other fields that concern themselves with the brain, such as
computer science (artificial intelligence and similar fields) and philosophy.
The oldest method of studying the brain is anatomical, and until the middle of the 20th century, much of the progress
in neuroscience came from the development of better stains and better microscopes—the neuroanatomist Floyd
Bloom famously quipped that "the gain in brain is mainly in the stain."[92] Neuroanatomists study the large-scale
structure of the brain as well as the microscopic structure of neurons and their components, especially synapses.
Among other tools, they employ a plethora of stains that reveal neural structure, chemistry, and connectivity. In
recent years, the development of immunostaining techniques has allowed staining of neurons that express specific
sets of genes. Also, functional neuroanatomy uses medical imaging techniques to correlate variations in human brain
structure with differences in cognition or behavior.
Neurophysiologists study the chemical, pharmacological, and electrical properties of the brain: their primary tools
are drugs and recording devices. Many thousands of experimentally developed drugs affect the nervous system,
some in highly specific ways. Recordings of brain activity can be made using electrodes, either glued to the skull as
in EEG studies, or implanted inside the brains of animals for extracellular recordings, which can detect action
potentials generated by individual neurons.[93] Because the brain does not contain pain receptors, it is possible using
these techniques to record from animals that are awake and behaving without causing distress. The same techniques
have occasionally been used to study brain activity in human patients suffering from intractable epilepsy, in cases
where there was a medical necessity to implant electrodes in order to localize the brain area responsible for
seizures.[94] It is also possible to study brain activity noninvasively in humans using functional imaging techniques
such as MRI—this field has expanded enormously over the past two decades.
A different approach to brain function is to examine the consequences of damage to specific brain areas. Even
though it is protected by the skull and meninges, surrounded by cerebrospinal fluid, and isolated from the
bloodstream by the blood-brain barrier, the delicate nature of the brain makes it vulnerable to numerous diseases and
several types of damage. In humans, the effects of strokes and other types of brain damage have been a key source of
information about brain function.[95] Because there is no ability to experimentally control the nature of the damage,
however, this information is often difficult to interpret. In animal studies, most commonly involving rats, it is
possible to use electrodes or locally injected chemicals to produce precise patterns of damage and then examine the
consequences for behavior.
Computational neuroscience encompasses two approaches: first, the use of computers to study the brain; second, the
study of how brains perform computation.[96] On one hand, it is possible to write a computer program to simulate the
operation of a group of neurons by making use of systems of equations that describe their electrochemical activity;
such simulations are known as biologically realistic neural networks. On the other hand, it is possible to study
algorithms for neural computation by simulating, or mathematically analyzing, the operations of simplified "units"
that have some of the properties of neurons but abstract out much of their biological complexity. The computational
functions of the brain are studied both by neuroscientists and computer scientists.
Recent years have seen the first applications of genetic engineering techniques to the study of the brain.[97] The most
common subjects are mice, because the technical tools are more advanced for this species than for any other. It is
25
Brain
26
now possible with relative ease to "knock out" or mutate a wide variety of genes, and then examine the effects on
brain function. More sophisticated approaches are also beginning to be used: for example, using the Cre-Lox
recombination method it is possible to activate or inactivate genes in specific parts of the brain, at specific times.
History
Early views were divided as to whether the seat of the soul lies in the brain or heart. On one hand, it was impossible
to miss the fact that awareness feels like it is localized in the head, and that blows to the head can cause
unconsciousness much more easily than blows to the chest, and that shaking the head causes dizziness. On the other
hand, the brain to a superficial examination seems inert, whereas the heart is constantly beating. Cessation of the
heartbeat means death; strong emotions produce changes in the heartbeat; and emotional distress often produces a
sensation of pain in the region of the heart ("heartache"). Aristotle favored the heart, and thought that the function of
the brain was merely to cool the blood. Democritus, the inventor of the atomic theory of matter, favored a three-part
soul, with intellect in the head, emotion in the heart, and lust in the vicinity of the liver.[98] Hippocrates, the "father
of medicine", was entirely in favor of the brain. In On the Sacred Disease, his account of epilepsy, he wrote:
Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows,
griefs, despondency, and lamentations. ... And by the same organ we become mad and delirious, and fears and
terrors assail us, some by night, and some by day, and dreams and untimely wanderings, and cares that are not
suitable, and ignorance of present circumstances, desuetude, and unskilfulness. All these things we endure
from the brain, when it is not healthy...
—Hippocrates, On the Sacred Disease[99]
The famous Roman physician Galen also advocated the importance of the brain, and theorized in some depth about
how it might work. Even after physicians and philosophers had accepted the primacy of the brain, though, the idea of
the heart as seat of intelligence continued to survive in popular idioms, such as "learning something by heart".[100]
Galen did a masterful job of tracing out the anatomical relationships among brain, nerves, and muscles,
demonstrating that all muscles in the body are connected to the brain via a branching network of nerves. He
postulated that nerves activate muscles mechanically, by carrying a mysterious substance he called pneumata
psychikon, usually translated as "animal spirits". His ideas were widely known during the Middle Ages, but not much
further progress came until the Renaissance, when detailed anatomical study resumed, combined with the theoretical
speculations of Descartes and his followers. Descartes, like Galen, thought of the nervous system in hydraulic terms.
He believed that the highest cognitive functions—language in particular—are carried out by a non-physical res
cogitans, but that the majority of behaviors of humans and animals could be explained mechanically. The first real
progress toward a modern understanding of nervous function, though, came from the investigations of Luigi Galvani,
who discovered that a shock of static electricity applied to an exposed nerve of a dead frog could cause its leg to
contract.
Brain
27
Each major advance in understanding has followed more or less
directly from the development of a new method of investigation.
Until the early years of the 20th century, the most important
advances were derived from new stains.[101] Particularly critical
was the invention of the Golgi stain, which (when correctly used)
stains only a small, and apparently random, fraction of neurons,
but stains them in their entirety, including cell body, dendrites, and
axon. Without such a stain, brain tissue under a microscope
appears as an impenetrable tangle of protoplasmic fibers, in which
it is impossible to determine any structure. In the hands of Camillo
Golgi, and especially of the Spanish neuroanatomist Santiago
Ramon y Cajal, the new stain revealed hundreds of distinct types
of neurons, each with its own unique dendritic structure and
pattern of connectivity.
Drawing by Santiago Ramon y Cajal of two types of
In the 20th century, progress in electronics enabled investigation
Golgi-stained
neurons from the cerebellum of a pigeon
of the electrical properties of nerve cells, culminating in the work
by Alan Hodgkin, Andrew Huxley, and others on the biophysics of
the action potential, and the work of Bernard Katz and others on the electrochemistry of the synapse.[102] The earliest
studies used special preparations, such as the "fast escape response" system of the squid, which involves a giant axon
as thick as a pencil lead, and giant synapses connecting to this axon. Steady improvements in electrodes and
electronics allowed ever finer levels of resolution. These studies complemented the anatomical picture with a
conception of the brain as a dynamic entity. Reflecting the new understanding, in 1942 Charles Sherrington
visualized the workings of the brain in action in somewhat breathless terms:
The great topmost sheet of the mass, that where hardly a light had twinkled or moved, becomes now a
sparkling field of rhythmic flashing points with trains of traveling sparks hurrying hither and thither. ... It is as
if the Milky Way entered upon some cosmic dance. Swiftly the head mass becomes an enchanted loom where
millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern though never an abiding
one; a shifting harmony of subpatterns.
—Sherrington, 1942, Man on his Nature[103]
The 1990s were known in the US as the "Decade of the Brain" to commemorate advances made in brain research,
and to promote funding for such research.[104] [105]
See also
• Brain–computer interface
• Mind
• Cephalization
References
• Abbott, LF (2001). Theoretical Neuroscience: Computational and Mathematical Modeling of Neural Systems
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30
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31
Further reading
• Bear, Mark F.; Barry W. Connors, Michael A. Paradiso (2006). Neuroscience. Philadelphia, Pennsylvania:
Lippincott Williams & Wilkins. ISBN 9780781760034. OCLC 62509134.
• Blackmore, Susan M. (2006). Conversations on Consciousness. Oxford; New York: Oxford University Press.
ISBN 9780195179583. OCLC 62555307.
• Buzsaki, Gyorgy (2006). Rhythms of the Brain. Oxford; New York: Oxford University Press.
ISBN 9780195301069. OCLC 63279497.
• Calvin, William H. (2001). The River That Flows Uphill: A Journey from the Big Bang to the Big Brain. Lincoln,
Nebraska: Iuniverse.com. ISBN 9780595167005. OCLC 48962546.
• Della Sala, Sergio (1999). Mind myths: Exploring popular assumptions about the mind and brain. Chichester
England; New York: J. Wiley & Sons. ISBN 0471983039. OCLC 39700332.
• Restak, Richard (2001). The Secret Life of the Brain. Washington, DC: Joseph Henry Press.
ISBN 9780309074353. OCLC 47863192.
• Shepherd, Gordon M. (2004). The Synaptic Organization of the Brain (Fifth ed.). Oxford; New York: Oxford
University Press. ISBN 9780195159561. OCLC 51769076.
Written for children 8 and older:
• Simon, Seymour (2000). The Brain. New York: Morrow Junior. ISBN 9780688170608. OCLC 35686089.
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Brain Research News from ScienceDaily [150]
BrainInfo for Neuroanatomy [151]
Neuroscience for kids [152]
BrainMaps.org [153], interactive high-resolution digital brain atlas based on scanned images of serial sections of
both primate and non-primate brains
The Brain from Top to Bottom [154]
The Department of Neuroscience at Wikiversity
The Secret Life of the Brain : History of the Brain [155] from PBS
University of Washington [156] 3D animations of brain regions - click through from "Click for copyright"
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Hart, 1996
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Neurophilosophy, Ch. 6
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Storrow, Outline of Clinical Psychiatry
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Neuron
Neuron: neuron (Nerve Cell)
Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. (A) Denotes Purkinje cells, an example of a multipolar
neuron. (B) Denotes granule cells which are also multipolar.
NeuroLex ID
sao1417703748
[1]
A neuron (pronounced /ˈnjʊərɒn/ N(Y)OOR-on, also known as a neurone or nerve cell) is an electrically excitable
cell that processes and transmits information by electrical and chemical signaling, the latter via synapses, specialized
connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of
the nervous system, which includes the brain, spinal cord, and peripheral ganglia. A number of specialized types of
neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the
sensory organs that then send signals to the spinal cord and brain. Motor neurons receive signals from the brain and
spinal cord and cause muscle contractions and affect glands. Interneurons connect neurons to other neurons within
Neuron
35
the same region of the brain or spinal cord.
A typical neuron possesses a cell body (often called the soma), dendrites, and an axon. Dendrites are filaments that
arise from the cell body, often extending for hundreds of microns and branching multiple times, giving rise to a
complex "dendritic tree". An axon is a special cellular filament that arises from the cell body at a site called the axon
hillock and travels for a distance, as far as 1 m in humans or even more in other species. The cell body of a neuron
frequently gives rise to multiple dendrites, but never to more than one axon, although the axon may branch hundreds
of times before it terminates. At the majority of synapses, signals are sent from the axon of one neuron to a dendrite
of another. There are, however, many exceptions to these rules: neurons that lack dendrites, neurons that have no
axon, synapses that connect an axon to another axon or a dendrite to another dendrite, etc.
All neurons are electrically excitable, maintaining voltage gradients across their membranes by means of
metabolically driven ion pumps, which combine with ion channels embedded in the membrane to generate
intracellular-versus-extracellular concentration differences of ions such as sodium, potassium, chloride, and calcium.
Changes in the cross-membrane voltage can alter the function of voltage-dependent ion channels. If the voltage
changes by a large enough amount, an all-or-none electrochemical pulse called an action potential is generated,
which travels rapidly along the cell's axon, and activates synaptic connections with other cells when it arrives.
Neurons of the adult brain do not generally undergo cell division, and usually cannot be replaced after being lost,
although there are a few known exceptions. In most cases they are generated by special types of stem cells, although
astrocytes (a type of glial cell) have been observed to turn into neurons as they are sometimes pluripotent.
Overview
Structure of a typical neuron
Neuron
Dendrite
Soma
Axon
Nucleus
Node of
Ranvier
Axon terminal
Schwann cell
Myelin sheath
Neuron
A neuron is a special type of cell that is found in the bodies of most animals (all members of the group Eumetazoa,
to be precise—this excludes only sponges and a few other very simple animals). The features that define a neuron
are electrical excitability and the presence of synapses, which are complex membrane junctions used to transmit
signals to other cells. The body's neurons, plus the glial cells that give them structural and metabolic support,
together constitute the nervous system. In vertebrates, the majority of neurons belong to the central nervous system,
but some reside in peripheral ganglia, and many sensory neurons are situated in sensory organs such as the retina and
cochlea.
Although neurons are very diverse and there are exceptions to nearly every rule, it is convenient to begin with a
schematic description of the structure and function of a "typical" neuron. A typical neuron is divided into three parts:
the soma or cell body, dendrites, and axon. The soma is usually compact; the axon and dendrites are filaments that
extrude from it. Dendrites typically branch profusely, getting thinner with each branching, and extending their
farthest branches a few hundred microns from the soma. The axon leaves the soma at a swelling called the axon
hillock, and can extend for great distances, giving rise to hundreds of branches. Unlike dendrites, an axon usually
maintains the same diameter as it extends. The soma may give rise to numerous dendrites, but never to more than
one axon. Synaptic signals from other neurons are received by the soma and dendrites; signals to other neurons are
transmitted by the axon. A typical synapse, then, is a contact between the axon of one neuron and a dendrite or soma
of another. Synaptic signals may be excitatory or inhibitory. If the net excitation received by a neuron over a short
period of time is large enough, the neuron generates a brief pulse called an action potential, which originates at the
soma and propagates rapidly along the axon, activating synapses onto other neurons as it goes.
Many neurons fit the foregoing schema in every respect, but there are also exceptions to most parts of it. There are
no neurons that lack a soma, but there are neurons that lack dendrites, and others that lack an axon. Furthermore, in
addition to the typical axodendritic and axosomatic synapses, there are axoaxonic (axon-to-axon) and
dendrodendritic (dendrite-to-dendrite) synapses.
The key to neural function is the synaptic signalling process, which is partly electrical and partly chemical. The
electrical aspect depends on properties of the neuron's membrane. Like all animal cells, every neuron is surrounded
by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid
bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane
are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane,
and ion pumps that actively transport ions from one side of the membrane to the other. Most ion channels are
permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched
between open and closed states by altering the voltage difference across the membrane. Others are chemically gated,
meaning that they can be switched between open and closed states by interactions with chemicals that diffuse
through the extracellular fluid. The interactions between ion channels and ion pumps produce a voltage difference
across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it
provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the
membrane; second, it provides a basis for electrical signal transmission between different parts of the membrane.
Neurons communicate by chemical and electrical synapses in a process known as synaptic transmission. The
fundamental process that triggers synaptic transmission is the action potential, a propagating electrical signal that is
generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of
depolarization.
36
Neuron
37
Anatomy and histology
Neurons are highly specialized for the
processing and transmission of cellular
signals. Given the diversity of
functions performed by neurons in
different parts of the nervous system,
there is, as expected, a wide variety in
the shape, size, and electrochemical
properties of neurons. For instance, the
soma of a neuron can vary from 4 to
100 micrometers in diameter.[2]
• The soma is the central part of the
neuron. It contains the nucleus of
the cell, and therefore is where most
protein synthesis occurs. The
nucleus ranges from 3 to 18
micrometers in diameter.[3]
Diagram of a typical myelinated vertebrate motoneuron.
• The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and
structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs.
• The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the
diameter of the soma in length. The axon carries nerve signals away from the soma (and also carries some types
of information back to it). Many neurons have only one axon, but this axon may—and usually will—undergo
extensive branching, enabling communication with many target cells. The part of the axon where it emerges from
the soma is called the axon hillock. Besides being an anatomical structure, the axon hillock is also the part of the
neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited
part of the neuron and the spike initiation zone for the axon: in neurological terms it has the most negative action
potential threshold. While the axon and axon hillock are generally involved in information outflow, this region
can also receive input from other neurons.
• The axon terminal contains synapses, specialized structures where neurotransmitter chemicals are released in
order to communicate with target neurons.
Although the canonical view of the neuron attributes dedicated functions to its various anatomical components,
dendrites and axons often act in ways contrary to their so-called main function.
Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the
peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is
not much larger than the cell nucleus it contains. The longest axon of a human motoneuron can be over a meter long,
reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal
columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire
length of their necks. Much of what is known about axonal function comes from studying the squid giant axon, an
ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters
long).
Fully differentiated neurons are permanently amitotic;[4] however, recent research shows that additional neurons
throughout the brain can originate from neural stem cells found throughout the brain but in particularly high
concentrations in the subventricular zone and subgranular zone through the process of neurogenesis.[5]
Neuron
38
Histology and internal structure
Nerve cell bodies stained with basophilic dyes show
numerous microscopic clumps of Nissl substance
(named after German psychiatrist and neuropathologist
Franz Nissl, 1860–1919), which consists of rough
endoplasmic reticulum and associated ribosomal RNA.
The prominence of the Nissl substance can be
explained by the fact that nerve cells are metabolically
very active, and hence are involved in large amounts of
protein synthesis.
The cell body of a neuron is supported by a complex
meshwork of structural proteins called neurofilaments,
which are assembled into larger neurofibrils. Some
Golgi-stained neurons in human hippocampal tissue.
neurons also contain pigment granules, such as
neuromelanin (a brownish-black pigment, byproduct
of synthesis of catecholamines) and lipofuscin (yellowish-brown pigment that accumulates with age).
There are different internal structural characteristics between axons and dendrites. Typical axons almost never
contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or
ribosomes, with diminishing amounts with distance from the cell body.
Classes
Neurons exist in a number of different shapes and sizes
and can be classified by their morphology and function.
The anatomist Camillo Golgi grouped neurons into two
types; type I with long axons used to move signals over
long distances and type II with short axons, which can
often be confused with dendrites. Type I cells can be
further divided by where the cell body or soma is
located. The basic morphology of type I neurons,
represented by spinal motor neurons, consists of a cell
body called the soma and a long thin axon which is
covered by the myelin sheath. Around the cell body is a
branching dendritic tree that receives signals from other
neurons. The end of the axon has branching terminals
(axon terminal) that release neurotransmitters into a
gap called the synaptic cleft between the terminals and
the dendrites of the next neuron.
Structural classification
Image of pyramidal neurons in mouse cerebral cortex expressing
green fluorescent protein. The red staining indicates GABAergic
interneurons. Source PLoS Biology [6]
Neuron
39
Polarity
Most neurons can be anatomically characterized as:
• Unipolar or pseudounipolar: dendrite and axon
emerging from same process.
• Bipolar: axon and single dendrite on opposite ends
of the soma.
• Multipolar: more than two dendrites:
• Golgi I: neurons with long-projecting axonal
processes; examples are pyramidal cells, Purkinje
cells, and anterior horn cells.
• Golgi II: neurons whose axonal process projects
locally; the best example is the granule cell.
SMI32-stained pyramidal neurons in cerebral cortex.
Other
Furthermore, some unique neuronal types can be identified according to their location in the nervous system and
distinct shape. Some examples are:
• Basket cells, interneurons that form a dense plexus of terminals around the soma of target cells, found in the
cortex and cerebellum.
• Betz cells, large motor neurons.
•
•
•
•
•
•
Medium spiny neurons, most neurons in the corpus striatum.
Purkinje cells, huge neurons in the cerebellum, a type of Golgi I multipolar neuron.
Pyramidal cells, neurons with triangular soma, a type of Golgi I.
Renshaw cells, neurons with both ends linked to alpha motor neurons.
Granule cells, a type of Golgi II neuron.
anterior horn cells, motoneurons located in the spinal cord.
Functional classification
Direction
• Afferent neurons convey information from tissues and organs into the central nervous system and are sometimes
also called sensory neurons.
• Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called
motor neurons.
• Interneurons connect neurons within specific regions of the central nervous system.
Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send
information from the brain region.
Action on other neurons
A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the
target neuron is determined not by the source neuron or by the neurotransmitter, but by the type of receptor that is
activated. A neurotransmitter can be thought of as a key, and a receptor as a lock: the same type of key can here be
used to open many different types of locks. Receptors can be classified broadly as excitatory (causing an increase in
firing rate), inhibitory (causing a decrease in firing rate), or modulatory (causing long-lasting effects not directly
related to firing rate).
Neuron
In fact, however, the two most common neurotransmitters in the brain, glutamate and GABA, have actions that are
largely consistent. Glutamate acts on several different types of receptors, but most of them have effects that are
excitatory. Similarly GABA acts on several different types of receptors, but all of them have effects (in adult
animals, at least) that are inhibitory. Because of this consistency, it is common for neuroscientists to simplify the
terminology by referring to cells that release glutamate as "excitatory neurons," and cells that release GABA as
"inhibitory neurons." Since well over 90% of the neurons in the brain release either glutamate or GABA, these labels
encompass the great majority of neurons. There are also other types of neurons that have consistent effects on their
targets, for example "excitatory" motor neurons in the spinal cord that release acetylcholine, and "inhibitory" spinal
neurons that release glycine.
The distinction between excitatory and inhibitory neurotransmitters is not absolute, however. Rather, it depends on
the class of chemical receptors present on the target neuron. In principle, a single neuron, releasing a single
neurotransmitter, can have excitatory effects on some targets, inhibitory effects on others, and modulatory effects on
others still. For example, photoreceptors in the retina constantly release the neurotransmitter glutamate in the
absence of light. So-called OFF bipolar cells are, like most neurons, excited by the released glutamate. However,
neighboring target neurons called ON bipolar cells are instead inhibited by glutamate, because they lack the typical
ionotropic glutamate receptors and instead express a class of inhibitory metabotropic glutamate receptors.[7] When
light is present, the photoreceptors cease releasing glutamate, which relieves the ON bipolar cells from inhibition,
activating them; this simultaneously removes the excitation from the OFF bipolar cells, silencing them.
Discharge patterns
Neurons can be classified according to their electrophysiological characteristics:
• Tonic or regular spiking. Some neurons are typically constantly (or tonically) active. Example: interneurons in
neurostriatum.
• Phasic or bursting. Neurons that fire in bursts are called phasic.
• Fast spiking. Some neurons are notable for their fast firing rates, for example some types of cortical inhibitory
interneurons, cells in globus pallidus, retinal ganglion cells.[8] [9]
• Thin-spike. Action potentials of some neurons are more narrow compared to the others. For example,
interneurons in the prefrontal cortex are thin-spike neurons.
Classification by neurotransmitter production
Neurons differ in the type of neurotransmitter they manufacture. Some examples are
• cholinergic neurons - acetylcholine
Acetylcholine is released from presynaptic neurons into the synaptic cleft. It acts as a ligand for Nicotinic
Acetylcholine receptors, which are ligand gated Na+ ion channels. Ligand binding opens the channel causing
depolarization and increases the probability of an action potential firing, occcuring once the threshold is reached.
• GABAergic neurons - gamma aminobutyric acid
GABA is one of two neuroinhibitors in the CNS, the other being Glycine. GABA has a homologous function to
ACh, gating anion channels that allow Cl- ions to enter the post synaptic neuron. Cl- causes hyperpolarization within
the neuron, decreasing the probability of an action potential firing as the voltage becomes more negative (recall that
for an action potential to fire, a positive voltage threshold must be reached).
• glutamatergic neurons - glutamate
Glutamate is one of two primary neuroexcitors, the other being Aspartate (not Aspartame). Glutamate receptors are
one of four categories, three of which are ion channels and one of which is a G-protein coupled receptor (often
referred to as GPCR). 1 - AMPA and Kainate receptors (really two different receptors) both function as Na+ cation
channels mediating fast excitatory synaptic transmission 2 - NMDA receptors are another cation channel, but for
Ca2+. The function of NMDA receptors is dependant on Glycine binding to a mediator binding spot on the channel
40
Neuron
pore. NMDA receptors will not function without both ligands present - antagonist drugs for Glycine will cause
NMDA receptors to malfunction. 3 - Metabotropic receptor, a GPCR that modulates synaptic transmission
Glutamate can cause excitotoxicity when blood flow to the brain is interrupted, resulting in brain damage. When
blood flow is suppressed, glutamate is released from presynaptic neurons causing NMDA and AMPA receptor
activation moreso than would normally be the case outside of stress conditions, leading to elevated Ca2+ and Na+
entering the post synaptic neuron and cell damage.
• dopaminergic neurons - dopamine
Dopamine is a neurotransmitter that acts on a GPCR. Dopamine is connected to mood and behaviour, and modulates
post synaptic neurotransmission. Loss of dopamine neurons has been linked to Parkinson's disease, schizophrenia,
and ADD.
• serotonergic neurons - serotonin
Serotonin, full name 5-Hydroxytryptamine, can act as excitatory or inhibitory. Of the four 5HT receptor classes, 3
are GPCR and 1 is ligand gated cation channel. Serotonin is synthesized from tryptophan by tryptophan hydroxylase,
and then further by aromatic acid decarboxylase. A lack of 5HT at postsynaptic neurons has been linked to
depression. Drugs that are antagonistic for reabsorption by presynaptic neurons are used for treatment, such as
Prozac and Zoloft.
Connectivity
Neurons communicate with one another via synapses, where the axon terminal or en passant boutons (terminals
located along the length of the axon) of one cell impinges upon another neuron's dendrite, soma or, less commonly,
axon. Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections
with tens of thousands of other cells; other neurons, such as the magnocellular neurons of the supraoptic nucleus,
have only one or two dendrites, each of which receives thousands of synapses. Synapses can be excitatory or
inhibitory and will either increase or decrease activity in the target neuron. Some neurons also communicate via
electrical synapses, which are direct, electrically-conductive junctions between cells.
In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon
terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes
synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the
synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic
neuron.
The human brain has a huge number of synapses. Each of the 1011 (one hundred billion) neurons has on average
7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about
1015 synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult,
ranging from 1014 to 5 x 1014 synapses (100 to 500 trillion).[10]
41
Neuron
42
Mechanisms for propagating action potentials
In 1937, John Zachary Young suggested that
the squid giant axon could be used to study
neuronal electrical properties.[11] Being larger
than but similar in nature to human neurons,
squid cells were easier to study. By inserting
electrodes into the giant squid axons, accurate
measurements were made of the membrane
potential.
The cell membrane of the axon and soma
contain voltage-gated ion channels which
allow the neuron to generate and propagate
an electrical signal (an action potential).
These signals are generated and propagated
by charge-carrying ions including sodium
(Na+), potassium (K+), chloride (Cl-), and
calcium (Ca2+).
There are several stimuli that can activate a
neuron leading to electrical activity,
including
pressure,
stretch,
chemical
transmitters, and changes of the electric
potential across the cell membrane.[12]
Stimuli cause specific ion-channels within the
cell membrane to open, leading to a flow of
ions through the cell membrane, changing the
membrane potential.
A signal propagating down an axon to the cell body and dendrites of the next cell.
Thin neurons and axons require less metabolic expense to produce and carry action potentials, but thicker axons
convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons
have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the
central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to
travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in
peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of
Ranvier which contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that
results from demyelination of axons in the central nervous system.
Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes
graded neurotransmitter release. Such nonspiking neurons tend to be sensory neurons or interneurons, because they
cannot carry signals long distances.
Neuron
Neural coding
Neural coding is concerned with how sensory and other information is represented in the brain by neurons. The main
goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble
neuronal responses, and the relationships amongst the electrical activities of the neurons within the ensemble.[13] It is
thought that neurons can encode both digital and analog information.[14]
All-or-none principle
The conduction of nerve impulses is an example of an all-or-none response. In other words, if a neuron responds at
all, then it must respond completely. The greater the intensity of stimulation does not produce a stronger signal but
can produce more impulses per second. There are different types of receptor response to stimulus, slowly adapting or
tonic receptors respond to steady stimulus and produce a steady rate of firing. These tonic receptors most often
respond to increased intensity of stimulus by increasing their firing frequency, usually as a power function of
stimulus plotted against impulses per second. This can be likened to an intrinsic property of light where to get greater
intensity of a specific frequency (color) there have to be more photons, as the photons can't become "stronger" for a
specific frequency.
There are a number of other receptor types that are called quickly-adapting or phasic receptors, where firing
decreases or stops with steady stimulus; examples include: skin when touched by an object causes the neurons to
fire, but if the object maintains even pressure against the skin, the neurons stop firing. The neurons of the skin and
muscles that are responsive to pressure and vibration have filtering accessory structures that aid their function. The
pacinian corpuscle is one such structure; it has concentric layers like an onion which form around the axon terminal.
When pressure is applied and the corpuscle is deformed, mechanical stimulus is transferred to the axon, which fires.
If the pressure is steady, there is no more stimulus; thus, typically these neurons respond with a transient
depolarization during the initial deformation and again when the pressure is removed, which causes the corpuscle to
change shape again. Other types of adaptation are important in extending the function of a number of other
neurons.[15]
History
The term neuron was coined by the German anatomist Heinrich Wilhelm Waldeyer. The neuron's place as the
primary functional unit of the nervous system was first recognized in the early 20th century through the work of the
Spanish anatomist Santiago Ramón y Cajal.[16] Cajal proposed that neurons were discrete cells that communicated
with each other via specialized junctions, or spaces, between cells.[16] This became known as the neuron doctrine,
one of the central tenets of modern neuroscience.[16] To observe the structure of individual neurons, Cajal used a
silver staining method developed by his rival, Camillo Golgi.[16] The Golgi stain is an extremely useful method for
neuroanatomical investigations because, for reasons unknown, it stains a very small percentage of cells in a tissue, so
one is able to see the complete micro structure of individual neurons without much overlap from other cells in the
densely packed brain.[17]
43
Neuron
The neuron doctrine
The neuron doctrine is the now fundamental idea that neurons are the basic structural and functional units of the
nervous system. The theory was put forward by Santiago Ramón y Cajal in the late 19th century. It held that neurons
are discrete cells (not connected in a meshwork), acting as metabolically distinct units.
Later discoveries yielded a few refinements to the simplest form of the doctrine. For example, glial cells, which are
not considered neurons, play an essential role in information processing.[18] Also, electrical synapses are more
common than previously thought,[19] meaning that there are direct, cytoplasmic connections between neurons. In
fact, there are examples of neurons forming even tighter coupling: the squid giant axon arises from the fusion of
multiple axons.[20]
Cajal also postulated the Law of Dynamic Polarization, which states that a neuron receives signals at its dendrites
and cell body and transmits them, as action potentials, along the axon in one direction: away from the cell body.[21]
The Law of Dynamic Polarization has important exceptions; dendrites can serve as synaptic output sites of
neurons[22] and axons can receive synaptic inputs.
Neurons in the brain
The number of neurons in the brain varies dramatically from species to species.[23] One estimate puts the human
brain at about 100 billion (
) neurons and 100 trillion (
) synapses.[23] Another estimate is 86 billion
neurons of which 16.3 billion are in the cerebral cortex and 69 billion in the cerebellum.[24] By contrast, the
nematode worm Caenorhabditis elegans has just 302 neurons making it an ideal experimental subject as scientists
have been able to map all of the organism's neurons. The fruit fly Drosophila melanogaster, a common subject in
biology experiments, has around 100,000 neurons and exhibits many complex behaviors. Many properties of
neurons, from the type of neurotransmitters used to ion channel composition, are maintained across species, allowing
scientists to study processes occurring in more complex organisms in much simpler experimental systems.
Neurological disorders
Charcot-Marie-Tooth disease (CMT), also known as Hereditary Motor and Sensory Neuropathy (HMSN),
Hereditary Sensorimotor Neuropathy (HMSN), or Peroneal Muscular Atrophy, is a heterogeneous inherited disorder
of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet
and legs but also in the hands and arms in the advanced stages of disease. Presently incurable, this disease is one of
the most common inherited neurological disorders, with 37 in 100,000 affected.
Alzheimer's disease (AD), also known simply as Alzheimer's, is a neurodegenerative disease characterized by
progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms
or behavioral changes. The most striking early symptom is loss of short-term memory (amnesia), which usually
manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative
preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the
domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and functions such as
decision-making and planning get impaired.
Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous
system that often impairs the sufferer's motor skills and speech. Parkinson's disease belongs to a group of conditions
called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement
(bradykinesia), and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results
of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and
action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include
high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.
44
Neuron
Myasthenia Gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatigability. Weakness is
typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular
junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with
immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy.
Demyelination
Demyelination is the act of demyelinating, or the loss of the myelin sheath insulating the nerves. When myelin
degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers. This leads
to certain neurodegenerative disorders like multiple sclerosis, chronic inflammatory demyelinating polyneuropathy.
Axonal degeneration
Although most injury responses include a calcium influx signaling to promote resealing of severed parts, axonal
injuries initially lead to acute axonal degeneration (AAD), which is rapid separation of the proximal and distal ends
within 30 minutes of injury. Degeneration follows with swelling of the axolemma, and eventually leads to bead like
formation. Granular disintegration of the axonal cytoskeleton and inner organelles occurs after axolemma
degradation. Early changes include accumulation of mitochondria in the paranodal regions at the site of injury.
Endoplasmic reticulum degrades and mitochondria swell up and eventually disintegrate. The disintegration is
dependent on Ubiquitin and Calpain proteases (caused by influx of calcium ion), suggesting that axonal degeneration
is an active process. Thus the axon undergoes complete fragmentation. The process takes about roughly 24 hrs in the
PNS, and longer in the CNS. The signaling pathways leading to axolemma degeneration are currently unknown.
Nerve regeneration
It has been demonstrated that neurogenesis can sometimes occur in the adult vertebrate brain, and it is often possible
for peripheral axons to regrow if they are severed. The latter can take a long time: after a nerve injury to the human
arm, for example, it may take months for feeling to return to the hands and fingers.
Sources
• Kandel E.R., Schwartz, J.H., Jessell, T.M. 2000. Principles of Neural Science, 4th ed., McGraw-Hill, New York.
• Bullock, T.H., Bennett, M.V.L., Johnston, D., Josephson, R., Marder, E., Fields R.D. 2005. The Neuron Doctrine,
Redux, Science, V.310, p. 791-793.
• Ramón y Cajal, S. 1933 Histology, 10th ed., Wood, Baltimore.
• Roberts A., Bush B.M.H. 1981. Neurones Without Impulses. Cambridge University Press, Cambridge.
• Peters, A., Palay, S.L., Webster, H, D., 1991 The Fine Structure of the Nervous System, 3rd ed., Oxford, New
York
External links
• NeuronBank [25] an online neuromics tool for cataloging neuronal types and synaptic connectivity.
• High Resolution Neuroanatomical Images of Primate and Non-Primate Brains [26].
• The Department of Neuroscience at Wikiversity, which presently offers two courses: Fundamentals of
Neuroscience and Comparative Neuroscience.
• NIF Search - Renshaw Cell [27] via the Neuroscience Information Framework
• Cell Centered Database - Neuron [28]
• NeuroMorpho.Org [29] an online database of digital reconstructions of neuronal morphology.
• Immunohistochemistry Image Gallery: Neuron [30]
• Interactive Overview of a Neuron [31]
45
Neuron
References
[1] http:/ / www. neurolex. org/ wiki/ sao1417703748
[2] Davies, Melissa (2002-04-09). "The Neuron: size comparison" (http:/ / www. ualberta. ca/ ~neuro/ OnlineIntro/ NeuronExample. htm).
Neuroscience: A journey through the brain. . Retrieved 2009-06-20.
[3] Chudler, Eric H.. "Brain Facts and Figures" (http:/ / faculty. washington. edu/ chudler/ facts. html). Neuroscience for Kids. . Retrieved
2009-06-20.
[4] Herrup K, Yang Y (May 2007). "Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?". Nat. Rev. Neurosci. 8 (5):
368–78. doi:10.1038/nrn2124. PMID 17453017.
[5] Alvarez-Buylla A, Garcia-Verdugo JM (February 1, 2002). "Neurogenesis in adult subventricular zone" (http:/ / www. jneurosci. org/ cgi/
pmidlookup?view=long& pmid=11826091). The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 22 (3):
629–34. PMID 11826091. . Retrieved 2009-06-20.
[6] http:/ / biology. plosjournals. org/ perlserv/ ?request=get-document& doi=10. 1371/ journal. pbio. 0040029
[7] Gerber U (2003). "Metabotropic glutamate receptors in vertebrate retina" (http:/ / www. springerlink. com/ content/ m748132506x00lm4/ ).
Doc Ophthalmol 106 (1): 83–87. doi:10.1023/A:1022477203420. PMID 12675489. .
[8] Kolodin, YO; Veselovskaia, NN; Veselovsky, NS; Fedulova, SA. "Ion conductances related to shaping the repetitive firing in rat retinal
ganglion cells" (http:/ / www. blackwellpublishing. com/ aphmeeting/ abstract. asp?MeetingID=& id=61198). Acta Physiologica Congress. .
Retrieved 2009-06-20.
[9] Ionic conductances underlying excitability in tonically firing retinal ganglion cells of adult rat (http:/ / ykolodin. 50webs. com/ )
[10] Drachman D (2005). "Do we have brain to spare?". Neurology 64 (12): 2004–5. doi:10.1212/01.WNL.0000166914.38327.BB.
PMID 15985565.
[11] Chudler, Eric H.. "Milestones in Neuroscience Research" (http:/ / faculty. washington. edu/ chudler/ hist. html). Neuroscience for Kids. .
Retrieved 2009-06-20.
[12] Patlak, Joe; Gibbons, Ray (2000-11-01). "Electrical Activity of Nerves" (http:/ / physioweb. med. uvm. edu/ cardiacep/ EP/ nervecells. htm).
Aps in Nerve Cells. . Retrieved 2009-06-20.
[13] Brown EN, Kass RE, and Mitra PP. 2004. Multiple neural spike train data analysis: state-of-the-art and future challenges. Nature
Neuroscience 7:456-61
[14] Spike arrival times: A highly efficient coding scheme for neural networks (http:/ / pop. cerco. ups-tlse. fr/ fr_vers/ documents/
thorpe_sj_90_91. pdf), SJ Thorpe - Parallel processing in neural systems, 1990
[15] Eckert, Roger; Randall, David (1983). Animal physiology: mechanisms and adaptations. San Francisco: W.H. Freeman. pp. 239.
ISBN 0-7167-1423-x.
[16] López-Muñoz, F.; Boya, J., Alamo, C. (16 October 2006). "Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel
Prize award to Santiago Ramón y Cajal" (http:/ / www. sciencedirect. com/ science/ article/ B6SYT-4KMYRRC-1/ 2/
b98a884961498c54452886842389ed72). Brain Research Bulletin 70 (4-6): 391–405. doi:10.1016/j.brainresbull.2006.07.010.
PMID 17027775. . Retrieved 2007-04-02.
[17] Grant, Gunnar; Boya, J; Alamo, C (9 January 2007 (online)). "How the 1906 Nobel Prize in Physiology or Medicine was shared between
Golgi and Cajal" (http:/ / www. sciencedirect. com/ science/ article/ B6SYS-4MSHXWR-1/ 2/ 51f3edfd18b81abbd0a9d56e98de6ceb). Brain
Research Reviews 55 (4-6): 490. doi:10.1016/j.brainresrev.2006.11.004. PMID 17027775. . Retrieved 2007-04-02.
[18] Witcher M, Kirov S, Harris K (2007). "Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus". Glia 55
(1): 13–23. doi:10.1002/glia.20415. PMID 17001633.
[19] Connors B, Long M (2004). "Electrical synapses in the mammalian brain". Annu Rev Neurosci 27: 393–418.
doi:10.1146/annurev.neuro.26.041002.131128. PMID 15217338.
[20] R. W. Guillery, Observations of synaptic structures: origins of the neuron doctrine and its current status (https:/ / wiki. brown. edu/
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1300).
[21] Sabbatini R.M.E. April-July 2003. Neurons and Synapses: The History of Its Discovery (http:/ / www. cerebromente. org. br/ n17/ history/
neurons3_i. htm). Brain & Mind Magazine, 17. Retrieved on March 19, 2007.
[22] Djurisic M, Antic S, Chen W, Zecevic D (2004). "Voltage imaging from dendrites of mitral cells: EPSP attenuation and spike trigger zones".
J Neurosci 24 (30): 6703–14. doi:10.1523/JNEUROSCI.0307-04.2004. PMID 15282273.
[23] Williams RW, Herrup K (1988). "The control of neuron number". Annual Review of Neuroscience 11: 423–53.
doi:10.1146/annurev.ne.11.030188.002231. PMID 3284447.
[24] Azevedo FA, Carvalho LR, Grinberg LT, et al. (April 2009). "Equal numbers of neuronal and nonneuronal cells make the human brain an
isometrically scaled-up primate brain". The Journal of Comparative Neurology 513 (5): 532–41. doi:10.1002/cne.21974. PMID 19226510.
[25] http:/ / NeuronBank. org
[26] http:/ / brainmaps. org
[27] http:/ / www. neuinfo. org/ nif/ nifgwt. html?query=%22Renshaw%20Cell%22
[28] http:/ / ccdb. ucsd. edu/ sand/ main?event=showMPByType& typeid=0& start=1& pl=y
[29] http:/ / NeuroMorpho. org
[30] http:/ / www. immunoportal. com/ modules. php?name=gallery2& g2_view=keyalbum. KeywordAlbum& g2_keyword=Neuron
46
Neuron
[31] http:/ / smartymaps. com/ map. php?s=neuron
47
48
Key People
Kevin Warwick
Kevin Warwick
Kevin Warwick, February 2008
Born
Nationality
9 February 1954
Coventry, UK
United Kingdom
Fields
Cybernetics, robotics
Institutions
University of Oxford
Newcastle University
University of Warwick
Reading University
Alma mater
Aston University
Imperial College London
Doctoral advisor
John Hugh Westcott
Doctoral students Mark Gasson
Known for
Project Cyborg
Kevin Warwick (born 9 February 1954 Coventry, UK) is a British scientist and professor of cybernetics at the
University of Reading, Reading, Berkshire, United Kingdom. He is best known for his studies on direct interfaces
between computer systems and the human nervous system, although he has also done much research in the field of
robotics.
Biography
Kevin Warwick was born in 1954 in Coventry in the United Kingdom. He attended Lawrence Sheriff School in
Rugby, Warwickshire. He left school in 1970 to join British Telecom, at the age of 16. In 1976 he took his first
degree at Aston University, followed by a Ph.D and a research post at Imperial College London.
He subsequently held positions at Oxford, Newcastle and Warwick universities before being offered the Chair in
Cybernetics at Reading University in 1987.
Warwick is a Chartered Engineer, a Fellow of the Institution of Engineering and Technology and a Fellow of the
City and Guilds of London Institute. He is Visiting Professor at the Czech Technical University in Prague and in
2004 was Senior Beckman Fellow at the University of Illinois at Urbana-Champaign, USA. He is also Director of
the Reading University Knowledge Transfer Partnerships Centre, which links the University with Companies and is
on the Advisory Board of the Instinctive Computing Laboratory, Carnegie Mellon University.[1] He has been
awarded higher doctorates (D.Sc.) by Imperial College and by the Academy of Sciences of the Czech Republic,
Kevin Warwick
49
Prague.
Work
Warwick carries out research in artificial intelligence, biomedical
engineering, control systems and robotics. Much of Warwick's
early research was in the area of discrete time adaptive control. He
introduced the first state space based self-tuning controller[2] and
unified discrete time state space representations of ARMA
models.[3] However he also contributed in mathematics,[4] power
engineering[5] and manufacturing production machinery.[6]
Artificial intelligence
Warwick presently heads an Engineering and Physical Sciences
Research Council supported research project which investigates
the use of machine learning and artificial intelligence techniques in
order to suitably stimulate and translate patterns of electrical
activity from living cultured neural networks in order to utilise the
networks for the control of mobile robots.[7] Hence a biological
brain actually provides the behaviour process for each robot. It is
expected that the method will be extended to the control of a robot
head.
Kevin Warwick speaking at the Tomorrow's People
conference in 2006 hosted by Oxford University.
Previously Warwick was behind a Genetic algorithm called Gershwyn, which was able to exhibit creativity in
producing pop songs, learning what makes a hit record by listening to examples of previous hit songs.[8] Gershwyn
appeared on BBC's Tomorrow's World having been successfully used to mix music for Manus, a group consisting of
the four younger brothers of Elvis Costello.
Another Warwick project involving artificial intelligence is the robot head, Morgui. The head contains 5 senses
(vision, sound, infrared, ultrasound and radar) and is being used to investigate sensor data fusion. The head was
X-rated by the University of Reading Research and Ethics Committee due to its image storage capabilities - anyone
under the age of 18 who wishes to interact with the robot must apriori obtain parental approval.[9]
Warwick has very outspoken views on the future, particularly with respect to artificial intelligence and its impact on
the human species, and argues that we will need to use technology to enhance ourselves in order to avoid being
overtaken.[10] He also points out that there are many limits, such as our sensorimotor abilities, that we can overcome
with machines, and is on record as saying that he wants to gain these abilities: "There is no way I want to stay a mere
human."[11]
Kevin Warwick
Bioethics
Warwick heads the Reading University team in a number of European Community projects such as FIDIS looking at
issues concerned with the future of identity and ETHICBOTS which is considering the ethical aspects of robots and
cyborgs. Warwick is also working with Daniela Cerqui, a social and cultural anthropologist from the University of
Lausanne, to address the main social, ethical, philosophical and anthropological issues related to his research.[12]
Warwick’s areas of interest have many ethical implications, some due to his Human enhancement experiments. The
ethical dilemmas in his research are highlighted as a case study for schoolchildren and science teachers by the
Institute of Physics[13] as a part of their formal Advanced level and GCSE studies. His work has also been directly
discussed by The President's Council on Bioethics and the President’s Panel on Forward Engagements.[14]
Deep brain stimulation
Along with Tipu Aziz and his team at John Radcliffe Hospital, Oxford, and John Stein of University of Oxford,
Warwick is helping to design the next generation of Deep brain stimulation for Parkinson's disease.[15] Instead of
stimulating the brain all the time, the aim is for the device to predict when stimulation is needed and to apply the
signals prior to any tremors occurring to stop them before they even start.
Public awareness
Warwick has headed a number of projects aimed at exciting schoolchildren about the technology with which he is
involved. In 2000 he received the Engineering and Physical Sciences Research Council Millennium Award for his
Schools Robot League. Meanwhile in 2007, 16 school teams were involved in designing a humanoid robot to dance
and then complete an assault course—a final competition being held at the Science Museum (London). The project,
entitled 'Androids Advance' was supported by EPSRC and was presented as an evening news item on Chinese
television.[16]
Warwick contributes significantly to the public understanding of science by giving regular public lectures, taking
part in radio programmes and through popular writing. He has appeared in numerous television documentary
programmes on artificial intelligence, robotics and the role of science fiction in science, such as How William
Shatner Changed the World, Future Fantastic and Explorations.[17] He has also guested on a number of TV chat
shows, including Late Night with Conan O'Brien, Først & sist, and Richard & Judy.[17] Warwick has appeared on
the cover of a number of magazines, for example the February 2000 edition of Wired.[18]
In 2005 he was congratulated for his work in attracting students to the field by Members of Parliament in the United
Kingdom in an Early day motion for making "the subject interesting and relevant so that more students will want to
develop a career in science".[19]
Robotics
Warwick's claims that robots that can program themselves to avoid each other while operating in a group raise the
issue of self-organisation, and as such might be the major impetus in following developments in this area. In
particular, the works of Francisco Varela and Humberto Maturana, once in the province of pure speculation now
have become immediately relevant with respect to synthetic intelligence.
Cyborg-type systems not only are homeostatic (meaning that they are able to preserve stable internal conditions in
various environments) but adaptive, if they are to survive. Testing the claims of Varela and Maturana via synthetic
devices is the larger and more serious concern in the discussion about Warwick and those involved in similar
research. "Pulling the plug" on independent devices cannot be as simple as it appears, for if the device displays
sufficient intelligence and assumes a diagnostic and prognostic stature, we may ultimately one day be forced to
decide between what it could be telling us as counterintuitive (but correct) and our impulse to disconnect because of
our limited and "intuitive" perceptions.
50
Kevin Warwick
Warwick's robots seemed to have exhibited behaviour not anticipated by the research, one such robot "committing
suicide" because it could not cope with its environment.[20] In a more complex setting, it may be asked whether a
"natural selection" may be possible, neural networks being the major operative.
The 1999 edition of the Guinness Book of Records recorded that Warwick carried out the first robot learning
experiment across the internet. One robot, with an Artificial Neural Network brain in Reading, UK, learnt how to
move around. It then taught, via the internet, another robot in SUNY Buffalo New York State, USA, to behave in the
same way. The robot in the USA was therefore not taught or programmed by a human, but rather by another robot
based on what it itself had learnt.[21]
Hissing Sid was a robot cat which Warwick took on a British Council lecture tour of Russia, it being presented in
lectures at such places as Moscow State University. Sid, which was put together as a student project, got its name
from the noise made by the Pneumatic actuators used to drive its legs when walking. The robot also appeared on
BBC TV's Blue Peter but became better known when it was refused a ticket by British Airways on the grounds that
they did not allow animals in the cabin.[22]
Warwick was also responsible for a robotic "magic chair" which Sir Jimmy Savile used on BBC TV's Jim'll Fix It.
The chair provided Jim with tea and stored Jim'll Fix it badges for him to hand out to guests.[23] Warwick even
appeared on the programme himself for a Fix it involving robots.[17]
Project Cyborg
Probably the most famous piece of research undertaken by Warwick (and the origin of the nickname, "Captain
Cyborg", given to him by The Register) is the set of experiments known as Project Cyborg, in which he had a chip
implanted into his arm, with the aim of "becoming a cyborg".
The first stage of this research, which began on 1998-08-24, involved a simple RFID transmitter being implanted
beneath Warwick's skin, and used to control doors, lights, heaters, and other computer-controlled devices based on
his proximity. The main purpose of this experiment was said to be to test the limits of what the body would accept,
and how easy it would be to receive a meaningful signal from the chip.[24]
The second stage involved a more complex neural interface which was designed and built especially for the
experiment by Dr. Mark Gasson and his team at the University of Reading. This device was implanted on 14 March
2002, and interfaced directly into Warwick's nervous system. The electrode array inserted contained 100 electrodes,
of which 25 could be accessed at any one time, whereas the median nerve which it monitored carries many times that
number of signals. The experiment proved successful, and the signal produced was detailed enough that a robot arm
developed by Warwick's colleague, Dr Peter Kyberd, was able to mimic the actions of Warwick's own arm.[25]
By means of the implant, Warwick's nervous system was connected onto the internet in Columbia University, New
York. From there he was able to control the robot arm in the University of Reading and to obtain feedback from
sensors in the finger tips. He also successfully connected ultrasonic sensors on a baseball cap and experienced a form
of extra sensory input.[26]
A highly publicised extension to the experiment, in which a simpler array was implanted into Warwick's wife—with
the aim of creating a form of telepathy or empathy using the Internet to communicate the signal from afar—was also
successful, resulting in the first purely electronic communication experiment between the nervous systems of two
humans.[27] Finally, the effect of the implant on Warwick's hand function was measured using the University of
Southampton Hand Assessment Procedure (SHAP).[28] It was feared that directly interfacing with the nervous
system might cause some form of damage or interference, but no measurable effect was found.
As well as the Project Cyborg work, Warwick has been involved in several of the major robotics developments
within the Cybernetics Department at Reading. These include the "seven dwarves", a version of which was given
away in kit form as Cybot on the cover of Real Robots Magazine.
51
Kevin Warwick
Implications and criticisms on Project Cyborg
Warwick and his colleagues claim that the Project Cyborg research could lead to new medical tools for treating
patients with damage to the nervous system, as well as opening the way for the more ambitious enhancements
Warwick advocates. Some transhumanists even speculate that similar technologies could be used for
technology-facilitated telepathy."[29] Warwick himself asserts that his controversial work is important because it
directly tests the boundaries of what is known about the human ability to integrate with computerised systems.
A controversy arose in August 2002, shortly after the Soham murders, when Warwick reportedly offered to implant a
tracking device into an 11-year-old girl as an anti-abduction measure. The plan produced a mixed reaction, with
support from many worried parents but ethical concerns from a number of children's societies. As a result, the idea
did not go ahead.
Anti-theft RFID chips are common in jewelry or clothing in some Latin American countries due to a high abduction
rate,[30] and the company VeriChip announced plans in 2001 to expand its line of currently available medical
information implants,[31] to be GPS trackable when combined with a separate GPS device.[32] [33]
Turing Interrogator
Warwick has participated as a Turing Interrogator, on two occasions, judging machines in the 2001 and 2006
Loebner Prize competitions, platforms for an 'imitation game' as devised by Alan Turing. The 2001 Prize, held at the
Science Museum in London, featured Turing's 'jury service' or one-to-one Turing tests and was won by A.L.I.C.E.[34]
The 2006 contest staged parallel-paired Turing tests at University College London and was won by Rollo Carpenter.
Kevin's findings can be found in a number of articles with co-author Huma Shah including Turing Test: Mindless
Game? – A Reflection on the Loebner Prize - a paper presented at the 2007 European conference on computing and
philosophy (ECAP),[35] and Emotion in the Turing Test - a chapter in a new Handbook on Synthetic Emotions and
Sociable Robotics: New Applications in Affective Computing and Artificial Intelligence.[36] He organised the 2008
Loebner Prize [37] at the University of Reading; a report on the contest's 'theatre of two Turing tests' can be found
here.[38]
Other
Warwick was a member of the 2001 Higher Education Funding Council for England (unit 29) Research Assessment
Exercise panel on Electrical and Electronic Engineering and was Deputy Chairman for the same panel (unit 24) in
2008.[39] He also sits on the research committee of The Guide Dogs for the Blind Association. In March 2009, he
was cited as being the inspiration of National Young Scientist of the Year, Peter Hatfield [40]
Awards and recognition
Warwick was presented with The Future of Health Technology Award from the Massachusetts Institute of
Technology, was made an Honorary Member of the Academy of Sciences, St. Petersburg, was awarded the
University of Malta medal from the Edward de Bono Institute and in 2004 received The Institution of Electrical
Engineers (IEE) Senior Achievement Medal.[41]
In 2008 Warwick was awarded the Mountbatten Medal[42] and received Honorary Doctor of Science degrees from
Aston University[43] and Coventry University.[44] In 2009 he received the Marcellin Champagnat award from
Universidad Marista Guadalajara and the Golden Eurydice Award[45]
52
Kevin Warwick
Quotations
• “Shouldn’t I join the ranks of philosophers and merely make unsubstantiated claims about the wonders of human
consciousness? Shouldn’t I stop trying to do some science and keep my head down? Indeed not”.[46]
• “I feel that we are all philosophers, and that those who describe themselves as a ‘philosopher’ simply do not have a
day job to go to”.[46]
• On Human Consciousness: “John Searle put forward the view that a shoe is not conscious therefore a computer
cannot be conscious. By the same sort of analogy though, a cabbage is not conscious therefore a human cannot be
conscious”.[47]
• On Machine Intelligence: “Our robots have roughly the equivalent of 50 to 100 brain cells. That means they are
about as intelligent as a slug or snail or a Manchester United supporter”.[47]
• “An actual robot walking machine which takes one step and then falls over is worth far more than a computer
simulation of 29,000 robots running the London Marathon in record time”.[47]
• “When comparing human memory and computer memory it is clear that the human version has two distinct
disadvantages. Firstly, as indeed I have experienced myself, due to ageing, human memory can exhibit very poor
short term recall”.[47]
• "There can be no absolute reality, there can be no absolute truth".[48]
• "Ask not what the surgeon can do for you - ask what you can do for the surgeon", Panel Discussion on Challenges
& Opportunities in Biomedical Engineering at BIOSTEC 2008 Conference, Madeira, Portugal, 28 January 2008.
• "Your girlfriend is not a linear system.", Control Systems Lecture, Autumn Term, 2009
Trivia
Warwick's Erdős–Bacon number is 6: he co-authored a number of scholarly articles with Yakov Tsypkin,[49] who
has an Erdős number of 3 and has appeared in several documentaries alongside people who have a Bacon number of
1, examples being Laurence Fishburne, William Shatner and Steven Spielberg.[50]
See also
•
•
•
•
•
•
God helmet
Ray Kurzweil and The Age of Intelligent Machines
Stelarc
Steve Mann
Transhumanism
Who's Who
Publications
Warwick has written several books, articles and papers. A selection of his books:
• Warwick, Kevin (2001). QI: The Quest for Intelligence. Piatkus Books. ISBN 0749922303.
• Warwick, Kevin (2004). I, Cyborg. University of Illinois Press. ISBN 0252072154.
• Warwick, Kevin (2004). March of the Machines: The Breakthrough in Artificial Intelligence. University of
Illinois Press. ISBN 0252072235.
Lectures (inaugural and keynote lectures):
• 1998, Robert Boyle Lecture at Oxford University,
• 2000, “The Rise of The Robots”, Royal Institution Christmas Lectures. These lectures were repeated in 2001 in a
tour of Japan, China and Korea.
• 2001, Gordon Higginson Lecture at Durham University, Hamilton institute inaugural lecture.
• 2003, Royal Academy of Engineering/Royal Society of Edinburgh Joint lecture in Edinburgh,
53
Kevin Warwick
•
•
•
•
•
•
•
•
2003, IEEE (UK) Annual Lecture in London; Pittsburgh International Science and Technology Festival.[51]
2004, Woolmer Lecture at University of York; Robert Hooke Lecture (Westminster)
2005, Einstein Lecture in Potsdam, Germany
2006, Bernard Price Lecture tour in South Africa; Institution of Mechanical Engineers Prestige Lecture in
London.
2007, Techfest plenary lecture in Mumbai; Kshitij keynote in Kharagpur (India); Engineer Techfest keynote in
NITK Surathkal (India); Annual Science Faculty lecture at University of Leicester; Graduate School in Physical
Sciences and Engineering Annual Lecture, Cardiff University.
2008, Leslie Oliver Oration[52] at Queen's Hospital; Techkriti keynote in Kanpur.
2008, Katholieke Universiteit Leuven, guest lecture "Four weddings and a Funeral" for the Microsoft Research
Chair.
2009, Cardiff University, 125th Anniversary Lecture; Orwell Society, Eton College.[53]
He is a regular presenter at the annual Careers Scotland Space School, University of Strathclyde.
He appeared at the 2009 World Science Festival[54] with Mary McDonnell, Nick Bostrom, Faith Salie and Hod
Lipson.
External links
• Kevin Warwick's official site [55]
• RTE Radio 1 debate with Kevin Warwick on Human Enhancement [56] [podcast link http://www.rte.ie/radio1/
podcast/podcast_sciencedebate.xml]
• Ananova story, with pictures of the chip and operation [57] (dead link, see archive [58])
• IET Robotics Network [59]
• List of articles mentioning "Captain Cyborg" [60] at the Register
• Kevin Warwick [61] at the Internet Movie Database
• Interview with Kevin Warwick [62] in The Future Fire 1 (2005)
• Video of Kevin Warwick speaking at WhatTheHack [63]
• Interview with Kevin Warwick [64] in mbr:points 1 (04.02.2008)
• Interview with Kevin Warwick on cyborgs, viruses, Cyborg Rights and cyborg-identity [65] (1 December 2008)
• Interview with Kevin Warwick [66] in IT-BHU Chronicle
• http://www.sciam.com/article.cfm?id=self-experimenters on-line Scientific American article
• Kevin Warwick at LIFT 08 [67]
References
[1] "Ambient Intelligence Lab (AIL) - Ambient Intelligence" (http:/ / www. cmu. edu/ vis/ ). Cmu.edu. . Retrieved 2009-09-26.
[2] Kevin, Warwick (1981). "Self-tuning regulators: A state-space approach". International Journal of Control 33 (5): 839–858.
[3] Warwick, K: "Relationship between Åström control and the Kalman linear regulator - Caines revisited", Journal of Optimal
Control:Applications and Methods, 11(3), pp.223-232, 1990
[4] Warwick,K:"Using the Cayley–Hamilton theorem with N partitioned matrices",IEEE Transactions on Automatic Control,
AC.28(12),pp.1127-1128, 1983
[5] Warwick, K, Ekwue, A and Aggarwal, R (eds). "Artificial intelligence techniques in power systems", Institution of Electrical Engineers Press,
1997
[6] Sutanto, E and Warwick, K: "Multivariable cluster analysis for high speed industrial machinery", IEE Proceedings - Science, Measurement
and Technology, 142, pp. 417-423, 1995
[7] "Rise of the rat-brained robots - tech - 13 August 2008 - New Scientist" (http:/ / technology. newscientist. com/ channel/ tech/ mg19926696.
100-rise-of-the-ratbrained-robots. html). Technology.newscientist.com. . Retrieved 2009-09-26.
[8] BBC News | Entertainment | To the beat of the byte (http:/ / news. bbc. co. uk/ 1/ hi/ entertainment/ 123983. stm)
[9] Radford, Tim (2003-07-13). "University robot ruled too scary" (http:/ / www. guardian. co. uk/ uk/ 2003/ jul/ 17/ highereducation. science).
The Guardian. Guardian Media Group. .
[10] (http:/ / www. timesonline. co. uk/ tol/ comment/ columnists/ guest_contributors/ article5798625. ece)
54
Kevin Warwick
[11]
[12]
[13]
[14]
[15]
Kevin Warwick, FAQ, http:/ / www. kevinwarwick. com/ faq. htm (last question)
www.kevinwarwick.com
PEEP Physics Ethics Education Project: People (http:/ / www. peep. ac. uk/ content/ 614. 0. html)
Introduction (http:/ / home. gwu. edu/ ~esialsf/ Final Report - Spring 2003. pdf)
The blade runner generation - Times Online (http:/ / www. timesonline. co. uk/ tol/ life_and_style/ health/ article2079637. ece)
[16] 英国类人机器人大赛 寓教于乐两相宜(机器人,教育,科技,发展,英国 ) - 新视界－全球资讯视频总汇 (http:/ / video. dvod. com. cn/
news/ 950835. shtml)
[17] Kevin Warwick (http:/ / www. imdb. com/ name/ nm0990120/ )
[18] Cover Browser - Wired Magazine (http:/ / www. wired. com/ wired/ coverbrowser/ 2000)
[19] www.edms.org.uk/edms/2004-2005/964.xml
[20] Warwick, K: “I, Cyborg”, University of Illinois Press, 2004, p 66
[21] Warwick, K: “I, Cyborg”, University of Illinois Press, 2004
[22] BA criticised over denying boarding to robotic cat | Airline Industry Information | Find Articles at BNET (http:/ / findarticles. com/ p/
articles/ mi_m0CWU/ is_/ ai_56752397)
[23] Sam Delaney meets Sir Jimmy Savile | Culture | The Guardian (http:/ / www. guardian. co. uk/ theguide/ tvradio/ story/ 0,,2045929,00. html)
[24] Wired Magazine 8.02 (Feb 2000), 'Cyborg 1.0: Interview with Kevin Warwick', http:/ / www. wired. com/ wired/ archive/ 8. 02/ warwick.
html . Retrieved 25-12-2006.
[25] Warwick, K, Gasson, M, Hutt, B, Goodhew, I, Kyberd, P, Andrews, B, Teddy, P and Shad, A:“The Application of Implant Technology for
Cybernetic Systems”, Archives of Neurology, 60(10), pp1369-1373, 2003
[26] Warwick, K, Hutt, B, Gasson, M and Goodhew, I:“An attempt to extend human sensory capabilities by means of implant technology”,
Proceedings IEEE International Conference on Systems, Man and Cybernetics, Hawaii, pp.1663-1668, October 2005
[27] Warwick, K, Gasson, M, Hutt, B, Goodhew, I, Kyberd, P, Schulzrinne, H and Wu, X: “Thought Communication and Control: A First Step
using Radiotelegraphy”, IEE Proceedings on Communications, 151(3), pp.185-189, 2004
[28] Kyberd, P, Murgia, A, Gasson, M, Tjerks, T, Metcalf, C, Chappell, P, Warwick, K, Lawson, S and Barnhill, T: "Case studies to demonstrate
the range of applications of the Southampton Hand Assessment Procedure", British Journal of Occupational Therapy, 72(5), pp.212-218, 2009
[29] George Dvorsky (2004-04-26). "Evolving Towards Telepathy" (http:/ / web. archive. org/ web/ 20070706064752/ http:/ / archives.
betterhumans. com/ Columns/ Column/ tabid/ 79/ Column/ 267/ Default. aspx). Betterhumans. Archived from the original (http:/ / archives.
betterhumans. com/ Columns/ Column/ tabid/ 79/ Column/ 267/ Default. aspx) on 2007-07-06. .
[30] missingbyline (missingdateline). "missingtitle" (http:/ / www. dailystar. com/ dailystar/ news/ 30069. php). Arizona Daily Star. .
[31] VeriChip. "Implantable Verification Solution for SE Asia" (http:/ / www. verichip. com. my/ index-2. html). Inforlexus. .
[32] Julia Scheeres (2002-01-25). "Kidnapped? GPS to the Rescue" (http:/ / www. wired. com/ news/ business/ 0,1367,50004,00. html). Wired
News. .
[33] Julia Scheeres (2002-02-15). "Politician Wants to 'Get Chipped'" (http:/ / www. wired. com/ news/ technology/ 0,1282,50435,00. html).
Wired News. .
[34] The A. L. I. C. E. Artificial Intelligence Foundation - chatbot - chat bot - chatterbots - verbots - natural language - chatterbot - bot - chat
robot - chat bots - AIML - take a Turing Test - Loebner ... (http:/ / www. alicebot. org/ )
[35] European Computing and Philosophy Conference (http:/ / www. utwente. nl/ ecap07/ )
[36] Handbook of Research on Synthetic Emotions and Sociable Robotics: New Applications in Affective Computing and Artificial Intelligence
(http:/ / www. igi-global. com/ reference/ details. asp?ID=34432& v=tableOfContents), IGI Global
[37] http:/ / www. loebner. net/ Prizef/ 2008_Contest/ loebner-prize-2008. html
[38] "Can a machine think? - results from the 18th Loebner Prize contest - University of Reading" (http:/ / www. rdg. ac. uk/ research/
Highlights-News/ featuresnews/ res-featureloebner. asp). Rdg.ac.uk. . Retrieved 2009-09-26.
[39] http:/ / www. rae. ac. uk/ Current official RAE website for 2008 exercise
[40] http:/ / www. rdg. ac. uk/ research/ Highlights-News/ featuresnews/ res-news-youngscientist. asp
[41] http:/ / www. theiet. org/ about/ scholarships-awards/ achievement/ medals-what. cfm
[42] Media-Newswire.com - Press Release Distribution (2008-11-20). "Press Release Distribution - PR Agency" (http:/ / media-newswire. com/
release_1079897. html). Media-Newswire.com. . Retrieved 2009-09-26.
[43] High profile graduates celebrated by Aston University (http:/ / www. aston. ac. uk/ about/ news/ 080715. jsp)
[44] "Honorary degree delight for outstanding individuals at Coventry University" (http:/ / www. coventry. ac. uk/ latestnewsandevents/ a/ 4879).
Coventry.ac.uk. . Retrieved 2009-09-26.
[45] http:/ / www. ictthatmakesthedifference. eu/ 2009. 1122. programme/
[46] Hendricks, V: “Feisty Fragments for Philosophy”, King’s College Publications, London,2004.
[47] Hendricks, V: “500 CC Computer Citations”, King’s College Publications, London, 2005
[48] Warwick, K:"The Matrix - Our Future?", Chapter in "Philosophers Explore the Matrix", edited by C.Grau, Oxford University Press, 2005
[49] Tsypkin, Ya. Z, Parks, P, Vishnyakov, A and Warwick, K:"Stability of Solutions of Linear Difference Equations with Periodic
Coefficients", International Journal of Control, 64(5), pp959-966, 1996
[50] "The Oracle of Bacon" (http:/ / oracleofbacon. org/ cgi-bin/ movielinks). The Oracle of Bacon. . Retrieved 2009-09-26.
[51] http:/ / www. scitechfestival. com/ 2004/ AR2003. pdf
55
Kevin Warwick
[52] BHR University Hospitals. "Inaugural Leslie Oliver Oration" (http:/ / www. bhrhospitals. nhs. uk/ neuro/ neuro4ha. php?id=964).
Bhrhospitals.nhs.uk. . Retrieved 2009-09-26.
[53] "Events" (http:/ / www. kevinwarwick. com/ events. asp?Date=15/ 9/ 2009). Kevinwarwick.com. . Retrieved 2009-09-26.
[54] "Battlestar Galactica Cyborgs on the Horizon" (http:/ / www. worldsciencefestival. com/ 2009/ battlestar-galactica). World Science Festival.
2009-06-12. . Retrieved 2009-09-26.
[55] http:/ / www. kevinwarwick. com/
[56] http:/ / www. rte. ie/ science
[57] http:/ / www. ananova. com/ news/ story/ sm_550084. html?menu=news. scienceanddiscovery
[58] http:/ / web. archive. org/ web/ 20050313100152/ http:/ / www. ananova. com/ news/ story/ sm_550084. html?menu=news.
scienceanddiscovery
[59] http:/ / kn. theiet. org/ communities/ robotics/ index. cfm
[60] http:/ / forms. theregister. co. uk/ search/ ?q=captain+ cyborg
[61] http:/ / www. imdb. com/ name/ nm0990120/
[62] http:/ / futurefire. net/ 2005. 01/ nonfiction/ cyborg. html
[63] http:/ / rehash. whatthehack. org/ wth/ rawtapes/ wth_cyborgs_practical_experimentation/ wth_cyborgs_practical_experimentation_18. mp4
[64] http:/ / www. mbrpoints. com/ blog/ 2008/ 02/ 04/ kybernetikprofessor-alias-captain-cyborg-kevin-warwick-im-interview-by-roland-kobald/
[65] http:/ / www. ngn. nl/ ngn?waxtrapp=tbmxbIsHyoOtvOXEaMzLD
[66] http:/ / www. itbhuglobal. org/ chronicle/ archives/ 2008/ 01/ #002112
[67] http:/ / www. liftconference. com/ four-weddings-and-funeral
56
Ivan Pavlov
57
Ivan Pavlov
Ivan Petrovich Pavlov
Иван Петрович Павлов
Nobel Prize portrait
Born
September 14, 1849
Ryazan, Russia
Died
February 27, 1936 (aged 86)
Leningrad, Soviet Union
Residence
Russian Empire, Soviet Union
Nationality
Russian, Soviet
Fields
Physiologist, psychologist, physician
Institutions
Military Medical Academy
Alma mater
Saint Petersburg University
Known for
Classical conditioning
Transmarginal inhibition
Behavior modification
Notable awards Nobel Prize in Physiology or Medicine (1904)
Ivan Petrovich Pavlov (Russian: Иван Петрович Павлов, September 14, 1849 – February 27, 1936) was a Russian,
and later Soviet, physiologist, psychologist, and physician. He was awarded the Nobel Prize in Physiology or
Medicine in 1904 for research pertaining to the digestive system. Pavlov is widely known for first describing the
phenomenon of classical conditioning.
Life and research
Ivan Pavlov was born in Ryazan, Russia.[1] He began his higher education as a student at the Ryazan Ecclesiastical
Seminary, but then dropped out and enrolled in the University of Saint Petersburg to study the natural sciences and
become a physiologist. He received his doctorate in 1879.
In the 1890s, Pavlov was investigating the gastric function of dogs by externalizing a salivary gland so he could
collect, measure, and analyze the saliva and what response it had to food under different conditions. He noticed that
the dogs tended to salivate before food was actually delivered to their mouths, and set out to investigate this "psychic
secretion", as he called it.
He decided that this was more interesting than the chemistry of saliva, and changed the focus of his research,
carrying out a long series of experiments in which he manipulated the stimuli occurring before the presentation of
food. He thereby established the basic laws for the establishment and extinction of what he called "conditional
reflexes" — i.e., reflex responses, like salivation, that only occurred conditionally upon specific previous experiences
Ivan Pavlov
of the animal. These experiments were carried out in the 1900s, and were known to western scientists through
translations of individual accounts, but first became fully available in English in a book published in 1927.
Unlike many pre-revolutionary scientists, Pavlov was highly regarded by the Soviet government, and he was able to
continue his research until he reached a considerable age. Moreover, he was praised by Lenin and as a Nobel
laureate.[2]
After the murder of Sergei Kirov in 1934, Pavlov wrote several letters to Molotov criticizing the mass persecutions
which followed and asking for the reconsideration of cases pertaining to several people he knew personally.
In later life he was particularly interested in trying to use conditioning to establish an experimental model of the
induction of neuroses. He died in Leningrad. His laboratory in Saint Petersburg has been carefully preserved as a
museum.
Conscious until his very last moment, Pavlov asked one of his students to sit beside his bed and to record the
circumstances of his dying. He wanted to create unique evidence of subjective experiences of this terminal phase of
life.[3]
Reflex system research
Pavlov contributed to many areas of physiology and neurology. Most of his work involved research in temperament,
conditioning and involuntary reflex actions. Pavlov performed and directed experiments on digestion, eventually
publishing The Work of the Digestive Glands in 1897, after 12 years of research. His experiments earned him the
1904 Nobel Prize in Physiology and Medicine[4] These experiments included surgically extracting portions of the
digestive system from animals, severing nerve bundles to determine the effects, and implanting fistulas between
digestive organs and an external pouch to examine the organ's contents. This research served as a base for broad
research on the digestive system.
Further work on reflex actions involved involuntary reactions to stress and pain. Pavlov extended the definitions of
the four temperament types under study at the time: phlegmatic, choleric, sanguine, and melancholic, updating the
names to "the strong and impetuous type, the strong equilibrated and quiet type, the strong equilibrated and lively
type, and the weak type." Pavlov and his researchers observed and began the study of transmarginal inhibition
(TMI), the body's natural response of shutting down when exposed to overwhelming stress or pain by electric
shock.[5] This research showed how all temperament types responded to the stimuli the same way, but different
temperaments move through the responses at different times. He commented "that the most basic inherited
difference. .. was how soon they reached this shutdown point and that the quick-to-shut-down have a fundamentally
different type of nervous system."[6]
Carl Jung continued Pavlov's work on TMI and correlated the observed shutdown types in animals with his own
introverted and extroverted temperament types in humans. Introverted persons, he believed, were more sensitive to
stimuli and reached a TMI state earlier than their extroverted counterparts. This continuing research branch is
gaining the name highly sensitive persons.
William Sargant and others continued the behavioral research in mental conditioning to achieve memory
implantation and brainwashing (any effort aimed at instilling certain attitudes and beliefs in a person).
58
Ivan Pavlov
Legacy
The concept for which Pavlov is famous is the "conditioned reflex" (or
in his own words the conditional reflex: the translation of условный
рефлекс into English is debatable) he developed jointly with his
assistant Ivan Filippovitch Tolochinov in 1901.[7] Tolochinov, whose
own term for the phenomenon had been "reflex at a distance",
communicated the results at the Congress of Natural Sciences in
Helsinki in 1903.[8] As Pavlov's work became known in the West,
particularly through the writings of John B. Watson, the idea of
One of Pavlov's dogs, Pavlov Museum, Ryazan,
"conditioning" as an automatic form of learning became a key concept
Russia
in the developing specialism of comparative psychology, and the
general approach to psychology that underlay it, behaviorism. The
British philosopher Bertrand Russell was an enthusiastic advocate of the importance of Pavlov's work for philosophy
of mind.
Pavlov's research on conditional reflexes greatly influenced not only science, but also popular culture. The phrase
"Pavlov's dog" is often used to describe someone who merely reacts to a situation rather than using critical thinking.
Pavlovian conditioning was a major theme in Aldous Huxley's dystopian novel, Brave New World, and also to a
large degree in Thomas Pynchon's Gravity's Rainbow.
It is popularly believed that Pavlov always signaled the occurrence of food by ringing a bell. However, his writings
record the use of a wide variety of stimuli, including electric shocks, whistles, metronomes, tuning forks, and a range
of visual stimuli, in addition to ringing a bell. Catania[9] cast doubt on whether Pavlov ever actually used a bell in his
famous experiments. Littman[10] tentatively attributed the popular imagery to Pavlov’s contemporaries Vladimir
Mikhailovich Bekhterev and John B. Watson, until Thomas[11] found several references that unambiguously stated
Pavlov did, indeed, use a bell.
See also
•
•
•
•
•
Classical conditioning
Orienting response
Behavior Modification
Ryazan
Georgii Zeliony
References
[1] Ivan Pavlov The Nobel Prize in Physiology or Medicine 1904 (http:/ / nobelprize. org/ nobel_prizes/ medicine/ laureates/ 1904/ pavlov-bio.
html)
[2] Ivan Petrovich Pavlov :: Opposition to Communism - Britannica Online Encyclopedia (http:/ / wwwa. britannica. com/ eb/ article-5560)
[3] Chance, Paul. Learning and Behaviour. Wadsworth Pub. Co., 1988. ISBN 0534085083. Page 48.
[4] 1904 Nobel prize laureates (http:/ / nobelprize. org/ nobel_prizes/ medicine/ laureates/ 1904/ press. html)
[5] Mazlish, Bruce (1995) Fourth Discontinuity: The Co-Evolution of Humans and Machines, Yale University Press, pgs. 122-123 ISBN
0-300-0541104
[6] Rokhin, L, Pavlov, I & Popov, Y. (1963) Psychopathology and Psychiatry, Foreign Languages Publication House: Moscow.
[7] Todes, Daniel Philip (2002). Pavlov's Physiology Factory. Baltimore MD: Johns Hopkins University Press. pp. 232 et sec.
ISBN 0801866901.
[8] Anrep (1927) p142
[9] Catania, A. Charles (1994); Query: Did Pavlov's Research Ring a Bell?, PSYCOLOQUY Newsletter, Tuesday, June 7, 1994
[10] Littman, Richard A. (1994); Bekhterev and Watson Rang Pavlov's Bell, Psycoloquy, Vol. 5, No. 49
[11] Thomas, Roger K. (1994); Pavlov's Rats "dripped Saliva at the Sound of a Bell", Psycoloquy, Vol. 5, No. 80 http:/ / www. cogsci. ecs.
soton. ac. uk/ cgi/ psyc/ newpsy?5. 80 (accessed 2006-aug-22)
59
Ivan Pavlov
• Boakes, Robert (1984). From Darwin to behaviourism. Cambridge: Cambridge University Press.
ISBN 978-0-521-23512-9.
• Firkin, Barry G.; J.A. Whitworth (1987). Dictionary of Medical Eponyms. Parthenon Publishing.
ISBN 978-1-85070-333-4.
• Pavlov, I. P. (1927). Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex.
Translated and Edited by G. V. Anrep. London: Oxford University Press. Available online (http://psychclassics.
yorku.ca/Pavlov/)
• Todes, D. P. (1997). "Pavlov's Physiological Factory," Isis. Vol. 88. The History of Science Society, p. 205-246.
External links
• PBS article (http://www.pbs.org/wgbh/aso/databank/entries/bhpavl.html)
• Nobel Prize website biography of I. P. Pavlov (http://www.nobel.se/medicine/laureates/1904/pavlov-bio.
html)
• Institute of Experimental Medicine article on Pavlov (http://iemrams.spb.ru:8100/english/pavlov.htm)
• A comic strip about Pavlov's work, by Wulffmorghenthaler. (http://www.wulffmorgenthaler.com/strip.
aspx?id=cd8cb971-635e-404c-9840-defc4d2ab895)
• Link to full text of Pavlov's lectures (http://www.ivanpavlov.com/)
• Link to a list of Pavlov's dogs with some pictures (http://dubnaulab.cshl.edu/data/JD_dogs.html)
• http://www.cam-pavlov.narod.ru/index.html
Tipu Aziz
Tipu Aziz is a professor of neurosurgery at the John Radcliffe Hospital in Oxford, and a lecturer at Magdalen
College, Oxford and the Imperial College London medical school. He specializes in the study and treatment of
Parkinson's disease, multiple sclerosis, dystonia, spasmodic torticollis, fixed abnormal posture of the neck, tremor,
and intractable neuropathic pain.[1] [2]
Aziz came to public prominence in the UK in February 2006 when he spoke out in favour of the use of animals in
medical research to several hundred demonstrators during a rally held by Pro-Test, a new British group set up to
promote the construction by Oxford University of a new biomedical centre in which research on animals will be
conducted.[3] Aziz is one of two Oxford neurosurgeons who sit on the Pro-Test committee.[4]
He came to public attention again in March 2006 when he defended the use of animals in cosmetics testing, which is
banned in Britain. His comments were described as "perhaps unfortunate" by one colleague.[5]
Early life and education
Aziz was born in East Pakistan, present day Bangladesh into what The Guardian called a "medical dynasty."[6] He
arrived in Britain at the age of 17 with just three O-levels, but after passing A-levels, he studied neurophysiology at
University College London, where he became interested in deep brain stimulation.
He went on to study for a doctorate at Manchester University, where he began his research on animals.
Research interests
Aziz's work involves inducing Parkinsonian symptoms in monkeys, either surgically or using drugs, then switching
off the symptoms using electrodes he has implanted in their brains. During development of his techniques he has
used around 30 monkeys in tests over 20 years, and many believe that as many as 40,000 people around the world
have benefitted from the techniques.[7]
60
Tipu Aziz
The Guardian writes that some patients have described the surgery as "miraculous." In a 2006 BBC Two
documentary Monkeys, Rats and Me: Animal Testing, animal rights philosopher Peter Singer described Aziz's
research as "justifiable" on utilitarian grounds.[8] Singer later clarified his statement saying that it would only be
justified, in his opinion, if Aziz were willing to do the same experiments on humans of a similar mental capacity. [8]
[9]
Aziz has said that his future research interests will focus on viral, gene, and stem cell therapy to treat Parkinson's and
similar movement disorders.
Research Criticism
According to the The Oxford Student, Malcolm Macleod, a clinical neuroscientist, was asked by Animal Aid to
conduct a systemic review into Aziz’s research. Macleod accidentally sent an email intended for a colleague to
animal rights group. The e-mail stated he felt that Deep Brain Stimulation was an “area of weakness often trumpeted
as a success, but which in reality is probably a failure”. He asked for “advice” and suggested he would "avoid, play a
straight bat or price [himself] out of the market” for the review requested.
Animal Aid said about the e-mail “He [Dr Macleod] feared that an objective investigation of the associated animal
research would expose the treatment's shortcomings. He was determined to avoid being drawn into the front line of
the vivisection debate.”
Dr Macleod claimed that he stood by his choice not to do the review “I was not comfortable taking part in a study
which was motivated by a desire to undermine Aziz.”[10]
Animal testing controversy
Aziz has been vocal in support of animal testing and his criticism of the animal liberation movement, calling them
"misinformed and sometimes illiterate anti-vivisectionists who adopt terrorist tactics" and who "[undermine] the
process of democracy" through "intimidation." Britain has "probably the most violent and absurd animal rights
movement in the world", he told The Guardian. "The problem with British society is it has a humanoid perception of
animals that's almost cartoon-like."[6]
On February 25, 2006, he spoke out in favour of animal testing at a rally in Oxford organized by Pro-Test in support
of the construction of a new biomedical research center, which will conduct experiments on animals, including
primates. Pro-Test was formed to counter SPEAK, an animal rights organisation aiming to end vivisection in the
UK.
Defence of cosmetics testing
In an interview published on March 4, 2005, Aziz condoned testing cosmetics on animals, a practice banned in the
UK since 1998 and due to be banned across the European Union by 2009. He said that to argue cosmetics testing is
wrong is "a very strange argument," and that "[p]eople talk about cosmetics being the ultimate evil. But beautifying
oneself has been going on since we were cavemen. If it's proven to reduce suffering through animal tests, it's not
wrong to use them. To say cosmetics is an absolute evil is absurd."[6]
Other scientists who use animals in research have "distanced themselves" from Aziz's remarks. Clive Page, a
researcher at the University of London, said: "I don't think we can justify using animals for cosmetics research. [Prof
Aziz], like myself and a few others who talk out about this have worked very hard to try and explain to the public
why we do medical research on animals and why it's still necessary. To muddy the waters by bringing back an issue
of using animals for something that's not actually approved in the UK is perhaps unfortunate."[5]
Simon Festing, director of the pro-animal experimentation lobby group Research Defence Society said of Aziz: "He's
not involved in cosmetic testing himself, [Britain's] not involved in cosmetic testing, it's been banned here. There's
no movement from the scientific community or the cosmetics industry to have it brought back in. I can't see it being
61
Tipu Aziz
particularly relevant apart from being his personal view."[5]
Felix
An animal rights campaign has formed around a seven-year-old macaque monkey that Aziz has used in his research.
Named Felix by Aziz himself, he is one of 100 purpose-bred monkeys used in animal experiments by Oxford
University.[11] Felix was featured in a November 2006 BBC documentary about Aziz's work, "Monkeys, Rats and
Me." The monkey was shown being "shaped," that is, being encouraged to perform certain tasks by having food and
water withheld, in advance of having the symptoms of Parkinson's disease induced. Electrodes were implanted in his
brain to test the effects of deep brain stimulation on the Parkinsonian symptoms and on his ability to perform the
tasks. He will be destroyed at the end of the experiment, which could continue for several years.[11] [7]
Since the BBC documentary aired, SPEAK, a British animal rights campaign formed in 2002, has focused on the
"Fight for Felix" as a symbol of their efforts to halt the construction of a new £20 million animal-testing facility in
South Park Road, Oxford.[12]
See also
• John Stein (Professor of Physiology)
• Kevin Warwick
• SPEAK campaign
Further reading
• Wishart, Adam. "Monkeys, Rats and Me: Animal Testing" [13], BBC 2, November 2006; a documentary about the
SPEAK campaign, featuring Tipu Aziz.
• Standing up for Science [14]
References
[1] "Prof. Tipu Aziz" (http:/ / www. oxfordprivatehealth. co. uk/ consultants/ consultants. asp?consultantid=452) a biography from John Radcliffe
Hospital, Oxford.
[2] "Oxford Movement Disorders Group" (http:/ / www. surgery. ox. ac. uk/ research/ neuro/ movementdisorders), The Nuffield Department of
Surgery, Oxford University.
[3] Laville, Sandra and Booth, Robert. "Scientists to speak out for animal tests" (http:/ / www. guardian. co. uk/ animalrights/ story/
0,,1716797,00. html?gusrc=rss), The Guardian, February 24, 2006.
[4] "The Pro-Test Committee" (http:/ / www. pro-test. org. uk/ about_committee. aspx), Pro-Test website, retrieved May 16, 2006.
[5] Jha, Alok & Lewis, Paul. "Scientist backs animal testing for cosmetics" (http:/ / www. guardian. co. uk/ animalrights/ story/ 0,,1723189,00.
html), The Guardian, March 4, 2006.
[6] Jeffries, Stuart. "Test driven" (http:/ / www. guardian. co. uk/ animalrights/ story/ 0,,1723372,00. html), The Guardian, March 4, 2006.
[7] Wishart, Adam. "What Felix the monkey taught me about animal research" (http:/ / www. thisislondon. co. uk/ news/
article-23375918-details/ What+ Felix+ the+ monkey+ taught+ me+ about+ animal+ research/ article. do), Evening Standard, November 25,
2006.
[8] Walsh, Gareth. "Father of animal activism backs monkey testing" (http:/ / www. timesonline. co. uk/ article/ 0,,2087-2471990,00. html), The
Sunday Times, November 26, 2006.
[9] http:/ / www. animalfreedom. org/ english/ column/ peter_singer. html
[10] "Top brain surgeon slams Aziz research", Rachel Bennett, Oxford Student
[11] Wishart, Adam. "Monkeys, Rats and Me," BBC 2, November 27, 2006.
[12] Wrong Again, Part I (http:/ / www. youtube. com/ watch?v=pv9g2iKzgQw& feature=related), Felix segment starts at six minutes; Wrong
again, part II (http:/ / www. youtube. com/ watch?v=ch0-h4uM0KI), SPEAK, The Voice for the Animals, accessed June 21, 2008.
[13] http:/ / www. archive. org/ details/ MonkeysRatsandMe
[14] http:/ / newgenerationsociety. com/ 2009/ 06/ 26/ animal-testing-%e2%80%93-%e2%80%98standing-up-for-science%e2%80%99
62
Eduard Hitzig
63
Eduard Hitzig
Eduard Hitzig
Eduard Hitzig
Born
February 6, 1839
Berlin
Died
August 20, 1907
Luisenheim zu St. Blasien
Nationality
Germany
Fields
neurology, psychiatry
Institutions University of Zurich, University of Halle
Alma mater University of Würzburg, University of Berlin
Known for
pioneer in neurophysiology
Influences
Rudolf Virchow, Emil Du Bois-Reymond
Eduard Hitzig (February 6, 1839 - August 20, 1907) was a German neurologist and neuropsychiatrist born in
Berlin.
He studied medicine in Berlin and Würzburg, and had as instructors, famous men such as Emil Du Bois-Reymond
(1818-1896), Rudolf Virchow (1821-1902), Moritz Heinrich Romberg (1795-1873) and Karl Friedrich Otto
Westphal (1833-1890). He received his doctorate in 1862, and subsequently practiced medicine in Berlin and
Würzburg. In 1875 he became director of the Burghölzli asylum, as well as professor of psychiatry at the University
of Zurich. In 1885 Hitzig became a professor at the University of Halle, where he remained until his retirement in
1903.
Hitzig is remembered for his work concerning the interaction between electrical current and the brain. In 1870,
Hitzig assisted by anatomist Gustav Fritsch (1837-1927), applied electricity via a thin probe to the exposed cerebral
cortex of a dog without anesthesia. They performed these studies at the home of Fritsch because the University of
Berlin would not allow such experimentation in their laboratories. What Hitzig and Fritsch had discovered is that
electrical stimulation of different areas of the cerebrum caused involuntary muscular contractions of specific parts of
the dog's body. They identified the brains' "motor strip" which is a vertical strip of brain tissue on the cerebrum in
the back of the frontal lobe which controls different muscles in the body. In 1870 Hitzig published his findings in an
essay called Ueber die elektrische Erregbarkeit des Grosshirns (On the Electrical Excitability of the Cerebrum). This
experimentation was considered the first time anyone had done any localized study regarding the brain and electrical
current.
However this was not the first time Hitzig had experienced the interaction between the brain and electricity; earlier
in his career as a physician working with the Prussian Army he experimented on wounded soldiers whose skulls
were fractured by bullets. Hitzig noticed that applying a small electrical current to the brains of these soldiers caused
Eduard Hitzig
64
involuntary muscular movement.
Hitzig and Fritsch's work opened the door to further localized testing of the brain by many others including Scottish
neurologist, David Ferrier.
References
• Mind as Mosaic (The Robot in the Machine), Bruce H. Hinrichs
• Parts of this article are based on a translation of an article from the German Wikipedia.
External links
• Eduard Hitzig [1] at Find a Grave
References
[1] http:/ / www. findagrave. com/ cgi-bin/ fg. cgi?page=gr& GRid=6617071
Gustav Fritsch
Gustav Theodor Fritsch (5 March 1838 – 12 June 1927) was a
German anatomist and physiologist from Cottbus, best known for his
work with neuropsychiatrist Eduard Hitzig (1839-1907) on the electric
localization of the motor areas of the brain. In 1870 they probed the
cerebral cortex of a dog to discover that electrical stimulation of
different areas of the cerebrum caused involuntary muscular
contractions of specific parts of the dog's body.
Fritsch studied natural science and medicine in Berlin, Breslau and
Heidelberg. In 1874 he became extraordinary professor of physiology
at the University of Berlin, and later was head of the histological
department of the physiological institute. Along with his medical
studies, Fritsch was also known for his ethnographical research in
South Africa (1863-68), study of electric eels, and archaeological and
zoological journeys to Egypt and Anatolia.
Selected works
Gustav Fritsch.
• Drei Jahre in Süd-Afrika: Reiseskizzen nach Notizen des Tagebuchs zusammengestellt. (Three years in South
Africa: Travelogs arranged after notes of the diary) Hirt, Breslau 1868
• Ueber die elektrische Erregbarkeit des Grosshirns. Archiv für Anatomie, Physiologie und wissenschaftliche
Medicin: (with Eduard Hitzig) 300-332, 1870
• Die Eingeborenen Süd-Afrika's: ethnographisch und anatomisch beschrieben. (Ethnographic and anatomic
research in South Africa) Hirt, Breslau 1872
• Vergleichend-anatomische Betrachtung der elektrischen Organe von Gymnotus electricus. (Comparative
anatomical view of the electrical organs of Gymnotus electricus) Veit, Leipzig 1881
Gustav Fritsch
65
References
• This article is based on a translation of the equivalent article from the German Wikipedia.
Miguel Nicolelis
Miguel Angelo Laporta
Nicolelis
Born
São Paulo, Brazil
Citizenship
Nationality
Fields
Neuroscientist
Miguel Angelo Laporta Nicolelis, MD, PhD, is a Brazilian physician and scientist, best known for his pioneering
work in "reading monkey thought". He and his colleagues implanted electrode arrays into a monkey's brain that were
able to detect the monkey's motor intent and thus able to control reaching and grasping movements performed by a
robotic arm. This was possible by decoding signals of hundreds of neurons recorded in volitional areas of the
cerebral cortex while the monkey played with a hand-held joystick to move a shape in a video game. These signals
were sent to the robot arm, which then mimicked the monkey's movements and thus controlled the game. After a
while the monkey realised that thinking about moving the shape was enough and it no longer needed to move the
joystick. So it let go of the joystick and controlled the game purely through thought. A system in which brain signals
directly control an artificial actuator is commonly referred to as brain-machine interface or brain-computer interface.
On January 15, 2008, Dr. Nicolelis's lab saw a monkey implanted with a new BCI successfully control a robot
walking on a treadmill in Kyoto, Japan. The monkey could see the robot, named CB, on a screen in front of him, and
was rewarded for walking in sync with the robot (which was under the control of the monkey). After an hour the
monkey's treadmill was turned off, but he was able to continue to direct the robot to walk normally for another few
minutes, indicating that a part of the brain not sufficient to induce a motor response in the monkey had become
dedicated to controlling the robot, as if it were an extension of itself.
Nicolelis also played a fundamental role in the foundation of the International Institute for Neuroscience of Natal, an
important research facility in Brazil.
Miguel Nicolelis
Selected Publications on Brain-Machine Interface
• Lebedev, M.A., Carmena, J.M., O’Doherty, J.E., Zacksenhouse, M., Henriquez, C.S., Principe, J.C., Nicolelis,
M.A.L. (2005) Cortical ensemble adaptation to represent actuators controlled by a brain machine interface. [1] J.
Neurosci. 25: 4681-4693.
• Santucci, D.M., Kralik, J.D., Lebedev , M.A., Nicolelis, M.A.L. (2005) Frontal and parietal cortical ensembles
predict single-trial muscle activity during reaching movements. [2] Eur. J. Neurosci., 22: 1529-1540.
• Carmena, J.M., Lebedev, M.A., Crist, R.E., O’Doherty, J.E., Santucci, D.M., Dimitrov, D.F., Patil, P.G.,
Henriquez, C.S., Nicolelis, M.A.L. (2003) Learning to control a brain-machine interface for reaching and
grasping by primates. [3] PLoS Biology, 1: 193-208.
• Nicolelis MA (2003) Brain-machine interfaces to restore motor function and probe neural circuits. [4] Nat Rev
Neurosci. 4: 417-422.
• Wessberg J, Stambaugh CR, Kralik JD, Beck PD, Laubach M, Chapin JK, Kim J, Biggs SJ, Srinivasan MA,
Nicolelis MA. (2000) Real-time prediction of hand trajectory by ensembles of cortical neurons in primates. [5]
Nature 16: 361-365.
Additional references
1. "The Scientific American 50" [6]. Scientific American. December 2004. pp. 46.
External links
•
•
•
•
•
Nicolelis Lab [7]
CV and awards [8]
New Scientist 2003 [9]
New Scientist 2004 [10]
International Institute for Neuroscience of Natal (IINN) [11]
References
[1] http:/ / www. jneurosci. org/ cgi/ content/ abstract/ 25/ 19/ 4681
[2] http:/ / www. blackwell-synergy. com/ doi/ abs/ 10. 1111/ j. 1460-9568. 2005. 04320. x
[3] http:/ / biology. plosjournals. org/ perlserv/ ?request=get-document& doi=10%2E1371%2Fjournal%2Epbio%2E0000042
[4] http:/ / www. nature. com/ nrn/ journal/ v4/ n5/ abs/ nrn1105_fs. html;jsessionid=6D87C4B29FF58C8DDB5ACF4E2A8560D3
[5] http:/ / www. nature. com/ nature/ journal/ v408/ n6810/ abs/ 408361a0. html
[6] http:/ / www. sciam. com/ article. cfm?articleID=000D5CA6-D59B-118F-91DD83414B7F0000& pageNumber=2& catID=9
[7] http:/ / www. nicolelislab. net
[8] http:/ / www. nicolelislab. net/ NLNet/ Load/ CVs/ Nicolelis_CV. pdf
[9] http:/ / www. newscientist. com/ article. ns?id=dn4262
[10] http:/ / www. newscientist. com/ article. ns?id=mg18224412. 400
[11] http:/ / www. natalneuro. com
66
José Manuel Rodriguez Delgado
José Manuel Rodriguez Delgado
Dr. José Manuel Rodriguez Delgado (born August 8, 1915) is a Spanish professor of physiology at Yale
University, famed for his research into mind control through electrical stimulation of regions in the brain.
Delgado was born in Ronda, Spain in 1915. He received a Doctor of Medicine degree from the University of Madrid
just before the outbreak of the Spanish Civil War, in which he served as a medical corpsman on the Republican side.
After the war he had to repeat his M.D. degree, and then took a Ph.D. at the Cajal Institute in Madrid.
In 1946 he began a fellowship at Yale, and was invited by the noted physiologist John Fulton to join the department
of physiology in 1950.
Delgado's research interests centered on the use of electrical signals to evoke responses in the brain. His earliest
work was with cats, but later did experiments with monkeys and humans, including mental patients.
Much of Delgado's work was with an invention he called a stimoceiver, a radio which joined a stimulator of brain
waves with a receiver which monitored E.E.G. waves and sent them back on separate radio channels. This allowed
the subject of the experiment full freedom of movement while allowing the experimenter to control the experiment.
The stimoceiver could be used to stimulate emotions and control behavior. According to Delgado, "Radio
Stimulation of different points in the amygdala and hippocampus in the four patients produced a variety of effects,
including pleasant sensations, elation, deep, thoughtful concentration, odd feelings, super relaxation, colored visions,
and other responses." Delgado stated that "brain transmitters can remain in a person's head for life. The energy to
activate the brain transmitter is transmitted by way of radio frequencies." (Source: Cannon; Delgado, J.M.R.,
"Intracerebral Radio Stimulation and recording in Completely Free Patients," in Schwitzgebel and Schwitzgebel
(eds.))
The most famous example of the stimoceiver in action occurred at a Cordoba bull breeding ranch. Delgado stepped
into the ring with a bull which had had a stimoceiver implanted. The bull charged Delgado, who pressed a remote
control button which caused the bull to stop its charge. Delgado claimed that the stimulus caused the bull to lose its
aggressive instinct.
Although the bull incident was widely mentioned in the popular media, Delgado believed that his experiment with a
female chimpanzee named Paddy was more significant. Paddy was fitted with a stimoceiver linked to a computer
that detected the brain signal called a spindle. When the spindle was recognized, the stimoceiver sent a signal to the
central gray area of Paddy's brain, producing an 'aversive reaction'. Within hours her brain was producing fewer
spindles.
In 1974, Delgado returned to Spain to help organize a new medical school at the Autonomous University of Madrid.
References
• John Horgan (October 2005). "The Forgotten Era of Brain Chips" [1]. Scientific American 293 (4): 66–73.
doi:10.1038/scientificamerican1005-66.
• Maggie Scarf (1971-11-25). "Brain Researcher Jose Delgado Asks "What Kind of Humans Would We Like to
Construct?"". New York Times.
Further reading
• José Manuel Rodriguez Delgado (1969). Physical Control of the Mind: Toward a Psychocivilized Society. Harper
and Row. ISBN 0060902086.
• Delgado JM (1977–1978). "Instrumentation, working hypotheses, and clinical aspects of neurostimulation".
Applied Neurophysiology 40 (2–4): 88–110. doi:10.1159/000102436. PMID 101139.
67
José Manuel Rodriguez Delgado
• John Horgan (October 2004). "The Myth of Mind Control: Will anyone ever decode the human brain?" [2] ( –
Scholar search [3]
). Discover 25 (10).
• Elliot S. Valenstein (1973). Brain Control: A Critical Examination of Brain Stimulation and Psychosurgery. John
Wiley & Sons. ISBN 0471897841.
External links
• "Wirehead Hedonism versus Paradise Engineering" [4]. Retrieved 2006-12-26.
• Adam Keiper (Winter 2006). "The Age of Neuroelectronics" [5]. The New Atlantis: 4–41.
References
[1] http:/ / www. wireheading. com/ delgado/ brainchips. pdf
[2] http:/ / www. discover. com/ issues/ oct-04/ cover/
[3] http:/ / scholar. google. co. uk/ scholar?hl=en& lr=& q=intitle%3AThe+ Myth+ of+ Mind+ Control%3A+ Will+ anyone+ ever+ decode+ the+
human+ brain%3F& as_publication=Discover& as_ylo=& as_yhi=& btnG=Search
[4] http:/ / www. wireheading. com/ index. html
[5] http:/ / www. thenewatlantis. com/ archive/ 11/ TNA11-Keiper. pdf
68
Aimee Mullins
69
Aimee Mullins
Mullins at the 2008 Tribeca Film Festival
Personal information
Nationality
American
Date of birth
1976
Place of birth
Allentown, Pennsylvania
Website
www.aimeemullins.com
[1]
Sport
Sport
Running
Event(s)
Long jump, sprinting
College/university team Georgetown University
Achievements and titles
Paralympics
1996 Paralympics
Aimee Mullins (born 1976 in Allentown, Pennsylvania) is an American athlete, actress, and fashion model best
known for her collegiate-level athletic accomplishments, despite a medical condition that resulted in the amputation
of both of her legs.
Background
Mullins was born with fibular hemimelia (missing fibula bones) and, as a result, had both of her legs amputated
below the knee when she was a year old. She is a graduate of Parkland High School in Allentown and Georgetown
University in Washington, D.C.
While attending Georgetown University, she competed against able-bodied athletes in NCAA Division I track and
field events. She competed in the Paralympics in 1996 in Atlanta, in which she ran the 100-meter dash in 17.01
seconds and jumped 3.14 meters in the long-jump.[2]
Also while at Georgetown, Mullins won a place on the Foreign Affairs internship program, working at The
Pentagon. She also makes appearances as a motivational speaker.
Aimee Mullins
70
Fashion model
In 1999, she modelled for British fashion designer Alexander McQueen in his London show, on a pair of
hand-carved wooden prosthetic legs made from solid ash, with integral boots.[3] She is able to change her height
between 5ft 8in and 6ft 1in by changing her legs.[3] She has been named one of the fifty most beautiful people in the
world by People.
Actress
In 2002, she appeared in Matthew Barney's Cremaster 3 as a cheetah woman (the Entered Novitiate and Oonagh
MacCumhail). In 2006, she appeared in World Trade Center, playing the role of a reporter. She also appeared, in
2003, in the made-for-television version of Agatha Christie's Five Little Pigs, as the woman who asks Hercule Poirot
to clear her dead mother of murder.
She appeared on The Colbert Report on April 15, 2010 and declared having 12 pairs of prosthetic legs, with "some in
museums".[4]
Films and television
• 2002 - Cremaster 3 (Cremaster Cycle), film directed by
Matthew Barney.
• 2003 - Five Little Pigs
• 2006 - Marvelous
• 2006 - World Trade Center as a reporter
• 2008 - Quid Pro Quo
Books
Mullins has been featured in the following books:
• Athlete (2002) ISBN 0-06-019553-3
• Laws of the Bandit Queens (2002) ISBN 0-609-80807-9
• The Prosthetic Impulse - Smith and Morra (eds.) (2006) ISBN
0-262-19530-5
External links
• Aimee Mullins's Official Site at AimeeMullins.com
• Aimee Mullins [5] at the Internet Movie Database
[1]
Aimee Mullins watches fellow bilateral amputee Hugh
Herr climb the wall at the MIT Media Lab's h2.0
symposium on May 9, 2007
• Aimee Mullins at AllAmericanSpeakers.com [6]
• TED Talks: Aimee Mullins: Running on high-tech legs, Filmed 1998 [7]
• TED Talks: Aimee Mullins: How my legs give me super-powers, Filmed 2009 [8]
• TED Talks: Aimee Mullins: The opportunity of adversity, Filmed Oct 2009 [9]
• Role Models interview from CaptainU [10]
• Official paralympic.org records page [11]
Aimee Mullins
References
[1] http:/ / www. aimeemullins. com/
[2] Paralympic.org official records site results (http:/ / paralympic. org/ Sport/ Results/ search. html?sport=all& games=all& medal=all&
npc=all& name=Mullins& fname=Aimee& gender=f)
[3] Aimee Mullins: How my legs give me super-powers TED conference - Feb 2009
[4] http:/ / www. colbertnation. com/ full-episodes/ thu-april-15-2010-aimee-mullins Colbert Report: April 15, 2010 - Aimee Mullins - Full
Episode]
[5] http:/ / www. imdb. com/ name/ nm1190429/
[6] http:/ / www. allamericanspeakers. com/ speakerbio/ Aimee_Mullins. php
[7] http:/ / www. ted. com/ index. php/ talks/ aimee_mullins_on_running. html
[8] http:/ / www. ted. com/ index. php/ talks/ aimee_mullins_prosthetic_aesthetics. html
[9] http:/ / www. ted. com/ talks/ aimee_mullins_the_opportunity_of_adversity. html
[10] http:/ / www. captainu. com/ buzz/ 382-aimee-mullins-the-interview-on-role-models
[11] http:/ / www. paralympic. org/ Sport/ Results/ results. html?eclass=T42-46& sport=athletics& competition=1996PG& gender=f&
discipline=& event=100%20m
71
72
Conditions
Parkinson's disease
Parkinson's disease
Classification and external resources
Illustration of the Parkinson disease by Sir William Richard Gowers from A Manual of Diseases of the Nervous System in 1886
[1]
[2]
ICD-10
G 20.
ICD-9
332
DiseasesDB
9651
MedlinePlus
000755
eMedicine
neuro/304
neuro/635
[8]
pmr/99
rehab
, F 02.3
[3]
[4]
[5]
[6]
[7]
in young
Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous
system that often impairs the sufferer's motor skills, speech, and other functions.[9]
Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle
rigidity, tremor, a slowing of physical movement (bradykinesia) and a loss of physical movement (akinesia) in
extreme cases. The primary symptoms are the results of decreased stimulation of the motor cortex by the basal
ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the
dopaminergic neurons of the brain (specifically the substantia nigra). Secondary symptoms may include high level
cognitive dysfunction and subtle language problems. PD is both chronic and progressive.
PD is the most common cause of chronic progressive parkinsonism, a term which refers to the syndrome of tremor,
rigidity, bradykinesia and postural instability. PD is also called "primary parkinsonism" or "idiopathic PD"
(classically meaning having no known cause). While many forms of parkinsonism are idiopathic, "secondary" cases
may result from toxicity most notably of drugs, head trauma, or other medical disorders. The disease is named after
English apothecary James Parkinson, who made a detailed description of the disease in his essay: "An Essay on the
Parkinson's disease
Shaking Palsy" (1817).
Classification
The term Parkinsonism is used for symptoms of tremor, stiffness, and slowing of movement caused by loss of
dopamine. "Parkinson's disease" is the synonym of "primary parkinsonism", i.e., isolated parkinsonism due to a
neurodegenerative process without any secondary systemic cause. In some cases, it would be inaccurate to say that
the cause is "unknown", because a small proportion is caused by genetic mutations. It is possible for a patient to be
initially diagnosed with Parkinson's disease but then to develop additional features, requiring revision of the
diagnosis.[10]
There are other disorders that are called Parkinson-plus diseases. These include: multiple system atrophy (MSA),
progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Some include dementia with Lewy
bodies (DLB) — while idiopathic Parkinson's disease patients also have Lewy bodies in their brain tissue, the
distribution is denser and more widespread in DLB. Even so, the relationship between Parkinson disease, Parkinson
disease with dementia (PDD), and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a
spectrum, with a discrete area of overlap between each of the three disorders. The cholinesterase inhibiting
medications have shown preliminary efficacy in treating the cognitive, psychiatric, and behavioral aspects of the
disease of both PD and DLB. The natural history and role of Lewy bodies is little understood.
These Parkinson-plus diseases may progress more quickly than typical idiopathic Parkinson disease. If cognitive
dysfunction occurs before or very early in the course of the movement disorder, then DLBD may be suspected. Early
postural instability with minimal tremor, especially in the context of ophthalmoparesis, should suggest PSP. Early
autonomic dysfunction, including erectile dysfunction and syncope, may suggest MSA. The presence of extreme
asymmetry with patchy cortical cognitive defects such as dysphasia and apraxias (especially with "alien limb"
phenomena) should suggest CBD.
The usual anti-Parkinson's medications are typically either less effective or completely ineffective in controlling
symptoms; patients may be exquisitely sensitive to neuroleptic medications like haloperidol, so correct differential
diagnosis is important.
Essential tremor may be mistaken for Parkinson's disease, but lacks all other features besides tremor, and has
particular characteristics distinguishing it from Parkinson's disease, such as improvement with beta blockers and
alcoholic beverages.[9]
Wilson's disease (hereditary copper accumulation) may present with parkinsonian features; young patients presenting
with parkinsonism or any other movement disorder are frequently screened for this rare condition, because it may
respond to medical treatment. Typical tests are liver function, slit lamp examination for Kayser-Fleischer rings, and
serum ceruloplasmin levels.
Signs and symptoms
Parkinson's disease affects movement, producing motor symptoms.[9] Non-motor symptoms, which include
autonomic dysfunction, cognitive and neurobehavioral problems, and sensory and sleep difficulties, are also
common but are under-appreciated.[9]
Motor
Four motor symptoms are considered cardinal in PD: tremor, rigidity, bradykinesia and postural instability.[9]
Tremor is the most apparent and well-known symptom.[9] It is most commonly a rest tremor: maximal when the limb
is at rest and disappearing with voluntary movement and sleep.[9] It affects to a greater extent the most distal part of
the extremity and is typically unilateral at onset.[9] Though around 30% of PD sufferers do not have tremor at disease
onset most of them would develop it along the course of the disease.[9] Rigidity is due to joint stiffness and increased
73
Parkinson's disease
muscle tone, which combined with a resting tremor produce a ratchety, "cogwheel rigidity" when the limb is
passively moved.[9] Rigidity may be associated with joint pain, such pain being a frequent initial manifestation of the
disease.[9] Bradykinesia (slowness of movement) is the most characteristic clinical feature of PD and it produces
difficulties not only with the execution of a movement but also with its planning and initiation.[9] The performance
of sequential and simultaneous movements is also hindered.[9] In the late stages of the disease postural instability is
typical, which leads to impaired balance and falls.[9]
PD motor symptomatology is not limited to these four symptoms. Gait and posture disturbances such as decreased
arm swing, a forward-flexed posture and the use of small steps when walking; speech and swallowing disturbances;
and other symptoms such as a mask-like face expression (also known as poker-face) or a small handwriting are only
examples of the ample range of common motor problems that can appear with the disease.[9]
Neuropsychiatric
Parkinson's disease causes neuropsychiatric disturbances, which include mainly cognition, mood and behavior
problems and can be as disabling as motor symptoms.[9]
Cognitive disturbances occur even in the initial stages of the disease in some cases.[11] A very high proportion of
sufferers will have mild cognitive impairment as the disease advances.[9] Most common cognitive deficits in
non-demented patients are executive dysfunction, which translates into impaired set shifting, poor problem solving,
and fluctuations in attention among other difficulties; Slowed cognitive speed, memory problems; specifically in
recalling learned information, with an important improvement with cues; and visuospatial skills difficulties, which
are seen when the person with PD is for example asked to perform tests of facial recognition and perception of line
orientation.[11]
Deficits tend to aggravate with time, developing in many cases into dementia. A person with PD has a sixfold
increased risk of suffering it,[9] and the overall rate in people with the disease is around 30%.[11] Moreover,
prevalence of dementia increases in relation to disease duration, going up to 80%.[11] Dementia has been associated
with a reduced quality of life in disease sufferers and caregivers, increased mortality and a higher probability of
attending a nursing home.[11]
Cognitive problems and dementia are usually accompanied by behavior and mood alterations, although these kind of
changes are also more common in those patients without cognitive impairment than in the general population. Most
frequent mood difficulties include depression, apathy and anxiety.[9] Obsessive–compulsive behaviors such as
craving, binge eating, hypersexuality, pathological gambling, or other, can also appear in PD, and have been related
to a dopamine dysregulation syndrome associated with the medications for the disease.[9]
Other
In addition to cognitive and motor symptoms PD can impair other body functions. Sleep problems can be worsened
by medications for PD, but they are a core feature of the disease.[9] They can manifest as excessive daytime
somnolence, disturbances in REM sleep or insomnia.[9] The autonomic system is altered which can lead for example
to orthostatic hypotension, oily skin and seborrheic dermatitis, excessive sweating, urinary incontinence and altered
sexual function.[9] Constipation and gastric dysmotility can be severe enough to endanger comfort and health.[12] PD
is also related to different ophthalmological abnormalities such as decreased blink rate and alteration in the tear film,
leading to irritation of the eye surface, abnormalities in ocular pursuit and saccadic movements and limitations in the
upward gaze.[9] Changes in perception include reduced sense of smell and sensation of pain and paresthesias.[9]
74
Parkinson's disease
Causes
Most people with Parkinson's disease are described as having idiopathic Parkinson's disease (having no specific
known cause). There are far less common causes of Parkinson's disease including genetic, toxins, head trauma,
cerebral anoxia, and drug-induced Parkinson's disease.
Genetic
Someone who has Parkinson's disease is more likely to have relatives that also have Parkinson's disease. However,
the inheritance of Parkinson's disease is usually complex and not due to a single gene defect.
A number of specific genetic mutations causing Parkinson's disease have been discovered. Genes identified as of
2008 are Alpha-synuclein (SNCA), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), parkin (PRKN),
leucine-rich repeat kinase 2 (LRRK2 or dardarin) , PINK 1 and DJ-1.[13] With the exception of LRRK2 they account
for a small minority of cases of PD.[13]
The most common known genetic risk factor for Parkinson's is a mutated glucocerebrosidase gene, which is involved
in Gaucher's disease; carriers of these mutations have a fivefold risk of developing Parkinson's.[14] There is also
recent evidence that a common gene defect contributes susceptibility to both Parkinson's Disease and Alzheimer's
disease.[15]
Toxins
One theory holds that many or even most cases of the disease may result from the combination of a genetically
determined vulnerability to environmental toxins along with exposure to those toxins.[16] This hypothesis is
consistent with the fact that Parkinson's disease is not distributed homogeneously throughout the population; its
incidence varies geographically. However, it is not consistent with the fact that the first appearance of the syndrome
predates the first synthesis of the compounds often attributed to causing Parkinson's disease. The toxins most
strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially
those that generate reactive oxygen species,[17] [18] and/or bind to neuromelanin, as originally suggested by G.C.
Cotzias.[19] [20]
In a longitudinal investigation, individuals who were exposed to pesticides had a 70% higher incidence of PD than
individuals who were not exposed.[21] Studies have found an increase in PD in individuals who consume rural well
water; researchers theorize that water consumption is a proxy measure of pesticide exposure. In agreement with this
hypothesis are studies which have found a dose-dependent increase in PD in persons exposed to agricultural
chemicals.
Signs of mercury poisoning share different symptoms with PD such as tremor, psychosis, memory deficits,
disturbances in muscle control and coordination,anosmia and failure of autonomic nervous system.[22] Mercury has
been suggested to have a role in the etiology of PD.[23] PD-like mercury poisoning can be treated with chelating
agents such as penicillamine.[24]
75
Parkinson's disease
76
Head trauma
Head trauma is considered a risk factor for PD since past episodes are reported more frequently by individuals with
Parkinson's disease than by others in the population.[25] Nevertheless recent primary studies have suggested that head
trauma may actually be a result of early symptoms of clumsiness associated with PD,[26] or that there is no true
relationship between severe head injury and the disease.[27]
Pathophysiology
The symptoms of Parkinson's disease result from the greatly reduced
activity of pigmented dopamine-secreting (dopaminergic) cells in the
pars compacta region of the substantia nigra (literally "black
substance"). These neurons project to the striatum and their loss leads
to alterations in the activity of the neural circuits within the basal
ganglia that regulate movement, in essence an inhibition of the direct
pathway and excitation of the indirect pathway.
Dopaminergic pathways of the human brain in
normal condition (left) and Parkinson's disease
(right). Red Arrows indicate suppression of the
target, blue arrows indicate stimulation of target
structure.
The direct pathway facilitates movement and the indirect pathway
inhibits movement, thus the loss of these cells leads to a hypokinetic
movement disorder. The lack of dopamine results in increased
inhibition of the ventral anterior nucleus of the thalamus, which sends
excitatory projections to the motor cortex, thus leading to hypokinesia.
There are four major dopamine pathways in the brain; the nigrostriatal
pathway, referred to above, mediates movement and is the most
conspicuously affected in early Parkinson's disease. The other
pathways are the mesocortical, the mesolimbic, and the
tuberoinfundibular. Disruption of dopamine along the non-striatal
pathways likely explains much of the neuropsychiatric pathology
associated with Parkinson's disease.
Black-staining granules of neuromelanin within
neurons of the substantia nigra
The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the
protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be
directed to the proteasome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy
bodies. The latest research on pathogenesis of disease has shown that the death of dopaminergic neurons by
alpha-synuclein is due to a defect in the machinery that transports proteins between two major cellular organelles —
the endoplasmic reticulum (ER) and the Golgi apparatus. Certain proteins like Rab1 may reverse this defect caused
by alpha-synuclein in animal models.[28]
Excessive accumulations of iron, which are toxic to nerve cells, are also typically observed in conjunction with the
protein inclusions. Iron and other transition metals such as copper bind to neuromelanin in the affected neurons of
the substantia nigra. Neuromelanin may be acting as a protective agent. The most likely mechanism is generation of
reactive oxygen species.[17] Iron also induces aggregation of synuclein by oxidative mechanisms.[29] Similarly,
Parkinson's disease
dopamine and the byproducts of dopamine production enhance alpha-synuclein aggregation. The precise mechanism
whereby such aggregates of alpha-synuclein damage the cells is not known. The aggregates may be merely a normal
reaction by the cells as part of their effort to correct a different, as-yet unknown, insult. Based on this mechanistic
hypothesis, a transgenic mouse model of Parkinson's has been generated by introduction of human wild-type
alpha-synuclein into the mouse genome under control of the platelet-derived-growth factor-β promoter.[30]
A recent view of Parkinson's disease implicates specialized calcium channels that allow substantia nigra neurons, but
not most neurons, to repetitively fire in a "pacemaker" like pattern. The consequent flooding of calcium into these
neurons may aggravate damage to mitochondria and may cause cell death. One study has found that, in experimental
animals, treatment with a calcium channel blocker isradapine had a substantial protective effect against the
development of Parkinson's disease.[31]
Diagnosis
Typically, the diagnosis is based on medical history and
neurological examination conducted by interviewing and
observing the patient in person using the Unified Parkinson's
Disease Rating Scale. A radiotracer for SPECT scanning machines
called DaTSCAN and made by General Electric is specialized for
diagnosing Parkinson's Disease, but it is only marketed in Europe.
Due to this, the disease can be difficult to diagnose accurately,
especially in its early stages. Due to symptom overlap with other
diseases, only 75% of clinical diagnoses of PD are confirmed to be
idiopathic PD at autopsy.[32] Early signs and symptoms of PD may
sometimes be dismissed as the effects of normal aging. The
physician may need to observe the person for some time until it is
18F PET scan shows decreased dopamine activity in
apparent that the symptoms are consistently present. Usually
the basal ganglia, a pattern which aids in diagnosing
doctors look for shuffling of feet and lack of swing in the arms.
Parkinson's disease.
Doctors may sometimes request brain scans or laboratory tests in
order to rule out other diseases. However, CT and MRI brain scans of people with PD usually appear normal.
Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis and follow-up of Parkinson's
disease should be done by a specialist in the disease, usually a neurologist or geriatrician with an interest in
movement disorders.[10]
Treatment
Parkinson's disease is a chronic disorder that requires broad-based management including patient and family
education, support group services, general wellness maintenance, physiotherapy, exercise, and nutrition.[10] One
could consult an occupational therapist on a broad range of methods, therapy, and assistive equipment to make
Parkinson's more manageable in the areas of personal care, productivity and leisure. At present, there is no cure for
PD, but medications or surgery can provide relief from the symptoms. Clozapine has been shown to be useful in PD
patients with psychoses, although with some risk of adverse effects. However, clozapine causes few extrapyramidal
symptoms and when used in low doses can block psychotic symptoms. Doses starting at 6.25 to 12.5 mg and
increasing to 50 mg are typical.[33]
77
Parkinson's disease
Levodopa
The most widely used form of treatment is L-dopa in various forms.
L-dopa is transformed into dopamine in the dopaminergic neurons by
L-aromatic amino acid decarboxylase (often known by its former name
dopa-decarboxylase). However, only 1-5% of L-DOPA enters the
dopaminergic neurons. The remaining L-DOPA is often metabolised to
dopamine elsewhere, causing a wide variety of side effects. Due to
feedback inhibition, L-dopa results in a reduction in the endogenous
formation of L-dopa, and so eventually becomes counterproductive.
Carbidopa and benserazide are dopa decarboxylase inhibitors. They
Stalevo for treatment of Parkinson's disease
help to prevent the metabolism of L-dopa before it reaches the
dopaminergic neurons and are generally given as combination preparations of carbidopa/levodopa (co-careldopa)
(e.g. Sinemet, Parcopa) and benserazide/levodopa (co-beneldopa) (e.g. Madopar). There are also controlled release
versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa
and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered
via a tube directly into the upper small intestine, where it is rapidly absorbed. Another drug, Stalevo (carbidopa,
levodopa and entacapone), is also available for treatment.
Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to
complement L-dopa. However, due to its possible side effects such as liver failure, it's limited in its availability. A
similar drug, entacapone has not been shown to cause significant alterations of liver function and maintains adequate
inhibition of COMT over time.[34]
Dopamine agonists
The dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole , piribedil, cabergoline, apomorphine, and
lisuride are moderately effective. These have their own side effects including those listed above in addition to
somnolence, hallucinations and/or insomnia. Several forms of dopamine agonism have been linked with a markedly
increased risk of problem gambling. Dopaminergic treatment for depression in patients with Parkinson disease may
be associated with impulse control disorders.[35] Dopamine agonists initially act by stimulating some of the
dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby
eventually increasing the symptoms.
Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as a result of high
doses of L-dopa. Apomorphine can be administered via subcutaneous injection using a small pump which is carried
by the patient. A low dose is automatically administered throughout the day, reducing the fluctuations of motor
symptoms by providing a steady dose of dopaminergic stimulation. After an initial "apomorphine challenge" in
hospital to test its effectiveness and brief patient and primary caregiver (often a spouse or partner), the latter of
whom takes over maintenance of the pump. The injection site must be changed daily and rotated around the body to
avoid the formation of nodules. Apomorphine is also available in a more acute dose as an autoinjector pen for
emergency doses such as after a fall or first thing in the morning. Nausea and vomiting are common, and may
require domperidone (an antiemetic).
Pramipexole was proposed in late 2009 as an early-stage treatment alternative to Levodopa.[36]
Recently there has been a consensus that younger patients first be treated with dopamine agonists while older
patients be given Levodopa[37]
78
Parkinson's disease
79
MAO-B inhibitors
Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B). MAO-B breaks down
dopamine secreted by the dopaminergic neurons, so inhibiting it will result in inhibition of the breakdown of
dopamine. Metabolites of selegiline include L-amphetamine and L-methamphetamine (not to be confused with the
more notorious and potent dextrorotary isomers). This might result in side effects such as insomnia. Use of L-dopa in
conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect
of the combination can be stomatitis. One report raised concern about increased mortality when MAO-B inhibitors
were combined with L-dopa;[38] however subsequent studies have not confirmed this finding.[39] Unlike other non
selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis.
Surgery and deep brain stimulation
Treating Parkinson's disease with surgery was once a common
practice, but after the discovery of levodopa, surgery was
restricted to only a few cases. Studies in the past few decades have
led to great improvements in surgical techniques, and surgery is
again being used in people with advanced PD for whom drug
therapy is no longer sufficient.
Deep brain stimulation is presently the most used surgical means
of treatment, but other surgical therapies that have shown promise
include surgical lesion of the subthalamic nucleus[40] and of the
internal segment of the globus pallidus, a procedure known as
pallidotomy.[41]
Neurorehabilitation
There is partial evidence that speech or mobility problems can
improve with rehabilitation although studies are still scarce and of
low quality.[42] [43] [44] [45] Regular physical exercise and/or
therapy can be beneficial to the patient for maintaining and
improving mobility, flexibility, strength, gait speed, and quality of
life;[44] and speech therapy may improve voice and speech
function.[45]
Illustration showing an electrode placed deep seated in
the brain
Other benefits that regular exercise can bring to patients include: balance improvement, joint function improvement,
rigidity relieve, cardiovascular fitness increase, muscle strength and flexibility increase, and stress levels reduction
among others. Also, exercise help patients perform daily activities, therefore, they experience greater confidence.
Furthermore, physical therapy can help with fatigue, immobility, and weakness. Some of the exercises may be
performed at home while others might need to be performed at a nursing or rehabilitation facility. [46] It is believed
that exercise could stop the progression of PD because it produces a neuroprotective mechanism. [47]
Although physical therapy can greatly improve the conditions, patients are advised to avoid sudden movements or
lean too far forwards or backwards in order to avoid falls. Also they are discouraged to carry things while walking
since this might affect balance. [48]
One of the most widely practiced treatment for the speech disorders associated with Parkinson's disease is the Lee
Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness.[49]
Moreover, speech therapy can be very helpful to improve dysarthria (difficulty speaking) as well as dysphagia
(difficulty swallowing), two severely symptoms of Parkinson's disease. It was not until 1984 that speech therapy was
Parkinson's disease
80
able to provide sustained improvement, when Lorraine Olson Ramig, PH.d., and Carolyn Mead, M.A., developed the
Lee Silverman Voice Treatment. Although it was first developed as a treatment program for PD, it now includes
other neurological disorders. This behavioral treatment is given in sixteen sessions in one month and it targets vocal
intensity, quality and variation. [50]
Diet
Muscles and nerves that control the digestive process may be affected by PD, therefore, it is common for patients to
experience constipation and gastroparesis. A balanced diet is hence recommended to help improve digestion. Diet
should include high-fiber foods including whole grain breads and cereals as well as fruits and vegetables and plenty
of water, while it is important to avoid caffeine and alcohol and iron salts. Excessive protein should also be avoided
because affects the absorption of Levodopa. [51]
Prognosis
PD is not considered to be a fatal disease by itself, but it progresses with time. The average life expectancy of a PD
patient is generally lower than for people who do not have the disease.[52] In the late stages of the disease, PD may
cause complications such as choking, pneumonia, and falls that can lead to death.
The progression of symptoms in PD may take 20 years or more. In some people, however, the disease progresses
more quickly. There is no way to predict what course the disease will take for an individual person. With appropriate
treatment, most people with PD can live productive lives for many years after diagnosis. There are some indications
that PD acquires resistance to drug treatment by evolving into a Parkinson-plus disorder, usually Lewy body
dementia, although transitions to progressive supranuclear palsy or multiple system atrophy are not unknown.[53] [54]
One commonly used system for describing how the symptoms of PD progress is called the Hoehn and Yahr scale.
Another commonly used scale is the Unified Parkinson's Disease Rating Scale (UPDRS). This much more
complicated scale has multiple ratings that measure motor function, and also mental functioning, behavior, mood,
and activities of daily living. Both the Hoehn and Yahr scale and the UPDRS are used to measure how individuals
are faring and how much treatments are helping them. It should be noted that neither scale is specific to Parkinson's
disease; that patients with other illnesses can score in the Parkinson's range.
Epidemiology
According to some sources, Parkinson's disease is marginally less
prevalent in those of African ancestry.[55] The average crude
prevalence is estimated at being from 120-180 out of 100,000 among
the caucasian (white) community.[56] For the Parsi community in
Mumbai, India the rate is approximately double.[56] [57]
Disability-adjusted life year for parkinson disease
per 100,000 inhabitants in 2002. no data
less than 5 5-12.5 12.5-20 20-27.5
27.5-35 35-42.5 42.5-50 50-57.5
57.5-65 65-72.5 72.5-80 more than
80
Parkinson's disease
81
History
Symptoms of Parkinson's disease have been known and treated since
medieval times, most notably by Averroes.[58]
However, it was not formally recognized and its symptoms were not
documented until 1817 in An Essay on the Shaking Palsy[59] by the
British physician James Parkinson. Parkinson's disease was then
known as paralysis agitans, the term "Parkinson's disease" being
coined later by Jean-Martin Charcot.[60]
The underlying biochemical changes in the brain were identified in the
1950s due largely to the work of Swedish scientist Arvid Carlsson,
who later won a Nobel Prize. L-dopa entered clinical practice in
1967,[61] and the first large study reporting improvements in patients
with Parkinson's disease resulting from treatment with L-dopa was
published in 1968.[62]
James Parkinson
Research directions
Animal models
The tragedy of a group of drug addicts in California in the early 1980s who consumed a contaminated and illicitly
produced batch of the synthetic opiate MPPP brought to light MPTP as a cause of Parkinson symptoms. This made it
possible to develop the first animal model for Parkinson's. MPTP's toxicity likely comes from the generation of
reactive oxygen species through tyrosine hydroxylation.[63] The book The Case of the Frozen Addicts by William
Langston documents this tragedy and describes the first attempts at fetal brain tissue transplants to treat PD.
Other toxin-based models employ PCBs,[64] paraquat[65] (a herbicide) in combination with maneb (a fungicide),[66]
rotenone[67] (an insecticide), and specific organochlorine pesticides including dieldrin[68] and lindane.[69]
Gene therapy
Currently under investigation is gene therapy.[70] This involves using a non-infectious virus to shuttle a gene into a
part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called
glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA.[71] GABA
acts as a direct inhibitor on the overactive cells in the STN.
GDNF infusion involves the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using
surgically implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa.
GDNF therapy is still in development.
Neuroprotective treatments
Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny.[72] These agents
could protect neurons from cell death induced by disease presence resulting in a slower progression of disease.
Agents currently under investigation as neuroprotective agents include anti-apoptotic drugs (CEP 1347 and
CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors.[73] Clinically evaluated
neuroprotective agents are the monoamine oxidase inhibitors selegiline[74] and rasagiline, dopamine agonists, and the
complex I mitochondrial fortifier coenzyme Q10.
Parkinson's disease
Neural transplantation
The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell transplants
failed to show an improvement in quality of life although some significant clinical improvements were seen in
patients below the age of 60.[75] A significant problem was the excess release of dopamine by the transplanted tissue,
leading to dystonias.[76] Research in African green monkeys suggests that the use of stem cells might in future
provide a similar benefit without inducing dystonias.[77]
In 2008, Swedish scientists reported to the European Science Foundation (ESF)they were developing new ways to
grow brain cells in the laboratory to be used some day to treat patients with PD.
One approach that has been discussed is the possibility of taking stem cells, growing them into new brain cells to
then transplant them into the patient. Professor Arenas said that the idea was to start with stem cells and induce them
to become neurons. Professor Arenas and his team identified a protein called Wnt5a. When they included this protein
in cultures of stem cells together with a protein called nogging much more DA neurons were produced which
showed good proficiency after several tests. Once they transplanted the cells into laboratory animals whose
substantia nigra of the brain was damaged, they obtained promising results. Professor Arenas said that “they reversed
almost completely the behavioral abnormalities, and neurons differentiated, survived and re-innervated the relevant
part of the brain better”.
According to experts this might become the next step in cell replacement therapy for PD. [78]
Alternative Treatments
Nutrients have been used in clinical studies and are used by people with PD in order to partially treat PD or slow
down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms.[79]
Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of
symptoms in 110 out of 110 patients.[80] [81] More limited efficacy has been obtained with the use of THFA, NADH,
and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis.[82] Vitamin C and
vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in
PD. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the
superoxide anion, a toxin commonly produced in damaged cells. However, in the randomized controlled trial,
DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen.[74]
Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance
that is similar in structure and function to coenzyme Q10. Most of these therapies are covered in Dr. Laurie
Mischley's Natural Therapies for Parkinson's Disease.[83]
Studies looking at qigong in PD have not reached consensus on its efficacy.[84] [85]
Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa, and has been under some investigation.[86]
Society and culture
Research and support organizations
In 1957, William Black, President of Chock full o'Nuts coffee company, founded the Parkinson's Disease Foundation
(PDF) after one of his company's employees was diagnosed with Parkinson's. Black launched the organization with a
$250,000 grant to support Parkinson's Research.[87] While at first a regional organization, PDF expanded the scope
of its activities throughout the U.S., and merged with the United Parkinson Foundation in 1999. Today, PDF focuses
on funding research to learn the causes of and find a cure for Parkinson's, as well as providing education and support
for people with Parkinson's in the U.S. Since it was founded in 1957, PDF has provided more than $80 million to
research.[88]
82
Parkinson's disease
The American Parkinson Disease Association was founded in 1961.[89] The European Parkinson's Disease
Association, founded in 1992, is an organization based in Europe that supports Parkinson's disease research.
Actor Michael J. Fox, whose book, Lucky Man (2000), focused on his experiences with the disease and his career
and family travails in the midst of it, established The Michael J. Fox Foundation for Parkinson's Research to develop
a cure for Parkinson's disease. Another foundation that supports Parkinson's research was established by professional
cyclist Davis Phinney. The Davis Phinney Foundation strives to improve the lives of those living with Parkinson's
disease.
Notable sufferers
In addition to Michael J. Fox and Davis Phinney, famous sufferers include the late Pope John Paul II, baseball
manager Sparky Anderson, playwright Eugene O'Neill, political commentator Michael Kinsley, artist Salvador Dalí,
hockey player Brent Peterson, boxer Muhammad Ali, basketball player Brian Grant, evangelist Billy Graham and
former US Attorney General Janet Reno. Political figures suffering from it have included Adolf Hitler (not
confirmed), Francisco Franco, Deng Xiaoping and Mao Zedong, and former Prime Minister of Canada Pierre
Trudeau. Numerous actors have also been afflicted with Parkinson's such as: Terry-Thomas, Deborah Kerr, Kenneth
More, Vincent Price, Jim Backus and Michael Redgrave. Helen Beardsley (of Yours, Mine and Ours fame) also
suffered from this disease toward the end of her life. James Doohan also suffered from Parkinson's disease, and later,
Alzheimer's. Director George Roy Hill (The Sting, Butch Cassidy and the Sundance Kid) also suffered from
Parkinson's disease.
The film Awakenings (starring Robin Williams and Robert De Niro and based on genuine cases reported by Oliver
Sacks) deals sensitively and largely accurately with a similar disease, postencephalitic parkinsonism.
External links
•
•
•
•
Parkinson's Disease [90] at the Open Directory Project
Parkinson's Disease: Hope Through Research (National Institute of Neurological Disorders and Stroke) [91]
World Parkinson Disease Association [92]
GeneReview/NIH/UW entry on LRRK2-Related Parkinson Disease [93]
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date=1994& volume=738& spage=25). Annals of the New York Academy of Sciences 738: 25–36. doi:10.1111/j.1749-6632.1994.tb21786.x
(inactive 2010-02-09). PMID 7832434. .
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medicalnews. php?newsid=19791). Medical News Today. .
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up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein". The Journal of Biological Chemistry 277 (3):
1641–4. doi:10.1074/jbc.C100560200. PMID 11707429.
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target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease" (http:/ / www. jneurosci. org/ cgi/ content/
full/ 20/ 24/ 9207). J. Neurosci. 20 (24): 9207–14. PMID 11124998. .
[67] Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (December 2000). "Chronic systemic pesticide exposure
reproduces features of Parkinson's disease". Nature Neuroscience 3 (12): 1301–6. doi:10.1038/81834. PMID 11100151.
[68] Kitazawa M, Anantharam V, Kanthasamy AG (December 2001). "Dieldrin-induced oxidative stress and neurochemical changes contribute
to apoptopic cell death in dopaminergic cells". Free Radical Biology & Medicine 31 (11): 1473–85. doi:10.1016/S0891-5849(01)00726-2.
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[69] Corrigan FM, Wienburg CL, Shore RF, Daniel SE, Mann D (February 2000). "Organochlorine insecticides in substantia nigra in Parkinson's
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trial". Lancet 369 (9579): 2097–105. doi:10.1016/S0140-6736(07)60982-9. PMID 17586305.
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86
Epilepsy
87
Epilepsy
Epilepsy
Classification and external resources
Generalized 3 Hz spike and wave discharges in EEG
[1]
ICD-10
G 40.
ICD-9
345
DiseasesDB
4366
MedlinePlus
000694
eMedicine
neuro/415
MeSH
D004827
-G 41.
[2]
[3]
[4]
[5]
[6]
[7]
Epilepsy (from the Ancient Greek ἐπιληψία (epilēpsía) — "to seize") is a common chronic neurological disorder
characterized by recurrent unprovoked seizures.[8] [9] These seizures are transient signs and/or symptoms of
abnormal, excessive or synchronous neuronal activity in the brain.[10] About 50 million people worldwide have
epilepsy, with almost 90% of these people being in developing countries.[11] Epilepsy is more likely to occur in
young children, or people over the age of 65 years, however it can occur at any time.[12] As a consequence of brain
surgery epileptic seizures may occur in recovering patients.
Epilepsy is usually controlled, but cannot be cured with medication, although surgery may be considered in difficult
cases. However, over 30% of people with epilepsy do not have seizure control even with the best available
medications.[13] [14] Not all epilepsy syndromes are lifelong – some forms are confined to particular stages of
childhood. Epilepsy should not be understood as a single disorder, but rather as syndromic with vastly divergent
symptoms but all involving episodic abnormal electrical activity in the brain.
Epilepsy
Classification
Epilepsies are classified in five ways:
1.
2.
3.
4.
5.
By their first cause (or etiology).
By the observable manifestations of the seizures, known as semiology.
By the location in the brain where the seizures originate.
As a part of discrete, identifiable medical syndromes.
By the event that triggers the seizures, as in primary reading epilepsy or musicogenic epilepsy.
In 1981, the International League Against Epilepsy [15] (ILAE) proposed a classification scheme for individual
seizures that remains in common use.[16] This classification is based on observation (clinical and EEG) rather than
the underlying pathophysiology or anatomy and is outlined later on in this article. In 1989, the ILAE proposed a
classification scheme for epilepsies and epileptic syndromes.[17] This can be broadly described as a two-axis scheme
having the cause on one axis and the extent of localization within the brain on the other. Since 1997, the ILAE have
been working on a new scheme that has five axes:
1. ictal phenomenon,(pertaining to an epileptic seizure)
2. seizure type,
3. syndrome,
4. etiology,
5. impairment. [18]
Seizure types
Seizure types are organized firstly according to whether the source of the seizure within the brain is localized
(partial or focal onset seizures) or distributed (generalized seizures). Partial seizures are further divided on the extent
to which consciousness is affected. If it is unaffected, then it is a simple partial seizure; otherwise it is a complex
partial (psychomotor) seizure. A partial seizure may spread within the brain - a process known as secondary
generalization. Generalized seizures are divided according to the effect on the body but all involve loss of
consciousness. These include absence (petit mal), myoclonic, clonic, tonic, tonic-clonic (grand mal) and atonic
seizures.
Children may exhibit behaviors that are easily mistaken for epileptic seizures but are not caused by epilepsy. These
include:
•
•
•
•
Inattentive staring
Benign shudders (among children younger than age 2, usually when they are tired or excited)
Self-gratification behaviors (nodding, rocking, head banging)
Conversion disorder (flailing and jerking of the head, often in response to severe personal stress such as physical
abuse)
Conversion disorder can be distinguished from epilepsy because the episodes never occur during sleep and do not
involve incontinence or self-injury.[19]
Epilepsy syndromes
There are over 40 different types of epilepsy, including: Absence seizures, atonic seizures, benign Rolandic epilepsy,
childhood absence, clonic seizures, complex partial seizures, frontal lobe epilepsy, Febrile seizures, Infantile spasms,
Juvenile Myoclonic Epilepsy, Juvenile Absence Epilepsy, Hot Water Epilepsy, lennox-gastaut syndrom,
Landau-Kleffner Syndrome , myoclonic seizures, Mitochondrial Disorders, Progressive Myoclonic Epilepsies,
Psychogenic Seizures , Reflex Epilepsy, Rasmussen's Syndrome, Simple Partial seizures, Secondarily Generalized
Seizures, Temporal Lobe Epilepsy, Toni-clonic seizures, Tonic seizures, Psychomotor Seizures, Limbic Epilepsy,
88
Epilepsy
Partial-Onset Seizures, generalised-onset seizures, Status Epilepticus, Abdominal Epilepsy, Akinetic Seizures,
Auto-nomic seizures, Massive Bilateral Myoclonus, Catamenial Epilepsy, Drop seizures, Emotional seizures, Focal
seizures, Gelastic seizures, Jacksonian March, Lafora Disease, Motor seizures, Multifocal seizures, Neonatal
seizures, Nocturnal seizures, Photosensitive seizure, Pseudo seizures, Sensory seizures, Subtle seizures, Sylvan
Seizures, Withdrawal seizures, Visual Reflex Seizures amongst others.[20]
Each type of epilepsy presents with its own unique combination of seizure type, typical age of onset, EEG findings,
treatment, and prognosis. The most widespread classification of the epilepsies [17] divides epilepsy syndromes by
location or distribution of seizures (as revealed by the appearance of the seizures and by EEG) and by cause.
Syndromes are divided into localization-related epilepsies, generalized epilepsies, or epilepsies of unknown
localization.
Localization-related epilepsies, sometimes termed partial or focal epilepsies, arise from an epileptic focus, a small
portion of the brain that serves as the irritant driving the epileptic response. Generalized epilepsies, in contrast, arise
from many independent foci (multifocal epilepsies) or from epileptic circuits that involve the whole brain. Epilepsies
of unknown localization remain unclear whether they arise from a portion of the brain or from more widespread
circuits.
Epilepsy syndromes are further divided by presumptive cause: idiopathic, symptomatic, and cryptogenic. Idiopathic
epilepsies are generally thought to arise from genetic abnormalities that lead to alteration of basic neuronal
regulation. Symptomatic epilepsies arise from the effects of an epileptic lesion, whether that lesion is focal, such as a
tumor, or a defect in metabolism causing widespread injury to the brain. Cryptogenic epilepsies involve a
presumptive lesion that is otherwise difficult or impossible to uncover during evaluation.
Some epileptic syndromes are difficult to fit within this classification scheme and fall in the unknown
localization/etiology category. People who only have had a single seizure, or those with seizures that occur only after
specific precipitants ("provoked seizures"), have "epilepsies" that fall into this category. Febrile convulsions are an
example of seizures bound to a particular precipitant. Landau-Kleffner syndrome is another epilepsy which, because
of its variety of EEG distributions, falls uneasily in clear categories. More confusingly, certain syndromes like West
syndrome featuring seizures such as Infantile spasms can be classified as idiopathic, syndromic, or cryptogenic
depending on cause and can arise from both focal or generalized epileptic lesions.
Below are some common seizure syndromes:
• Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an idiopathic localization-related epilepsy
that is an inherited epileptic disorder that causes seizures during sleep. Onset is usually in childhood. These
seizures arise from the frontal lobes and consist of complex motor movements, such as hand clenching, arm
raising/lowering, and knee bending. Vocalizations such as shouting, moaning, or crying are also common.
ADNFLE is often misdiagnosed as nightmares. ADNFLE has a genetic basis[21] . These genes encode various
nicotinic acetylcholine receptors.
• Benign centrotemporal lobe epilepsy of childhood or Benign rolandic epilepsy is an idiopathic
localization-related epilepsy that occurs in children between the ages of 3 and 13 years with peak onset in
prepubertal late childhood. Apart from their seizure disorder, these patients are otherwise normal. This syndrome
features simple partial seizures that involve facial muscles and frequently cause drooling. Although most episodes
are brief, seizures sometimes spread and generalize. Seizures are typically nocturnal and confined to sleep. The
EEG may demonstrate spike discharges that occur over the centrotemporal scalp over the central sulcus of the
brain (the Rolandic sulcus) that are predisposed to occur during drowsiness or light sleep. Seizures cease near
puberty.[22] Seizures may require anticonvulsant treatment, but sometimes are infrequent enough to allow
physicians to defer treatment.
• Benign occipital epilepsy of childhood (BOEC) is an idiopathic localization-related epilepsy and consists of an
evolving group of syndromes. Most authorities include two subtypes, an early subtype with onset between 3–5
years and a late onset between 7–10 years. Seizures in BOEC usually feature visual symptoms such as scotoma or
89
Epilepsy
fortifications (brightly colored spots or lines) or amaurosis (blindness or impairment of vision). Convulsions
involving one half the body, hemiconvulsions, or forced eye deviation or head turning are common. Younger
patients typically experience symptoms similar to migraine with nausea and headache, and older patients typically
complain of more visual symptoms. The EEG in BOEC shows spikes recorded from the occipital (back of head)
regions. The EEG and genetic pattern suggest an autosomal dominant transmission as described by Ruben
Kuzniecky et al.[23] Lately, a group of epilepsies termed Panayiotopoulos syndrome[24] that share some clinical
features of BOEC but have a wider variety of EEG findings are classified by some as BOEC.
• Catamenial epilepsy (CE) is when seizures cluster around certain phases of a woman's menstrual cycle.
• Childhood absence epilepsy (CAE) is an idiopathic generalized epilepsy that affects children between the ages
of 4 and 12 years of age, although peak onset is around 5–6 years old. These patients have recurrent absence
seizures, brief episodes of unresponsive staring, sometimes with minor motor features such as eye blinking or
subtle chewing. The EEG finding in CAE is generalized 3 Hz spike and wave discharges. Some go on to develop
generalized tonic-clonic seizures. This condition carries a good prognosis because children do not usually show
cognitive decline or neurological deficits, and the seizures in the majority cease spontaneously with onging
maturation.
• Dravet's syndrome Severe myoclonic epilepsy of infancy (SMEI). This generalized epilepsy syndrome is
distinguished from benign myoclonic epilepsy by its severity and must be differentiated from the Lennox-Gastaut
syndrome and Doose’s myoclonic-astatic epilepsy. Onset is in the first year of life and symptoms peak at about 5
months of age with febrile hemiclonic or generalized status epilepticus. Boys are twice as often affected as girls.
Prognosis is poor. Most cases are sporadic. Family history of epilepsy and febrile convulsions is present in around
25 percent of the cases.[25]
• Frontal lobe epilepsy, usually a symptomatic or cryptogenic localization-related epilepsy, arises from lesions
causing seizures that occur in the frontal lobes of the brain. These epilepsies can be difficult to diagnose because
the symptoms of seizures can easily be confused with nonepileptic spells and, because of limitations of the EEG,
be difficult to "see" with standard scalp EEG.
• Juvenile absence epilepsy is an idiopathic generalized epilepsy with later onset that CAE, typically in
prepubertal adolescence, with the most frequent seizure type being absence seizures. Generalized tonic-clonic
seizures can occur. 3 Hz spike-wave or multiple spike discharges can be seen on EEG. Prognosis is mixed, with
some patients going on to a syndrome that is poorly distinguishable from JME.
• Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy that occurs in patients aged 8 to 20
years. Patients have normal cognition and are otherwise neurologically intact. The most common seizures are
myoclonic jerks, although generalized tonic-clonic seizures and absence seizures may occur as well. Myoclonic
jerks usually cluster in the early morning after awakening. The EEG reveals generalized 4–6 Hz spike wave
discharges or multiple spike discharges. Interestingly, these patients are often first diagnosed when they have their
first generalized tonic-clonic seizure later in life when they experience sleep deprivation (e.g., freshman year in
college after staying up late to study for exams). Alcohol withdrawal can also be a major contributing factor in
breakthrough seizures as well. The risk of the tendency to have seizures is lifelong; however, the majority have
well-controlled seizures with anticonvulsant medication and avoidance of seizure precipitants.
• Lennox-Gastaut syndrome (LGS) is a generalized epilepsy that consists of a triad of developmental delay or
childhood dementia, mixed generalized seizures, and EEG demonstrating a pattern of approximately 2 Hz "slow"
spike-wave. Onset occurs between 2–18 years. As in West syndrome, LGS result from idiopathic, symptomatic,
or cryptogenic causes, and many patients first have West syndrome. Authorities emphasize different seizure types
as important in LGS, but most have astatic seizures (drop attacks), tonic seizures, tonic-clonic seizures, atypical
absence seizures, and sometimes, complex partial seizures. Anticonvulsants are usually only partially successful
in treatment.
90
Epilepsy
• Ohtahara Syndrome is a rare but severe form of epilepsy syndrome combined with cerebral palsy and
characterised with frequent seizures which typically start in the first few days of life. Sufferers trend to be
severely disabled and their lives very short (they are unlikely to reach adulthood).
• Primary reading epilepsy is a reflex epilepsy classified as an idiopathic localization-related epilepsy. Reading in
susceptible individuals triggers characteristic seizures.[26]
• Progressive myoclonic epilepsies define a group of symptomatic generalized epilepsies characterized by
progressive dementia and myoclonic seizures. Tonic-clonic seizures may occur as well. Diseases usually
classified in this group are Unverricht-Lundborg disease, myoclonus epilepsy with ragged red fibers (MERRF
syndrome), Lafora disease, neuronal ceroid lipofucinosis, and sialdosis.
• Rasmussen's encephalitis is a symptomatic localization-related epilepsy that is a progressive, inflammatory
lesion affecting children with onset before the age of 10. Seizures start as separate simple partial or complex
partial seizures and may progress to epilepsia partialis continuata (simple partial status epilepticus).
Neuroimaging shows inflammatory encephalitis on one side of the brain that may spread if not treated. Dementia
and hemiparesis are other problems. The cause is hypothesized to involve an immulogical attack against
glutamate receptors, a common neurotransmitter in the brain.[27]
• Symptomatic localization-related epilepsies Symptomatic localization-related epilepsies are divided by the
location in the brain of the epileptic lesion, since the symptoms of the seizures are more closely tied to the brain
location rather than the cause of the lesion. Tumors, atriovenous malformations, cavernous malformations,
trauma, and cerebral infarcts can all be causes of epileptic foci in different brain regions.
• Temporal lobe epilepsy (TLE), a symptomatic localization-related epilepsy, is the most common epilepsy of
adults who experience seizures poorly controlled with anticonvulsant medications. In most cases, the
epileptogenic region is found in the midline (mesial) temporal structures (e.g., the hippocampus, amygdala, and
parahippocampal gyrus). Seizures begin in late childhood and adolescence. Most of these patients have complex
partial seizures sometimes preceded by an aura, and some TLE patients also suffer from secondary generalized
tonic-clonic seizures. If the patient does not respond sufficiently to medical treatment, epilepsy surgery may be
considered.
• West syndrome is a triad of developmental delay, seizures termed infantile spasms, and EEG demonstrating a
pattern termed hypsarrhythmia. Onset occurs between 3 months and 2 years, with peak onset between 8–9
months. West syndrome may arise from idiopathic, symptomatic, or cryptogenic causes. The most common cause
is tuberous sclerosis. The prognosis varies with the underlying cause. In general most surviving patients remain
with significant cognitive impairment and continuing seizures and may evolve to another eponymic syndrome,
Lennox-Gastaut syndrome.
Causes
The diagnosis of epilepsy usually requires that the seizures occur spontaneously. Nevertheless, certain epilepsy
syndromes require particular precipitants or triggers for seizures to occur. These are termed reflex epilepsy. For
example, patients with primary reading epilepsy have seizures triggered by reading. Photosensitive epilepsy can be
limited to seizures triggered by flashing lights. Other precipitants can trigger an epileptic seizure in patients who
otherwise would be susceptible to spontaneous seizures. For example, children with childhood absence epilepsy may
be susceptible to hyperventilation. In fact, flashing lights and hyperventilation are activating procedures used in
clinical EEG to help trigger seizures to aid diagnosis. Finally, other precipitants can facilitate, rather than obligately
trigger, seizures in susceptible individuals. Emotional stress, sleep deprivation, sleep itself, heat stress, alcohol and
febrile illness are examples of precipitants cited by patients with epilepsy. Notably, the influence of various
precipitants varies with the epilepsy syndrome.[28] . Likewise, the menstrual cycle in women with epilepsy can
influence patterns of seizure recurrence. Catamenial epilepsy is the term denoting seizures linked to the menstrual
cycle.[29]
91
Epilepsy
Pathophysiology
Mutations in several genes have been linked to some types of epilepsy. Several genes that code for protein subunits
of voltage-gated and ligand-gated ion channels have been associated with forms of generalized epilepsy and infantile
seizure syndromes.[30] Several ligand-gated ion channels have been linked to some types of frontal and generalized
epilepsies. One speculated mechanism for some forms of inherited epilepsy are mutations of the genes which code
for sodium channel proteins; these defective sodium channels stay open for too long thus making the neuron
hyper-excitable. Glutamate, an excitatory neurotransmitter, may thereby be released from these neurons in large
amounts which—by binding with nearby glutamatergic neurons—triggers excessive calcium (Ca2+) release in these
post-synaptic cells. Such excessive calcium release can be neurotoxic to the affected cell. The hippocampus, which
contains a large volume of just such glutamanergic neurons (and NMDA receptors, which are permeable to Ca2+
entry after binding of both sodium and glutamate), is especially vulnerable to epileptic seizure, subsequent spread of
excitation, and possible neuronal death. Another possible mechanism involves mutations leading to ineffective
GABA (the brain's most common inhibitory neurotransmitter) action. Epilepsy-related mutations in some non-ion
channel genes have also been identified.
Epileptogenesis is the process by which a normal brain develops epilepsy after an insult. One interesting finding in
animals is that repeated low-level electrical stimulation to some brain sites can lead to permanent increases in seizure
susceptibility: in other words, a permanent decrease in seizure "threshold." This phenomenon, known as kindling (by
analogy with the use of burning twigs to start a larger fire) was discovered by Dr. Graham Goddard in 1967.
Chemical stimulation can also induce seizures; repeated exposures to some pesticides have been shown to induce
seizures in both humans and animals. One mechanism proposed for this is called excitotoxicity. The roles of kindling
and excitotoxicity, if any, in human epilepsy are currently hotly debated.
Other causes of epilepsy are brain lesions, where there is scar tissue or another abnormal mass of tissue in an area of
the brain.
The complexity of understanding what seizures are have led to considerable efforts to use computational models of
epilepsy [31] to both interpret experimental and clinical data, as well as guide strategies for therapy.
Management
Epilepsy is usually treated with medication prescribed by a physician; primary caregivers, neurologists, and
neurosurgeons all frequently care for people with epilepsy. However, it has been stressed that accurate differentiation
between generalized and partial seizures is especially important in determining the appropriate treatment.[32] In some
cases the implantation of a stimulator of the vagus nerve, or a special diet can be helpful. Neurosurgical operations
for epilepsy can be palliative, reducing the frequency or severity of seizures; or, in some patients, an operation can
be curative.
Responding to a seizure
In most cases, the proper emergency response to a generalized tonic-clonic epileptic seizure is simply to prevent the
patient from self-injury by moving him or her away from sharp edges, placing something soft beneath the head, and
carefully rolling the person into the recovery position to avoid asphyxiation. In some cases the person may seem to
start snoring loudly following a seizure, before coming to. This merely indicates that the person is beginning to
breathe properly and does not mean he or she is suffocating. Should the person regurgitate, the material should be
allowed to drip out the side of the person's mouth by itself. If a seizure lasts longer than 5 minutes, or if the seizures
begin coming in 'waves' one after the other - then Emergency Medical Services should be contacted immediately.
Prolonged seizures may develop into status epilepticus, a dangerous condition requiring hospitalization and
emergency treatment.
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Epilepsy
Objects should never be placed in a person's mouth by anybody - including paramedics - during a seizure as this
could result in serious injury to either party. Despite common folklore, it is not possible for a person to swallow their
own tongue during a seizure. However, it is possible that the person will bite their own tongue, especially if an object
is placed in the mouth.
With other types of seizures such as simple partial seizures and complex partial seizures where the person is not
convulsing but may be hallucinating, disoriented, distressed, or unconscious, the person should be reassured, gently
guided away from danger, and sometimes it may be necessary to protect the person from self-injury, but physical
force should be used only as a last resort as this could distress the person even more. In complex partial seizures
where the person is unconscious, attempts to rouse the person should not be made as the seizure must take its full
course. After a seizure, the person may pass into a deep sleep or otherwise they will be disoriented and often
unaware that they have just had a seizure, as amnesia is common with complex partial seizures. The person should
remain observed until they have completely recovered, as with a tonic-clonic seizure.
After a seizure, it is typical for a person to be exhausted and confused (this is known as post-ictal state). Often the
person is not immediately aware that they have just had a seizure. During this time one should stay with the person reassuring and comforting them - until they appear to act as they normally would. Seldom during seizures do people
lose bladder or bowel control. In some instances the person may vomit after coming to. People should not be allowed
to wander about unsupervised until they have returned to their normal level of awareness. Many patients will sleep
deeply for a few hours after a seizure - this is common for those having just experienced a more violent type of
seizure such as a tonic-clonic. In about 50% of people with epilepsy, headaches may occur after a seizure. These
headaches share many features with migraines, and respond to the same medications.
It is helpful if those present at the time of a seizure make note of how long and how severe the seizure was. It is also
helpful to note any mannerisms displayed during the seizure. For example, the individual may twist the body to the
right or left, may blink, might mumble nonsense words, or might pull at clothing. Any observed behaviors, when
relayed to a neurologist, may be of help in diagnosing the type of seizure which occurred.
Pharmacologic treatment
The mainstay of treatment of epilepsy is anticonvulsant medications. Often, anticonvulsant medication treatment will
be lifelong and can have major effects on quality of life. The choice among anticonvulsants and their effectiveness
differs by epilepsy syndrome. Mechanisms, effectiveness for particular epilepsy syndromes, and side effects, of
course, differ among the individual anticonvulsant medications. Some general findings about the use of
anticonvulsants are outlined below.
History and Availability- The first anticonvulsant was bromide, suggested in 1857 by Charles Locock who used it
to treat women with "hysterical epilepsy" (probably catamenial epilepsy). Potassium bromide was also noted to
cause impotence in men. Authorities concluded that potassium bromide would dampen sexual excitement thought to
cause the seizures. In fact, bromides were effective against epilepsy, and also caused impotence; it is now known that
impotence is a side effect of bromide treatment, which is not related to its anti-epileptic effects. It also suffered from
the way it affected behaviour, introducing the idea of the 'epileptic personality' which was actually a result of the
medication. Phenobarbital was first used in 1912 for both its sedative and antiepileptic properties. By the 1930s, the
development of animal models in epilepsy research lead to the development of phenytoin by Tracy Putnam and H.
Houston Merritt, which had the distinct advantage of treating epileptic seizures with less sedation[33] . By the 1970s,
an National Institutes of Health initiative, the Anticonvulsant Screening Program, headed by J. Kiffin Penry, served
as a mechanism for drawing the interest and abilities of pharmaceutical companies in the development of new
anticonvulsant medications.
Currently there are 20 medications approved by the Food and Drug Administration for the use of treatment of
epileptic seizures in the US: carbamazepine (common US brand name Tegretol), clorazepate (Tranxene),
clonazepam (Klonopin), ethosuximide (Zarontin), felbamate (Felbatol), fosphenytoin (Cerebyx), gabapentin
93
Epilepsy
(Neurontin), lacosamide (Vimpat), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal),
phenobarbital (Luminal), phenytoin (Dilantin), pregabalin (Lyrica), primidone (Mysoline), tiagabine (Gabitril),
topiramate (Topamax), valproate semisodium (Depakote), valproic acid (Depakene), and zonisamide (Zonegran).
Most of these appeared after 1990.
Medications commonly available outside the US but still labelled as "investigational" within the US are clobazam
(Frisium) and vigabatrin (Sabril). Medications currently under clinical trial under the supervision of the FDA include
retigabine, brivaracetam, and seletracetam.
Other drugs are commonly used to abort an active seizure or interrupt a seizure flurry; these include diazepam
(Valium, Diastat) and lorazepam (Ativan). Drugs used only in the treatment of refractory status epilepticus include
paraldehyde (Paral), midazolam (Versed), and pentobarbital (Nembutal).
Some anticonvulsant medications do not have primary FDA-approved uses in epilepsy but are used in limited trials,
remain in rare use in difficult cases, have limited "grandfather" status, are bound to particular severe epilepsies, or
are under current investigation. These include acetazolamide (Diamox), progesterone, adrenocorticotropic hormone
(ACTH, Acthar), various corticotropic steroid hormones (prednisone), or bromide.
Effectiveness - The definition of "effective" varies. FDA-approval usually requires that 50% of the patient treatment
group had at least a 50% improvement in the rate of epileptic seizures. About 20% of patients with epilepsy continue
to have breakthrough epileptic seizures despite best anticonvulsant treatment.[13] [14] .
Safety and Side Effects - 88% of patients with epilepsy, in a European survey, reported at least one anticonvulsant
related side effect.[34] Most side effects are mild and "dose-related" and can often be avoided or minimized by the
use of the smallest effective amount. Some examples include mood changes, sleepiness, or unsteadiness in gait.
Some anticonvulsant medications have "idiosyncratic" side-effects that can not be predicted by dose. Some examples
include drug rashes, liver toxicity (hepatitis), or aplastic anemia. Safety includes the consideration of teratogenicity
(the effects of medications on fetal development) when women with epilepsy become pregnant.
Principles of Anticonvulsant Use and Management - The goal for individual patients is, of course, no seizures and
no side effects, and the job of the physician is to aid the patient to find the best balance between the two during the
prescribing of anticonvulsants. Most patients can achieve this balance best with monotherapy, the use of a single
anticonvulsant medication. Some patients, however, require polypharmacy; the use of two or more anticonvulsants.
Serum levels of AEDs can be checked to determine medication compliance, to assess the effects of new drug-drug
interactions upon previous stable medication levels, or to help establish if particular symptoms such as instability or
sleepiness can be considered a drug side-effect or are due to different causes. Children or impaired adults who may
not be able to communicate side effects may benefit from routine screening of drug levels. Beyond baseline
screening, however, trials of recurrent, routine blood or urine monitoring show no proven benefits and may lead to
unnecessary medication adjustments in most older children and adults using routine anticonvulsants.[35] [36]
If a person's epilepsy cannot be brought under control after adequate trials of two or three (experts vary here)
different drugs, that person's epilepsy is generally said to be medically refractory. A study of patients with previously
untreated epilepsy demonstrated that 47% achieved control of seizures with the use of their first single drug. 14%
became seizure free during treatment with a second or third drug. An additional 3% became seizure-free with the use
of two drugs simultaneously.[37] Other treatments, in addition to or instead of, anticonvulsant medications may be
considered by those people with continuing seizures.
94
Epilepsy
Surgical treatment
Epilepsy surgery is an option for patients whose seizures remain resistant to treatment with anticonvulsant
medications who also have symptomatic localization-related epilepsy; a focal abnormality that can be located and
therefore removed. The goal for these procedures is total control of epileptic seizures [38] , although anticonvulsant
medications may still be required.[39]
The evaluation for epilepsy surgery is designed to locate the "epileptic focus" (the location of the epileptic
abnormality) and to determine if resective surgery will affect normal brain function. Physicians will also confirm the
diagnosis of epilepsy to make sure that spells arise from epilepsy (as opposed to non-epileptic seizures). The
evaluation typically includes neurological examination, routine EEG, Long-term video-EEG monitoring,
neuropsychological evaluation, and neuroimaging such as MRI, Single photon emission computed tomography
(SPECT), positron emission tomography (PET). Some epilepsy centers use intracarotid sodium amobarbital test
(Wada test), functional MRI or Magnetoencephalography (MEG) as supplementary tests.
Certain lesions require Long-term video-EEG monitoring with the use of intracranial electrodes if noninvasive
testing was inadequate to identify the epileptic focus or distinguish the surgical target from normal brain tissue and
function. Brain mapping by the technique of cortical electrical stimulation or Electrocorticography are other
procedures used in the process of invasive testing in some patients.
The most common surgeries are the resection of lesions like tumors or arteriovenous malformations which, in the
process of treating the underlying lesion, often result in control of epileptic seizures caused by these lesions.
Other lesions are more subtle and feature epilepsy as the main or sole symptom. The most common form of
intractable epilepsy in these disorders in adults is temporal lobe epilepsy with hippocampal sclerosis, and the most
common type of epilepsy surgery is the anterior temporal lobectomy, or the removal of the front portion of the
temporal lobe including the amygdala and hippocampus. Some neurosurgeons recommend selective
amygdalahippocampectomy because of possible benefits in postoperative memory or language function. Surgery for
temporal lobe epilepsy is effective, durable, and results in decreased health care costs.[40] [41] . Despite the efficacy
of epilepsy surgery, some patients decide not to undergo surgery owing to fear or the uncertainty of having a brain
operation.
Palliative surgery for epilepsy is intended to reduce the frequency or severity of seizures. Examples are callosotomy
or commissurotomy to prevent seizures from generalizing (spreading to involve the entire brain), which results in a
loss of consciousness. This procedure can therefore prevent injury due to the person falling to the ground after losing
consciousness. It is performed only when the seizures cannot be controlled by other means. Multiple subpial
transection can also be used to decrease the spread of seizures across the cortex especially when the epileptic focus is
located near important functional areas of the cortex. Resective surgery can be considered palliative if it is
undertaken with the expectation that it will reduce but not eliminate seizures.
Hemispherectomy involves removal or a functional disconnection of most or all of one half of the cerebrum. It is
reserved for people suffering from the most catastrophic epilepsies, such as those due to Rasmussen syndrome. If the
surgery is performed on very young patients (2–5 years old), the remaining hemisphere may acquire some
rudimentary motor control of the ipsilateral body; in older patients, paralysis results on the side of the body opposite
to the part of the brain that was removed. Because of these and other side effects it is usually reserved for patients
who have exhausted other treatment options.
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Epilepsy
Other treatment
Ketogenic diet- a high fat, low carbohydrate diet developed in the 1920s, largely forgotten with the advent of
effective anticonvulsants, and resurrected in the 1990s. The mechanism of action is unknown. It is used mainly in the
treatment of children with severe, medically-intractable epilepsies.
Electrical stimulation [42] - methods of anticonvulsant treatment with both currently approved and investigational
uses. A currently approved device is vagus nerve stimulation (VNS). Investigational devices include the responsive
neurostimulation system and deep brain stimulation.
Vagus nerve stimulation (VNS)- The VNS (US manufacturer = Cyberonics) consists of a computerized electrical
device similar in size, shape and implant location to a heart pacemaker that connects to the vagus nerve in the neck.
The device stimulates the vagus nerve at pre-set intervals and intensities of current. Efficacy has been tested in
patients with localization-related epilepsies demonstrating that 50% of patients experience a 50% improvement in
seizure rate. Case series have demonstrated similar efficacies in certain generalized epilepsies such as
Lennox-Gastaut syndrome. Although success rates are not usually equal to that of epilepsy surgery, it is a reasonable
alternative when the patient is reluctant to proceed with any required invasive monitoring, when appropriate
presurgical evaluation fails to uncover the location of epileptic foci, or when there are multiple epileptic foci.
Responsive Neurostimulator System (RNS) (US manufacturer Neuropace) consists of a computerized electrical
device implanted in the skull with electrodes implanted in presumed epileptic foci within the brain. The brain
electrodes send EEG signal to the device which contains seizure-detection software. When certain EEG seizure
criteria are met, the device delivers a small electrical charge to other electrodes near the epileptic focus and disrupt
the seizure. The efficacy of the RNS is under current investigation with the goal of FDA approval.
Deep brain stimulation (DBS) (US manufacturer Medtronic) consists of a computerized electrical device implanted
in the chest in a manner similar to the VNS, but electrical stimulation is delivered to deep brain structures through
depth electrodes implanted through the skull. In epilepsy, the electrode target is the anterior nucleus of the thalamus.
The efficacy of the DBS in localization-related epilepsies is currently under investigation.
Noninvasive surgery- The use of the Gamma Knife or other devices used in radiosurgery are currently being
investigated as alternatives to traditional open surgery in patients who would otherwise qualify for anterior temporal
lobectomy.[43]
Avoidance therapy- Avoidance therapy consists of minimizing or eliminating triggers in patients whose seizures are
particularly susceptible to seizure precipitants (see above). For example, sunglasses that counter exposure to
particular light wavelengths can improve seizure control in certain photosensitive epilepsies.[44]
Warning systems- A seizure response dog is a form of service dog that is trained to summon help or ensure personal
safety when a seizure occurs. These are not suitable for everybody and not all dogs can be so trained. Rarely, a dog
may develop the ability to sense a seizure before it occurs.[45] Development of electronic forms of seizure detection
systems are currently under investigation.
Seizure prediction based devices Seizure prediction based on long-term EEG recordings is presently being
evaluated as a new way to stop epileptic seizures before they appear clinically.
Alternative or complementary medicine- A number of systematic reviews by the Cochrane Collaboration into
treatments for epilepsy looked at acupuncture,[46] psychological interventions,[47] vitamins[48] and yoga[49] and
found there is no reliable evidence to support the use of these as treatments for epilepsy.
96
Epilepsy
Epidemiology
Epilepsy is one of the most common of the serious neurological
disorders.[50] Genetic, congenital, and developmental conditions are
mostly associated with it among younger patients; tumors are more
likely over age 40; head trauma and central nervous system infections
may occur at any age. The prevalence of active epilepsy is roughly in
the range 5–10 per 1000 people. Up to 5% of people experience non
Disability-adjusted life year for epilepsy per
febrile seizures at some point in life; epilepsy's lifetime prevalence is
100,000 inhabitants in 2002. no data less
than 50 50-72.5 72.5-95 95-117.5
relatively high because most patients either stop having seizures or
117.5-140 140-162.5 162.5-185
(less commonly) die of it. Epilepsy's approximate annual incidence rate
185-207.5 207.5-230 230-252.5
is 40–70 per 100,000 in industrialized countries and 100–190 per
252.5-275 more than 275
100,000 in resource-poor countries; socioeconomically deprived
people are at higher risk. In industrialized countries the incidence rate
decreased in children but increased among the elderly during the three decades prior to 2003, for reasons not fully
understood.[51]
Beyond symptoms of the underlying diseases that can be a part of certain epilepsies, people with epilepsy are at risk
for death from four main problems: status epilepticus (most often associated with anticonvulsant noncompliance),
suicide associated with depression, trauma from seizures, and sudden unexpected death in epilepsy (SUDEP) [52] [53]
[54]
Those at highest risk for epilepsy-related deaths usually have underlying neurological impairment or poorly
controlled seizures; those with more benign epilepsy syndromes have little risk for epilepsy-related death.
The NICE National Sentinel Audit of Epilepsy-Related Deaths[55] , led by "Epilepsy Bereaved" drew attention to this
important problem. The Audit revealed; "1,000 deaths occur every year in the UK as a result of epilepsy" and most
of them are associated with seizures and 42% of deaths were potentially avoidable". [56]
Certain diseases also seem to occur in higher than expected rates in people with epilepsy, and the risk of these
"comorbidities" often varies with the epilepsy syndrome. These diseases include depression and anxiety disorders,
migraine and other headaches, infertility and low sexual libido. Attention-deficit/hyperactivity disorder (ADHD)
affects three to five times more children with epilepsy than children in the general population. [57] Epilepsy is
prevalent in autism.[58]
History
The word epilepsy is derived from the Ancient Greek ἐπιληψία epilēpsía, which was from ἐπιλαμβάνειν
epilambánein "to take hold of", which in turn was combined from ἐπί epí "upon" and λαμβάνειν lambánein "to
take".[59] In the past, epilepsy was associated with religious experiences and even demonic possession. In ancient
times, epilepsy was known as the "Sacred Disease" because people thought that epileptic seizures were a form of
attack by demons, or that the visions experienced by persons with epilepsy were sent by the gods. Among animist
Hmong families, for example, epilepsy was understood as an attack by an evil spirit, but the affected person could
become revered as a shaman through these otherworldly experiences.[60]
However, in most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned; in the
Salpêtrière, the birthplace of modern neurology, Jean-Martin Charcot found people with epilepsy side-by-side with
the mentally retarded, those with chronic syphilis, and the criminally insane. In Tanzania to this day, as with other
parts of Africa, epilepsy is associated with possession by evil spirits, witchcraft, or poisoning and is believed by
many to be contagious.[61] In ancient Rome, epilepsy was known as the Morbus Comitialis ('disease of the assembly
hall') and was seen as a curse from the gods.
Stigma continues to this day, in both the public and private spheres, but polls suggest it is generally decreasing with
time, at least in the developed world; Hippocrates remarked that epilepsy would cease to be considered divine the
97
Epilepsy
day it was understood.[62]
Society and culture
Legal implications
Many jurisdictions forbid certain activities to persons suffering from epilepsy. The most commonly prohibited
activities involve operation of vehicles or machinery, or other activities in which continuous vigilance is required.
However, there are usually exceptions for those who can prove that they have stabilized their condition. Those few
whose seizures do not cause impairment of consciousness, have a lengthy aura preceding impairment of
consciousness, or whose seizures only arise from sleep, may be exempt from such restrictions, depending on local
laws. There is an ongoing debate in bioethics over who should bear the burden of ensuring that an epilepsy patient
does not drive a car or fly an airplane.
Automobiles
In the U.S., people with epilepsy can drive if their seizures are controlled with treatment and they meet the licensing
requirements in their state. The amount of time someone needs to be free of seizures varies in different states, but is
most likely to be between three months and a year.[63] [64] The majority of the 50 states place the burden on patients
to report their condition to appropriate licensing authorities so that their privileges can be revoked where appropriate.
A minority of states place the burden of reporting on the patient's physician. After reporting is carried out, it is
usually the driver's licensing agency that decides to revoke or restrict a driver's license.
In the UK, it is the responsibility of the patients to inform the Driver and Vehicle Licensing Agency (DVLA) if they
have epilepsy.[65] The DVLA rules are quite complex,[66] but in summary,[67] those that continue to have seizures or
who are within 6 months of medication change may have their licence revoked. A person must be seizure free of an
'awake' seizure for 12 months (or had only 'sleep' seizures for 3 years or more) before they can apply for a licence.[68]
A doctor who becomes aware that a patient with uncontrolled epilepsy is continuing to drive has, after reminding the
patient of their responsibility, a duty to break confidentiality and inform the DVLA. The doctor should advise the
patient of the disclosure and the reasons why their failure to notify the agency obliged the doctor to act.
Aircraft
Persons with a history of epilepsy are usually allowed to obtain a flying license in the interest of avoiding
discrimination. In the United States, a history of epilepsy is rarely a disqualifier for the medical certification of
pilots.[69]
Notable people with epilepsy
Many notable people, past and present, have carried the diagnosis of epilepsy. In many cases, their epilepsy is a
footnote to their accomplishments; for some, it played an integral role in their fame. Historical diagnoses of epilepsy
are not always certain; there is controversy about what is considered an acceptable amount of evidence in support of
such a diagnosis.
Research
Important investigators of epilepsy
• Jean-Martin Charcot
• John Hughlings Jackson
• Hans Berger
• Herbert Jasper
• Wilder Penfield
98
Epilepsy
•
•
•
•
H. Houston Merritt
William G. Lennox
Fritz E. Dreifuss
Gregory L. Holmes
See also
•
•
•
•
•
•
•
•
•
•
•
Seizure
Convulsion
Seizure trigger
Breakthrough seizure
Non-epileptic seizures
Psychogenic non-epileptic seizures
Epilepsy in animals
Seizure response dog
Sudden Unexpected Death in Epilepsy
Jacksonian seizure
Photosensitive epilepsy
•
•
•
•
•
•
•
•
Post-traumatic epilepsy
Temporal lobe epilepsy
Abdominal epilepsy
Generalised epilepsy
ISAS (Ictal-Interictal SPECT Analysis by SPM)
Postictal state
Epilepsy Phenome/Genome Project
Pyridoxine-dependent epilepsy
External links
•
•
•
•
Epilepsy [70] at the Open Directory Project
Hippocrates: On the Sacred Disease [119]
Epilepsy & Seizures [71] Columbia Neurosurgery
SUDEP: Sudden Unexpected Death in Epilepsy [72]
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[27] Rogers et al.; Andrews, PI; Gahring, LC; Whisenand, T; Cauley, K; Crain, B; Hughes, TE; Heinemann, SF et al. (1994). "Autoantibodies to
glutamate receptor GluR3 in Rasmussen's encephalitis". Science 265 (5172): 648–651. doi:10.1126/science.8036512. PMID 8036512.
[28] Frucht MM, Quigg M, Schwaner C, Fountain NB. (2000). "Distribution of seizure precipitants among epilepsy syndromes.". Epilepsia 41
(12): 1534–1539.. doi:10.1111/j.1499-1654.2000.001534.x. PMID 11114210.
[29] Herzog AG, Harden CL, Liporace J, Pennell P, Schomer DL, Sperling M, et al. (2004). "Frequency of catamenial seizure exacerbation in
women with localization-related epilepsy". Annals Neurology 56 (3): 431–34. doi:10.1002/ana.20214. PMID 15349872.
[30] Miriam H. Meisler and Jennifer A. Kearney (2005). "Sodium channel mutations in epilepsy and other neurological disorders" (http:/ / www.
pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1180547). Journal of Clinical Investigation 115 (8): 2010–2017.
doi:10.1172/JCI25466. PMID 16075041 doi:10.1172/JCI25466. PMC 1180547.
[31] http:/ / www. scholarpedia. org/ article/ Models_of_epilepsy
[32] Trost LF, Wender RC, Suter CC, Von Worley AM, Brixner DI, Rosenberg JH, Gunter MJ (December 2005). "Management of epilepsy in
adults. Treatment guidelines" (http:/ / www. postgradmed. com/ index. php?art=pgm_12_2005?article=1769). Postgraduate Medicine 118 (6):
29–33. PMID 16382763. .
[33] Eadie MJ, Bladin PF (2001). A Disease Once Sacred: a History of the Medical Understanding of Epilepsy.
[34] Baker GA, Jacoby A, Buck D, et al. (1997). "Quality in life in people with epilepsy: a European study". Epilepsia 38 (3): 353–362.
doi:10.1111/j.1528-1157.1997.tb01128.x. PMID 9070599.
[35] Camfiled C, Camfield P, Smith E, et al. (1986). "Asymptomatic children with epilepsy: little benefit from screening for
anticonvulsant-induced liver, blood, or renal damage.". Neurology 36 (6): 838–841. PMID 3703292.
[36] mattson RH, Cramer J, COllins JF. (1985). "Comparison of carbemazipine, phenobarbital, phenytoin, and primidone in complex partial
seizures.". NEJM 313 (3): 145–151. PMID 3925335.
[37] Kwan P, Brodie MJ. (2000). "Early identification of refractory epilepsy.". NEJM 342 (5): 314–319. doi:10.1056/NEJM200002033420503.
PMID 10660394.
[38] Birbeck GL, Hays RD, Cui X, Vickrey BG. (2002). "Seizure reduction and quality of life improvements in people with epilepsy". Epilepsia
43 (5): 535–538. doi:10.1046/j.1528-1157.2002.32201.x. PMID 12027916.
[39] Berg AT, Langfitt JT, Spencer SS, Vickrey BG. (2007). "Stopping antiepileptic drugs after epilepsy surgery: a survey of U.S. epilepsy
center neurologists" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1868701). Epilepsy Behav 10 (2):
219–222. doi:10.1016/j.yebeh.2006.12.001. PMID 17251061. PMC 1868701.
[40] Kelley K, Theodore WH (2005). "Prognosis 30 years after temporal lobectomy". Neurology 64 (11): 1974–6.
doi:10.1212/01.WNL.0000163998.01543.CF. PMID 15955959.
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[41] Wiebe S, Blume WT, Girvin JP, Eliasziw M. (2001). "A randomized, controlled trial of surgery for temporal-lobe epilepsy". N Engl J Med
345 (5): 311–318. doi:10.1056/NEJM200108023450501. PMID 11484687.
[42] Theodore WH, Fisher RS (2004). "Brain stimulation for epilepsy". Lancet Neurol 3 (2): 111–118. doi:10.1016/S1474-4422(03)00664-1.
PMID 14747003.
[43] Regis, J., M. Rey, F. Bartolomei, V. Vladyka, R. Liscak, O. Schrottner and G. Pendl (2004). "Gamma knife surgery in mesial temporal lobe
epilepsy: a prospective multicenter study". Epilepsia 45 (5): 504–515. doi:10.1111/j.0013-9580.2004.07903.x. PMID 15101832.
[44] Takahashi, T. and Y. Tsukahara (1992). "Usefulness of blue sunglasses in photosensitive epilepsy". Epilepsia 33 (3): 517–521.
doi:10.1111/j.1528-1157.1992.tb01702.x. PMID 1592030.
[45] Barriaux, Marianne (2006-10-16). "Dogs trained to warn of an imminent epileptic fit" (http:/ / business. guardian. co. uk/ story/
0,,1923146,00. html). The Guardian. . Retrieved 2006-11-24.
[46] Cheuk D, Wong V (2006). "Acupuncture for epilepsy". Cochrane Database Syst Rev (2): CD005062.
doi:10.1002/14651858.CD005062.pub2. PMID 16625622.
[47] Ramaratnam S, Baker GA, Goldstein LH (2005). "Psychological treatments for epilepsy". Cochrane Database Syst Rev (4): CD002029.
doi:10.1002/14651858.CD002029.pub2. PMID 16235293.
[48] Ranganathan LN, Ramaratnam S (2005). "Vitamins for epilepsy". Cochrane Database Syst Rev (2): CD004304.
doi:10.1002/14651858.CD004304.pub2. PMID 15846704.
[49] Ramaratnam S, Sridharan K (2000). "Yoga for epilepsy". Cochrane Database Syst Rev (3): CD001524. doi:10.1002/14651858.CD001524.
PMID 10908505.
[50] Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R (2007-01-30). "How common are the 'common' neurologic
disorders?". Neurology 68 (5): 326–37. doi:10.1212/01.wnl.0000252807.38124.a3. PMID 17261678.
[51] Sander JW (2003). "The epidemiology of epilepsy revisited". Curr Opin Neurol 16 (2): 165–70. doi:10.1097/00019052-200304000-00008.
PMID 12644744.
[52] Walczak TS, Leppik IE, D'Amelio M, Rarick J, So E, Ahman P, Ruggles K, Cascino GD, Annegers JF, Hauser WA (2001). "SIncidence and
risk factors in sudden unexpected death in epilepsy: a prospective cohort study.". Neurology 56 (4): 519–525. PMID 11222798.
[53] Lathers, C. and P. Schraeder (1990). Epilepsy and Sudden Death. Dekker, NY, NY..
[54] Hitiris, N., R. Mohanraj, J. Norrie and M. J. Brodie (2007). "Mortality in epilepsy". Epilepsy Behavior 10 (3): 363–376.
doi:10.1016/j.yebeh.2007.01.005. PMID 17337248.
[55] Hanna et al 2002
[56] Hanna et al, (2002) The National Sentinel Audit of Epilepsy Related Death, The Stationary Office, London.
[57] Plioplys S, Dunn DW, Caplan R (2007). "10-year research update review: psychiatric problems in children with epilepsy". J Am Acad Child
Adolesc Psychiatry 46 (11): 1389–402. doi:10.1097/chi.0b013e31815597fc. PMID 18049289.
[58] Levisohn PM (2007). "The autism-epilepsy connection". Epilepsia 48 (Suppl 9): 33–5. doi:10.1111/j.1528-1167.2007.01399.x (inactive
2009-12-06). PMID 18047599.
[59] OED. Retrieved 8 September 2009.
[60] When Epilepsy Goes By Another Name | epilepsy.com (http:/ / www. epilepsy. com/ articles/ ar_1063680870. html)
[61] Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures. (http:/ / www. ncbi. nlm. nih. gov/ entrez/ query.
fcgi?cmd=Retrieve& db=PubMed& list_uids=10080524& dopt=Abstract) Jilek-Aall L. PMID: 10080524 Retrieved 8 October 2006.
[62] Hippocrates quotes (http:/ / quote. wikipedia. org/ wiki/ Hippocrates)
[63] Epilepsy Foundation Driving and You - Can you drive an automobile if you have epilepsy? (http:/ / www. epilepsyfoundation. org/
answerplace/ Social/ driving/ drivingu. cfm).
[64] Epilepsy Foundation Driver Information by State (http:/ / www. epilepsyfoundation. org/ living/ wellness/ transportation/ drivinglaws. cfm)
[65] UK Epilepsy Action: Driving and Epilepsy, I've had a seizure. What should I do? (http:/ / www. epilepsy. org. uk/ info/ driving/ seizure.
html)
[66] UK Driver and Vehicle Licensing Agency Guide to the Current Medical Standards Of Fitness to Drive (http:/ / www. dvla. gov. uk/
at_a_glance/ content. htm). Full details for doctors regarding epilepsy are given in the Appendix (http:/ / www. dvla. gov. uk/ at_a_glance/
ch1_neurological. htm#appendix). Information for drivers can be found in Medical Rules - Group 1 Licence Holders (http:/ / www. dvla. gov.
uk/ drivers/ dmed1_files/ group1. htm#nc)
[67] UK Epilepsy Action: booklet with further details about driving PDF (http:/ / www. epilepsy. org. uk/ downloads/ pdf/
epilepsyaction_driving. pdf)
[68] Epilepsy Action (2009), Driving law relating to seizures. Available from http:/ / www. epilepsy. org. uk/ info/ driving/ lawseizure (Accessed
on 15 February 2009)
[69] People with Epilepsy and the Joy of Flying: Is There Discrimination?. P. Gouldman, J. Smith. (2008) Epilepsy & Behavior 15 p.483-497.
[70] http:/ / www. dmoz. org/ Health/ Conditions_and_Diseases/ Neurological_Disorders/ Epilepsy/
[71] http:/ / www. columbianeurosurgery. org/ conditions/ epilepsy-seizures/
[72] http:/ / www. sudep. org:
101
Obsessive–compulsive disorder
102
Obsessive–compulsive disorder
Obsessive–compulsive disorder
Classification and external resources
Frequent hand washing is a common compulsion in OCD sufferers.
[1]
ICD-10
F 42.
ICD-9
300.3
DiseasesDB
33766
MeSH
D009771
[2]
[3]
[4]
Obsessive–compulsive disorder (OCD) is a mental disorder characterized by intrusive thoughts that produce
anxiety, by repetitive behaviors aimed at reducing anxiety, or by a combination of such thoughts (obsessions) and
behaviors (compulsions). The symptoms of this anxiety disorder include repetitive hand-washing; extensive
hoarding; preoccupation with sexual or aggressive impulses, or with particular religious beliefs; aversion to odd
numbers; and nervous habits, such as opening a door and closing it a certain number of times before one enters or
leaves a room. These symptoms can be alienating and time-consuming, and often cause severe emotional and
economic loss. The acts of those who have OCD may appear paranoid and come across to others as psychotic.
However, OCD sufferers generally recognize their thoughts and subsequent actions as irrational, and they may
become further distressed by this realization.
OCD is the fourth-most common mental disorder and is diagnosed nearly as often as asthma and diabetes mellitus.[5]
In the United States, one in 50 adults has OCD.[6] The phrase "obsessive–compulsive" has become part of the
English lexicon, and is often used in an informal or caricatured manner to describe someone who is meticulous,
perfectionistic, absorbed in a cause, or otherwise fixated on something or someone.[7] Although these signs may be
present in OCD, a person who exhibits them does not necessarily have OCD, and may instead have
obsessive–compulsive personality disorder (OCPD), an autism spectrum disorder, or no clinical condition. Multiple
psychological and biological factors may be involved in causing obsessive–compulsive syndromes.
Obsessive–compulsive disorder
Signs and symptoms
Obsessions
A typical person with OCD performs tasks,
or compulsions, to seek relief from
obsession-related anxiety. Within and
among individuals, the initial obsessions, or
intrusive thoughts, can vary in their clarity
and vividness. A relatively vague obsession
could involve a general sense of disarray or
tension, accompanied by a belief that life
cannot proceed as normal while the
World Health Organization map of obsessive compulsive disorders, 2002.
imbalance remains. A more articulable
obsession could be a preoccupation with the
thought or image of someone close to them dying.[8] [9] A survey of healthy university students found that virtually
all of them had these types of thoughts from time to time.[10] Like these students, people with OCD do not enact or
enjoy these violent thoughts[11] [12] by these ideas—and by the sense that they could inexplicably possess them.
Other obsessions concern the possibility that someone or something other than oneself—such as God, the Devil, or
disease—will harm either the person with OCD or the people or things that the that person cares about. Some people
dread entire concepts, fearing their materialization by causes that may seem implausible or indiscriminate to others.
For example, a generalized fear of contamination might entail not only wariness of bodily secretions or excretions,
but also apprehension toward household chemicals, radioactivity, newsprint, pets, or even soap.[13]
Sexual obsessions may involve intrusive thoughts or images of "kissing, touching, fondling, oral sex, anal sex,
intercourse, and rape" with "strangers, acquaintances, parents, children, family members, friends, coworkers, animals
and religious figures", and can include "heterosexual or homosexual content" with persons of any age.[14] As with
other intrusive, unpleasant thoughts or images, most people have some disquieting sexual thoughts at times, but
people with OCD may attach extraordinary significance to the thoughts. For example, obsessive fears about sexual
orientation can appear to the person with OCD, and even to those around them, as a crisis of sexual identity.[15] [16]
The doubt that accompanies OCD leads to uncertainty regarding whether one might act on the troubling thoughts,
resulting in self-criticism or self-loathing.[14]
Some people with OCD may sense that the physical world is qualified by certain immaterial conditions. These
people might intuit invisible protrusions from their bodies,[17] or could feel that inanimate objects are ensouled.
These intuitions and feelings do not stem from socially accepted religious or metaphysical convictions, such as
animism; even a child with OCD might find their obsessive notions ultimately silly.[17] However, even though the
person with OCD understands that their notions do not correspond with the external world, they feel that they must
act as though their notions were correct. For example, an individual who engages in compulsive hoarding might be
inclined to treat inorganic matter as if it had the sentience or rights of living organisms, but such an individual might
find their consequent behavior irrational on a more intellectual level. However, Insel and Akiskal (1986) noted that
in severe OCD, obsessions can shift into delusions when resistance to the obsession is abandoned and insight into its
senselessness is lost.
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Obsessive–compulsive disorder
Compulsions
While some with OCD perform compulsive rituals because they inexplicably feel they must, others act compulsively
so as to mitigate the anxiety that stems from particular obsessive thoughts. The person with OCD might feel that
these actions somehow either will prevent a dreaded event from occurring, or will push the event from their
thoughts. In any case, the individual's reasoning is so idiosyncratic or distorted that it results in significant distress
for the individual with OCD or for those around them.
Some common compulsions include counting specific things (such as footsteps) or in specific ways (for instance, by
intervals of two) and doing other repetitive actions, often with atypical sensitivity to numbers or patterns. People
might repeatedly wash their hands[18] or clear their throats, repeatedly check that their parked cars have been locked
before leaving them, turn lights on and off, keep doors shut or closed at all times, touch objects a certain number of
times before exiting a room, walk in a certain routine way like only stepping on a certain color of tile, or have a
routine for using stairs, such as always finishing a flight on the same foot.
People rely on compulsions as an escape from their obsessive thoughts; however, they are aware that the relief is
only temporary, that the intrusive thoughts will soon come back. Some people use compulsions to avoid situations
that may trigger their obsessions. Although some people do certain things over and over again, they don't necessarily
perform these actions compulsively. For example, bedtime routines, learning a new skill, and religious practices are
not compulsions. Whether or not behaviors are compulsions or mere habit depends on the context in which the
behaviors are performed. For example, arranging and ordering DVDs or videos for eight hours a day would be
expected of one who works in a video store, but would seem abnormal in other situations. Put another way, if the
activity helps bring efficiency to one's life, it is probably a habit, if it interferes with one's normal enjoyment of life,
it is probably a compulsion. [19]
For some people with OCD, these tasks, along with the attendant anxiety and fear, can take hours of each day,
making it hard for the person to fulfill their work, family, or social roles. In some cases, these behaviors can also
cause adverse physical symptoms: People who obsessively wash their hands with antibacterial soap and hot water (to
remove germs) can make their skin red and raw with dermatitis.[20] To others, these tasks may appear odd and
unnecessary. But for the person with OCD, such tasks can feel critically important, and must be performed in
particular ways. Individuals with OCD are aware that their thoughts and behavior are not rational,[21] but they feel
bound to comply with them to fend off feelings of panic or dread.
OCD without overt compulsions
OCD sometimes manifests without overt compulsions.[22] Nicknamed "Pure-O",[23] OCD without overt compulsions
could, by one estimate, characterize as many as 50 percent to 60 percent of OCD cases.[24] Rather than engaging in
observable compulsions, the person with this subtype might perform more covert, mental rituals, or might feel driven
to avoid the situations in which particular thoughts seem likely to intrude.[23] As a result of this avoidance, people
can struggle to fulfill both public and private roles, even if they place great value on these roles and even if they had
fulfilled the roles successfully in the past.[23] Moreover, the individual's avoidance can confuse others who do not
know its origin or intended purpose, as it did in the case of a man whose wife began to wonder why he would not
hold their infant child.[23]
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Obsessive–compulsive disorder
Etiology
Scholars generally agree that both psychological and biological factors play a role in causing the disorder, although
they differ in their degree of emphasis upon either type of factor.
Psychological
From the 14th to the 16th century in Europe, it was believed that people who experienced blasphemous, sexual, or
other obsessive thoughts were possessed by the Devil.[25] Based on this reasoning, treatment involved banishing the
"evil" from the "possessed" person through exorcism.[26] In the early 1910s, Sigmund Freud attributed
obsessive–compulsive behavior to unconscious conflicts which manifested as symptoms.[26] Freud describes the
clinical history of a typical case of "touching phobia" as starting in early childhood, when the person has a strong
desire to touch an item. In response, the person develops an "external prohibition" against this type of touching.
However, this "prohibition does not succeed in abolishing" the desire to touch; all it can do is repress the desire and
"force it into the unconscious".[27]
The cognitive–behavioral model suggests that compulsive behaviour is carried out to remove anxiety-provoking
intrusive thoughts. Unfortunately this only brings about temporary relief as the thought re-emerges. Each time the
behaviour occurs it is negatively reinforced by the relief from anxiety, thereby explaining why the dysfunctional
activity increases and generalizes (extends to other, related stimuli) over a period of time. For example, after
touching a door-knob a person might have the thought that they may develop a disease as a result of contamination.
They then experience anxiety, which is relieved when they wash their hands. This might be followed by the thought
"but did I wash them properly?" causing an increase in anxiety once more, the hand-washing once again rewarded by
the removal of anxiety (albeit briefly) and the cycle being repeated when thoughts of contamination re-occur. The
distressing thoughts might then spread to fear of contamination from e.g. a chair (someone might have touched the
chair after touching the door handle). The National Institute of Mental Health estimates that more than two percent
of the U.S. population has from obsessive–compulsive disorder or OCD. Approximately 50% of men who have
obsessive–compulsive disorder, have sexual side-effects as a result of OCD, and that 37% of men who have OCD
are plagued with erectile dysfunction.[28]
Biological
OCD has been linked to abnormalities with the neurotransmitter serotonin, although it could be either a cause or an
effect of these abnormalities. Serotonin is thought to have a role in regulating anxiety. To send chemical messages
from one neuron to another, serotonin must bind to the receptor sites located on the neighboring nerve cell. It is
hypothesized that the serotonin receptors of OCD sufferers may be relatively understimulated. This suggestion is
consistent with the observation that many OCD patients benefit from the use of selective serotonin reuptake
inhibitors (SSRIs), a class of antidepressant medications that allow for more serotonin to be readily available to other
nerve cells.[29]
A possible genetic mutation may contribute to OCD. A mutation has been found in the human serotonin transporter
gene, hSERT, in unrelated families with OCD[30] . Moreover, data from identical twins supports the existence of a
"heritable factor for neurotic anxiety".[31] Further, individuals with OCD are more likely to have first-degree family
members exhibiting the same disorders than do matched controls. In cases where OCD develops during childhood,
there is a much stronger familial link in the disorder than cases in which OCD develops later in adulthood. In
general, genetic factors account for 45-65% of OCD symptoms in children diagnosed with the disorder.[32]
Environmental factors also play a role in how these anxiety symptoms are expressed; various studies on this topic are
in progress and the presence of a genetic link is not yet definitely established.
Abnormal brain development and subsequent malfunction may contribute to the manifestation of OCD. A
miscommunication between the orbitofrontal cortex (OFC), caudate nucleus, and thalamus may be a factor. The
caudate nucleus lies between the OFC and thalamus and ordinarily prevents signals from being returned to the
105
Obsessive–compulsive disorder
thalamus; if the caudate nucleus does not function normally the thalamus may become hyperactive and create an
unceasing cycle of activity between the OFC and the thalamus, resulting in heightened anxiety. People with OCD
evince increased grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, while decreased
grey matter volumes in bilateral dorsal medial frontal/anterior cingulate gyri. [33] OFC overactivity is attenuated in
patients who have successfully responded to SSRI medication, a result believed to be caused by increased
stimulation of serotonin receptors 5-HT2A and 5-HT2C.[34] The striatum, linked to planning and the initiation of
appropriate actions, has also been implicated; mice genetically engineered with a striatal abnormality exhibit
OCD-like behavior, grooming themselves three times as frequently as ordinary mice. [35] Recent evidence supports
the possibility of a heritable predisposition for neurological development favoring OCD[36] .
Rapid onset of OCD in children may be caused by Group A streptococcal infection, a condition identified by its
acronym PANDAS.[37] It has been suggested that PANDAS should be addressed as a possible cause of child OCD
before other pharmacological remedies are attempted. [38]
Diagnosis
Formal diagnosis may be performed by a psychologist or a psychiatrist. To be diagnosed with OCD, a person must
have obsessions, compulsions, or both, according to the Diagnostic and Statistical Manual of Mental Disorders
(DSM). The Quick Reference to the 2000 edition of the DSM[39] suggests that several features characterize clinically
significant obsessions and compulsions. Such obsessions, the DSM says, are recurrent and persistent thoughts,
impulses, or images that are experienced as intrusive and that cause marked anxiety or distress. These thoughts,
impulses, or images are of a degree or type that lies outside the normal range of worries about conventional
problems. A person may attempt to ignore or suppress such obsessions, or to neutralize them with some other
thought or action, and will tend to recognize the obsessions as idiosyncratic or irrational.
Compulsions become clinically significant when a person feels driven to perform them in response to an obsession,
or according to rules that must be applied rigidly, and when the person consequently feels or causes significant
distress. Therefore, while many people who do not suffer from OCD may perform actions often associated with
OCD (such as ordering items in a pantry by height), the distinction with clinically significant OCD lies in the fact
that the person who suffers from OCD must perform these actions, otherwise they will experience significant
psychological distress. These behaviors or mental acts are aimed at preventing or reducing distress or preventing
some dreaded event or situation; however, these activities are not logically or practically connected to the issue, or
they are excessive. In addition, at some point during the course of the disorder, the individual must realize that their
obsessions or compulsions are unreasonable or excessive. Moreover, the obsessions or compulsions must be
time-consuming (taking up more than one hour per day) or cause impairment in social, occupational, or scholastic
functioning.[39] It is helpful to quantify the severity of symptoms and impairment before and during treatment for
OCD. In addition to the patient’s estimate of the time spent each day harboring obsessive-compulsive thoughts or
behaviors, Fenske and Schwenk in their article “Obsessive-Compulsive Disorder: Diagnosis and Management,”
argue that more concrete tools should be used to gauge the patient’s condition (2009). This may be done with rating
scales, such as the most trusted Yale-Brown Obsessive Compulsive Scale (Y-BOCS). With measurements like these,
psychiatric consultation can be more appropriately determined because it has been standardized. [40]
Differential diagnosis
OCD is often confused with the separate condition obsessive–compulsive personality disorder. The two are not the
same condition, however. OCD is ego dystonic, meaning that the disorder is incompatible with the sufferer's
self-concept.[25] [41] Because disorders that are ego dystonic go against a person's self-concept, they tend to cause
much distress. OCPD, on the other hand, is ego syntonic—marked by the person's acceptance that the characteristics
displayed as a result of this disorder are compatible with his or her self-image. Ego syntonic disorders
understandably cause no distress. People with OCD are often aware that their behavior is not rational and are
106
Obsessive–compulsive disorder
unhappy about their obsessions but nevertheless feel compelled by them. People with OCPD are not aware of
anything abnormal about themselves; they will readily explain why their actions are rational, and it is usually
impossible to convince them otherwise. People with OCD are ridden with anxiety; by contrast, people with OCPD
tend to derive pleasure from their obsessions or compulsions.[42]
Equally frequently, these rationalizations do not apply to the overall behavior but to each instance individually; for
example, a person compulsively checking the front door may argue that the time taken and stress caused by one
more check of the front door is much less than the time and stress associated with being robbed, and thus the check is
the better option. In practice, after that check, the person is still not sure and deems it is still better in terms of time
and stress to do one more check, and this reasoning can continue as long as necessary.
Some OCD sufferers exhibit what is known as overvalued ideas. In such cases, the person with OCD will truly be
uncertain whether the fears that cause them to perform their compulsions are irrational or not. After some discussion,
it is possible to convince the individual that their fears may be unfounded. It may be more difficult to do ERP
therapy on such patients because they may be unwilling to cooperate, at least initially. For this reason OCD has often
been likened to a disease of pathological doubt, in which the sufferer, though not usually delusional, is often unable
to realize fully which dreaded events are reasonably possible and which are not. There are severe cases in which the
sufferer has an unshakeable belief in the context of OCD that is difficult to differentiate from psychosis.[43]
OCD is different from behaviors such as gambling addiction and overeating. People with these disorders typically
experience at least some pleasure from their activity; OCD sufferers do not actively want to perform their
compulsive tasks and experience no pleasure from doing so. OCD is characterized as an anxiety disorder, but like
many forms of chronic stress it can lead to clinical depression over time. The constant stress of the condition can
cause sufferers to develop a deadening of spirit, a numbing frustration, or sense of hopelessness. OCD's effects on
day-to-day life—particularly its substantial consumption of time—can produce difficulties with work, finances, and
relationships. There is no known cure for OCD, but a number of successful treatment options are available.
Management
According to a team of Duke University-led psychiatrists, behavioral therapy (BT), cognitive behavioral therapy
(CBT), and medications should be regarded as first-line treatments for OCD.[44] Psychodynamic psychotherapy may
help in managing some aspects of the disorder. The American Psychiatric Association notes a lack of controlled
demonstrations that psychoanalysis or dynamic psychotherapy are effective "in dealing with the core symptoms of
OCD."[45]
Behavioral therapy
The specific technique used in BT/CBT is called exposure and ritual prevention (also known as "exposure and
response prevention") or ERP; this involves gradually learning to tolerate the anxiety associated with not performing
the ritual behavior. At first, for example, someone might touch something only very mildly "contaminated" (such as
a tissue that has been touched by another tissue that has been touched by the end of a toothpick that has touched a
book that came from a "contaminated" location, such as a school.) That is the "exposure". The "ritual prevention" is
not washing. Another example might be leaving the house and checking the lock only once (exposure) without going
back and checking again (ritual prevention). The person fairly quickly habituates to the anxiety-producing situation
and discovers that their anxiety level has dropped considerably; they can then progress to touching something more
"contaminated" or not checking the lock at all—again, without performing the ritual behavior of washing or
checking.
Exposure ritual/response prevention (ERP) has been demonstrated to be the most effective treatment for OCD. Using
ERP alone, one can become completely symptom free. However, the individual must be highly motivated and
consistent. It has generally been accepted that psychotherapy, in combination with psychotropic medication, is more
effective than either option alone. However, more recent studies have shown no difference in outcomes for those
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Obsessive–compulsive disorder
treated with the combination of medicine and CBT versus CBT alone.[46]
Association splitting is a new technique aimed at reducing obsessive thoughts. The method draws upon the “fan
effect” of associative priming[47] : The sprouting of new associations diminishes the strength of existing ones. As
OCD patients show marked biases or restrictions in OCD-related semantic networks (e.g., cancer is only associated
with “illness” or “death”, fire is only associated with “danger” or “destruction”)[48] , they are encouraged to imagine
neutral or positive associations to OCD-related cognitions (cancer = zodiac sign, animal, lobster; fire = fireflies,
fireworks, candlelight-dinner). First studies tentatively confirm the feasibility and effectiveness of the approach for a
subgroup of patients[49] .
Medication
Medications as treatment include selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, sertraline,
fluoxetine, escitalopram, and fluvoxamine and the tricyclic antidepressants, in particular clomipramine. SSRIs
prevent excess serotonin from being pumped back into the original neuron that released it. Instead, serotonin can
then bind to the receptor sites of nearby neurons and send chemical messages or signals that can help regulate the
excessive anxiety and obsessive thoughts. In some treatment-resistant cases, a combination of clomipramine and an
SSRI has shown to be effective even when neither drug on its own has been efficacious.
Treatment of obsessive–compulsive disorder is an area needing significant improvement in prescribing regimens.[50]
Benzodiazepines are sometimes used for obsessive compulsive disorder, although they are generally believed to be
ineffective for this indication; however, effectiveness was found in one small study.[51] Benzodiazepines can be
considered as a treatment option in treatment resistant cases.[52] Morphine and other less potent pain killers, which
possess agonist actions at the μ-opioid receptor and inhibit the reuptake of norepinephrine and serotonin, have shown
effectiveness in the treatment of OCD.[53]
Serotonergic antidepressants typically take longer to show benefit in OCD than with most other disorders they are
used to treat. It is common for 2–3 months to elapse before any tangible improvement is noticed. In addition to this,
treatment usually requires high dosages. Fluoxetine, for example, is usually prescribed in dosages of 20 mg per day
for clinical depression, whereas with OCD the dosage often ranges from 20 mg to 80 mg or higher, if necessary. In
most cases antidepressant therapy alone provides only a partial reduction in symptoms, even in cases that are not
deemed treatment resistant. Much current research is devoted to the therapeutic potential of the agents that affect the
release of the neurotransmitter glutamate or the binding to its receptors. These include riluzole, memantine,
gabapentin, N-Acetylcysteine, and lamotrigine. MDMA, which is a powerful and illicit serotonergic drug, has also
been anecdotally reported to temporarily alleviate the symptoms of OCD.
Low dosages of the newer atypical antipsychotics olanzapine, quetiapine, ziprasidone, and risperidone have also
been found to be useful as adjuncts in the treatment of OCD. The use of antipsychotics in OCD must be undertaken
carefully, however, because although there is very strong evidence that at low dosages they are beneficial (probably
because of their dopamine receptor antagonism), at high dosages these same antipsychotics have caused dramatic
obsessive–compulsive symptoms even in patients who do not normally have OCD. This can be because the
antagonism of 5-HT2A receptors becomes very prominent at these dosages and outweighs the benefits of dopamine
antagonism. However, the antidepressant mirtazapine, which is a 5-HT2A antagonist, has been shown to benefit
OCD patients.[54] This could be explained partially by the fact that Clomipramine (often regarded as the most
effective medication against OCD symptoms) and Mirtazapine share a similar potency with regard to antagonism at
5-HT2A and 5-HT2C receptors, with Ki values for the 5-HT2A receptor as 36nM and 69nM respectively, and for the
5-HT2C receptor as 65nM and 39nM respectively.
Another point that must be noted with antipsychotic treatment is that SSRIs inhibit the chief enzyme that is
responsible for metabolising antipsychotics—CYP2D6—so the dosage will be effectively higher than expected when
these are combined with SSRIs. Also, it must be noted that antipsychotic treatment should be considered as
augmentation treatment when SSRI treatment does not bring positive results.
108
Obsessive–compulsive disorder
Alternative drug treatments
The naturally occurring sugar inositol has been suggested as a treatment for OCD[55] , as it appears to modulate the
actions of serotonin and reverse desensitisation of neurotransmitter receptors. St John's Wort has been claimed to be
of benefit due to its (non-selective) serotonin re-uptake inhibiting qualities, although a double-blind study using a
flexible-dose schedule (600–1800 mg/day) found no difference between St John's Wort and a placebo[56] .
Nutrition deficiencies may also contribute to OCD and other mental disorders. Vitamin and mineral supplements
may aid in such disorders and provide nutrients necessary for proper mental functioning[57] .
Opioids may rapidly ameliorate OCD symptoms. Tramadol is an atypical opioid that appears to provide the
anti-OCD effects of an opiate and inhibit the re-uptake of serotonin (in addition to norepinephrine)[58] . Oral
morphine, administered once weekly, has been shown to reduce OCD symptoms in some treatment-resistant patients.
The mechanism of therapeutic action is unknown.[59]
Psychedelics such as LSD, peyote, and tryptamine alkaloid psilocybin have been proposed as treatment due to their
observed effects on OCD symptoms[60] [61] . It has been hypothesised that hallucinogens may stimulate 5-HT2A
receptors and, less significantly, 5-HT2C receptors, causing an inhibitory effect on the orbitofrontal cortex, an area
of the brain strongly associated with hyperactivity and OCD[62] .
Regular nicotine treatment may ameliorate symptoms of OCD, although the pharmacodynamical mechanism by
which this is achieved is not yet known, and more detailed studies are needed to fully confirm this hypothesis[63] .
Electroconvulsive therapy (ECT)
This has been found effective in severe and refractory cases.[64]
Psychosurgery
For some, neither medication, support groups nor psychological treatments are helpful in alleviating
obsessive–compulsive symptoms. These patients may choose to undergo psychosurgery as a last resort. In this
procedure, a surgical lesion is made in an area of the brain (the cingulate cortex). In one study, 30% of participants
benefited significantly from this procedure.[12] Deep-brain stimulation and vagus nerve stimulation are possible
surgical options which do not require destruction of brain tissue. In the US, the Food and Drug Administration
approved deep-brain stimulation for the treatment of OCD under a humanitarian device exemption requiring that the
procedure be performed only in a hospital with specialist qualifications to do so.[65]
In the US, psychosurgery for OCD is a treatment of last resort and will not be performed until the patient has failed
several attempts at medication (at the full dosage) with augmentation, and many months of intensive
cognitive–behavioral therapy with exposure and ritual/response prevention.[66] Likewise, in the UK, psychosurgery
cannot be performed unless a course of treatment from a suitably qualified cognitive–behavioral therapist has been
carried out.
Treatment in children and adolescents
Although the causes of OCD in younger age groups range from brain abnormalities to psychological preoccupations,
life stress may also contribute to childhood cases of OCD—acknowledging these stressors plays an important role in
treating the disorder. In her article “Factors Influencing the Onset of Childhood Obsessive Compulsive Disorder”
Tina M. D’Alessandro reports that such stressors as bullying and traumatic familial deaths have caused anxiety and
depression in children, conditions that have led to their development of OCD. In order to reduce suffering and
prevent OCD-related mortality in adulthood, D’Alessandro emphasizes the importance of considering these stressors
early-on so as to guide the child toward treatment as soon as possible.[67]
As with adults, behavioral treatment has proven to be quite effective in reducing ritual behaviors of OCD. A key
component to the success of such treatments in children and adolescents consists of family member involvement
109
Obsessive–compulsive disorder
110
which can be established in a number of different ways. Dr. Judith L. Rapoport stresses the importance of familial
participation during the child’s therapy sessions as well as outside the sessions, in the form of creating behavioral
observations and reports.[68] Additionally, parental intervention aids in providing positive reinforcement for the child
when s/he exhibits appropriate behaviors as alternatives to his/her compulsive response. Therapy, in general, has
proven very helpful to children and adolescents with OCD according to Dr. Paul L. Adams. Parents may expect the
duration of weekly sessions to last one to two years, but the results are quite valuable. Adams reports such changes
in his own patients as the acquisition of a larger circle of friends, the child exhibiting less shyness, and being far less
self-critical after considering the true meaning behind his/her obsession and learning how to cope with it in therapy
sessions.[69]
For phasing out obsessive thoughts, Rapoport reports that the mental technique of “thought stopping” has been
successful particularly among adolescents. In this procedure, whenever the individual has an obsessive thought, s/he
is encouraged to either mentally or verbally pronounce “STOP” in mid-thought to interrupt the obsession.
Additionally, Rapoport reports a modification of this process so as to prevent “STOP” for becoming a stimulus to the
obsessive thoughts: the child is to call to mind the thought, interrupt by loudly counting backward from ten, and then
evoke a pleasant scene—in one subject, this reduced the obsessive frequencies by 80% in just one week and
eliminated them in four.[70]
Epidemiology
OCD does not have a higher affinity for a specific gender. It can begin
as early as the age of two, but most often begins in the late teens for
males and the early twenties for females. Studies have placed the
prevalence between one and three percent, although the prevalence of
clinically recognized OCD is much lower, suggesting that many
individuals with the disorder may not be diagnosed.[71] The fact that
many individuals do not seek treatment may be due in part to stigma
associated with OCD.
Disability-adjusted life year for
obsessive-compulsive disorder per
100,000 inhabitants in 2002. no data less
than 45 45-52.5 52.5-60 60-67.5
67.5-75 75-82.5 82.5-90 90-97.5
97.5-105 105-112.5 112.5-120 more
than 120
In a 1980 study of adults from several U.S. cities, the lifetime
prevalence rate of OCD for both sexes was recorded at 2.5 percent.
Education also appears to be a factor. The lifetime prevalence of OCD
is lower for those who have graduated high school than for those who
have not (1.9 percent versus 3.4 percent). However, in the case of college education, lifetime prevalence is higher for
those who graduate with a degree (3.1 percent) than it is for those who have only some college background (2.4
percent). As far as age is concerned, the onset of OCD usually ranges from the late teenage years until the mid-20s in
both sexes, but the age of onset tends to be slightly younger in males than in females.[72]
A study suggests that OCD symptoms in Japanese patients are similar to those found in Western countries,
suggesting that this disorder transcends culture and geography. The study, published in 2008, appears to contradict
previous theories, said the study’s lead author, Hisato Matsunaga. Having "hypothesized that symptom structure
might be substantially influenced by the sociocultural differences", Hisato said that he was surprised by the results.
It has been proposed that sufferers are generally of above-average intelligence, as the very nature of the disorder
necessitates complicated thinking patterns.[73]
Obsessive–compulsive disorder
Comorbidity
People with OCD may be diagnosed with other conditions, such as major depressive disorder, generalized anxiety
disorder, anorexia nervosa, social anxiety disorder, bulimia nervosa, Tourette syndrome, Asperger syndrome,
compulsive skin picking, body dysmorphic disorder, trichotillomania, and (as already mentioned)
obsessive–compulsive personality disorder. There is some research demonstrating a link between drug addiction and
OCD as well. Many who suffer from OCD also suffer from panic attacks. There is a higher risk of drug addiction
among those with any anxiety disorder (possibly as a way of coping with the heightened levels of anxiety), but drug
addiction among OCD patients may serve as a type of compulsive behavior and not just as a coping mechanism.
Depression is also extremely prevalent among sufferers of OCD. One explanation for the high depression rate among
OCD populations was posited by Mineka, Watson, and Clark (1998), who explained that people with OCD (or any
other anxiety disorder) may feel depressed because of an "out of control" type of feeling.[74] In further consideration
of OCD comorbidities, the research of Fenske and Schwenk reports that studies have shown that depression among
those with OCD is particularly alarming because their risk of suicide is high; more than 50 percent of patients
experience suicidal tendencies, and 15 percent have attempted suicide.[75] Individuals with OCD have also been
found to be affected by delayed sleep phase syndrome at a substantially higher rate than the general public.[76]
Prognosis
Cognitive performance
OCD is associated with higher IQ.[73] [77]
A 2009 study which conducted "a battery of neuropsychological tasks to assess nine cognitive domains with a
special focus on executive functions" concluded that "few neuropsychological differences emerged between the
OCD and healthy participants when concomitant factors were controlled."[78]
Law
Although research suggests that individuals with obsessive-compulsive disorder may be unusually inclined to ensure
the safety of themselves and others,[79] [80] [81] some jurisdictions have passed catch-all "mental illness" legislation
that may inadvertently and adversely affect the civil liberties of OCD sufferers.
Society and culture
• British poet, essayist, and lexicographer Samuel Johnson is an example of a historical figure with a retrospective
diagnosis of OCD. He had elaborate rituals for crossing the thresholds of doorways, repeatedly walked up and
down staircases counting the steps, and had compulsions regarding repetitive prayer which were most likely a
form of religious scrupulosity.[82] [83] [84]
• American aviator and filmmaker Howard Hughes is known to have suffered from OCD and it is believed that his
mother may have also been a sufferer. Friends of Hughes have mentioned his obsession with minor flaws in
clothing and he is reported to have had a great fear of germs, common among OCD patients.[85] He also suffered
from Social Anxiety Disorder (SAD) and Post-traumatic Stress Disorder (PTSD) due to an aviation accident in
which he was severely injured. This resulted in him becoming reclusive later in life.
• English footballer David Beckham has been outspoken regarding his struggle with OCD. He has told media that
he has to count all of his clothes, and that magazines have to lie in a straight line. If there are three soda cans in
his refrigerator, he will throw one out to make an even pair, and if there are any more at home they have to be
placed in a cupboard. In hotels, any books that are on a shelf must be moved into a drawer. He has also explained
that his reason for getting more tattoos is that he feels addicted to the pain of the needle. He has expressed a desire
to get help for his problems.[86]
111
Obsessive–compulsive disorder
• American game show host Marc Summers has written a book about how OCD has affected his life. The book is
titled Everything in Its Place: My Trials and Triumphs with Obsessive Compulsive Disorder.[87]
• Movies and television often portray accurately-idealized representations of disorders such as OCD. These
depictions may lead to increased public awareness, understanding, and sympathy for such disorders.[88]
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[69] Adams, P. L. (1973). Obsessive Children: A Sociopsychiatric Study. Philadelphia: Brunner / Mazel.
[70] Rapoport, J. E. (1989). Obsessive-compulsive Disorder In Children & Adolescents. Washington: American Psychiatric Press.
[71] Fireman B, Koran LM, Leventhal JL, Jacobson A (2001). "The prevalence of clinically recognized obsessive–compulsive disorder in a large
health maintenance organization". The American journal of psychiatry 158 (11): 1904–10. doi:10.1176/appi.ajp.158.11.1904.
PMID 11691699.
[72] Antony, M. M.; F. Downie & R. P. Swinson. "Diagnostic issues and epidemiology in obsessive–compulsive disorder". in
Obsessive–Compulsive Disorder: Theory, Research, and Treatment, eds. M. M. Antony; S. Rachman; M. A. Richter & R. P. Swinson. New
York: The Guilford Press, 1998, pp. 3-32.
[73] Yaryura-Tobias, José; Fugen A. Neziroglu (1997). Obsessive-compulsive disorder spectrum: pathogenesis, diagnosis, and treatment (http:/ /
books. google. com/ books?id=vzFN_g-d7aoC& pg=PA19& lpg=PA19& dq=ocd+ high+ intelligence& source=web& ots=JOgDKEj9X_&
sig=0UyjOlDNLpUaw879g9PBsNBkHmM& hl=en& sa=X& oi=book_result& resnum=10& ct=result). American Psychiatric Publishing.
pp. 19–20. ISBN 978-0880487078. .
[74] Mineka S, Watson D, Clark LA (1998). "Comorbidity of anxiety and unipolar mood disorders". Annual review of psychology 49: 377–412.
doi:10.1146/annurev.psych.49.1.377. PMID 9496627.
[75] Fenske, J., & Schwenk, T.. (2009). Obsessive-Compulsive Disorder: Diagnosis and Management. American Family Physician, 80(3),
239-45. Platinum Periodicals. (Document ID: 1803225831).
[76] Turner, Jo; Lynne Drummond, Suman Mukhopadhyay, Hamid Ghodse, Sarah White, Anusha Pillay, Naomi Fineberg (2007 June). "A
prospective study of delayed sleep phase syndrome in patients with severe resistant obsessive–compulsive disorder" (http:/ / www.
pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=2219909). World Psychiatry 6 (2): 108–111. PMID 18235868.
PMID 18235868. PMC 2219909.
[77] Peterson, B.S.; D.S. Pine, P. Cohen, J.S. Brook (2001). "Prospective, longitudinal study of tic, obsessive-compulsive, and
attention-deficit/hyperactivity disorders in an epidemiological sample". J Am Acad Child Adolesc Psychiatry 40 (6): 685–695.
doi:10.1097/00004583-200106000-00014. PMID 11392347. PMID 11392347.
[78] Bédarda, Marie-Josée; Christian C. Joyala, Lucie Godbouta, Sophie Chantalb (2009). "Executive Functions and the Obsessive-Compulsive
Disorder: On the Importance of Subclinical Symptoms and Other Concomitant Factors". Archives of Clinical Neuropsychology 24 (6):
585–598. doi:10.1093/arclin/acp052. PMID 19689989 doi:10.1093/arclin/acp052. PMID 19689989.
[79] Couglea, Jesse; Han-Joo Leea, Paul M. Salkovskis (2007). "Are responsibility beliefs inflated in non-checking OCD patients?". Journal of
Anxiety Disorders 21 (1): 153–159. doi:10.1016/j.janxdis.2006.03.012. PMID 16647241 doi:10.1016/j.janxdis.2006.03.012. "Results
indicated that both OC groups showed greater responsibility beliefs relative to anxious and non-anxious
controls.".|url=|format=|accessdate=2010-02-02|quote=Results|pmid=16647241|doi_brokendate=2010-03-17}}
[80] Apterab, Alan; Netta Horeshc, Doron Gothelfab, Gil Zalsmanbd, Zippy Erliche, Noam Sorenibc, Abraham Weizmanbcf (2003). "Depression
and suicidal behavior in adolescent inpatients with obsessive compulsive disorder". Journal of Affective Disorders 75 (2): 181–189.
doi:10.1016/S0165-0327(02)00038-1. PMID 12798258 doi:10.1016/S0165-0327(02)00038-1. "Although suicidal ideation and depressive
symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between
suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other
psychiatrically ill adolescents.".|url=|format=|accessdate=2010-02-02|quote=Although|pmid=12798258|doi_brokendate=2010-03-17}}
[81] Veale, David; Mark Freeston, Georgina Krebs, Isobel Heyman, Paul Salkovskis (2009). "Risk assessment and management in
obsessive–compulsive disorder". Advances in Psychiatric Treatment 15 (5): 332–343. doi:10.1192/apt.bp.107.004705. "A person with OCD is
at no greater risk of causing harm than is any other member of the public (they may even be at a lower risk)".
[82] Samuel Johnson, literary genius and OCD victim. (http:/ / connection. ebscohost. com/ content/ article/ 1025069545.
html;jsessionid=938C34157D8D0790770F0238141B4493. ehctc1)Nutrition Health Review: The Consumer's Medical Journal; Winter91,
Issue 57, p5.
[83] http:/ / westsuffolkpsych. homestead. com/ Johnson. html SAMUEL JOHNSON (1709-1784): A Patron Saint of OCD? by Fred Penzel,
Ph.D. from the Scientific Advisory Board of the International OCD Foundation
[84] http:/ / www. mindpub. com/ art067. htm Obsessive Thinking, Compulsive Behaviors. Vijai P. Sharma, Ph.D. Clinical Psychologist
[85] "Hughes's germ phobia revealed in psychological autopsy" (http:/ / www. apa. org/ monitor/ julaug05/ hughes. html). APA Online: Monitor
on Psychology 36 (7). July/August 2005. .
[86] http:/ / www. dailymail. co. uk/ tvshowbiz/ article-381802/ The-obsessive-disorder-haunts-life. html
114
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[87] http:/ / www. viryours. com/ ms/
[88] Goldberg FR (2007). "Turn box office movies into mental health opportunities: A literature review and resource guide for clinicians and
educators" (http:/ / secure. ce4alliance. com/ articles/ 101188/ Turn_Box_Office_Movies-CE[1]. pdf), p. 8. Beneficial Film Guides, Inc.
Retrieved 17 February, 2010.
http://www.yaletrials.org/clinicalTrials/displayTrial.asp?nctID=NCT00539513&trialListing=Y&row=527
Further reading
• My Worktime Routine, ISBN 1-59-113901-5, by David Vince.
• Abramowitz, Jonathan, S. (2009). Getting over OCD: A 10 step workbook for taking back your life. New York:
Guilford Press. ISBN 0-06-098711-1.
• Beyette, Beverly; Schwartz, Jeffrey H. (1997). Brain lock: free yourself from obsessive–compulsive behavior: a
four-step self-treatment method to change your brain chemistry. New York: ReganBooks. ISBN 0-06-098711-1.
• Salzman, Leon (1985). Treatment of the obsessive personality. Northvale, N.J: J. Aronson. ISBN 0-87668-881-4.
• Neziroglu, Fugen; Yaryura-Tobias, Jose A. (1991). Over and Over Again: Understanding Obsessive Compulsive
Disorder. New York: Jossey Bass. ISBN 0787908762.
• Jonathan Grayson (2003). Freedom From Obsessive–Compulsive Disorder: A Personalized Recovery Program
For Living With Uncertainty. New York: Jeremy P. Tarcher. ISBN 1-58542-246-0.
• Rachman, Stanley; Rachman, S. J. (2003). The treatment of obsessions. Oxford [Oxfordshire]: Oxford University
Press. ISBN 0-19-851537-5.
• Sharon Begley; Schwartz, Jeffrey H. (2003). The Mind and the Brain : Neuroplasticity and the Power of Mental
Force. New York: Regan Books. ISBN 0-06-098847-9.
• Lee, PhD. Baer (2002). The Imp of the Mind: Exploring the Silent Epidemic of Obsessive Bad Thoughts. New
York: Plume Books. ISBN 0-452-28307-8.
• Penzel, Fred (2000). Obsessive–compulsive disorders: a complete guide to getting well and staying well. Oxford
[Oxfordshire]: Oxford University Press. ISBN 0-19-514092-3.
• Seligman, Martin E. P. (1995). "Obsessions". What you can change—and what you can't: the complete guide to
successful self-improvement: learning to accept who you are. New York: Fawcett Columbine.
ISBN 0-449-90971-9.
• IAN OSBORN (1999). Tormenting Thoughts and Secret Rituals : The Hidden Epidemic of
Obsessive–Compulsive Disorder. New York: Dell. ISBN 0-440-50847-9.
• Cooper, David A. (2005). The Art of Meditation. Jaico Publishing House. ISBN 81-7992-164-6.
• Wilson, Rob; David Veale (2005). Overcoming Obsessive–Compulsive Disorder. Constable & Robinson Ltd.
ISBN 1-84119-936-2.
• John B. (2008). The Boy Who Finally Stopped Washing: OCD From Both Sides of the Couch. Cooper Union
Press. ISBN 9780979133961.
• Davis, Lennard J. (2008). Obsession: A History. University of Chicago Press. ISBN 9780226137827.
External links
• American Psychiatric Association OC Spectrum Disorders Conference (http://www.psych.org/MainMenu/
Research/DSMIV/DSMV/DSMRevisionActivities/ConferenceSummaries/
ObsessiveCompulsiveSpectrumDisordersConference.aspx)
• Canadian Mental Health Association (http://www.cmha.ca/bins/content_page.asp?cid=3-94-95)
• International OCD Foundation (http://www.ocfoundation.org/index.aspx)
• The Royal College of Psychiatrists (http://www.rcpsych.ac.uk/mentalhealthinfoforall/problems/
obsessivecompulsivedisorder/obsessivecomplusivedisorder.aspx)
• National Institute Of Mental Health (http://www.nimh.nih.gov/health/topics/
obsessive-compulsive-disorder-ocd/index.shtml)
115
Obsessive–compulsive disorder
• OCD Action (http://www.ocdaction.org.uk)
116
117
Procedures
Deep brain stimulation
Deep brain stimulation (DBS) is a surgical treatment involving the implantation of a medical device called a brain
pacemaker, which sends electrical impulses to specific parts of the brain. DBS in select brain regions has provided
remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders such as chronic
pain, Parkinson’s disease, tremor and dystonia.[1] Despite the long history of DBS,[2] its underlying principles and
mechanisms are still not clear. DBS directly changes brain activity in a controlled manner, its effects are reversible
(unlike those of lesioning techniques) and is one of only a few neurosurgical methods that allows blinded studies.
The Food and Drug Administration (FDA) approved DBS as a treatment for essential tremor in 1997, for Parkinson's
disease in 2002,[3] and dystonia in 2003.[4] DBS is also routinely used to treat chronic pain and has been used to treat
various affective disorders, including major depression. While DBS has proven helpful for some patients, there is
potential for serious complications and side effects.
Components and placement
The deep brain stimulation system consists of three components: the implanted pulse generator (IPG), the lead, and
the extension. The IPG is a battery-powered neurostimulator encased in a titanium housing, which sends electrical
pulses to the brain to interfere with neural activity at the target site. The lead is a coiled wire insulated in
polyurethane with four platinum iridium electrodes and is placed in one of three areas of the brain. The lead is
connected to the IPG by the extension, an insulated wire that runs from the head, down the side of the neck, behind
the ear to the IPG, which is placed subcutaneously below the clavicle or in some cases, the abdomen.[5] The IPG can
be calibrated by a neurologist, nurse or trained technician to optimize symptom suppression and control side
effects.[6]
DBS leads are placed in the brain according to the type of symptoms to be addressed. For non-Parkinsonian essential
tremor the lead is placed in the ventrointermedial nucleus (VIM) of the thalamus. For dystonia and symptoms
associated with Parkinson's disease (rigidity, bradykinesia/akinesia and tremor), the lead may be placed in either the
globus pallidus or subthalamic nucleus.[7]
All three components are surgically implanted inside the body. Under local anesthesia, a hole about 14 mm in
diameter is drilled in the skull and the electrode is inserted, with feedback from the patient for optimal placement.
The installation of the IPG and lead occurs under general anesthesia.[8] The right side of the brain is stimulated to
address symptoms on the left side of the body and vice versa.
Deep brain stimulation
118
Biochemistry
It has been shown in thalamic slices from mice[9] that DBS causes nearby astrocytes to release adenosine
triphosphate (ATP), a precursor to adenosine (through a catabolic process). In turn, adenosine A1 receptor activation
depresses excitatory transmission in the thalamus, thus causing an inhibitory effect that mimicks ablation or
"lesioning".
Applications
Parkinson's disease
Parkinson's disease is a neurodegenerative disease
whose primary symptoms are tremor, rigidity,
bradykinesia and postural instability.[10] DBS does not
cure Parkinson's, but it can help manage some of its
symptoms and subsequently improve the patient’s
quality of life.[11] At present, the procedure is used only
for patients whose symptoms cannot be adequately
controlled with medications, or whose medications have
severe side effects.[5] Its direct effect on the physiology
of brain cells and neurotransmitters is currently debated,
but by sending high frequency electrical impulses into
specific areas of the brain it can mitigate symptoms[12]
and/or directly diminish the side effects induced by
Parkinsonian medications,[13] allowing a decrease in
medications, or making a medication regimen more
tolerable.
There are a few sites in the brain that can be targeted to
achieve differing results, so each patient must be
assessed individually, and a site will be chosen based on
their needs. Traditionally, the two most common sites
are the subthalamic nucleus (STN) and the globus
pallidus interna (GPi), but other sites, such as the caudal
zona incerta and the pallidofugal fibers medial to the
STN, are being evaluated and showing promise.[14]
Insertion of electrode during surgery
Research is being conducted as of 2007 to predict the onset of tremors before they occur by monitoring activity in
the subthalamic nucleus. The goal is to provide stimulating pulses only when they are needed, to stop any tremors
occurring before they start.[15]
DBS is approved in the United States by the Food and Drug Administration for the treatment of Parkinson's.[3] DBS
carries the risks of major surgery, with a complication rate related to the experience of the surgical team.
Deep brain stimulation
Major depression
There is insufficient evidence to support DBS as a therapeutic modality for depression, however, the procedure may
be an effective treatment modality in the future.[16] Researchers reported in 2005 that electrical stimulation of a small
area of the frontal cortex brought about a "striking and sustained remission" in four out of six patients suffering from
major depression. Their symptoms had previously been resistant to medication, psychotherapy and electroconvulsive
therapy.[17]
Using brain imaging, the researchers had noticed that activity in the subgenual cingulate region (SCR or Brodmann
area 25)—the lowest part of a band of tissue that runs along the midline of the brain—seemed to correlate with
symptoms of sadness and depression. They implanted electrodes into six patients while they were locally
anesthetised, but alert. While the current was switched on, four of the patients reported feeling a black cloud lifting,
and became more alert and interested in their environments. The changes reversed when the current was switched
off.[17]
The effects of continuous SCR stimulation have produced sustained remission from depression in the four patients
for six months. When reporting the results, the team did caution that the trial was so small that the findings must be
considered only provisional.[17]
Another hypothetically interesting site for DBS in depression is the nucleus accumbens,[18] as that region appears to
be associated with pleasure and reward mechanisms. A 2007 study reported that experimental use of deep brain
stimulation of the nucleus accumbens showed promising results, with patients suffering from profound depression
reporting relief from their symptoms.[19]
A systematic review of DBS for treatment resistant depression and obsessive–compulsive disorder identified 23
cases—nine for OCD, seven for TRD, and one for both. It found that "about half the patients did show dramatic
improvement" and that adverse events were "generally trivial" given the younger psychiatric patient population than
with movements disorders.[20]
Tourette syndrome
Deep brain stimulation has been used experimentally in treating a few patients with severe Tourette syndrome.
Despite widely publicized early successes, DBS remains a highly experimental procedure for the treatment of
Tourette's, and more study is needed to determine whether long-term benefits outweigh the risk.[21] The procedure is
well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of
stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation
parameters".[22] As of 2006, there were five published reports of DBS in patients with TS; all experienced reduction
in tics and the disappearance of obsessive-compulsive behaviors. "Only patients with severe, debilitating, and
treatment-refractory illness should be considered; while those with severe personality disorders and substance abuse
problems should be excluded."[22] There may be serious short- and long-term risks associated with DBS in persons
with head and neck tics. The procedure is invasive and expensive, and requires long-term expert care. Benefits for
severe Tourette's are not conclusive, considering less robust effects of this surgery seen in the Netherlands. Tourette's
is more common in pediatric populations, tending to remit in adulthood, so this would not generally be a
recommended procedure for use on children. Because diagnosis of Tourette's is made based on a history of
symptoms rather than analysis of neurological activity, it may not always be clear how to apply DBS for a particular
patient. Due to concern over the use of DBS in the treatment of Tourette syndrome, the Tourette Syndrome
Association convened a group of experts to develop recommendations guiding the use and potential clinical trials of
DBS for TS.[23]
119
Deep brain stimulation
Other clinical applications
In August 2007, Nature reported that scientists in the US had stimulated a 38-year-old man who had been in a
minimally conscious state for six years using DBS.[24] The patient initially had increased arousal and sustained
eye-opening, as well as rapid bilateral head-turning to voice. After further stimulation, the previously non-verbal
patient became capable of naming objects and using objects with his hands—for example, bringing a cup to his
mouth. Moreover, he could swallow food and take meals by mouth, meaning he was no longer dependent on a
gastrostomy tube.[25]
This result follows research carried out over 40 years, which has analyzed the effects of deep brain stimulation in the
thalamus (and elsewhere) in patients with post-traumatic coma.[26] [27] [28] While this research has shown some
potential, deep brain stimulation is not yet a reliable cure for patients in post-traumatic coma.
DBS has been used in the treatment of obsessive-compulsive disorder[29] and phantom limb pain.[30] Although the
clinical efficacy is not questioned, the mechanisms by which DBS works are still debated.[31] Long-term clinical
observation has shown that the mechanism is not due to a progressive lesion, given that interruption of stimulation
reverses its effects.[31] Results of DBS in dystonia patients, where positive effects often appear gradually over a
period of weeks to months, indicate a role of functional reorganization in at least some cases.[32] The procedure is
being tested for effectiveness in patients with severe epilepsy.[33]
DBS has been tried for patients with Lesch-Nyhan syndrome in Japan, Switzerland and France.
Potential complications and side effects
While DBS is helpful for some patients, there is also the potential for neuropsychiatric side effects. Reports in the
literature describe the possibility of apathy, hallucinations, compulsive gambling, hypersexuality, cognitive
dysfunction, and depression. However, these may be temporary and related to correct placement and calibration of
the stimulator and so are potentially reversible.[34] A recent trial of 99 Parkinson's patients who had undergone DBS
suggested a decline in executive functions relative to patients who had not undergone DBS, accompanied by
problems with word generation, attention and learning. About 9% of patients had psychiatric events, which ranged in
severity from a relapse in voyeurism to a suicide attempt. Most patients in this trial reported an improvement in their
quality of life following DBS, and there was an improvement in their physical functioning.[35]
Because the brain can shift slightly during surgery, there is the possibility that the electrodes can become displaced
or dislodged. This may cause more profound complications such as personality changes, but electrode misplacement
is relatively easy to identify using CT or MRI. There may also be complications of surgery, such as bleeding within
the brain.
After surgery, swelling of the brain tissue, mild disorientation and sleepiness are normal. After 2–4 weeks, there is a
follow-up to remove sutures, turn on the neurostimulator and program it.
See also
•
•
•
•
•
•
•
Neurosurgery
Stereotactic surgery
Psychosurgery
Neuroprosthetics
Brain implant
Vagus nerve stimulation
Electroconvulsive therapy
120
Deep brain stimulation
References
• Appleby BS, Duggan PS, Regenberg A, Rabins PV (2007). "Psychiatric and neuropsychiatric adverse events
associated with deep brain stimulation: A meta-analysis of ten years' experience". Movement Disorders
22:1722–1728 PMID 17721929
• Bekar L, Libionka W, Tian G, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos
R, Nedergaard M (2008). "Adenosine is crucial for deep brain stimulation–mediated attenuation of tremor".
Nature Medicine, v.14, n.1, pp. 75–80.
• Fins JJ. Deep Brain Stimulation (2004) In, Encyclopedia of Bioethics, 3rd Edition. Post, SG, Editor-in-Chief.
New York: MacMillan Reference. Volume 2, pp. 629–634.
• Gildenberg Philip L and Tasker, Ronald R (1998). Textbook of stereotactic and functional neurosurgery,
McGraw-Hill Publishing.
• Gildenberg Philip L (2005). "Evolution of neuromodulation". Stereotact Funct Neurosurg, 83(2–3), 71–79. PMID
16006778
• Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation".
Nature Reviews Neuroscience. 8:623–635. PMID 17637800
• McIntyre CC, Grill WM (2000). "Selective microstimulation of central nervous system neurons". Annals of
Biomedical Engineering 38:219–233. PMID 10784087
• McIntyre CC, Grill WM, Sherman DL, Thakor NV (2004). "Cellular effects of deep brain stimulation:
model-based analysis of activation and inhibition". Journal of Neurophysiology 91:1457–1469. PMID 14668299
• Ropper Allan H and Brown, Robert H. (2005) Adams and Victor's Principles of Neurology (8th Edition),
McGraw-Hill Medical Publishing. ISBN 007141620X
External links
• Deep brain stimulation for movement disorders [36]
• Deep brain electrodes are real hope for mental illness [37]
References
[1] Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation". Nature Reviews
Neuroscience. 8:623–635. PMID 17637800.
[2] Gildenberg PL (2005). "Evolution of neuromodulation". Stereotact Funct Neurosurg, 83(2–3), 71–79. PMID 16006778.
[3] U.S. Department of Health and Human Services. FDA approves implanted brain stimulator to control tremors. (http:/ / www. fda. gov/ bbs/
topics/ NEWS/ NEW00580. html) Retrieved October 18, 2006.
[4] 'Brain pacemaker' treats dystonia. (http:/ / knbc-tvhealth. ip2m. com/ index. cfm?pt=itemDetail& item_id=97349& site_cat_id=470) KNBC
TV, April 22, 2003. Retrieved October 18, 2006.
[5] National Institute of Neurological Disorders and Stroke. Deep brain stimulation for Parkinson's Disease information page. (http:/ / www.
ninds. nih. gov/ disorders/ deep_brain_stimulation/ deep_brain_stimulation. htm) Retrieved November 23, 2006.
[6] Volkmann J, Herzog J, Kopper F, Deuschl G. "Introduction to the programming of deep brain stimulators". Mov Disord. 2002 17, S181–187.
PMID 11948775.
[7] Deep brain stimulation. (http:/ / www. surgeryencyclopedia. com/ Ce-Fi/ Deep-Brain-Stimulation. html) Surgery Encyclopedia. Retrieved
January 25, 2007.
[8] Deep Brain Stimulation (http:/ / www. neurosurgery. pitt. edu/ imageguided/ movement/ stimulation. html), Department of Neurological
Surgery, University of Pittsburgh. Retrieved May 13, 2008.
[9] Bekar L, Libionka W, Tian G, et al. (2008). "Adenosine is crucial for deep brain stimulation–mediated attenuation of tremor". Nature
Medicine 14 (1): 75–80. doi:10.1038/nm1693.
[10] Ropper (2005), p. 916
[11] Kleiner-Fisman G, Herzog J, Fisman DN, et al. "Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes."
Mov Disord. 2006 Jun;21 Suppl 14:S290–304 PMID 16892449
[12] Moro E, Lang AE. "Criteria for deep-brain stimulation in Parkinson's disease: review and analysis". Expert Review of Neurotherapeutics.
2006 Nov;6(11):1695–705. PMID 17144783
[13] Apetauerova D, Ryan RK, Ro SI, Arle J, et al. "End of day dyskinesia in advanced Parkinson's disease can be eliminated by bilateral
subthalamic nucleus or globus pallidus deep brain stimulation". Movement Disorders. 2006 Aug;21(8):1277–9. PMID 16637040
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[14] Plaha P, Ben-Shlomo Y, Patel NK, Gill SS. "Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in
improving contralateral parkinsonism". Brain (2006). 129, 1732–1747 PMID 16720681
[15] The blade runner generation. (http:/ / www. timesonline. co. uk/ tol/ life_and_style/ health/ article2079637. ece) The Sunday Times, July 22,
2007. Retrieved on March 20, 2008.
[16] Curr Opin Psychiatry. 2009 May;22(3):306–11
[17] Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (March 3, 2005). "Deep brain
stimulation for treatment-resistant depression". Neuron. 45(5):651–60. PMID 15748841.
[18] Schlaepfer TE, Lieb K. "Deep brain stimulation for treatment of refractory depression". Lancet. 2005 Oct 22–28;366(9495):1420–2. PMID
16243078.
[19] Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. "Deep Brain Stimulation
to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression". Neuropsychopharmacology. April 11, 2007. PMID 17429407.
[20] Lakhan SE, Callaway H. "Deep brain stimulation for obsessive-compulsive disorder and treatment-resistant depression: systematic review".
BMC Research Notes. 2010 Mar 4;3(1):60. PMID 20202203.
[21] Tourette Syndrome Association. Statement: Deep Brain Stimulation and Tourette Syndrome. (http:/ / web. archive. org/ web/
20051122154536/ http:/ / tsa-usa. org/ news/ DBS-Statement. htm) Retrieved November 22, 2005.
[22] Malone DA Jr, Pandya MM (2006). "Behavioral neurosurgery". Adv Neurol. 99:241–7. PMID 16536372
[23] Mink JW, Walkup J, Frey KA, et al. (November 2006). "Patient selection and assessment recommendations for deep brain stimulation in
Tourette syndrome". Mov Disord. 21(11):1831–8. PMID 16991144
[24] Implant boosts activity in injured brain. (http:/ / www. nature. com/ news/ 2007/ 070730/ full/ 448522a. html) Nature news (August 1,
2007). Retrieved on August 1, 2007
[25] Schiff N. D. et al. "Behavioural improvements with thalamic stimulation after severe traumatic brain injury". Nature. 448, 600–3. (2007)
PMID 17671503
[26] Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Maejima S, Moriya T. "Deep-brain stimulation in a persistent vegetative state:
follow-up results and criteria for selection of candidates". Brain Inj. 1990 Oct–Dec;4(4):315–27. PMID 2252964
[27] Sturm V, Kühner A, Schmitt HP, Assmus H, Stock G. "Chronic electrical stimulation of the thalamic unspecific activating system in a
patient with coma due to midbrain and upper brain stem infarction". Acta Neurochir (Wien). 1979;47(3–4):235–44. PMID 314229
[28] Hassler R, Dalle Ore G, Dieckmann G, Bricolo A, Dolce G. "Behavioural and EEG arousal induced by stimulation of unspecific projection
systems in a patient with post-traumatic apallic syndrome". Electroencephalogr. Clin. Neurophysiol. 27, 306–310 (1969). PMID 4185661
[29] Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B (1999). "Electrical stimulation in anterior limbs of internal capsules in
patients with obsessive-compulsive disorder". Lancet. 1999 Oct 30;354(9189):1526 PMID 10551504
[30] Kringelbach, Morten L. et al. (2007). "Deep brain stimulation for chronic pain investigated with magnetoencephalography". Neuroreport,
18(3), pp. 223–228.
[31] Benabid AL, Wallace B, Mitrofanis J, Xia R, Piallat B, Chabardes S, Berger F. (2005). "A putative generalized model of the effects and
mechanism of action of high frequency electrical stimulation of the central nervous system". Acta Neurol Belg. 2005 Sep;105(3):149–57.
PMID 16255153
[32] Krauss JK (2002). "Deep brain stimulation for dystonia in adults. Overview and developments". Stereotactic and Functional Neurosurgery
78 (3–4): 168–182. doi:10.1159/000068963. PMID 12652041.
[33] Velasco F, Velasco M, Velasco AL, Jimenez F, Marquez I, Rise M (1995). "Electrical stimulation of the centromedian thalamic nucleus in
control of seizures: long-term studies". Epilepsia 36: 63–71. PMID 8001511
[34] Burn D, Troster A (2004). "Neuropsychiatric Complications of Medical and Surgical Therapies for Parkinson's Disease". Journal of
Geriatric Psychiatry and Neurology 17 (3): 172–180. doi:10.1177/0891988704267466. PMID 15312281.
[35] Smeding H, Speelman J, Koning-Haanstra M, et al. (2006). "Neuropsychological effects of bilateral STN stimulation in Parkinson disease:
A controlled study". Neurology 66 (12): 1830–1836. doi:10.1212/01.wnl.0000234881.77830.66. PMID 16801645.
[36] http:/ / www. med. ege. edu. tr/ ~norolbil/ 2001/ NBD15501. html
[37] http:/ / www. newscientist. com/ article/ mg20627552. 500-deep-brain-electrodes-are-real-hope-for-mental-illness. html
122
Brain implant
Brain implant
Brain implants, often referred to as neural implants, are technological devices that connect directly to a biological
subject's brain - usually placed on the surface of the brain, or attached to the brain's cortex. A common purpose of
modern brain implants and the focus of much current research is establishing a biomedical prosthesis circumventing
areas in the brain, which became dysfunctional after a stroke or other head injuries. This includes sensory
substitution, e.g. in vision. Other brain implants are used in animal experiments simply to record brain activity for
scientific reasons. Some brain implants involve creating interfaces between neural systems and computer chips,
which are part of a wider research field called brain-computer interfaces. (Brain-computer interface research also
includes technology such as EEG arrays that allow interface between mind and machine but do not require direct
implantation of a device.)
Neural-implants such as deep brain stimulation and Vagus nerve stimulation are increasingly becoming routine for
patients with Parkinson's disease and clinical depression respectively, proving themselves as a boon for people with
diseases which were previously regarded as incurable.[1]
Purpose
Brain implants electrically stimulate or block[2] or record (or both record and stimulate simultaneously[3] ) from
single neurons or groups of neurons (biological neural networks) in the brain. The blocking technique is called
intra-abdominal vagal blocking[2] . This can only be done where the functional associations of these neurons are
approximately known. Because of the complexity of neural processing and the lack of access to action potential
related signals using neuroimaging techniques, the application of brain implants has been seriously limited until
recent advances in neurophysiology and computer processing power.
Research
Research in sensory substitution has made slow progress in recent years. Especially in vision, due to the knowledge
of the working of the visual system, eye implants (often involving some brain implants or monitoring) have been
applied with demonstrated success. For hearing, cochlear implants are used to stimulate the auditory nerve directly.
The vestibulocochlear nerve is part of the peripheral nervous system, but the interface is similar to that of true brain
implants.
Multiple projects have demonstrated success at recording from the brains of animals for long periods of time. As
early as 1976, researchers at the NIH led by Ed Schmidt made action potential recordings of signals from Rhesus
monkey motor cortexes using immovable "hatpin" electrodes,[4] including recording from single neurons for over 30
days, and consistent recordings for greater than three years from the best electrodes.
The "hatpin" electrodes were made of pure iridium and insulated with Parylene-c, materials that are currently used in
the Cyberkinetics implementation of the Utah array.[5] These same electrodes, or derivations thereof using the same
biocompatible electrode materials, are currently used in visual prosthetics laboratories,[6] laboratories studying the
neural basis of learning,[7] and motor prosthetics approaches other than the Cyberkinetics probes.[8]
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Brain implant
A competing series of electrodes and projects is sold by
Plexon including Plextrode Series of Electrodes [9].
These are variously the "Michigan Probes",[10] the
microwire arrays first used at MIT,[11] and the FMAs
from MicroProbe that emerged from the visual
prosthetic project collaboration between Phil Troyk,
David Bradley, and Martin Bak.[12]
Other laboratory groups produce their own implants to
provide unique capabilities not available from the
commercial products.[13] [14] [15] [16]
Schematic of the "Utah" Electrode Array
Breakthroughs include studies of the process of
functional brain re-wiring throughout the learning of a
sensory discrimination,[17] control of physical devices by rat brains,[18] monkeys over robotic arms,[19] remote
control of mechanical devices by monkeys and humans,[20] remote control over the movements of roaches,[21]
electronic-based neuron transistors for leeches,[22] the first reported use of the Utah Array in a human for
bidirectional signalling.[23] Currently a number of groups are conducting preliminary motor prosthetic implants in
humans. These studies are presently limited to several months by the longevity of the implants.
Rehabilitation
Brain pacemakers have been in use since 1997 to ease the symptoms of such diseases as epilepsy, Parkinson's
Disease, dystonia and recently depression.
Current brain implants are made from a variety of materials such as tungsten, silicon, platinum-iridium, or even
stainless steel. Future brain implants may make use of more exotic materials such as nanoscale carbon fibers
(nanotubes), and polycarbonate urethane.
(see also nanotechnology, cognotechnology, and neurotechnology)
Historical research on brain implants
See also: History of brain imaging
In 1870, Eduard Hitzig and Gustav Fritsch demonstrated that electrical stimulation of certain areas of the brains of
dogs could produce movements. Robert Bartholow showed the same to be true for humans in 1874. By the start of
the 20th century Fedor Krause began to systematically map human brain areas, using patients that had undergone
brain surgery.
Prominent research was conducted in the 1950s. Robert G. Heath experimented with aggressive mental patients,
aiming to influence his subjects' moods through electrical stimulation.
Yale University physiologist Jose Delgado demonstrated limited control of animal and human subjects' behaviours
using electronic stimulation. He invented the stimoceiver or transdermal stimulator a device implanted in the brain
to transmit electrical impulses that modify basic behaviours such as aggression or sensations of pleasure.
Delgado was later to write a popular book on mind control, called "Physical Control of the Mind", where he stated:
"the feasibility of remote control of activities in several species of animals has been demonstrated [...] The ultimate
objective of this research is to provide an understanding of the mechanisms involved in the directional control of
animals and to provide practical systems suitable for human application."
In the 1950s, the CIA also funded research into mind control techniques, through programs such as MKULTRA.
Perhaps because he received funding for some research through the US Office of Naval Research, it has been
suggested (but not proven) that Delgado also received backing through the CIA. He denied this claim in a 2005
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Brain implant
article in Scientific American describing it only as a speculation by conspiracy-theorists. He stated that his research
was only progressively scientifically-motivated to understand how the brain works.
Ethical considerations
Whilst deep brain stimulation is increasingly becoming routine for patients with Parkinson's disease, there may be
some behavioural side effects. Reports in the literature describe the possibility of apathy, hallucinations, compulsive
gambling, hypersexuality, cognitive dysfunction, and depression. However, these may be temporary and related to
correct placement and calibration of the stimulator and so are potentially reversible.[24]
Some transhumanists, such as Raymond Kurzweil and Kevin Warwick, see brain implants as part of a next step for
humans in progress and evolution, whereas others, especially bioconservatives, view them as unnatural, with
humankind losing essential human qualities. It raises controversy similar to other forms of human enhancement. For
instance, it is argued that implants would technically change people into cybernetic organisms (cyborgs). Some
people fear implants may be used for mind control, e.g. to change human perception of reality.
Brain implants in fiction and philosophy
Brain implants are now part of modern popular culture but there were early philosophical references of relevance as
far back as René Descartes.
In his 1638 Discourse on the Method, a study on proving self existence, Descartes wrote that a person would not
know if an evil demon had trapped his mind in a black box and was controlling all inputs and outputs. Philosopher
Hilary Putnam provided a modern parallel of Descartes argument in his 1989 discussion of a brain in a vat, where he
argues that brains which were directly fed with an input from a computer would not know the deception from reality.
Popular science fiction discussing brain implants and mind control became widespread in the 20th century, often
with a dystopian outlook. Literature in the 1970s delved into the topic, including The Terminal Man by Michael
Crichton, where a man suffering from brain damage receives an experimental surgical brain implant designed to
prevent seizures, which he abuses by triggering for pleasure.
Fear that the technology will be misused by the government and military is an early theme. In the 1981 BBC serial
The Nightmare Man the pilot of a high-tech mini submarine is linked to his craft via a brain implant but becomes a
savage killer after ripping out the implant.
Perhaps the most influential novel exploring the world of brain implants was William Gibson's 1984 Neuromancer.
This novel is the first in a genre that has come to be known as "cyberpunk" and follows a computer hacker through a
world where mercenaries are augmented with brain implants to enhance strength, vision, memory, etc. Gibson coins
the term "matrix" and introduces the concept of "jacking in" with head electrodes or direct implants. He also explores
possible entertainment applications of brain implants such as the "simstim" (simulated stimulation) which is a device
used to record and playback experiences.
Gibson's work led to an explosion in popular culture references to brain implants. Its influences are felt, for example,
in the 1989 roleplaying game Shadowrun, which borrowed his term "datajack" to describe a brain-computer
interface. The implants in Gibson's novels and short stories formed the template for the 1995 film Johnny Mnemonic
and later, The Matrix Trilogy.
The Gap Cycle (The Gap into): In Stephen R. Donaldson's series of novels, the use (and misuse) of "zone implant"
technology is key to several plotlines.
Pulp fiction with implants or brain implants include the novel series Typers, film Spider-Man 2, the TV series Earth:
Final Conflict, and numerous computer/video games.
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Brain implant
Ghost in the Shell anime and manga franchise:
Cyberbrain neural augmentation technology is the
focus. Implants of powerful computers provide vastly
increased memory capacity, total recall, as well as the
ability to view his or her own memories on an external
viewing device. Users can also initiate a telepathic
conversation with other cyberbrain users, the
downsides being cyberbrain hacking, malicious
memory alteration, and the deliberate distortion of
subjective reality and experience.
126
Cyberbrain implants in the Ghost in the Shell TV series
In the video games Planetside and Chrome, players can
use implants to improve their aim, run faster, and see better, along with other enhancements.
Film
Brainstorm (1983): The military tries to take control over a new technology that can record and transfer thoughts,
feelings, and sensations.
The Mancurian Candidate (2004): For a means of mind control, the presidential hopeful Raymond Shaw
unknowingly has a chip implanted in his head by Manchurian Global, a fictional geopolitical organization aimed at
making parts of the government sleeper cells, or puppets for their monetary advancement.
South Park: Bigger, Longer & Uncut: The "V-chip" implant is a satirical implant for foul-mouthed children, and
serves a related purpose to the true V-chip (it delivers an electric shock to the child whenever they swear).
The extreme box office success of the Matrix films, combined with earlier science fiction references, have made
brain implants ubiquitous in popular literature.
Television
Blake's 7: A character has a brain implant which is supposed to prevent future aggression after being convicted of
killing an officer from the oppressive Federation.
Dark Angel: The notorious Red Series use neuro-implants pushed into their brain stem at the base of their skull to
amp them up and hyper-adrenalize them and make them almost unstoppable. Unfortunately the effects of the implant
burn out their system between six months to a year and kill them.
The X-Files (episode?): FBI Agent Dana Scully discovers an implant set under the skin at the back of her neck which
can read her every thought and change memory through electrical signals that alter the brain chemistry.
Star Trek franchise: Members of the Borg collective are equipped with brain implants which connect them to the
Borg "hive mind" and allow them to be manipulated by the Borg Queen.
Brain implant
External links
•
•
•
•
•
•
•
Information site on electronic implants (also called intelligent implants or smart implants) [25]
Exclusive: A robot with a biological brain | Emerging Technology Trends | ZDNet.com [26]
Theodore Berger's Website [27]
Scientific American article on Jose Delgado [28]
Discover Magazine article on brain implants [29]
Neurotech Reports article on neural-silicon hybrid chips [30]
Brain Machine implant website [31]
Further reading
• Theodore W. Berger's book Toward Replacement Parts for the Brain [32] ISBN 0-262-02577-9.
• Jose Delgado's book Physical Control of the Mind [33]
References
[1] http:/ / en. wikipedia. org/ wiki/ Parkinson%27s_disease#Surgery_and_deep_brain_stimulation
[2] http:/ / www. medscape. com/ viewarticle/ 577292
[3]
[4]
[5]
[6]
http:/ / machinedesign. com/ ContentItem/ 67966/ Wirelessisgettingunderourskin. aspx
xp Neurol. 1976 Sep;52(3):496-506
Cyberkinetics array (http:/ / www. cyberkineticsinc. com/ pdf/ cyber. pdf)
Blackwell Synergy - Artificial Organs, Volume 27 Issue 11 Page 1005-1015, November 2003 (Article Abstract) (http:/ / www.
blackwell-synergy. com/ links/ doi/ 10. 1046/ j. 1525-1594. 2003. 07308. x/ abs/ )
[7] Neuron - Blake et al. (http:/ / www. neuron. org/ content/ article/ abstract?uid=PIIS0896627306006313)
[8] Caltech Press Release, 7/8/2004, Dr. Richard Andersen (http:/ / pr. caltech. edu/ media/ Press_Releases/ PR12553. html)
[9] http:/ / www. plexoninc. com/ products/ electrodes/ plextrode_top. html
[10] (http:/ / www. neuronexustech. com/ Products/ AcuteProbe. aspx) Neuronexus "Michigan" probes
[11] (http:/ / www. ncbi. nlm. nih. gov/ pubmed/ 4670862) Sweet Microelectrode Array
[12] (http:/ / www. ncbi. nlm. nih. gov/ pubmed/ 17281985) Visual Prosthetic project
[13] (http:/ / www. riken. jp/ engn/ r-world/ research/ lab/ nokagaku/ cognitive/ integrative/ index. html) Tanifuji lab at RIKEN
[14] (http:/ / www. mcg. edu/ centers/ SCNC/ blakelab/ index. htm) Blake lab at MCG
[15] (http:/ / www. nei. nih. gov/ Intramural/ lsr/ wurtz/ wurtz. asp) Wurtz lab at NEI
[16] (http:/ / faculty. bri. ucla. edu/ institution/ personnel?personnel_id=9023) Itzhak Fried Neurosurgical lab at UCLA
[17] "Making the connection between a sound and a reward changes brain and behavior" (http:/ / www. physorg. com/ news80492303. html).
Physorg.com. 2006-10-19. . Retrieved 2008-04-25.
[18] Chapin, John K.. "Robot arm controlled using command signals recorded directly from brain neurons" (http:/ / www. downstate. edu/
pharmacology/ faculty/ chapin. html). SUNY Downstate Medical Center. . Retrieved 2008-04-25.
[19] Graham-Rowe, Duncan (2003-10-13). "Monkey's brain signals control 'third arm'" (http:/ / www. newscientist. com/ article. ns?id=dn4262).
New Scientist. . Retrieved 2008-04-25.
[20] Mishra, Raja (2004-10-09). "Implant could free power of thought for paralyzed" (http:/ / www. wireheading. com/ misc/ implant. html).
Boston Globe. . Retrieved 2008-04-25.
[21] Talmadoe, Eric (2001-07). "Japan's latest innovation: a remote-control roach" (http:/ / www. wireheading. com/ roboroach/ ). Associated
Press. . Retrieved 2008-04-25.
[22] Gross, Michael (2004-09). "Plugging brains into computers" (http:/ / www. rsc. org/ chemistryworld/ Issues/ 2004/ September/ computers.
asp). Chemistry World (Royal Society of Chemistry). . Retrieved 2008-04-25.
[23] Warwick,K, Gasson,M, Hutt,B, Goodhew,I, Kyberd,P, Andrews,B, Teddy,P and Shad,A:“The Application of Implant Technology for
Cybernetic Systems”, Archives of Neurology, 60(10), pp1369–1373, 2003
[24] Burn D, Troster A (2004). "Neuropsychiatric Complications of Medical and Surgical Therapies for Parkinson's Disease". Journal of
Geriatric Psychiatry and Neurology 17 (3): 172–180. doi:10.1177/0891988704267466. PMID 15312281.
[25] http:/ / www. electronic-implants. com/
[26] http:/ / blogs. zdnet. com/ emergingtech/ ?p=1009
[27] http:/ / www. neural-prosthesis. com/
[28] http:/ / www. mesolimbic. com/ delgado/ brainchips. pdf
[29] http:/ / viterbi. usc. edu/ tools/ download/ ?asset=/ assets/ 002/ 16239. pdf& name=berger_discovery_piece. pdf
[30] http:/ / www. neurotechreports. com/ pages/ hybrids. html
[31] http:/ / www. braingate. com
127
Brain implant
128
[32] http:/ / www. amazon. com/ dp/ 0262025779/
[33] http:/ / www. angelfire. com/ or/ mctrl/ delgado. htm
Krukenberg procedure
The Krukenberg procedure also known as the Krukenberg
operation is a surgical technique that converts a forearm stump into a
pincer. It was first described in 1917 by the German army surgeon
Hermann Krukenberg.[1] [2]
The Pronator teres muscle usually flexes the
elbow and pronates the forearm
Krukenberg procedure
129
Procedure
The procedure involves separating the ulna and radius for below-elbow amputations, and
in cases of congenital absence of the hand, to provide a pincerlike grasp that is motored
by the pronator teres muscle. The prerequisites for the operation are a stump over 10 cm
long from the tip of the olecranon, no elbow contracture, and good psychological
preparation and acceptance [3] [4] [5]
The success of the Krukenberg procedure depends directly on the strength of the
pronator teres, the sensibility of the skin surrounding both ulna and radius, elbow
mobility, and mobility of the ulna and radius at the proximal radioulnar joint. Individual
patient expectations and motivations, although more difficult to assess, probably play a
major role in outcomes as well.
Advantages
The procedure is mostly performed on patients in developing countries who lack the
means to obtain expensive prostheses. In the Western world, the Krukenberg procedure
is usually reserved for blind patients with bilateral amputations, because it can provide
the patient with tactile sensation.[6] [7]
The procedure preserves proprioception and stereognosis in the functional stump and so
allows for effective maneuvering. Once this procedure is performed, it does not preclude
the use of a functional prosthesis giving the patient is afforded the option to use either
functional strategy.
The Krukenburg procedure
separates the bony
remnants of the forearm
into a makeshift pincer.
Objections are usually cosmetic, and indeed for this reason and for cultural reasons, in
South America it is usually not done.[8] While in developed countries the operation is
rarely done, patients can prefer it to sophisticated prosethetics. In one case of a Dutch woman reported in 2002.
Initially after traumatic bilateral forearm amputation she was provided with mechanical prostheses.
Eventually she stopped using them because she chose to use her bare stumps as pincers. She explained
that being able to feel helped her a lot in her tasks... an excellent functional result was obtained, from
both the surgical and the rehabilitation point of view. The patient lives with her family, takes care of the
household, and does art and crafts, which she is currently selling, and is very happy with the procedure.
A year and a half has gone by and she is still gaining dexterity and strength.[8]
The patient "After this first procedure the patient also asked for the Krukenberg procedure for her left arm."[8]
Krukenberg procedure
Noted patients
The German physicist Burkhard Heim had two Krukenberg hands as a result of a laboratory accident.
External links
• Wrist and Forearm Amputations [9]. emedicine
• Digital Amputations [10]. emedicine
• Picture showing the completed procedure [11]
References
[1] Krukenberg H. (1917). Uber Plastische Umwertung von Amputationstumpfen. Stuttgart: Ferdinand Enke.
[2] Krukenberg H. (1931). Erfahrungen mit der Krukenberg-hand. Arch Klin Chir 165:191 – 201.
[3] Garst, R.J. (1991). The Krukenberg Hand (http:/ / www. jbjs. org. uk/ cgi/ reprint/ 73-B/ 3/ 385) The Journal of Bone and Joint Surgery
385(3) PMID 1670433
[4] Singh BG, Jain SK, Ravindranath G, Pithawa AK. (2005). Krukenberg Operation: Revisited (http:/ / www. ijpmr. com/ ijpmr0501/ 20050105.
pdf). IJPMR 16 (1) : 20-23
[5] Tubiana R, Stack HG, Hakstian RW. (1966). Restoration of prehension after severe mutilations of the hand (http:/ / www. jbjs. org. uk/ cgi/
reprint/ 48-B/ 3/ 455. pdf). J Bone Joint Surg Br. 48(3):455-73. PMID 5330433
[6] Sinaki M, Dobyns JH, Kinnunen JM. (1982).Krukenberg's kineplasty and rehabilitation in a blind, bilateral full-hand amputee. Clin Orthop
Relat Res. Sep;(169):163-6. PMID 7105574
[7] Swanson AB. (1964). THE Krukenberg procedure in the juvenile amputee (http:/ / www. ejbjs. org/ cgi/ reprint/ 46/ 7/ 1540. pdf). J Bone
Joint Surg Am. 46:1540-8. PMID 14213413
[8] Freire J, Schiappacasse C, Heredia A, Martina JD, Geertzen JH. (2005). Functional results after a Krukenberg amputation (http:/ / www. rug.
nl/ gradschoolshare/ pdf_downloads/ Freire 2005 Prosthet Orthot Int. pdf). Prosthet Orthot Int. 29(1):87-92. PMID 16180381
[9] http:/ / www. emedicine. com/ orthoped/ topic620. htm
[10] http:/ / emedicine. medscape. com/ article/ 1238395-overview
[11] http:/ / public. fotki. com/ sierraleone/ sl_series/ atrocities/ chopped_03. html
130
Neuroprosthetics
Neuroprosthetics
Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical
engineering concerned with developing neural prostheses. Neural prostheses are a series of devices that can
substitute a motor, sensory or cognitive modality that might have been damaged as a result of an injury or a disease.
An example of such devices is Cochlear implants. This device substitutes the functions performed by the ear drum,
Stapes, frequency analysis in the cochlea and stimulates the auditory nerves directly. A microphone on an external
unit gathers the sound and processes it, the processed signal is then transferred to an implanted unit that stimulates
the auditory nerves through a microelectrode array.
The development of such devices has a profound impact on the quality of human life, and research in this field
intends to resolve disabilities.
There is another side to the application of neural prostheses. These implantable devices can also be used in animal
experiments as a tool for neuroscientists in order to develop a better understanding of how the brain works. Wireless
neuro recording from the brain of awake, freely behaving animals can open many important doors into understanding
how the brain handles different functions. Accurately probing and recording the electrical signals in the brain would
help better understand the relationship among a local population of neurons that are responsible for a specific
function. In order to substitute sensory, motor or cognitive modalities, we need to first understand which part of the
brain is responsible for those modalities and how those functions are performed. Neuro prosthetics and neuro science
have a very intertwined relationship. Neuro prostheses contribute to better understanding of the neural system and
this better understanding helps develop better, more application-specific neural prostheses.
In order to achieve these devices there are many challenges. Any implanted device has to be very small in order to be
to minimally invasive, especially in the brain, eye, cochlea. Also this implant would have to communicate with the
outside world wirelessly. Having wires sticking out of the head, eye, etc is not an option. Besides the discomfort and
restrictions it would impose on the subject this could lead to infection in the tissue. This bidirectional wireless
communication requires a high bandwidth for real-time data transmission; this is a great challenge considering that
this data link has to operate through the skin. The minimal size of the implant means no battery can be embedded in
the implant, the implant works on wireless power transmission through the skin which is equally challenging as the
data transmission. The tissue surrounding the implant is usually very sensitive to temperature rise so the implant
must have very low power consumption in order to assure it won't harm the tissue. Another very important issue is
the bio compatibility of the material that the implants are coated with. The more biocompatible these materials are
the less tissue reaction they will cause thus resulting less implant risk and longer implant period.
Gradually as these devices become safer and the our understanding of how the brain works enhances the use of these
devices will become more and more common and help people with severe disabilities live a normal life. The
neuroprosthetic seeing the most widespread use is the cochlear implant, with approximately 100,000 in use
worldwide as of 2006.[1]
Today, the use of cochlear implants and pacemakers has become an undeniable fact of life. The future holds an
exciting prospect for the every day use of a variety of neural prostheses.
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Neuroprosthetics
History
The first cochlear implant dates back to 1957. Other landmarks include the first motor prosthesis for foot drop in
hemiplegia in 1961, the first auditory brainstem implant in 1977 and a peripheral nerve bridge implanted into spinal
cord of adult rat in 1981.[2] Paraplegics were helped in standing with a lumbar anterior root implant (1988) and in
walking with Functional Electrical Stimulation (FES).
Regarding the development of electrodes implanted in the brain, an early difficulty was reliably locating the
electrodes, originally done by inserting the electrodes with needles and breaking off the needles at the desired depth.
Recent systems utilize more advanced probes, such as those used in deep brain stimulation to alleviate the symptoms
of Parkinson's Disease. The problem with either approach is that the brain floats free in the skull while the probe
does not, and relatively minor impacts, such as a low speed car accident, are potentially damaging. Some
researchers, such as Kensall Wise at the University of Michigan, have proposed tethering 'electrodes to be mounted
on the exterior surface of the brain' to the inner surface of the skull. However, even if successful, tethering would not
resolve the problem in devices meant to be inserted deep into the brain, such as in the case of deep brain stimulation
(DBS).
Sensory prosthetics
Visual prosthetics
A visual prosthesis can create a sense of image by electrically stimulating neuro cells in the visual system. A camera
would wirelessly transmit to an implant, the implant would map the image across an array of electrodes. The array of
electrodes has to effectively stimulate 600-1000 locations, stimulating these optic neurons in the retina thus will
create an image. The stimulation can also be done anywhere along the optic signal's path way. The optical nerve can
be stimulated in order to create an image, or the visual cortex can be stimulated, although clinical tests have proven
most successful for retinal implants.
A visual prosthesis system consists of an external (or implantable) imaging system which acquires and processes the
video. Power and data will be transmitted to the implant wirelessly by the external unit. The implant uses the
received power/data to convert the digital data to an analog output which will be delivered to the nerve via micro
electrodes.
Photoreceptors are the specialized neurons that convert photons into electrical signals. They are part of the retina, a
multilayer neural structure about 200 um thick that lines the back of the eye. The processed signal is sent to the brain
through the optical nerve. If any part of this path way is damaged blindness can occur.
Blindness can result from damage to the optical pathway (cornea, aqueous humor, crystalline lens, and vitreous).
This can happen as a result of accident or disease. The two most common retinal degenerative diseases that result in
blindness secondary to photoreceptor loss is age related macular degeneration (AMD) and retinitis pigmentosa (RP).
The first clinical trial of a permanently implanted retinal prosthesis was a device with a passive microphotodiod
array with 3500 elements.[3] This trial was implemented at Optobionics, Inc., in 2000. In 2002, Second Sight
Medical Products, Inc. (Sylmar, CA) began a trial with a prototype epiretinal implant with 16 electrodes. The
subjects were six individuals with bare light perception secondary to RP. The subjects demonstrated their ability to
distinguish between three common objects (plate, cup, and knife) at levels statistically above chance. An active sub
retinal device developed by Retina Implant GMbH (Reutlingen, Germany) began clinical trials in 2006. An IC with
1500 microphotodiods was implanted under the retina. The microphotodiods serve to modulate current pulses based
on the amount of light incident on the photo diode.[4]
The seminal experimental work towards the development of visual prostheses was done by cortical stimulation using
a grid of large surface electrodes. In 1968 Giles Brindley implanted an 80 electrode device on the visual cortical
surface of a 52-year-old blind woman. As a result of the stimulation the patient was able to see phosphenes in 40
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Neuroprosthetics
different positions of the visual field.[5] This experiment showed that an implanted electrical stimulator device could
restore some degree of vision. Recent efforts in visual cortex prosthesis have evaluated efficacy of visual cortex
stimulation in a non-human primate. In this experiment after a training and mapping process the monkey is able to
perform the same visual saccade task with both light and electrical stimulation.
The requirements for a high resolution retinal prosthesis should follow from the needs and desires of blind
individuals who will benefit from the device. Interactions with theses patients indicate that mobility without a cane,
face recognition and reading are the main necessary enabling capabilities.[6]
The results and implications of fully-functional visual prostheses are exciting. However, the challenges are grave. In
order for a good quality image to be mapped in the retina a high number of micro-scale electrode arrays are needed.
Also, the image quality is dependent on how much information can be sent over the wireless link. Also this high
amount of information must be received and processed by the implant without much power dissipation which can
damage the tissue. The size of the implant is also of great concern. Any implant would be preferred to be minimally
invasive.[6]
With this new technology, several scientists, including Karin Moxon at Drexel, John Chapin at SUNY, and Miguel
Nicolelis at Duke University, started research on the design of a sophisticated visual prosthesis. Other scientists have
disagreed with the focus of their research, arguing that the basic research and design of the densely populated
microscopic wire was not sophisticated enough to proceed.
Auditory prosthetics
Cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs) are the three
main categories for auditory prostheses. CI electrode arrays are implanted in the cochlea, ABI electrode arrays
stimulate the cochlear nucleus complex in the lower brain stem, and AMIs stimulates auditory neurons in the inferior
colliculus. Cochlear implants have been very successful among these three categories. Today Advanced Bionics and
Medtronic are the major commercial providers of cochlea implants.
In contrast to traditional hearing aids that amplify sound and send it through the external ear, cochlear implants
acquire and process the sound and convert it into electrical energy for subsequent delivery to the auditory nerve. The
microphone of the CI system receives sound from the external environment and sends it to processor. The processor
digitizes the sound and filters it into separate frequency bands that are sent to the appropriate tonotonic region in the
cochlea that approximately corresponds to those frequencies.
In 1957, French researchers A. Djourno and C. Eyries, with the help of D. Kayser, provided the first detailed
description of directly stimulation the auditory nerve in a human subject.[7] The individuals described hearing
chirping sounds during simulation. In 1972, the first portable cochlear implant system in an adult was implanted at
the House Ear Clinic. The U.S. Food and Drug Administration (FDA) formally approved the marketing of the
House-3M cochlear implant in November 1984.[8]
Improved performance in cochlea implants not only depends on understanding the physical and biophysical
limitations of implant stimulation but also on an understanding of the brain's pattern processing requirements.
Modern signal processing represents the most important speech information while also providing the brain the
pattern recognition information that it needs. Pattern recognition in the brain is more effective than algorithmic
preprocessing at identifying important features in speech. A combination of engineering, signal processing,
biophysics, and cognitive neuroscience was necessary to produce the right balance of technology to maximize the
performance of auditory prosthesis.[9]
Since the early 2000s FDA has been involved in a clinical trial of device termed the "Hybrid" by Cochlear
Corporation. This trial is aimed at examining the usefulness of cochlea implantation in patients with residual
low-frequency hearing. The "Hybrid" utilizes a shorter electrode than the standard cochlea implant, since the
electrode is shorter it stimulates the basil region of the cochlea and hence the high-frequency tonotopic region. In
theory these devices would benefit patients with significant low-frequency residual hearing who have lost perception
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in the speech frequency range and hence have decreased discrimination scores.[10]
Prosthetics for pain relief
The SCS (Spinal Cord Stimulator) device has two main components: an electrode and a generator. The technical
goal of SCS for neuropathic pain is to mask the area of a patient's pain with a stimulation induced tingling, known as
"paresthesia", because this overlap is necessary (but not sufficient) to achieve pain relief.[11] Paresthesia coverage
depends upon which afferent nerves are stimulated. The most easily recruited by a dorsal midline electrode, close to
the pial surface of spinal cord, are the large dorsal column afferents, which produce broad paresthesia covering
segments caudally.
In ancient times the electrogenic fish was used as a shocker to subside pain. Healers had developed specific and
detailed techniques to exploit the generative qualities of the fish to treat various types of pain, including headache.
Because of the awkwardness of using a living shock generator, a fair level skill was required to deliver the therapy to
the target for the proper amount of time. (Including keeping the fish alive as long as possible) Electro analgesia was
the first deliberate application of electricity. By the nineteenth century, most western physicians were offering their
patients electrotherapy delivered by portable generator.[12] In the mid-1960s, however, three things converged to
insure the future of electro stimulation.
1. Pacemaker technology, which had it start in 1950, became available.
2. Melzack and Wall published their gate control theory of pain, which proposed that the transmission of pain could
be blocked by stimulation of large afferent fibers.[13]
3. Pioneering physicians became interested in stimulating the nervous system to relieve patients from pain.
The design options for electrodes include their size, shape, arrangement, number, and assignment of contacts and
how the electrode is implanted. The design option for the pulse generator include the power source, target anatomic
placement location, current or voltage source, pulse rate, pulse width, and number of independent channels.
Programming options are very numerous (a four-contact electrode offers 50 functional bipolar combinations). The
current devices use computerized equipment to find the best options for use. This reprogramming option
compensates for postural changes, electrode migration, changes in pain location, and suboptimal electrode
placement.[14]
Today, Boston Scientific, Medtronic are the main providers of commercial SCS devices.
Motor prosthetics
Devices which support the function of autonomous nervous system include the implant for bladder control. In the
somatic nervous system attempts to aid conscious control of movement include Functional electrical stimulation and
the lumbar anterior root stimulator.
Bladder control implants
Where a spinal cord lesion leads to paraplegia, patients have difficulty emptying their bladders and this can cause
infection. From 1969 onwards Brindley developed the sacral anterior root stimulator, with successful human trials
from the early 1980s onwards.[15] This device is implanted over the sacral anterior root ganglia of the spinal cord;
controlled by an external transmitter, it delivers intermittent stimulation which improves bladder emptying. It also
assists in defecation and enables male patients to have a sustained full erection.
The related procedure of sacral nerve stimulation is for the control of incontinence in able-bodied patients.[16]
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Motor prosthetics for conscious control of movement
Researchers are attempting to build motor neuroprosthetics that will help restore movement and the ability to
communicate with the outside world to persons with motor disabilities such as tetraplagia or amyotrophic lateral
sclerosis.
To capture electrical signals from the brain, scientists have developed microelectrode arrays smaller than a square
centimeter that can be implanted in the skull to record electrical activity, transducing recorded information through a
thin cable. After decades of research in monkeys, neuroscientists have been able to decode neuronal signals into
movements. Completing the translation, researchers have built interfaces that allow patients to move computer
cursors, and they are beginning to build robotic limbs and exoskeletons that patients can control by thinking about
movement.
The technology behind motor neuroprostheses is still in its infancy. Investigators and study participants continue to
experiment with different ways of using the prostheses. Having a patient think about clenching a fist, for example,
produces a different result than having him or her think about tapping a finger. The filters used in the prostheses are
also being fine-tuned, and in the future, doctors hope to create an implant capable of transmitting signals from inside
the skull wirelessly, as opposed to through a cable.
Preliminary clinical trials suggest that the devices are safe and that they have the potential to be effective. Some
patients have worn the devices for over two years with few, if any, ill effects.
Prior to these advancements, Philip Kennedy (Emory and Georgia Tech) had an operable if somewhat primitive
system which allowed an individual with paralysis to spell words by modulating their brain activity. Kennedy's
device used two neurotrophic electrodes: the first was implanted in an intact motor cortical region (e.g. finger
representation area) and was used to move a cursor among a group of letters. The second was implanted in a
different motor region and was used to indicate the selection.[17]
Developments continue in replacing lost arms with cybernetic replacements by using nerves normally connected to
the pectoralis muscles. These arms allow a slightly limited range of motion, and reportedly are slated to feature
sensors for detecting pressure and temperature.[18]
Dr. Todd Kuiken at Northwestern University and Rehabilitation Institute of Chicago has developed a method called
targeted reinnervation for an amputee to control motorized prosthetic devices and to regain sensory feedback.
Sensory/motor prosthetics
In 2002 an array of 100 electrodes was implanted directly into the median nerve fibers of the scientist Kevin
Warwick. The recorded signals were used to control a robot arm developed by Warwick's colleague, Peter Kyberd
and was able to mimic the actions of Warwick's own arm.[19] Additionally, a form of sensory feedback was provided
via the implant by passing small electrical currents into the nerve. This caused a contraction of the first lumbrical
muscle of the hand and it was this movement that was perceived.[19]
Cognitive prostheses
Cognitive prostheses seek to restore cognitive function to individuals with brain tissue loss due to injury, disease, or
stroke by performing the function of the damaged tissue with integrated circuits.[20] The theory of localization states
that brain functions are localized to a specific portion of the brain.[21] However, recent studies on brain plasticity
suggest that the brain is capable of rewiring itself so that an area of the brain traditionally associated with a particular
function (i.e. auditory cortex) can perform functions associated with another portion of the brain. (i.e. auditory cortex
processing visual information).[22] Implants could take advantage of brain plasticity to restore cognitive function
even if the native tissue has been destroyed.
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Applications
Alzheimer's Disease
Alzheimer's Disease is projected to affect more than 107 million people worldwide by the year 2050.[23] Due to
increased life spans, more and more people are being affected by Alzheimer's disease. In the United States this fact
has important repercussions. With many baby boomers reaching retirement age the strain on the medicare and
medicaid systems may become too great. Alzheimer's disease renders individuals incapable of supporting
themselves. Unfortunately many of the more severe cases of Alzheimer's patients end up in nursing homes. Even a
small measure of success by cognitive implants would help keep Alzheimer's patients out of nursing homes longer
and lessen the load on medicare and medicaid.
Hippocampal Deficits
Dr. Theodore Berger [24] at the University of Southern California is developing a prosthetic for treatments of
hippocampal detriments including Alzheimer's.[20] Degenerative hippocampal neurons are the root cause of the
memory disorders that accompany Alzheimer's disease. Also, hippocampal pyramidal cells are extremely sensitive to
even brief periods of anoxia, like those that occur during stroke. Loss of hippocampal neurons in the dentate gyrus,
an area associated with new memory formation has been attributed to blunt head trauma.[25] Hippocampal
dysfunction has also been linked to epileptic activity.[20] This demonstrates the wide scope of neural damage and
neurodegenerative disease conditions for which a hippocampal prosthesis would be clinically relevant.
Traumatic Brain Injury
More than 1.4 million people in the United States suffer traumatic brain injury.[26] Orthosis for TBI patients to
control limb movement via devices that read neurons in brain, calculate limb trajectory, and stimulate needed motor
pools to make movement. (Anderson Paper, Cole at NIH - specifically "Computer software as an orthosis for Brain
Injury",
Parkinson's Disease
Nearly 1 million people in the United States are affected by Parkinson's Disease.[27] Deep Brain Stimulation relieves
symptoms of Parkinson's Disease for numerous patients.[28] Parkinson's Disease patients could benefit from a
cortical device that mimics the natural signals needed to promote dopamine production. Another possible avenue for
mitigation of PD is a device that supplements dopamine when given specific neuronal inputs which would let the
body regulate dopamine levels with its intrinsic sensors.
Speech Deficits
Approximately 7.5 million people in the United States have trouble speaking.[29] Many of these can be attributed to
aphasias. The success of cochlear implants suggest that cortical implants to the speech areas of the brain can be
developed to improve speech in such patients.
Paralysis
According to the Christopher and Dana Reeve Foundation's [30] Paralysis Resource Center, approximately 6 million
people are living with paralysis in the United States. Paralysis results from many sources, stroke, traumatic brain
injury, neurodegenerative diseases like multiple sclerosis and Lou Gehrig's Disease, and congenital sources. Many
patients would benefit from a prosthetic device that controls limb movement via devices that read neurons in brain,
calculate limb trajectory, and stimulate the needed motor pools to make movement. This technology is being
developed at the Andersen Lab [31], located at the California Institute of Technology [32]. The goal is to develop a
device to enable locked in patients, those without the ability to move or speak, to communicate with other persons.
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Societal Impact/Market Information
Nearly 1 million people in the United States are affected by Parkinson's Disease.[27]
Alzheimer's Disease is projected to affect more than 107 million people worldwide by the year 2050.[23]
Just these two diseases indicate that there is already a large market for cognitive neural prosthetics, with more
potential markestspace revealed in traumatic brain injury and speech problems (particularly damage to Broca's or
Wernicke's areas).
More than 1.4 million people in the United States suffer traumatic brain injury.[26]
Approximately 7.5 million people in the United States have trouble speaking.[29] Many of these can be attributed to
aphasias.
More than 6.5 million people in the United States have suffered stroke.[33]
Obstacles
Mathematical Modeling
Accurate characterization of the nonlinear input/output (I/O) parameters of the normally functioning tissue to be
replaced is paramount to designing a prosthetic that mimics normal biologic synaptic signals.[34] [35] Mathematical
modeling of these signals is a complex task "because of the nonlinear dynamics inherent in the cellular/molecular
mechanisms comprising neurons and their synaptic connections." [36] [37] [38] The output of nearly all brain neurons
are dependent on which post-synaptic inputs are active and in what order the inputs are received. (spatial and
temporal properties, respectively).[20]
Once the I/O parameters are modeled mathematically, integrated circuits are designed to mimic the normal biologic
signals. For the prosthetic to perform like normal tissue, it must process the input signals, a process known as
transformation, in the same way as normal tissue.
Size
Implantable devices must by very small to be implanted directly in the brain, roughly the size of a quarter.
Wireless Controlling Devices can be mounted outside of the skull and should be smaller than a pager.
Power Consumption
Power consumption drives battery size. Optimization of the implanted circuits reduces power needs. Implanted
devices currently need on-board power sources. Once the battery runs out, surgery is needed to replace the unit.
Longer battery life correlates to fewer surgeries needed to replace batteries. One option that could be used in the
medical field to recharge implant batteries without surgery or wires is being used in powered toothbrushes. These
devices make of inductive coupling to recharge batteries. Another strategy is to convert electromagnetic energy into
electrical energy, as in radio frequency identification tags.
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Bio Compatibility
Cognitive prostheses are implanted directly in the brain, so biocompatibility is very important obstacle to overcome.
Materials used in the housing of the device, the electrode material, and electrode insulation must be chosen for long
term implantation. Subject to Standards: ISO 14708-3 2008-11-15, Implants for Surgery - Active implantable
medical devices Part 3: Implantable neurostimulators.
Crossing the Blood Brain Barrier can introduce pathogens or other materials that may cause an immune response.
The brain has its own immune system that acts differently than the immune system of the rest of the body.
Questions to answer:How does this affect material choice? Does the brain have unique phages that act differently
and may affect materials thought to be bio compatible in other areas of the body?
Data Transmission
Wireless Transmission is being developed to allow continuous recording of neuronal signals of individuals in their
daily life. This allows physicians and clinicians to capture more data, ensuring that short term events like epileptic
seizures can be recorded, allowing better treatment and characterization of neural disease.
A small, light weight device has been developed that allows constant recording of primate brain neurons at Stanford
University.[39] This technology also enables neuroscientists to study the brain outside of the controlled environment
of a lab.
Methods of data transmission must be robust and secure. Neurosecurity is a new issue. Makers of cognitive implants
must prevent unwanted downloading of information or thoughts from and uploading of detrimental data to the device
that may interrupt function.
Correct Implantation
Implantation of the device presents many problems. First, the correct presynaptic inputs must be wired to the correct
postsynaptic inputs on the device. Secondly, the outputs from the device must be targeted correctly on the desired
tissue. Thirdly, the brain must learn how to use the implant. Various studies in brain plasticity (int link) suggest that
this may be possible through exercises designed with proper motivation.
Current Developments
Andersen Lab
The Andersen Lab [40] builds on research done previously by Musallam and show that high-level cognitive signals in
the post parietal cortex, or PPC, can be used to decode the target position of reaching motions.[41] Signals like these
could be used to directly control a prosthetic device. Functionally speaking, the PPC is situated between sensory and
motor areas in the brain. It is involved in converting sensory inputs into plans for action, a phenomenon known as
sensory – motor integration.
Within the PPC is an area known as the post parietal reach region, or PRR for short. This area has been shown to be
most active when an individual is planning and executing a movement. The PRR receives direct visual information,
indicating that vision may be the primary sensory input. The PRR encodes the targets for reaching in visual
coordinates relative to the current direction of gaze AKA retinal coordinates.[42] Because it is coding the goal of the
movement and not all the different variables required for the limb to contact the target, the planning signals of the
PRR are considered cognitive in nature. Decoding these signals is important to help paralyzed patients, especially
those with damage to areas of the brain that calculate limb movement variables, or relay this information to motor
neurons. Perhaps the most astonishing possibility is utilizing these signals to provide 'locked in' individuals, those
without the ability to move or speak, an avenue of communication.
First, Andersen and colleagues placed electrode arrays onto the dorsal premotor cortex, the PRR, and medial
interparietal area (MIP) of monkeys to record signals made by these regions while the monkeys looked at a computer
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screen. After the monkeys touched a central cue spot on the screen and looked at a central fixation point (red),
another cue (green) popped up briefly then disappeared. The monkeys were given a juice reward if they reached to
where the newly vanished target was at the end of a short memory period, about 1.5 seconds. The recordings were
made when the monkeys were planning movement, but sitting motionless in the dark absent of eye movements,
ensuring that motor and sensory information were not influencing the planning activity.
Next, the researchers conducted brain-control trials using neural activity data recorded from 2 tenths of a second to 1
second of the memory period to decode the intended reach destination. A brain-machine interface used the decoded
data to move a cursor to the spot on the screen where the monkeys planned to move, without using their limbs.
Monkeys were rewarded with juice if the correct target was decoded and the cue was flashed again, providing visual
reinforcement. After a month or two of training, the monkeys were much better at hitting the target. This learning is
a testament to the brain's natural plasticity, and creates an opportunity for patients to improve how they operate the
prosthesis with training. Each time the patient uses the prosthetic system, the brain could automatically make subtle
adjustments to the input signal recorded by the system.
Finally, the researchers used reach trials to decode intentions in healthy monkeys. However, paralyzed patients
cannot perform reach trials for the scientists to record reach intention data. Adaptive databases overcome this
scenario. Each time a reach decoding is successful, it is added to the database. If the number of database entries is
kept constant, one trial, (a less successful one) must be deleted. Eventually the database will contain only successful
decodes, making the system work better each time the patient uses it. This suggests a FIFO, or first-in, first-out,
setup. The oldest data drops out first. Initially filling the database will be difficult, but with rigorous training and
many trials, the system will be able to accurately discern the user's intentions. This process, along with the brain's
plasticity, should enable people to control a myriad of prostheses, and perhaps even motorized wheel chairs.
Furthermore, in the future precision devices such as surgical tools could be controlled directly by the brain instead of
controls manipulated by the motor system.
Hippocampal Prosthetic
Dr. Theodore Berger's research lab at the University of Southern California seeks to develop models of mammalian
neural systems, currently the hippocampus, essential for learning and memory. The goal is to make an implantable
device that replicates the way living hippocampal neurons behave and exchange electrical signals. If successful, it
would be a large step towards a biomedical solution for Alzheimer's symptoms. Complications from brain injury to
motor areas of the brain like reduced coordination could be improved. Speech and language problems caused by
stroke could be reversed. To accomplish this, the device will listen for neuronal signals going to the hippocampus
with implanted electrode arrays, calculate what the outgoing response of normal hippocampus neurons would be, and
then to stimulate neurons in other parts of the brain, hopefully just like the tissue did before damage or degeneration.
Technologies Involved
Local Field Potentials
Local field potentials (LFPs) are electrophysiological signals that are related to the sum of all dendritic synaptic
activity within a volume of tissue. Recent studies suggest goals and expected value are high-level cognitive functions
that can be used for neural cognitive prostheses.[43]
• explain how they are used
• how they are better than other methods
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Neuroprosthetics
Automated Movable Electrical Probes
One hurdle to overcome is the long term implantation of electrodes. If the electrodes are moved by physical shock or
the brain moves in relation to electrode position, the electrodes could be recording different nerves. Adjustment to
electrodes is necessary to maintain an optimal signal. Individually adjusting multi electrode arrays is a very tedious
and time consuming process. Development of automatically adjusting electrodes would mitigate this problem.
Anderson's group is currently collaborating with Yu-Chong Tai's lab and the Burdick lab (all at Cal Tech) to make
such a system that uses electrolysis-based actuators to independently adjust electrodes in a chronically implanted
array of electrodes.[44]
MRI
Used for imaging to determine correct positionings
Imaged Guided Surgical Techniques
Image-Guided Surgery is used to precisely position brain implants.[43]
Future Directions
Self-charging implants that use bioenergy to recharge would eliminate the need for costly and risky surgeries to
change implant batteries.
Memory/Brain off-loading and subsequent uploading to learn new information quickly. Researchers at the Georgia
Institute of Technology are researching mammalian memory cells to determine exactly how we learn. The
techniques used in the Potter Lab [45] can be used to study and enhance the activities of neural prosthetics devices.
Controlling complex machinery with thoughts instead of converting motor movements into commands for machines
would allow greater accuracy and enable users to distance themselves from hazardous environments.
Other future directions include devices to maintain focus, to stabilize/induce mood, to help patients with damaged
cortices feel and express emotions, and to enable true telepathic communication, not simply picking up
visual/auditory cues and guessing emotional state or subject of thought from context.
See also
•
•
•
•
Prosthetics
Cyborg
Biomedical engineering
Neurosecurity
Commercial technology
Medtronic and Advanced Bionics are significant commercial names in the emergent market of Deep Brain
Stimulation. Cyberkinetics is the first venture capital funded neural prosthetic company.
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Neuroprosthetics
Further reading
Santhanam G, Ryu SI, Yu BM, Afshar A, Shenoy KV. 2006. A high-performance brain-computer interface. Nature
442:195-8
Patil PG, Turner DA. 2008. The development of brain-machine interface neuroprosthetic devices. Neurotherapeutics
5:137-46
Liu WT, Humayun MS, Liker MA. 2008. Implantable biomimetic microelectronics systems. Proceedings of the Ieee
96:1073-4
Harrison RR. 2008. The design of integrated circuits to observe brain activity. Proceedings of the Ieee 96:1203-16
Abbott A. 2006. Neuroprosthetics: In search of the sixth sense. Nature 442:125-7
Velliste M, Perel S, Spalding MC, Whitford AS, Schwartz AB (2008) "Cortical control of a prosthetic arm for
self-feeding." Nature. 19;453(7198):1098-101.
Schwartz AB, Cui XT, Weber DJ, Moran DW "Brain-controlled interfaces: movement restoration with neural
prosthetics." (2006) Neuron 5;52(1):205-20
Santucci DM, Kralik JD, Lebedev MA, Nicolelis MA (2005) "Frontal and parietal cortical ensembles predict
single-trial muscle activity during reaching movements in primates." Eur J Neurosci. 22(6): 1529-1540.
Lebedev MA, Carmena JM, O'Doherty JE, Zacksenhouse M, Henriquez CS, Principe JC, Nicolelis MA (2005)
"Cortical ensemble adaptation to represent velocity of an artificial actuator controlled by a brain-machine interface."
J Neurosci. 25: 4681-4893.
Nicolelis MA (2003) "Brain-machine interfaces to restore motor function and probe neural circuits." Nat Rev
Neurosci. 4: 417-422.
Wessberg J, Stambaugh CR, Kralik JD, Beck PD, Laubach M, Chapin JK, Kim J, Biggs SJ, Srinivasan MA,
Nicolelis MA. (2000) "Real-time prediction of hand trajectory by ensembles of cortical neurons in primates." Nature
16: 361-365.
External links
(for a list of universities see Neural Engineering - Neural Engineering Labs)
• Information site on electronic implants (also called intelligent implants or smart implants) [25]
• The open-source Electroencephalography project [46] and Programmable chip version [47], Sourceforge open
source EEG projects
• Dr. Theodore W. Berger's website [27]
• CIMIT - Center For Integration Of Medicine And Innovative Technology - Advances & Research in
Neuroprosthetics [48]
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[29] National Institute on Deafness and Other Communication Disorders, National Institutes of Health. http:/ / www. nidcd. nih. gov/ health/
statistics/ vsl. asp Accessed 11/21/2009. Updated 6/18/2009.
[30] http:/ / www. christopherreeve. org/
[31] http:/ / vis. caltech. edu/
[32] http:/ / www. caltech. edu/
[33] National Center for Health Statistics, Hyattsville, MD. Center for Disease Control and Prevention (http:/ / www. cdc. gov/ nchs/ FASTATS/
stroke. htm) Accessed 11/28/2009. Updated 05/15/2009.
[34] Bertaccini, D., & Fanelli, S. (2009). Computational and conditioning issues of a discrete model for cochlear sensorineural hypoacusia.
[Article]. Applied Numerical Mathematics, 59(8), 1989-2001.
[35] Marmarelis, V. Z. (1993). IDENTIFICATION OF NONLINEAR BIOLOGICAL-SYSTEMS USING LAGUERRE EXPANSIONS OF
KERNELS. [Article]. Annals of Biomedical Engineering, 21(6), 573-589.
[36] T.W. Berger, T.P. Harty, X. Xie, G. Barrionuevo, and R.J. Sclabassi, "Modeling of neuronal networks through experimental
decomposition," in Proc. IEEE 34th Mid Symp. Cir. Sys., Monterey, CA, 1991, vol. 1, pp. 91–97.
[37] T.W. Berger, G. Chauvet, and R.J. Sclabassi, "A biologically based model of functional properties of the hippocampus," Neural Netw., vol.
7, no. 6–7, pp. 1031–1064, 1994.
[38] S.S. Dalal, V.Z. Marmarelis, and T.W. Berger, "A nonlinear positive feedback model of glutamatergic synaptic transmission in dentate
gyrus," in Proc. 4th Joint Symp. Neural Computation, California, 1997, vol. 7, pp. 68–75.
[39] HermesC: Low-Power Wireless Neural Recording System for Freely Moving Primates Chestek, C.A.; Gilja, V.; Nuyujukian, P.; Kier, R.J.;
Solzbacher, F.; Ryu, S.I.; Harrison, R.R.; Shenoy, K.V.; Neural Systems and Rehabilitation Engineering, IEEE Transactions on Volume 17,
Issue 4, Aug. 2009 Page(s):330 - 338.
[40] http:/ / vis. caltech. edu/ Research/ Research. html
[41] Anderson, R.A. et al. (2008) Decoding Trajectories from Posterior Parietal Cortex. The Journal of Neuroscience 28(48):12913–12926.
[42] Batista, A.P. et al. (1999) Reach plans in eye-centered coordinates. Science 285, 257–260.
[43] Andersen, R. A., Burdick, J. W., Musallam, S., Pesaran, B., & Cham, J. G. (2004). Cognitive neural prosthetics. Trends in Cognitive
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http:/ / www. neuro. gatech. edu/ groups/ potter/ index. html
http:/ / openeeg. sourceforge. net/ doc/
http:/ / pceeg. sourceforge. net/
http:/ / www. cimit. org/
Cardiopulmonary bypass
Cardiopulmonary bypass (CPB) is a
technique that temporarily takes over
the function of the heart and lungs
during surgery, maintaining the
circulation of blood and the oxygen
content of the body. The CPB pump
itself is often referred to as a
Heart-Lung Machine or the Pump.
Cardiopulmonary bypass pumps are
operated by allied health professionals
known as perfusionists in association
with surgeons who connect the pump to
the patient's body. CPB is a form of
extracorporeal circulation.
Uses of cardiopulmonary
bypass
A Heart-Lung Machine (upper right) in a coronary artery bypass surgery.
Cardiopulmonary bypass is commonly used in heart surgery because of the difficulty of operating on the beating
heart. Operations requiring the opening of the chambers of the heart require the use of CPB to support the circulation
during that period.
CPB can be used for the induction of total body hypothermia, a state in which the body can be maintained for up to
45 minutes without perfusion (blood flow). If blood flow is stopped at normal body temperature, permanent brain
damage normally occurs in three to four minutes — death may follow shortly afterward.
Extracorporeal membrane oxygenation (ECMO) is a simplified form of CPB sometimes used as life-support for
newborns with serious birth defects, or to oxygenate and maintain recipients for organ transplantation until new
organs can be found.
CPB mechanically circulates and oxygenates blood for the body while bypassing the heart and lungs. It uses a
heart-lung machine to maintain perfusion to other body organs and tissues while the surgeon works in a bloodless
surgical field. The surgeon places a cannula in right atrium, vena cava, or femoral vein to withdraw blood from the
body. The cannula is connected to tubing filled with isotonic crystalloid solution. Venous blood that is removed from
the body by the cannula is filtered, cooled or warmed, oxygenated, and then returned to the body. The cannula used
to return oxygenated blood is usually inserted in the ascending aorta, but it may be inserted in the femoral artery. The
patient is administered heparin to prevent clotting, and protamine sulfate is given after to reverse effects of heparin.
During the procedure, hypothermia is maintained; body temperature is usually kept at 28ºC to 32ºC (82.4-89.6ºF).
The blood is cooled during CPB and returned to the body. The cooled blood slows the body’s basal metabolic rate,
decreasing its demand for oxygen. Cooled blood usually has a higher viscosity, but the crystalloid solution used to
prime the bypass tubing dilutes the blood.
Cardiopulmonary bypass
Surgical procedures in which cardiopulmonary bypass is used
•
•
•
•
•
•
•
•
Coronary artery bypass surgery
Cardiac valve repair and/or replacement (aortic valve, mitral valve, tricuspid valve, pulmonic valve)
Repair of large septal defects (atrial septal defect, ventricular septal defect, atrioventricular septal defect)
Repair and/or palliation of congenital heart defects (Tetralogy of Fallot, transposition of the great vessels)
Transplantation (heart transplantation, lung transplantation, heart-lung transplantation)
Repair of some large aneurysms (aortic aneurysms, cerebral aneurysms)
Pulmonary thromboendarterectomy
Pulmonary thrombectomy
History
Dr. Clarence Dennis led the team that conducted the first known
operation involving open cardiotomy with temporary mechanical
takeover of both heart and lung functions on April 5, 1951 at the
University of Minnesota Hospital. The patient did not survive due to an
unexpected complex congenital heart defect. This followed four years
of laboratory experimentation with dogs.[1]
The first successful open heart procedure on a human utilizing the
heart lung machine was performed by John Gibbon on May 6, 1953 at
Thomas Jefferson University Hospital in Philadelphia. He repaired an
atrial septal defect in an 18-year-old woman.[2]
The oxygenator was first conceptualised in the 17th century by Robert
Hooke and developed into practical extracorporeal oxygenators by
A heart lung machine dating from 1958
French and German experimental physiologists in the 19th century.
Bubble oxygenators have no intervening barrier between blood and
oxygen, these are called 'direct contact' oxygenators. Membrane oxygenators introduce a gas-permeable membrane
between blood and oxygen that decreases the blood trauma of direct-contact oxygenators. Much work since the
1960s focused on overcoming the gas exchange handicap of the membrane barrier, leading to the development of
high-performance microporous hollow-fibre oxygenators that eventually replaced direct-contact oxygenators in
cardiac theatres.[3]
Components of cardiopulmonary bypass
Cardiopulmonary bypass consists of two main functional units, the pump and the oxygenator which remove
oxygen-deprived blood from a patient's body and replace it with oxygen-rich blood through a series of hoses.
Tubing
The components of the CPB circuit are interconnected by a series of tubes made of silicone rubber or PVC.
Pumps
Roller pump
The pump console usually comprises several rotating motor-driven pumps that peristaltically "massage" tubing . This
action gently propels the blood through the tubing. This is commonly referred to as a roller pump, or peristaltic
pump.
144
Cardiopulmonary bypass
145
Centrifugal pump
Many CPB circuits now employ a centrifugal pump for the maintenance and control of blood flow during CPB. By
altering the speed of revolution (RPM) of the pump head, blood flow is produced by centrifugal force. This type of
pumping action is considered to be superior to the action of the roller pump by many because it is thought to produce
less blood damage (Hemolysis, etc.).
Oxygenator
The oxygenator is designed to transfer oxygen to infused blood and remove carbon dioxide from the venous blood.
Cardiac surgery was made possible by CPB using bubble oxygenators, but membrane oxygenators have supplanted
bubble oxygenators since the 1980s.
Another type of oxygenator gaining favour recently is the heparin-coated blood oxygenator which is believed to
produce less systemic inflammation and decrease the propensity for blood to clot in the CPB circuit.
Cannulae
Multiple cannulae are sewn into the patient's body in a variety of locations, depending on the type of surgery. A
venous cannula removes oxygen deprived blood from a patient's body. An arterial cannula is sewn into a patient's
body and is used to infuse oxygen-rich blood. A cardioplegia cannula is sewn into the heart to deliver a cardioplegia
solution to cause the heart to stop beating.
Venous
Arterial
Cardioplegia
Right atrium Proximal aorta, distal to the cross-clamp Proximal aorta, proximal to the cross-clamp
Vena cavae
Femoral artery
Femoral vein Axillary artery
Distal aorta
Coronary sinus (retrograde delivery)
Coronary ostia
Bypass grafts (during CABG)
Apex of the heart
Cardioplegia
A CPB circuit consists of a systemic circuit for oxygenating blood and reinfusing blood into a patient's body
(bypassing the heart); and a separate circuit for infusing a solution into the heart itself to produce cardioplegia (i.e. to
stop the heart from beating), and to provide myocardial protection (i.e. to prevent death of heart tissue).
Operation
A CPB circuit must be primed with fluid and all air expunged before connection to the patient. The circuit is primed
with a crystalloid solution and sometimes blood products are also added. The patient must be fully anticoagulated
with an anticoagulant such as heparin to prevent massive clotting of blood in the circuit.
Cardiopulmonary bypass
Complications
CPB is not benign and there are a number of associated problems:
•
•
•
•
•
•
Postperfusion syndrome (also known as Pumphead)
Hemolysis
Capillary leak syndrome
Clotting of blood in the circuit - can block the circuit (particularly the oxygenator) or send a clot into the patient.
Air embolism
Leakage - a patient can rapidly exsanguinate (lose blood perfusion of tissues) if a line becomes disconnected.
As a consequence, CPB is only used during the several hours a cardiac surgery may take. Most oxygenators come
with a manufacturer's recommendation that they are only used for a maximum of 6 hours, although they are
sometimes used for up to 10 hours, with care being taken to ensure they do not clot off and stop working. For longer
periods than this, an ECMO (extra-corporeal membrane oxygenation) or VAD (ventricular assist device) circuit is
used, which can be in operation for up to 31 days - such as in this Taiwanese case, for 16 days, after which the
patient received a heart transplant.[4]
External links
• International Consortium For Evidence-Based Perfusion [5]
• Hessel EA, Edmunds LH (2003). "Extracorporeal Circulation: Perfusion Systems" [6]. in Cohn LH, Edmunds LH
Jr. Cardiac Surgery in the Adult. New York: McGraw-Hill. pp. 317–38.
• Multimedia Manual of Cardiothoracic Surgery. Cardiopulmonary bypass collection. [7]
• Perfusion Line [8]
• The Virtual Textbook Of Extracorporeal Technology [9]
• Video of early USSR heart-lung machine experiments [10]
References
[1] Dennis C, Spreng DS, Nelson GE, et al. (October 1951). "Development of a pump-oxygenator to replace the heart and lungs; an apparatus
applicable to human patients, and application to one case" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez&
artid=1802968). Ann. Surg. 134 (4): 709–21. PMID 14878382. PMC 1802968.
[2] Cohn LH (May 2003). "Fifty years of open-heart surgery" (http:/ / circ. ahajournals. org/ cgi/ pmidlookup?view=long& pmid=12732590).
Circulation 107 (17): 2168–70. doi:10.1161/01.CIR.0000071746.50876.E2. PMID 12732590. .
[3] Lim M (2006). "The history of extracorporeal oxygenators". Anaesthesia 61 (10): 984–95. doi:10.1111/j.1365-2044.2006.04781.x.
PMID 16978315.
[4] Man survives 16 days without a heart (http:/ / www. physorg. com/ news126460484. html) united Press International. April 3, 2008.
[5] http:/ / www. bestpracticeperfusion. org
[6] http:/ / cardiacsurgery. ctsnetbooks. org/ cgi/ content/ full/ 2/ 2003/ 317
[7] http:/ / mmcts. ctsnetjournals. org/ cgi/ collection/ cardiopulmonary_bypass
[8] http:/ / perfline. com/ index. htm
[9] http:/ / perfline. com/ textbook/ textbook. html
[10] http:/ / video. google. com/ videoplay?docid=4187970374764805675
146
Artificial pacemaker
147
Artificial pacemaker
A pacemaker (or artificial pacemaker, so as not to be confused with
the heart's natural pacemaker) is a medical device which uses electrical
impulses, delivered by electrodes contacting the heart muscles, to
regulate the beating of the heart. The primary purpose of a pacemaker
is to maintain an adequate heart rate, either because the heart's native
pacemaker is not fast enough, or there is a block in the heart's electrical
conduction system. Modern pacemakers are externally programmable
and allow the cardiologist to select the optimum pacing modes for
individual patients. Some combine a pacemaker and defibrillator in a
single implantable device. Others have multiple electrodes stimulating
differing positions within the heart to improve synchronisation of the
lower chambers of the heart.
A pacemaker, scale in centimeters
An artificial pacemaker with electrode for
transvenous insertion (from St. Jude Medical).
The body of the device is about 4 centimeters
long, the electrode measures between 50 and 60
centimeters (20 to 24 inches).
Artificial pacemaker
148
History
In 1899, J A McWilliam reported in the British Medical
Journal of his experiments in which application of an
electrical impulse to the human heart in asystole caused a
ventricular contraction and that a heart rhythm of 60-70 beats
per minute could be evoked by impulses applied at spacings
equal to 60-70/minute.[1]
In 1926, Dr Mark C Lidwell of the Royal Prince Alfred
Hospital of Sydney, supported by physicist Edgar H Booth of
the University of Sydney, devised a portable apparatus which
"plugged into a lighting point" and in which "One pole was
applied to a skin pad soaked in strong salt solution" while the
other pole "consisted of a needle insulated except at its point,
and was plunged into the appropriate cardiac chamber". "The
pacemaker rate was variable from about 80 to 120 pulses per
minute, and likewise the voltage variable from 1.5 to 120
volts" In 1928, the apparatus was used to revive a stillborn
infant at Crown Street Women's Hospital, Sydney whose
heart continued "to beat on its own accord", "at the end of 10
minutes" of stimulation.[2] [3]
The first implantable pacemaker.
In 1932, American physiologist Albert Hyman, working
independently, described an electro-mechanical instrument
of his own, powered by a spring-wound hand-cranked motor.
Hyman himself referred to his invention as an "artificial
pacemaker", the term continuing in use to this day.[4] [5]
An apparent hiatus in publication of research conducted
between the early 1930s and World War II may be attributed
to the public perception of interfering with nature by
'reviving the dead'. For example, "Hyman did not publish
data on the use of his pacemaker in humans because of
adverse publicity, both among his fellow physicians, and due
to newspaper reporting at the time. Lidwell may have been
aware of this and did not proceed with his experiments in
humans".[3]
In 1958, Arne Larsson (1915-2001) became the first to receive
an implantable pacemaker. He had a total of 26 devices during
his life and campaigned for other patients needing
pacemakers.
An external pacemaker was designed and built by the Canadian electrical engineer John Hopps in 1950 based upon
observations by cardio-thoracic surgeon Wilfred Gordon Bigelow at Toronto General Hospital . A substantial
external device using vacuum tube technology to provide transcutaneous pacing, it was somewhat crude and painful
to the patient in use and, being powered from an AC wall socket, carried a potential hazard of electrocution of the
patient by inducing ventricular fibrillation.
A number of innovators, including Paul Zoll, made smaller but still bulky transcutaneous pacing devices in the
following years using a large rechargeable battery as the power supply.[6]
In 1967, Dr. William L. Weirich published the results of research performed at the University of Minnesota. These
studies demonstrated the restoration of heart rate, cardiac output and mean aortic pressures in animal subjects with
complete heart block through the use of a myocardial electrode. This effective control of postsurgical heart block
Artificial pacemaker
proved to be a significant contribution to decreasing mortality of open heart surgery in this time period.[7]
The development of the silicon transistor and its first commercial availability in 1956 was the pivotal event which
led to rapid development of practical cardiac pacemaking.
In 1957, engineer Earl Bakken of Minneapolis, Minnesota, produced the first wearable external pacemaker for a
patient of Dr. C. Walton Lillehei. This transistorised pacemaker, housed in a small plastic box, had controls to permit
adjustment of pacing heart rate and output voltage and was connected to electrode leads which passed through the
skin of the patient to terminate in electrodes attached to the surface of the myocardium of the heart.
The first clinical implantation into a human of a fully implantable pacemaker was in 1958 at the Karolinska Institute
in Solna, Sweden, using a pacemaker designed by Rune Elmqvist and surgeon Åke Senning, connected to electrodes
attached to the myocardium of the heart by thoracotomy. The device failed after three hours. A second device was
then implanted which lasted for two days. The world's first implantable pacemaker patient, Arne Larsson, went on to
receive 26 different pacemakers during his lifetime. He died in 2001, at the age of 86[8] .
In 1969, temporary transvenous pacing was first demonstrated by Furman et al. in which the catheter electrode was
inserted via the patient's basilic vein.[9]
In February 1970, an improved version of the Swedish Elmqvist design was implanted in Montevideo, Uruguay in
the Casmu Hospital by Doctors Fiandra and Rubio. That device lasted until the patient died of other ailments, 9
months later. The early Swedish-designed devices used rechargeable batteries, which were charged by an induction
coil from the outside.
Implantable pacemakers constructed by engineer Wilson Greatbatch entered use in humans from April 1960
following extensive animal testing. The Greatbatch innovation varied from the earlier Swedish devices in using
primary cells (mercury battery) as the energy source. The first patient lived for a further 18 months.
The first use of transvenous pacing in conjunction with an implanted pacemaker was by Parsonnet in the USA [10]
[11] [12]
, Lagergren in Sweden[13] [14] and Jean-Jaques Welti in France[15] in 1962-63. The transvenous, or
pervenous, procedure involved incision of a vein into which was inserted the catheter electrode lead under
fluoroscopic guidance, until it was lodged within the trabeculae of the right ventricle. This method was to become
the method of choice by the mid-1960s.
The preceding implantable devices all suffered from the unreliability
and short lifetime of the available primary cell technology which was
mainly that of the mercury battery. In the late 1960s, several
companies, including ARCO in the USA, developed isotope powered
pacemakers, but this development was overtaken by the development
in 1971 of the lithium-iodide cell by Wilson Greatbatch.
Lithium-iodide or lithium anode cells became the standard for future
pacemaker designs.
A further impediment to reliability of the early devices was the
diffusion of water vapour from the body fluids through the epoxy resin
World's first Lithium-iodide cell powered
encapsulation affecting the electronic circuitry. This phenomenon was
pacemaker. Cardiac Pacemakers Inc. 1972
overcome by encasing the pacemaker generator in an hermetically
sealed metal case, initially by Telectronics of Australia in 1989 followed by Cardiac Pacemakers Inc of Minneapolis
in 1992. This technology, using titanium as the encasing metal, became the standard by the mid-1990s.
Others who contributed significantly to the technological development of the pacemaker in the pioneering years were
Bob Anderson of Medtronic Minneapolis, J.G (Geoffrey) Davies of St George's Hospital London, Barouh Berkovits
and Sheldon Thaler of American Optical, Geoffrey Wickham of Telectronics Australia, Walter Keller of Cordis
Corp. of Miami, Hans Thornander who joined previously mentioned Rune Elmquist of Elema-Schonander in
Sweden, Janwillem van den Berg of Holland and Anthony Adducci of Cardiac Pacemakers Inc.Guidant.
149
Artificial pacemaker
150
Methods of pacing
Percussive pacing
Percussive pacing, also known as transthoracic mechanical pacing, is the use of the closed fist, usually on the left
lower edge of the sternum over the right ventricle in the vena cava, striking from a distance of 20 - 30 cm to induce a
ventricular beat (the British Journal of Anesthesia suggests this must be done to raise the ventricular pressure to 10 15mmhg to induce electrical activity). This is an old procedure used only as a life saving means until an electrical
pacemaker is brought to the patient.[16]
Transcutaneous pacing
Transcutaneous pacing (TCP), also called external pacing, is recommended for the initial stabilization of
hemodynamically significant bradycardias of all types. The procedure is performed by placing two pacing pads on
the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The rescuer selects the
pacing rate, and gradually increases the pacing current (measured in mA) until electrical capture (characterized by a
wide QRS complex with a tall, broad T wave on the ECG) is achieved, with a corresponding pulse. Pacing artifact on
the ECG and severe muscle twitching may make this determination difficult. External pacing should not be relied
upon for an extended period of time. It is an emergency procedure that acts as a bridge until transvenous pacing or
other therapies can be applied.
Epicardial pacing (temporary)
Temporary epicardial pacing is used during open heart surgery should the surgical procedure create atrio ventricular
block. The electrodes are placed in contact with the outer wall of the ventricle (epicardium) to maintain satisfactory
cardiac output until a temporary transvenous electrode has been inserted.
ECG rhythm strip of a threshold determination in a patient with a temporary (epicardial)
ventricular pacemaker. The epicardial pacemaker leads were placed after the patient
collapsed during aortic valve surgery. In the first half of the tracing, pacemaker stimuli at
60 beats per minute result in a wide QRS complex with a right bundle branch block
pattern. Progressively weaker pacing stimuli are administered, which results in asystole in
the second half of the tracing. At the end of the tracing, distortion results from muscle
contractions due to a (short) hypoxic seizure. Because decreased pacemaker stimuli do
not result in a ventricular escape rhythm, the patient can be said to be
pacemaker-dependent and needs a definitive pacemaker.
Transvenous pacing (temporary)
Transvenous pacing, when used for temporary pacing, is an alternative to transcutaneous pacing. A pacemaker wire
is placed into a vein, under sterile conditions, and then passed into either the right atrium or right ventricle. The
pacing wire is then connected to an external pacemaker outside the body. Transvenous pacing is often used as a
bridge to permanent pacemaker placement. It can be kept in place until a permanent pacemaker is implanted or until
there is no longer a need for a pacemaker and then it is removed.
Artificial pacemaker
151
Permanent pacing
Permanent pacing with an implantable pacemaker involves transvenous
placement of one or more pacing electrodes within a chamber, or
chambers, of the heart. The procedure is performed by incision of a
suitable vein into which the electrode lead is inserted and passed along
the vein, through the valve of the heart, until positioned in the
chamber. The procedure is facilitated by fluoroscopy which enables the
physician or cardiologist to view the passage of the electrode lead.
After satisfactory lodgement of the electrode is confirmed the opposite
end of the electrode lead is connected to the pacemaker generator.
There are three basic types of permanent pacemakers, classified
according to the number of chambers involved and their basic
operating mechanism:[17]
• Single-chamber pacemaker. In this type, only one pacing lead is
placed into a chamber of the heart, either the atrium or the
ventricle.[17]
Right atrial and right ventricular leads as
visualized under x-ray during a pacemaker
implant procedure. The atrial lead is the curved
one making a U shape in the upper left part of the
figure.
• Dual-chamber pacemaker. Here, wires are placed in two chambers of the heart. One lead paces the atrium and
one paces the ventricle. This type more closely resembles the natural pacing of the heart by assisting the heart in
coordinating the function between the atria and ventricles.[17]
• Rate-responsive pacemaker. This pacemaker has sensors that detect changes in the patient's physical activity and
automatically adjust the pacing rate to fulfill the body's metabolic needs.[17]
The pacemaker generator is a hermetically sealed device containing a power source, usually a lithium battery, a
sensing amplifier which processes the electrical manifestation of naturally occurring heart beats as sensed by the
heart electrodes, the computer logic for the pacemaker and the output circuitry which delivers the pacing impulse to
the electrodes.
Most commonly, the generator is placed below the subcutaneous fat of the chest wall, above the muscles and bones
of the chest. However, the placement may vary on a case by case basis.
The outer casing of pacemakers is so designed that it will rarely be rejected by the body's immune system. It is
usually made of titanium, which is inert in the body. The whole thing will not be rejected, and will be encapsulated
by scar tissue, in the same way a piercing is.
Basic function
Modern pacemakers usually have multiple functions. The most basic form monitors the heart's native electrical
rhythm. When the pacemaker fails to sense a heartbeat within a normal beat-to-beat time period, it will stimulate the
ventricle of the heart with a short low voltage pulse. This sensing and stimulating activity continues on a beat by beat
basis.
The more complex forms include the ability to sense and/or stimulate both the atrial and ventricular chambers.
Artificial pacemaker
152
The revised NASPE/BPEG generic code for antibradycardia pacing[18]
I
II
III
IV
V
Chamber(s)
paced
Chamber(s) sensed Response to
sensing
Rate modulation
Multisite pacing
O = None
O = None
O = None
O = None
O = None
A = Atrium
A = Atrium
T = Triggered
R = Rate
modulation
A = Atrium
V = Ventricle
V = Ventricle
I = Inhibited
V = Ventricle
D = Dual (A+V)
D = Dual (A+V)
D = Dual (T+I)
D = Dual (A+V)
From this the basic ventricular "on demand" pacing mode is VVI or with automatic rate adjustment for exercise
VVIR - this mode is suitable when no synchronization with the atrial beat is required, as in atrial fibrillation. The
equivalent atrial pacing mode is AAI or AAIR which is the mode of choice when atrioventricular conduction is
intact but the natural pacemaker the sinoatrial node is unreliable - sinus node disease (SND) or sick sinus syndrome.
Where the problem is atrioventricular block (AVB) the pacemaker is required to detect (sense) the atrial beat and
after a normal delay (0.1-0.2 seconds) trigger a ventricular beat, unless it has already happened - this is VDD mode
and can be achieved with a single pacing lead with electrodes in the right atrium (to sense) and ventricle (to sense
and pace). These modes AAIR and VDD are unusual in the US but widely used in Latin America and Europe[19] [20]
. The DDDR mode is most commonly used as it covers all the options though the pacemakers require separate atrial
and ventricular leads and are more complex, requiring careful programming of their functions for optimal results.
Artificial pacemaker
153
Biventricular pacing (BVP)
Three leads can be seen in this example of a cardiac resynchronization device: a right
atrial lead (solid black arrow), a right ventricular lead (dashed black arrow), and a
coronary sinus lead (red arrow). The coronary sinus lead wraps around the outside of the
left ventricle, enabling pacing of the left ventricle. Note that the right ventricular lead in
this case has 2 thickened aspects that represent conduction coils and that the generator is
larger than typical pacemaker generators, demonstrating that this device is both a
pacemaker and a cardioverter-defibrillator, capable of delivering electrical shocks for
dangerously fast abnormal ventricular rhythms.
A biventricular pacemaker, also known as CRT (cardiac resynchronization therapy) is a type of pacemaker that can
pace both the septal and lateral walls of the left ventricle. By pacing both sides of the left ventricle, the pacemaker
can resynchronize a heart whose opposing walls do not contract in synchrony, which occurs in approximately 25-50
% of heart failure patients. CRT devices have at least two leads, one in the right ventricle to stimulate the septum,
and another inserted through the coronary sinus to pace the lateral wall of the left ventricle. Often, for patients in
normal sinus rhythm, there is also a lead in the right atrium to facilitate synchrony with the atrial contraction. Thus,
timing between the atrial and ventricular contractions, as well as between the septal and lateral walls of the left
ventricle can be adjusted to achieve optimal cardiac function. CRT devices have been shown to reduce mortality and
improve quality of life in patients with heart failure symptoms; a LV ejection fraction less than or equal to 35% and
QRS duration on EKG of 120 msec or greater.[21] [22] [23] CRT can be combined with an implantable
cardioverter-defibrillator (ICD).[24]
Artificial pacemaker
154
Advancements in function
A major step forward in pacemaker function has been to attempt to
mimic nature by utilizing various inputs to produce a rate-responsive
pacemaker using parameters such as the QT interval, pCO - pCO2
(dissolved oxygen or carbon dioxide levels) in the arterial-venous
system, physical activity as determined by an accelerometer, body
temperature, ATP levels, adrenaline, etc. Instead of producing a static,
predetermined heart rate, or intermittent control, such a pacemaker, a
'Dynamic Pacemaker', could compensate for both actual respiratory
loading and potentially anticipated respiratory loading. The first
dynamic pacemaker was invented by Dr. Anthony Rickards of the
National Health Hospital, London, UK, in 1982. .
X-ray image of installed pacemaker showing wire
routing
Dynamic pacemaking technology could also be applied to future
artificial hearts. Advances in transitional tissue welding would support this and other artificial organ/joint/tissue
replacement efforts. Stem cells may or may not be of interest to transitional tissue welding.
Many advancements have been made to improve the control of the pacemaker once implanted. Many of these have
been made possible by the transition to microprocessor controlled pacemakers. Pacemakers that control not only the
ventricles but the atria as well have become common. Pacemakers that control both the atria and ventricles are called
dual-chamber pacemakers. Although these dual-chamber models are usually more expensive, timing the contractions
of the atria to precede that of the ventricles improves the pumping efficiency of the heart and can be useful in
congestive heart failure.
Rate responsive pacing allows the device to sense the physical activity of the patient and respond appropriately by
increasing or decreasing the base pacing rate via rate response algorithms.
The DAVID trials[25] have shown that unnecessary pacing of the right ventricle can lead to heart failure and an
increased incidence of atrial fibrillation. The newer dual chamber devices can keep the amount of right ventricle
pacing to a minimum and thus prevent worsening of the heart disease.
Patient considerations
Insertion
A pacemaker is typically inserted into the patient through a simple surgery using either local anesthetic or a general
anesthetic. The patient may be given a drug for relaxation before the surgery as well. An antibiotic is typically
administered to prevent infection.[26] In most cases the pacemaker is inserted in the left shoulder area where an
incision is made below the collar bone creating a small pocket where the pacemaker is actually housed in the
patient's body. The lead or leads (the number of leads varies depending on the type of pacemaker) are fed into the
heart through a large vein using a fluoroscope to monitor the progress of lead insertion. A temporary drain may be
installed and removed the following day. The actual surgery may take about an hour.
Following surgery the patient should exercise reasonable care about the wound as it heals. There is a followup
session during which the pacemaker is checked using a "programmer" that can communicate with the device and
allows a health care professional to evaluate the system's integrity and determine the settings such as pacing voltage
output.
The patient may want to consider some basic preparation before the surgery. The most basic preparation is that
people who have body hair on the chest may want to remove the hair by shaving or using a depilatory agent as the
surgery will involve bandages and monitoring equipment to be afixed to the body.
Artificial pacemaker
155
Since a pacemaker uses batteries, the device itself will need replacement as the batteries lose power. Device
replacement is usually a simpler procedure than the original insertion as it does not normally require leads to be
implanted. The typical replacement requires a surgery in which an incision is made to remove the existing device,
the leads are removed from the existing device, the leads are attached to the new device, and the new device is
inserted into the patient's body replacing the previous device.
Pacemaker patient identification card
International pacemaker patient identification cards carry information such as; patient data (between others,
symptom primary, ECG, aetiology), pacemaker center (doctor, hospital), IPG (rate, mode, date of implantation,
MFG, type) and lead [27] [28] .
Living with a pacemaker
Periodic pacemaker checkups
Once the pacemaker is implanted, it is periodically checked to ensure
the device is operational and performing appropriately. Depending on
the frequency set by the following physician, the device can be
checked as often as is necessary. Routine pacemaker checks are
typically done in-office every six (6) months, though will vary
depending upon patient/device status and remote monitoring
availability.
At the time of in-office follow-up, the device will be interrogated to
perform diagnostic testing. These tests include:
Two types of remote monitoring devices used by
pacemaker patients.
• Sensing: the ability of the device to "see" intrinsic cardiac activity (Atrial and ventricular depolarization).
• Impedance: A test to measure lead integrity. Large and/or sudden increases in impedance can be indicative of a
lead fracture while large and/or sudden decreases in impedance can signify a breach in lead insulation.
• Threshold: this test confirms the minimum amount of energy (Both volts and pulse width) required to reliably
depolarize (capture) the chamber being tested. Determining the threshold allows the Allied Professional,
Representative, or Physician to program an output that recognizes an appropriate safety margin while optimizing
device longevity.
As modern pacemakers are "on-demand", meaning that they only pace when necessary, device longevity is affected
by how much it is utilized. Other factors affecting device longevity include programmed output and algorithms
(features) causing a higher level of current drain from the battery.
An additional aspect of the in-office check is to examine any events that were stored since the last follow-up. These
are typically stored based on specific criteria set by the physician and specific to the patient. Some devices have the
availability to display intracardiac electrograms of the onset of the event as well as the event itself. This is especially
helpful in diagnosing the cause or origin of the event and making any necessary programming changes.
Artificial pacemaker
156
Lifestyle considerations
A patient's lifestyle is usually not modified to any great degree after insertion of a pacemaker. There are a few
activities that are unwise such as full contact sports and activities that involve intense magnetic fields.
The pacemaker patient may find that some types of everyday actions need to be modified. For instance, the shoulder
harness of a vehicle seatbelt may be uncomfortable if the harness should fall across the pacemaker insertion site.
Any kind of an activity that involves intense magnetic fields should be avoided. This includes activities such as arc
welding possibly, with certain types of equipment[29] , or maintaining heavy equipment that may generate intense
magnetic fields (such as an MRI (Magnetic Resonance Imaging Machine)).
A 2008 U.S. study has found[30] that the magnets in some portable music players, when placed within an inch of
pacemakers, may cause interference.
Some medical procedures may require the use of antibiotics to be administered before the procedure. The patient
should inform all medical personnel that they have a pacemaker. Some standard medical procedures such as the use
of Magnetic resonance imaging (MRI) may be ruled out by the patient having a pacemaker.
In addition, according to the American Heart Association, some home devices have a remote potential to cause
interference by occasionally inhibiting a single beat. Cellphones available in the United States (less than 3 watts) do
not seem to damage pulse generators or affect how the pacemaker works.[31]
Privacy and security
Security and privacy concerns have been raised with pacemakers that allow wireless communication. Unauthorized
third parties may be able to read patient records contained in the pacemaker, or reprogram the devices, as has been
demonstrated by a team of researchers.[32] The demonstration worked at short range; they did not attempt to develop
a long range antenna. The proof of concept exploit helps demonstrate the need for better security and patient alerting
measures in remotely accessible medical implants.[32]
Other devices with pacemaker function
Sometimes devices resembling pacemakers, called implantable cardioverter-defibrillators (ICDs) are implanted.
These devices are often used in the treatment of patients at risk from sudden cardiac death. An ICD has the ability to
treat many types of heart rhythm disturbances by means of pacing, cardioversion, or defibrillation. Some ICD
devices can distinguish between ventricular fibrillation and ventricular tachycardia (VT), and may try to pace the
heart faster than its intrinsic rate in the case of VT, to try to break the tachycardia before it progresses to ventricular
fibrillation. This is known as fast-pacing, overdrive pacing, or anti-tachycardia pacing (ATP). ATP is only effective
if the underlying rhythm is ventricular tachycardia, and is never effective if the rhythm is ventricular fibrillation.
NASPE / BPEG Defibrillator (NBD) code - 1993[33]
I
II
III
IV
Shock chamber
Antitachycardia pacing chamber Tachycardia
detection
Antibradycardia pacing chamber
O = None
O = None
E = Electrogram
O = None
A = Atrium
A = Atrium
H = Hemodynamic
A = Atrium
V = Ventricle
V = Ventricle
D = Dual (A+V) D = Dual (A+V)
V = Ventricle
D = Dual (A+V)
Artificial pacemaker
157
Short form of the NASPE/BPEG Defibrillator (NBD) code[33]
ICD-S ICD with shock capability only
ICD-B ICD with bradycardia pacing as well as shock
ICD-T ICD with tachycardia (and bradycardia) pacing as well as shock
See also
•
•
•
•
•
•
Biological pacemaker
Cardiology
Electrical conduction system of the heart
Transcutaneous pacing
Pacemaker syndrome
Infective endocarditis
External links
• PreOp Patient Education Permanent Pacemaker Implant Surgery [34]
• Biventricular Pacemaker: What is Cardiac Resynchronization Therapy? Podcast from the Medical University of
South Carolina [35]
• Current indications for CRT-P and CRT-D: Webinar from the European Heart Rhythm Association (EHRA) [36]
References
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"Electrical Stimulation of the Heart in Man - 1899" (http:/ / www. hrsonline. org/ News/ ep-history/ timeline/ 1800s. cfm#elec), Heart Rhythm
Society, Accessed May 11, 2007.
[2] Lidwell M C, "Cardiac Disease in Relation to Anaesthesia" in Transactions of the Third Session, Australasian Medical Congress, Sydney,
Australia, Sept. 2-7 1929, p 160.
[3] Mond H, Sloman J, Edwards R (1982). "The first pacemaker". Pacing and clinical electrophysiology : PACE 5 (2): 278–82.
doi:10.1111/j.1540-8159.1982.tb02226.x. PMID 6176970.
[4] Aquilina O, " A brief history of cardiac pacing (http:/ / www. impaedcard. com/ issue/ issue27/ aquilinao2/ AquilinaO. htm)", Images
Paediatr Cardiol 27 (2006), pp.17-81.
[5] Furman S, Szarka G, Layvand D (2005). "Reconstruction of Hyman's second pacemaker" (http:/ / www. blackwell-synergy. com/
openurl?genre=article& sid=nlm:pubmed& issn=0147-8389& date=2005& volume=28& issue=5& spage=446). Pacing Clin Electrophysiol
28 (5): 446–53. doi:10.1111/j.1540-8159.2005.09542.x. PMID 15869680. .
[6] Harvard Gazette: Paul Maurice Zoll (http:/ / www. hno. harvard. edu/ gazette/ 2001/ 04. 19/ 12-zoll. html)
[7] Weirich W, Gott V, Lillehei C (1957). "The treatment of complete heart block by the combined use of a myocardial electrode and an artificial
pacemaker". Surg Forum 8: 360–3. PMID 13529629.
[8] Success Stories : Larsson, Arne : St. Jude Medical (http:/ / www. sjm. com/ successstories/ successstory. aspx?name=Larsson,+ Arne)
[9] Furman S, Schwedel JB (1959). "An intracardiac pacemaker for Stokes-Adams seizures" (http:/ / www. blackwell-synergy. com/
openurl?genre=article& sid=nlm:pubmed& issn=0147-8389& date=2006& volume=29& issue=5& spage=453). N. Engl. J. Med. 261: 943–8.
doi:10.1111/j.1540-8159.2006.00399.x. PMID 16689837. .
[10] "Permanent Transvenous Pacing in 1962", Parsonnet V, PACE,1:285, 1978
[11] "Preliminary Investigation of the Development of a Permanent Implantable Pacemaker Using an Intracardiac Dipolar Electrode", Parsonnet
V, Zucker I R, Asa M M, Clin. Res., 10:391, 1962
[12] Parsonnet V, Zucker IR, Maxim Asa M (1962). "An intracardiac bipolar electrode for interim treatment of complete heart block". Am. J.
Cardiol. 10: 261–5. doi:10.1016/0002-9149(62)90305-3. PMID 14484083.
[13] Lagergren H (1978). "How it happened: my recollection of early pacing". Pacing Clin Electrophysiol 1 (1): 140–3.
doi:10.1111/j.1540-8159.1978.tb03451.x. PMID 83610.
[14] Lagergren H, Johansson L (1963). "Intracardiac stimulation for complete heart block". Acta Chir Scand 125: 562–6. PMID 13928055.
[15] Jean Jaques Welti:Biography, Heart Rhythm Foundation
[16] Eich C, Bleckmann A, Paul T (October 2005). "Percussion pacing in a three-year-old girl with complete heart block during cardiac
catheterization" (http:/ / bja. oxfordjournals. org/ cgi/ content/ full/ 95/ 4/ 465). Br J Anaesth 95 (4): 465–7. doi:10.1093/bja/aei209.
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PMID 16051649. .
[17] "Pacemakers, Patient and Public Information Center : Heart Rhythm Society" (http:/ / www. hrspatients. org/ patients/ treatments/
pacemakers. asp). .
[18] Bernstein A, Daubert J, Fletcher R, Hayes D, Lüderitz B, Reynolds D, Schoenfeld M, Sutton R (2002). "The revised NASPE/BPEG generic
code for antibradycardia, adaptive-rate, and multisite pacing. North American Society of Pacing and Electrophysiology/British Pacing and
Electrophysiology Group". Pacing Clin Electrophysiol 25 (2): 260–4. PMID 11916002.
[19] Bohm A, Pinter A, Szekely A, Preda I (1998). "Clinical Observations with Long-term Atrial Pacing" (http:/ / www3. interscience. wiley.
com/ journal/ 119941339/ abstract). Pacing Clin Electrophysiol 21 (1): 246–9. doi:10.1111/j.1540-8159.1998.tb01097.x. .
[20] Pitts Crick JC for the European Multicenter Study Group (1991). "European Multicenter Prospective Follow-Up Study of 1,002 Implants of
a Single Lead VDD Pacing System" (http:/ / www3. interscience. wiley. com/ journal/ 119992153/ abstract). Pacing Clin Electrophysiol 14
(11): 1742–4. doi:10.1111/j.1540-8159.1991.tb02757.x. .
[21] Cleland JG, Daubert JC, Erdmann E, et al. (2005). "The effect of cardiac resynchronization on morbidity and mortality in heart failure"
(http:/ / content. nejm. org/ cgi/ content/ full/ 352/ 15/ 1539). N. Engl. J. Med. 352 (15): 1539–49. doi:10.1056/NEJMoa050496.
PMID 15753115. .
[22] Bardy GH, Lee KL, Mark DB, et al. (2005). "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure" (http:/ /
content. nejm. org/ cgi/ pmidlookup?view=short& pmid=15659722& promo=ONFLNS19). N. Engl. J. Med. 352 (3): 225–37.
doi:10.1056/NEJMoa043399. PMID 15659722. .
[23] Cleland J, Daubert J, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L (2005). "The effect of cardiac resynchronization on
morbidity and mortality in heart failure". N Engl J Med 352 (15): 1539–49. doi:10.1056/NEJMoa050496. PMID 15753115.
[24] Bristow M, Saxon L, Boehmer J, Krueger S, Kass D, De Marco T, Carson P, DiCarlo L, DeMets D, White B, DeVries D, Feldman A
(2004). "Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure". N Engl J Med 350
(21): 2140–50. doi:10.1056/NEJMoa032423. PMID 15152059.
[25] Wilkoff BL, Cook JR, Epstein AE, et al. (December 2002). "Dual-chamber pacing or ventricular backup pacing in patients with an
implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial" (http:/ / jama. ama-assn. org/ cgi/ content/ full/
288/ 24/ 3115). JAMA 288 (24): 3115–23. doi:10.1001/jama.288.24.3115. PMID 12495391. .
[26] de Oliveira JC, Martinelli M, D'Orio Nishioka SA, et al. (2009). "Efficacy of antibiotic prophylaxis prior to the implantation of pacemakers
and cardioverter-defibrillators: Results of a large, prospective, randomized, double-blinded, placebo-controlled trial". Circ Arrhythmia
Electrophysiol 2: 29–34. doi:10.1161/CIRCEP.108.795906.
[27] European Pacemaker Patient Identification card (http:/ / www. xs4all. nl/ ~fbaart/ aktueel/ pm. htm)
[28] Eucomed (http:/ / www. eucomed. com/ )
[29] "Testing of work environments for electromagnetic interference (Pacing Clin Electrophysiol. 1992) - PubMed Result" (http:/ / www. ncbi.
nlm. nih. gov/ pubmed/ 1279591). www.ncbi.nlm.nih.gov. . Retrieved 2008-11-10.
[30] "MP3 Headphones Interfere With Implantable Defibrillators, Pacemakers - Beth Israel Deaconess Medical Center" (http:/ / www. bidmc.
org/ News/ InResearch/ 2008/ November/ MP3PlayerStudy. aspx). www.bidmc.org. . Retrieved 2008-11-10.
[31] http:/ / www. americanheart. org/ presenter. jhtml?identifier=4676
[32] Halperin, Daniel; Thomas S. Heydt-Benjamin, Benjamin Ransford, Shane S. Clark, Benessa Defend, Will Morgan, Kevin Fu, Tadayoshi
Kohno, and William H. Maisel (May 2008). "Pacemakers and Implantable Cardiac Defibrillators: Software Radio Attacks and Zero-Power
Defenses" (http:/ / www. secure-medicine. org/ icd-study/ icd-study. pdf) (PDF). IEEE Symposium on Security and Privacy. . Retrieved
2008-08-10.
[33] Bernstein A, Camm A, Fisher J, Fletcher R, Mead R, Nathan A, Parsonnet V, Rickards A, Smyth N, Sutton R (1993). "North American
Society of Pacing and Electrophysiology policy statement. The NASPE/BPEG defibrillator code". Pacing Clin Electrophysiol 16 (9):
1776–80. PMID 7692407.
[34] http:/ / www. youtube. com/ watch?v=UdaTqPSO3Rs
[35] http:/ / www. muschealth. com/ multimedia/ Podcasts/ displayPod. aspx?podid=293& autostart=false& groupid=6
[36] http:/ / www. escardio. org/ communities/ EHRA/ education/ webinars/ Pages/ welcome. aspx
158
Electroencephalography
159
Electroencephalography
In neurology, the main diagnostic application of EEG is in the case of
epilepsy, as epileptic activity can create clear abnormalities on a
standard EEG study.[2] A secondary clinical use of EEG is in the
diagnosis of coma, encephalopathies, and brain death. EEG used to be
a first-line method for the diagnosis of tumors, stroke and other focal
brain disorders, but this use has decreased with the advent of
anatomical imaging techniques such as MRI and CT.
Derivatives of the EEG technique include evoked potentials (EP),
which involves averaging the EEG activity time-locked to the
presentation of a stimulus of some sort (visual, somatosensory, or
auditory). Event-related potentials refer to averaged EEG responses
that are time-locked to more complex processing of stimuli; this
technique is used in cognitive science, cognitive psychology, and
psychophysiological research.
Source of EEG activity
The electrical activity of the brain can be described in spatial scales
from the currents within a single dendritic spine to the relatively gross
potentials that the EEG records from the scalp, much the same way that
economics can be studied from the level of a single individual's
personal finances to the macro-economics of nations. Neurons, or
nerve cells, are electrically active cells which are primarily responsible
for carrying out the brain's functions. Neurons create action potentials,
which are discrete electrical signals that travel down axons and cause
the release of chemical neurotransmitters at the synapse, which is an
area of near contact between two neurons. This neurotransmitter then
activates a receptor in the dendrite or body of the neuron that is on the
other side of the synapse, the post-synaptic neuron. The
neurotransmitter, when combined with the receptor, typically causes an
electrical current within the dendrite or body of the post-synaptic
neuron. Thousands of post-synaptic currents from a single neuron's
dendrites and body then sum up to cause the neuron to generate an
action potential. This neuron then synapses on other neurons, and so
on.
An EEG recording net (Electrical Geodesics, Inc.
[1]
) being used on a participant in a brain wave
study.
Epileptic spike and wave discharges monitored
with EEG.
EEG reflects correlated synaptic activity caused by post-synaptic potentials of cortical neurons. The ionic currents
involved in the generation of fast action potentials may not contribute greatly to the averaged field potentials
representing the EEG .[3] [4] More specifically, the scalp electrical potentials that produce EEG are generally thought
to be caused by the extracellular ionic currents caused by dendritic electrical activity, whereas the fields producing
magnetoencephalographic signals[5] are associated with intracellular ionic currents [6] .
The electric potentials generated by single neurons are far too small to be picked by EEG or MEG.[4] EEG activity
therefore always reflects the summation of the synchronous activity of thousands or millions of neurons that have
similar spatial orientation, radial to the scalp. Currents that are tangential to the scalp are not picked up by the EEG.
Electroencephalography
The EEG therefore benefits from the parallel, radial arrangement of apical dendrites in the cortex. Because voltage
fields fall off with the fourth power of the radius, activity from deep sources is more difficult to detect than currents
near the skull[7] .
Scalp EEG activity shows oscillations at a variety of frequencies. Several of these oscillations have characteristic
frequency ranges, spatial distributions and are associated with different states of brain functioning (e.g., waking and
the various sleep stages). These oscillations represent synchronized activity over a network of neurons. The neuronal
networks underlying some of these oscillations are understood (e.g., the thalamocortical resonance underlying sleep
spindles), while many others are not (e.g., the system that generates the posterior basic rhythm). Research that
measures both EEG and neuron spiking finds the relationship between the two is complex with the power of surface
EEG only in two bands that of gamma and delta relating to neuron spike activity.[8]
Clinical use
A routine clinical EEG recording typically lasts 20–30 minutes (plus preparation time) and usually involves
recording from 25 scalp electrodes. Routine EEG is typically used in the following clinical circumstances:
• to distinguish epileptic seizures from other types of spells, such as psychogenic non-epileptic seizures, syncope
(fainting), sub-cortical movement disorders and migraine variants.
•
•
•
•
to differentiate "organic" encephalopathy or delirium from primary psychiatric syndromes such as catatonia
to serve as an adjunct test of brain death
to prognosticate, in certain instances, in patients with coma
to determine whether to wean anti-epileptic medications
At times, a routine EEG is not sufficient, particularly when it is necessary to record a patient while he/she is having a
seizure. In this case, the patient may be admitted to the hospital for days or even weeks, while EEG is constantly
being recorded (along with time-synchronized video and audio recording). A recording of an actual seizure (i.e., an
ictal recording, rather than an inter-ictal recording of a possibly epileptic patient at some period between seizures)
can give significantly better information about whether or not a spell is an epileptic seizure and the focus in the brain
from which the seizure activity emanates.
Epilepsy monitoring is typically done:
• to distinguish epileptic seizures from other types of spells, such as psychogenic non-epileptic seizures, syncope
(fainting), sub-cortical movement disorders and migraine variants.
• to characterize seizures for the purposes of treatment
• to localize the region of brain from which a seizure originates for work-up of possible seizure surgery
Additionally, EEG may be used to monitor certain procedures:
• to monitor the depth of anesthesia
• as an indirect indicator of cerebral perfusion in carotid endarterectomy
• to monitor amobarbital effect during the Wada test
EEG can also be used in intensive care units for brain function monitoring:
• to monitor for non-convulsive seizures/non-convulsive status epilepticus
• to monitor the effect of sedative/anesthesia in patients in medically induced coma (for treatment of refractory
seizures or increased intracranial pressure)
• to monitor for secondary brain damage in conditions such as subarachnoid hemorrhage (currently a research
method)
If a patient with epilepsy is being considered for resective surgery, it is often necessary to localize the focus (source)
of the epileptic brain activity with a resolution greater than what is provided by scalp EEG. This is because the
cerebrospinal fluid, skull and scalp smear the electrical potentials recorded by scalp EEG. In these cases,
neurosurgeons typically implant strips and grids of electrodes (or penetrating depth electrodes) under the dura mater,
160
Electroencephalography
161
through either a craniotomy or a burr hole. The recording of these signals is referred to as electrocorticography
(ECoG), subdural EEG (sdEEG) or intracranial EEG (icEEG)--all terms for the same thing. The signal recorded
from ECoG is on a different scale of activity than the brain activity recorded from scalp EEG. Low voltage, high
frequency components that cannot be seen easily (or at all) in scalp EEG can be seen clearly in ECoG. Further,
smaller electrodes (which cover a smaller parcel of brain surface) allow even lower voltage, faster components of
brain activity to be seen. Some clinical sites record from penetrating microelectrodes.[9]
Research use
EEG, and its derivative, ERPs, are used extensively in neuroscience,
cognitive science, cognitive psychology, and psychophysiological
research. Many techniques used in research contexts are not
standardized sufficiently to be used in the clinical context.
A different method to study brain function is functional magnetic
resonance imaging (fMRI). Some benefits of EEG compared to fMRI
include:
An early EEG recording, obtained by Hans
Berger in 1924. The upper tracing is EEG, and
the lower is a 10 Hz timing signal.
• Hardware costs are significantly lower for EEG sensors versus an fMRI machine
•
•
•
•
•
EEG sensors can be deployed into a wider variety of environments than can a bulky, immobile fMRI machine
EEG enables higher temporal resolution, on the order of milliseconds, rather than seconds
EEG is relatively tolerant of subject movement versus an fMRI (where the subject must remain completely still)
EEG is silent, which allows for better study of the responses to auditory stimuli
EEG does not aggravate claustrophobia
Limitations of EEG as compared with fMRI include:
• Significantly lower spatial resolution
• Need to apply electrodes to the scalp (which may bother people with severe tactile sensitivities, e.g., some
individuals with autism)
• ERP studies require relatively simple paradigms, compared with block-design fMRI studies
EEG recordings have been successfully obtained simultaneously with fMRI scans, though successful simultaneous
recording requires that several technical issues be overcome, such as the presence of ballistocardiographic artifact,
MRI pulse artifact and the induction of electrical currents in EEG wires that move within the strong magnetic fields
of the MRI.
EEG also has some characteristics that compare favorably with behavioral testing:
•
•
•
•
EEG can detect covert processing (i.e., that which does not require a response)
EEG can be used in subjects who are incapable of making a motor response
Some ERP components can be detected even when the subject is not attending to the stimuli
As compared with other reaction time paradigms, ERPs can elucidate stages of processing (rather than just the
final end result)
Electroencephalography
162
Method
In conventional scalp EEG, the recording is obtained by placing
electrodes on the scalp with a conductive gel or paste, usually after
preparing the scalp area by light abrasion to reduce impedance due to
dead skin cells. Many systems typically use electrodes, each of which
is attached to an individual wire. Some systems use caps or nets into
which electrodes are embedded; this is particularly common when
high-density arrays of electrodes are needed.
Computer Electroencephalograph
Electrode locations and names are specified by the International 10–20
Neurovisor-BMM 40
system[10] for most clinical and research applications (except when
high-density arrays are used). This system ensures that the naming of electrodes is consistent across laboratories. In
most clinical applications, 19 recording electrodes (plus ground and system reference) are used. A smaller number of
electrodes are typically used when recording EEG from neonates. Additional electrodes can be added to the standard
set-up when a clinical or research application demands increased spatial resolution for a particular area of the brain.
High-density arrays (typically via cap or net) can contain up to 256 electrodes more-or-less evenly spaced around the
scalp.
Each electrode is connected to one input of a differential amplifier (one amplifier per pair of electrodes); a common
system reference electrode is connected to the other input of each differential amplifier. These amplifiers amplify the
voltage between the active electrode and the reference (typically 1,000–100,000 times, or 60–100 dB of voltage
gain). In analog EEG, the signal is then filtered (next paragraph), and the EEG signal is output as the deflection of
pens as paper passes underneath. Most EEG systems these days, however, are digital, and the amplified signal is
digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital
sampling typically occurs at 256–512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz are used in some
research applications.
During the recording, a series of activation procedures may be used. These procedures may induce normal or
abnormal EEG activity that might not otherwise be seen. These procedures include hyperventilation, photic
stimulation (with a strobe light), eye closure, mental activity, sleep and sleep deprivation. During (inpatient) epilepsy
monitoring, a patient's typical seizure medications may be withdrawn.
The digital EEG signal is stored electronically and can be filtered for display. Typical settings for the high-pass filter
and a low-pass filter are 0.5-1 Hz and 35–70 Hz, respectively. The high-pass filter typically filters out slow artifact,
such as electrogalvanic signals and movement artifact, whereas the low-pass filter filters out high-frequency
artifacts, such as electromyographic signals. An additional notch filter is typically used to remove artifact caused by
electrical power lines (60 Hz in the United States and 50 Hz in many other countries).[9] As part of an evaluation for
epilepsy surgery, it may be necessary to insert electrodes near the surface of the brain, under the surface of the dura
mater. This is accomplished via burr hole or craniotomy. This is referred to variously as "electrocorticography
(ECoG)", "intracranial EEG (I-EEG)" or "subdural EEG (SD-EEG)". Depth electrodes may also be placed into brain
structures, such as the amygdala or hippocampus, structures which are common epileptic foci and may not be "seen"
clearly by scalp EEG. The electrocorticographic signal is processed in the same manner as digital scalp EEG
(above), with a couple of caveats. ECoG is typically recorded at higher sampling rates than scalp EEG because of the
requirements of Nyquist theorem—the subdural signal is composed of a higher predominance of higher frequency
components. Also, many of the artifacts which affect scalp EEG do not impact ECoG, and therefore display filtering
is often not needed.
A typical adult human EEG signal is about 10µV to 100 µV in amplitude when measured from the scalp
about 10–20 mV when measured from subdural electrodes.
[11]
and is
Electroencephalography
Since an EEG voltage signal represents a difference between the voltages at two electrodes, the display of the EEG
for the reading encephalographer may be set up in one of several ways. The representation of the EEG channels is
referred to as a montage.
Bipolar montage
Each channel (i.e., waveform) represents the difference between two adjacent electrodes. The entire montage
consists of a series of these channels. For example, the channel "Fp1-F3" represents the difference in voltage
between the Fp1 electrode and the F3 electrode. The next channel in the montage, "F3-C3," represents the
voltage difference between F3 and C3, and so on through the entire array of electrodes.
Referential montage
Each channel represents the difference between a certain electrode and a designated reference electrode. There
is no standard position at which this reference is always placed; it is, however, at a different position than the
"recording" electrodes. Midline positions are often used because they do not amplify the signal in one
hemisphere vs. the other. Another popular reference is "linked ears," which is a physical or mathematical
average of electrodes attached to both earlobes or mastoids.
Average reference montage
The outputs of all of the amplifiers are summed and averaged, and this averaged signal is used as the common
reference for each channel.
Laplacian montage
Each channel represents the difference between an electrode and a weighted average of the surrounding
electrodes.[12]
When analog (paper) EEGs are used, the technologist switches between montages during the recording in order to
highlight or better characterize certain features of the EEG. With digital EEG, all signals are typically digitized and
stored in a particular (usually referential) montage; since any montage can be constructed mathematically from any
other, the EEG can be viewed by the electroencephalographer in any display montage that is desired.
The EEG is read by a neurologist, optimally one who has specific training in the interpretation of EEGs. This is done
by visual inspection of the waveforms. The use of computer signal processing of the EEG—so-called quantitative
EEG—is somewhat controversial when used for clinical purposes (although there are many research uses).
Limitations
EEG has several limitations. Most important is its poor spatial resolution. EEG is most sensitive to a particular set of
post-synaptic potentials: those which are generated in superficial layers of the cortex, on the crests of gyri directly
abutting the skull and radial to the skull. Dendrites which are deeper in the cortex, inside sulci, in midline or deep
structures (such as the cingulate gyrus or hippocampus), or producing currents which are tangential to the skull, have
far less contribution to the EEG signal.
The meninges, cerebrospinal fluid and skull "smear" the EEG signal, obscuring its intracranial source.
It is mathematically impossible to reconstruct a unique intracranial current source for a given EEG signal[9] , as some
currents produce potentials that cancel each other out. This is referred to as the inverse problem. However, much
work has been done to produce remarkably good estimates of, at least, a localized electric dipole that represents the
recorded currents.
163
Electroencephalography
164
EEG vs fMRI and PET
EEG has several strong points as a tool for exploring brain activity. EEG's can detect changes within a millisecond
timeframe, excellent considering an action potential takes approximately 0.5-130 milliseconds to propagate across a
single neuron, depending on the type of neuron[13] . Other methods of looking at brain activity, such as PET and
fMRI have time resolution between seconds and minutes. EEG measures the brain's electrical activity directly, while
other methods record changes in blood flow (e.g., SPECT, fMRI) or metabolic activity (e.g., PET), which are
indirect markers of brain electrical activity. EEG can be used simultaneously with fMRI so that
high-temporal-resolution data can be recorded at the same time as high-spatial-resolution data, however, since the
data derived from each occurs over a different time course, the data sets do not necessarily represent the exact same
brain activity. There are technical difficulties associated with combining these two modalities, including the need to
remove the MRI gradient artifact present during MRI acquisition and the ballistocardiographic artifact (resulting
from the pulsatile motion of blood and tissue) from the EEG. Furthermore, currents can be induced in moving EEG
electrode wires due to the magnetic field of the MRI.
EEG can be recorded at the same time as MEG so that data from these complementary high-time-resolution
techniques can be combined.
Normal activity
The EEG is typically described in
terms of (1) rhythmic activity and (2)
transients. The rhythmic activity is
divided into bands by frequency. To
some degree, these frequency bands
One second of EEG signal
are a matter of nomenclature (i.e., any
rhythmic activity between 8–12 Hz can
be described as "alpha"), but these designations arose because rhythmic activity within a certain frequency range was
noted to have a certain distribution over the scalp or a certain biological significance. Frequency bands are usually
extracted using spectral methods (for instance Welch) as implemented for instance in freely available EEG software
such as EEGLAB.
Most of the cerebral signal observed in the scalp EEG falls in the range of 1–20 Hz (activity below or above this
range is likely to be artifactual, under standard clinical recording techniques).
Comparison table
Comparison of EEG bands
Type
Frequency
(Hz)
Delta
up to 4
Location
frontally in adults,
posteriorly in children;
high amplitude waves
Normally
•
•
•
adults slow wave sleep
in babies
Has been found during some continuous
attention tasks (Kirmizi-Alsan et. al. 2006)
Pathologically
•
•
•
•
subcortical lesions
diffuse lesions
metabolic encephalopathy hydrocephalus
deep midline lesions
Electroencephalography
Theta
4 – 7 Hz
Found in locations not
related to task at hand
165
•
•
•
•
young children
drowsiness or arousal in older children and
adults
idling
Associated with inhibition of elicited
responses (has been found to spike in
situations where a person is actively trying
to repress a response or action)
(Kirmizi-Alsan et al 2006).
•
•
•
•
focal subcortical lesions
metabolic encephalopathy
deep midline disorders
some instances of hydrocephalus
Alpha
8 – 12 Hz
posterior regions of head,
both sides, higher in
amplitude on dominant
side. Central sites (c3-c4)
at rest .
•
•
•
relaxed/reflecting
closing the eyes
Also associated with inhibition control,
seemingly with the purpose of timing
inhibitory activity in different locations
across the brain (Klimesch, Sauseng, &
Hanslmayr 2007; Coan & Allen 2008).
•
coma
Beta
12 – 30 Hz
both sides, symmetrical
distribution, most evident
frontally; low amplitude
waves
•
•
alert/working
active, busy or anxious thinking, active
concentration
•
benzodiazepines
Somatosensory cortex
•
Displays during cross-modal sensory
processing (perception which combines
two different senses, such as sound and
sight) (Kisley & Cornwell 2006;
Kanayama, Sato, & Ohira 2007;
Nieuwenhuis, Yeung, & Cohen 2004)
Also is shown during short term memory
matching of recognized objects, sounds, or
tactile sensations (Herrmann, Frund, &
Lenz 2009)
•
A decrease in gamma band activity may
be associated with cognitive decline,
especially when related the theta band;
however, this has not been proven for use
as a clinical diagnostic measurement yet
(Moretti et. al. 2009).
Gamma 30 – 100 +
•
It should be noted that while these are the universally recognized ranges, they are not concrete definitions of the
range of brain-waves. While researchers tend to follow these guidelines, many scholars use their own specific
boundaries depending on the range in which they choose to focus; additionally, some researchers define the bands
using decimal values rather than rounding to whole numbers (for example, one researcher may define the lower Beta
band cut-off as 12.1, while another may use the value 13), while still others sometimes divide the bands into
sub-bands. Generally, this is only done for the sake of analysis.
Wave patterns
• Delta is the frequency range up to 4
Hz. It tends to be the highest in
amplitude and the slowest waves. It
is seen normally in adults in slow
wave sleep. It is also seen normally
delta waves.
in babies. It may occur focally with
subcortical lesions and in general
distribution with diffuse lesions, metabolic encephalopathy hydrocephalus or deep midline lesions. It is usually
most prominent frontally in adults (e.g. FIRDA - Frontal Intermittent Rhythmic Delta) and posteriorly in children
(e.g. OIRDA - Occipital Intermittent Rhythmic Delta).
Electroencephalography
166
• Theta is the frequency range from 4
Hz to 7 Hz. Theta is seen normally
in young children. It may be seen in
drowsiness or arousal in older
children and adults; it can also be
theta waves.
seen in meditation.[14] Excess theta
for age represents abnormal
activity. It can be seen as a focal disturbance in focal subcortical lesions; it can be seen in generalized distribution
in diffuse disorder or metabolic encephalopathy or deep midline disorders or some instances of hydrocephalus.
On the contrary this range has been associated with reports of relaxed, meditative, and creative states.
• Alpha is the frequency range from 8
Hz to 12 Hz. Hans Berger named
the first rhythmic EEG activity he
saw, the "alpha wave." This is
activity in the 8–12 Hz range seen
alpha waves.
in the posterior regions of the head
on both sides, being higher in
amplitude on the dominant side. It is brought out by closing the eyes and by relaxation. It was noted to attenuate
with eye opening or mental exertion. This activity is now referred to as "posterior basic rhythm," the "posterior
dominant rhythm" or the "posterior alpha rhythm." The posterior basic rhythm is actually slower than 8 Hz in
young children (therefore technically in the theta range). In addition to the posterior basic rhythm, there are two
other normal alpha rhythms that are typically discussed: the mu rhythm and a temporal "third rhythm". Alpha can
be abnormal; for example, an EEG that has diffuse alpha occurring in coma and is not responsive to external
stimuli is referred to as "alpha coma".
• Mu rhythm is alpha-range activity
that is seen over the sensorimotor
cortex. It characteristically
attenuates with movement of the
contralateral arm (or mental
imagery of movement of the
contralateral arm).
sensorimotor rhythm aka mu rhythm.
• Beta is the frequency range from 12
Hz to about 30 Hz. It is seen usually
on both sides in symmetrical
distribution and is most evident
frontally. Beta activity is closely
beta waves.
linked to motor behavior and is
generally attenuated during active
movements.[15] Low amplitude beta with multiple and varying frequencies is often associated with active, busy or
anxious thinking and active concentration. Rhythmic beta with a dominant set of frequencies is associated with
various pathologies and drug effects, especially benzodiazepines. It may be absent or reduced in areas of cortical
damage. It is the dominant rhythm in patients who are alert or anxious or who have their eyes open.
Electroencephalography
• Gamma is the frequency range
approximately 30–100 Hz. Gamma
rhythms are thought to represent
binding of different populations of
neurons together into a network for
the purpose of carrying out a certain
cognitive or motor function.
167
gamma waves.
"Ultra-slow" or "near-DC" activity is recorded using DC amplifiers in some research contexts. It is not typically
recorded in a clinical context because the signal at these frequencies is susceptible to a number of artifacts.
Some features of the EEG are transient rather than rhythmic. Spikes and sharp waves may represent seizure activity
or interictal activity in individuals with epilepsy or a predisposition toward epilepsy. Other transient features are
normal: vertex waves and sleep spindles are transient events which are seen in normal sleep.
It should also be noted that there are types of activity which are statistically uncommon but are not associated with
dysfunction or disease. These are often referred to as "normal variants." The mu rhythm is an example of a normal
variant.
The normal Electroencephalography (EEG) varies by age. The neonatal EEG is quite different from the adult EEG.
The EEG in childhood generally has slower frequency oscillations than the adult EEG.
The normal EEG also varies depending on state. The EEG is used along with other measurements (EOG, EMG) to
define sleep stages in polysomnography. Stage I sleep (equivalent to drowsiness in some systems) appears on the
EEG as drop-out of the posterior basic rhythm. There can be an increase in theta frequencies. Santamaria and
Chiappa cataloged a number of the variety of patterns associated with drowsiness. Stage II sleep is characterized by
sleep spindles—transient runs of rhythmic activity in the 12–14 Hz range (sometimes referred to as the "sigma"
band) that have a frontal-central maximum. Most of the activity in Stage II is in the 3–6 Hz range. Stage III and IV
sleep are defined by the presence of delta frequencies and are often referred to collectively as "slow-wave sleep."
Stages I-IV comprise non-REM (or "NREM") sleep. The EEG in REM (rapid eye movement) sleep appears
somewhat similar to the awake EEG.
EEG under general anesthesia depends on the type of anesthetic employed. With halogenated anesthetics, such as
halothane or intravenous agents, such as propofol, a rapid (alpha or low beta), nonreactive EEG pattern is seen over
most of the scalp, especially anteriorly; in some older terminology this was known as a WAR (widespread anterior
rapid) pattern, contrasted with a WAIS (widespread slow) pattern associated with high doses of opiates. Anesthetic
effects on EEG signals are beginning to be understood at the level of drug actions on different kinds of synapses and
the circuits that allow synchronized neuronal activity (see: http://www.stanford.edu/group/maciverlab/).
Artifacts
Biological artifacts
Electrical signals detected along the scalp by an EEG, but that originate from non-cerebral origin are called artifacts.
EEG data is almost always contaminated by such artifacts. The amplitude of artifacts can be quite large relative to
the size of amplitude of the cortical signals of interest. This is one of the reasons why it takes considerable
experience to correctly interpret EEGs clinically. Some of the most common types of biological artifacts include:
• Eye-induced artifacts (includes eye blinks and eye movements)
• EKG (cardiac) artifacts
• EMG (muscle activation)-induced artifacts
• Glossokinetic artifacts
Electroencephalography
Eye-induced artifacts are caused by the potential difference between the cornea and retina, which is quite large
compared to cerebral potentials. When the eye is completely still, this does not affect EEG. But there are nearly
always small or large reflexive eye movements, which generates a potential which is picked up in the frontopolar and
frontal leads. Involuntary eye movements, known as saccades, are caused by ocular muscles, which also generate
electromyographic potentials. Purposeful or reflexive eye blinking also generates electromyographic potentials, but
more importantly there is reflexive movement of the eyeball during blinking which gives a characteristic artifactual
appearance of the EEG (see Bell's phenomenon).
Eyelid fluttering artifacts of a characteristic type were previously called Kappa rhythm (or Kappa waves). It is
usually seen in the prefrontal leads, that is, just over the eyes. Sometimes they are seen with mental activity. They
are usually in the Theta (4–7 Hz) or Alpha (8–13 Hz) range. They were named because they were believed to
originate from the brain. Later study revealed they were generated by rapid fluttering of the eyelids, sometimes so
minute that it was difficult to see. They are in fact noise in the EEG reading, and should not technically be called a
rhythm or wave. Therefore, current usage in electroencephalography refers to the phenomenon as an eyelid fluttering
artifact, rather than a Kappa rhythm (or wave).[16]
Some of these artifacts are useful. Eye movements are very important in polysomnography, and is also useful in
conventional EEG for assessing possible changes in alertness, drowsiness or sleep.
EKG artifacts are quite common and can be mistaken for spike activity. Because of this, modern EEG acquisition
commonly includes a one-channel EKG from the extremities. This also allows the EEG to identify cardiac
arrhythmias that are an important differential diagnosis to syncope or other episodic/attack disorders.
Glossokinetic artifacts are caused by the potential difference between the base and the tip of the tongue. Minor
tongue movements can contaminate the EEG, especially in parkinsonian and tremor disorders.
Environmental artifacts
In addition to artifacts generated by the body, many artifacts originate from outside the body. Movement by the
patient, or even just settling of the electrodes, may cause electrode pops, spikes originating from a momentary
change in the impedance of a given electrode. Poor grounding of the EEG electrodes can cause significant 50 or 60
Hz artifact, depending on the local power system's frequency. A third source of possible interference can be the
presence of an IV drip; such devices can cause rhythmic, fast, low-voltage bursts, which may be confused for spikes.
Artifact correction
Recently, independent component analysis techniques have been used to correct or remove EEG contaminates.
These techniques attempt to "unmix" the EEG signals into some number of underlying components. There are many
source separation algorithms, often assuming various behaviors or natures of EEG. Regardless, the principle behind
any particular method usually allow "remixing" only those components that would result in "clean" EEG by
nullifying (zeroing) the weight of unwanted components.
Abnormal activity
Abnormal activity can broadly be separated into epileptiform and non-epileptiform activity. It can also be separated
into focal or diffuse.
Focal epileptiform discharges represent fast, synchronous potentials in a large number of neurons in a somewhat
discrete area of the brain. These can occur as interictal activity, between seizures, and represent an area of cortical
irritability that may be predisposed to producing epileptic seizures. Interictal discharges are not wholly reliable for
determining whether a patient has epilepsy nor where his/her seizure might originate. (See focal epilepsy.)
Generalized epileptiform discharges often have an anterior maximum, but these are seen synchronously throughout
the entire brain. They are strongly suggestive of a generalized epilepsy.
168
Electroencephalography
Focal non-epileptiform abnormal activity may occur over areas of the brain where there is focal damage of the cortex
or white matter. It often consists of an increase in slow frequency rhythms and/or a loss of normal higher frequency
rhythms. It may also appear as focal or unilateral decrease in amplitude of the EEG signal.
Diffuse non-epileptiform abnormal activity may manifest as diffuse abnormally slow rhythms or bilateral slowing of
normal rhythms, such as the PBR.
More advanced measures of abnormal EEG signals have also recently received attention as possible biomarkers for
different disorders such as Alzheimer's disease.[17]
History
A timeline of the history of EEG is given by Swartz.[18] Richard Caton (1842–1926), a physician practicing in
Liverpool, presented his findings about electrical phenomena of the exposed cerebral hemispheres of rabbits and
monkeys in the British Medical Journal in 1875. In 1890, Polish physiologist Adolf Beck published an investigation
of spontaneous electrical activity of the brain of rabbits and dogs which included rhythmic oscillations altered by
light.
In 1912, Russian physiologist, Vladimir Vladimirovich Pravdich-Neminsky published the first EEG and the evoked
potential of the mammalian (dog).[19] In 1914, Napoleon Cybulski and Jelenska-Macieszyna photographed
EEG-recordings of experimentally induced seizures.
German physiologist and psychiatrist Hans Berger (1873–1941) began his studies of the human EEG in 1920. He
gave the device its name and is sometimes credited with inventing the EEG, though others had performed similar
experiments. His work was later expanded by Edgar Douglas Adrian. In 1934, Fisher and Lowenback first
demonstrated epileptiform spikes. In 1935 Gibbs, Davis and Lennox described interictal spike waves and the 3
cycles/s pattern of clinical absence seizures, which began the field of clinical electroencephalography. Subsequently,
in 1936 Gibbs and Jasper reported the interictal spike as the focal signature of epilepsy. The same year, the first EEG
laboratory opened at Massachusetts General Hospital.
Franklin Offner (1911–1999), professor of biophysics at Northwestern University developed a prototype of the EEG
which incorporated a piezoelectric inkwriter called a Crystograph (the whole device was typically known as the
Offner Dynograph).
In 1947, The American EEG Society was founded and the first International EEG congress was held. In 1953
Aserinsky and Kleitman describe REM sleep.
In the 1950s, William Grey Walter developed an adjunct to EEG called EEG topography which allowed for the
mapping of electrical activity across the surface of the brain. This enjoyed a brief period of popularity in the 1980s
and seemed especially promising for psychiatry. It was never accepted by neurologists and remains primarily a
research tool.
Various uses
The EEG has been used for many purposes besides the conventional uses of clinical diagnosis and conventional
cognitive neuroscience. Long-term EEG recordings in epilepsy patients are used for seizure prediction.
Neurofeedback remains an important extension, and in its most advanced form is also attempted as the basis of brain
computer interfaces. The EEG is also used quite extensively in the field of neuromarketing. There are many
commercial products substantially based on the EEG.
Honda is attempting to develop a system to move its Asimo robot using EEG, a technology which it eventually
hopes to incorporate into its automobiles.[20]
EEGs have been used as evidence in trials in the Indian state of Maharastra.[21]
169
Electroencephalography
170
EEG and Telepathy
DARPA has budgeted $4 million in 2009 to investigate technology to enable soldiers on the battlefield to
communicate via computer-mediated telepathy. The aim is to analyse neural signals that exist in the brain before
words are spoken. [22]
Games
• In late 2009, an Australian company called Emotiv launched a wireless 14-channel EEG system targeted for
usage with video games.[23]
• Announced at the turn of 2008/2009 were two one-player tabletop gadgets, based on the EEG technology of the
company Neurosky. MindFlex by Mattel consists of a ball on a small obstacle course,[24] Force Trainer by Uncle
Milton Industries of a ball in a transparent tube.[25] Both feature a headset and a motor to levitate the ball.
Images
Person wearing
electrodes for EEG
See also
•
•
•
•
•
•
•
•
•
Binaural beats
Brain-computer interface
Brainwave synchronization
Direct brain interfaces
EEG measures during anesthesia
Electropalatograph
European data format
Event-related potential
Evoked potential
• Hemoencephalography
• Induced activity
Portable recording device for EEG
EEG
electroencephalophone
used during a music
performance in which
bathers from around
the world were
networked together as
part of a collective
musical performance,
using their brainwaves
to control sound,
lighting, and the bath
environment
Electroencephalography
•
•
•
•
•
•
•
Local field potentials
Magnetoencephalography
Mind machine
Neural oscillations
Neurofeedback
Ongoing brain activity
Intracranial EEG
External links
• Scholarpedia EEG [26]
References
[1] A Hydrocel Geodesic Sensor Net by Electrical Geodesics, Inc.
[2] Atlas of EEG & Seizure Semiology. B. Abou-Khalil; Musilus, K.E.; Elsevier, 2006.
[3] Creutzfeldt OD, Watanabe S, Lux HD (1966). "Relations between EEG phenomena and potentials of single cortical cells. I. Evoked responses
after thalamic and epicortical stimulation". Electroencephalogr Clin Neurophysiol 20 (1): 1–18. doi:10.1016/0013-4694(66)90136-2.
PMID 4161317.
[4] Nunez PL, Srinivasan R (1981). Electric fields of the brain: The neurophysics of EEG. Oxford University Press.
[5] Hamalainen M, Hari R, Ilmoniemi RJ, Knuutila J, Lounasmaa OV (1993). "Magnetoencphalography - Theory, instrumentation, and
applications to noninvasive studies of the working human brain". Reviews of Modern Physics 65: 413–497. doi:10.1103/RevModPhys.65.413.
[6] Buzsaki G (2006). Rhythms of the brain. Oxford University Press.
[7] Klein, S., & Thorne, B. M. (2007). Biological psychology. New York, N.Y.: Worth.
[8] Whittingstall K, Logothetis NK. (2009). Frequency-band coupling in surface EEG reflects spiking activity in monkey visual cortex. Neuron.
64(2):281-9. PMID 19874794
[9] Niedermeyer E, Lopes da Silva F (2004). Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincot
Williams & Wilkins.
[10] Towle VL, Bolaños J, Suarez D, Tan K, Grzeszczuk R, Levin DN, Cakmur R, Frank SA, Spire JP. (1993). "The spatial location of EEG
electrodes: locating the best-fitting sphere relative to cortical anatomy". Electroencephalogr Clin Neurophysiol 86 (1): 1–6.
doi:10.1016/0013-4694(93)90061-Y. PMID 7678386.
[11] H. Aurlien, I.O. Gjerde, J. H. Aarseth, B. Karlsen, H. Skeidsvoll, N. E. Gilhus (March 2004). "EEG background activity described by a
large computerized database.". Clinical Neurophysiology 115 (3): 665–673. doi:10.1016/j.clinph.2003.10.019. PMID 15036063.
[12] Nunez PL, Pilgreen KL (1991). "The spline-Laplacian in clinical neurophysiology: a method to improve EEG spatial resolution". J Clin
Neurophysiol 8 (4): 397–413. PMID 1761706.
[13] J. Anderson, Cognitive Psychology and It's Implications, 6th Ed., 2005, Worth Publishers, New York, NY, 17 pp.
[14] Cahn BR, & Polich J. (2006). Meditation states and traits: EEG, ERP, and neuroimaging studies. Psychological Bulletin. 132 (2), 180-211.
[15] Pfurtscheller G, Lopes da Silva FH (1999). "Event-related EEG/MEG synchronization and desynchronization: basic principles". Clin
Neurophysiol 110 (11): 1842–1857. doi:10.1016/S1388-2457(99)00141-8. PMID 10576479.
[16] Epstein, Charles M. (1983). Introduction to EEG and evoked potentials. J. B. Lippincot Co.. ISBN 0-397-50598-1.
[17] Montez T, Poil S-S, Jones BF, Manshanden I, Verbunt JPA, van Dijk BW, Brussaard AB, van Ooyen A, Stam CJ, Scheltens P,
Linkenkaer-Hansen K (2009). "Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer
disease" (http:/ / www. pnas. org/ content/ 106/ 5/ 1614. abstract). PNAS 106 (5): 1614–1619. doi:10.1073/pnas.0811699106. .
[18] Swartz, B.E; Goldensohn, ES (1998). "Timeline of the history of EEG and associated fields" (http:/ / www. sciencedirect. com/
science?_ob=MImg& _imagekey=B6SYX-4FV4S6H-1-1& _cdi=4846& _user=10& _orig=browse& _coverDate=02/ 28/ 1998&
_sk=998939997& view=c& wchp=dGLbVzz-zSkWb& md5=47fbbe7e51a806779716fba415b96ab7& ie=/ sdarticle. pdf) (PDF).
Electroencephalography and clinical Neurophysiology 106 (2): 173–176. doi:10.1016/S0013-4694(97)00113-2. PMID 9741779. .
[19] Pravdich-Neminsky VV. Ein Versuch der Registrierung der elektrischen Gehirnerscheinungen (In German). Zbl Physiol 27: 951–960, 1913.
[20] (http:/ / search. japantimes. co. jp/ cgi-bin/ nb20090401a2. html) 1 Apr 20009, Japan Times
[21] This brain test maps the truth (http:/ / timesofindia. indiatimes. com/ Cities/ This_brain_test_maps_the_truth/ articleshow/ 3257032. cms) 21
Jul 2008, 0348 hrs IST, Nitasha Natu,TNN
[22] Katie, Drummond; Noah Schachtman (2009-05-14). "Pentagon Preps Soldier Telepathy Push" (http:/ / www. wired. com/ dangerroom/
2009/ 05/ pentagon-preps-soldier-telepathy-push/ ). Wired. . Retrieved 2009-06-14.
[23] "Emotiv Systems Homepage" (http:/ / emotiv. com/ ). Emotiv.com. . Retrieved 2009-12-29.
[24] http:/ / www. physorg. com/ news150781868. html
[25] http:/ / www. usatoday. com/ life/ lifestyle/ 2009-01-06-force-trainer-toy_N. htm
[26] http:/ / www. scholarpedia. org/ article/ Electroencephalogram
171
Cochlear implant
172
Cochlear implant
A cochlear implant (CI) is a surgically implanted
electronic device that provides a sense of sound to a
person who is profoundly deaf or severely hard of
hearing. The cochlear implant is often referred to as a
bionic ear.
As of April 2009, approximately 188,000 people
worldwide had received cochlear implants;[1] in the
United States, about 30,000 adults and over 30,000
children are recipients.[2] The vast majority are in
developed countries due to the high cost of the device,
surgery and post-implantation therapy. A small but
growing segment of recipients have bilateral implants
(one implant in each cochlea).[3]
There is disagreement whether providing cochlear
implants to children is ethically justifiable, renewing a
century-old debate about models of deafness that often
pits hearing parents of deaf children against the Deaf
community.
Cochlear implant
History
The discovery that electrical stimulation in the auditory system can create a perception of sound occurred around
1790, when Alessandro Volta (the developer of the electric battery) placed metal rods in his own ears and connected
them to a 50-volt circuit, experiencing a jolt and hearing a noise "like a thick boiling soup". Other experiments
occurred sporadically, until electrical (sound-amplifying) hearing aids began to be developed in earnest in the 20th
century.
The first direct stimulation of an acoustic nerve with an electrode was performed in the 1950s by the
French-Algerian surgeons André Djourno and Charles Eyriès. They placed wires on nerves exposed during an
operation, and reported that the patient heard sounds like "a roulette wheel" and "a cricket" when a current was
applied.
The first attempt to develop a clinical CI was in 1957 by Djourno and Eyriès [1]. A recipient was implanted with a
single channel device. Unprocessed sounds were transmitted via a pair of solenoid-like coils. The link was therefore
transcutaneous; it did not require a break in the skin after implantation. This device failed after a short time and
another device was implanted. After this second device failed, Eyriès refused to implant a third device. He urged
Djourno to collaborate with an industry partner to build a more reliable device. This Djourno refused to do because
he believed that academia should not be tainted by commerce. Djourno found another surgeon, Roger Maspétiol who
implanted a second patient in 1958. Although these recipients were unable to understand speech with the device
alone, it helped with lipreading by providing the rhythm of the speech.
In 1961 Dr William House (an otologist), John Doyle (a neurosurgeon) and James Doyle (an electrical engineer)
commenced work on a single channel device in Los Angeles. In one case a five-wire electrode was used but the same
signal was applied to all contacts. House’s work continued in the 1970s in collaboration with engineer Jack Urban.
Their implant was also a single channel device but in this case the speech was modulated onto a carrier of 16 kHz.
The device, manufactured by 3M, was ultimately implanted in some thousand or so recipients and paved the way for
Cochlear implant
future clinical development of multichannel CIs.[4] The House/3M unit was the first approved by the FDA (Food and
Drug Administration of the USA) for implantation in adults in 1984.
In 1964, Blair Simmons at Stanford University implanted some recipients with a six-channel device. This device
used a percutaneous plug to enable the electrodes to be individually stimulated. Recipients could still not understand
speech via the device but importantly, it did demonstrate that by stimulating in different areas of the cochlea,
different pitch percepts could be produced.[5]
In 1970, Robin Michelson, M.D. reported preliminary results of cochlear implantation in three deaf adults implanted
with gold wire electrodes. Initially he teamed with Mel Bartz, an electrical engineer working with Storz, Inc.
Michelson's report to the American Academy of Otolaryngology and Ophthalmology created a tempest. Orthodox
auditory theory was in confusion at the time, and it was not thought possible for direct electrical stimulation of
neural tissue to convey meaningful sound to the brain. Michelson conducted some work in San Francisco, in the
Coleman Laboratory at the University of California, a foundation funded by the wealthy ENT department chairman
at UCSF, Francis Sooy, MD. Michelson's implantation of humans before animal physiology experiments caused
consternation among physiologists, audiologists, and many otologists who questioned Michelson's veracity and
professional ethics, and the matter became a concern to the ENT department. An otolaryngology resident, C. Robert
Pettit, heard Michelson results of his cochlear implantations at a department educational meeting. He ran to the
Coleman Laboratory where Michelson spent one-half day per week away from his Redwood City private ENT
practice, and told the older surgeon of his dream since college of a multi-channel electrode resembling a hairbrush.
Michelson said so many stimulus points were not necessary, and that his patients were hearing "in stereo" with a
two-channel electrode he had designed. Michelson and Pettit teamed up to build the bipolar electrodes embedded in
silastic which replaced the broken gold electrodes in Michelson's three patients. The reimplantation procedures were
carried out in Redwood City Community Hospital, not at UC San Francisco, as were the original implants.
When Michelson reported initial results of the reimplantation, in 1971, another hue and outcry arose, and he was
accused of lying about results,and of unethical human experimentation. Michelson could not bring his brainchild to
the university setting yet. Pettit was incensed when he witnessed Michelson's humiliation at the meeting. He had
assisted in the reimplantation surgeries and witnessed the fact that the patients, when tested on the operating room
table, could hear something meaningful, so he decided to document in film the results of testing on the reimplanted
patients to prove to the scientific community that electrical stimulation could result in meaningful sound perception.
Sooy, the UCSF department chairman, recruited Michael Merzenich, a young PhD, to carry out his research interests
in neurophysiology, mapping the inferior colliculus, and to investigate the potential of cochlear implantation.
Merzenich was enormously skeptical of the cochlear implant project, but agreed to test cats Michelson and Pettit had
implanted. Merzenich was skilled at constructing micro-electrode needles capable of penetrating single nerve cells
without rupturing the cell membranes and spilling cell contents. He agreed to monitor electrical activity in inferior
colliculus cells of cats stimulated by normal sound in one ear, and electrical input from a cochlear implant in the
other ear, finding both auditory stimuli similar. Merzenich had constructed an advanced electronic bank of signal
generating and monitoring equipment for use for in his mapping experiments, and also a carefully shielded
soundproof booth for testing. Over the course of months of animal testing Merzenich became convinced that the
electrical signal from the cochlear implant was entering the brain, and was "phase-locked". Understanding what
humans heard with the cochlear implant was another matter. New tests were devised for implanted patients. One was
congenitally deaf and had never heard sound. Pettit employed a music professor to synthesize simple tunes and
sounds in various sound envelopes, and new pitch and loudness-scaling tests were devised. When one of the
reimplanted patients was tested by the team under carefully controlled laboratory conditions, in 1972, a Moog
synthesized version of "Where have all the Flowers Gone" was presented to the patient through the cochlear implant.
The camera caught the patient humming the melody and tapping a pencil to the tempo of the tune. That sequence
convinced the Department chairman to support the cochlear implant project, and when the film was shown to a
meeting of otologists later in 1972, convinced the scientific community that meaningful sound could be conveyed to
the brain by electrical stimulation of the auditory nerve.[6] [7]
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Cochlear implant
In 1976 a paper (received Feb 1975) was published by Pialoux, Chouard and McLeod which stated that in the 6
months prior to the paper being submitted seven patients were implanted with an 8 channel device.[8] Although it
was reported that about 50% of ordinary words were understood without lipreading, this has not been supported by
audiological data in the literature.
In 1972 the House 3M single-electrode implant was the first to be commercially marketed.[9] However, it was Dr.
Michelson's patents and ultimately device which are thought of as the first cochlear implants.[10]
Parallel to the developments in California, in the seventies there were two other groups, working on the development
of the Cochlear Implant in Vienna, Austria and Melbourne, Australia. On December 16, 1977 Prof. Kurt Burian
implanted a multichannel cochlear implant. The device was developed by the Scientists Ingeborg and Erwin
Hochmair, who founded MED-EL, producer of hearing implants, in 1989. Burian K,Hochmair E,Hochmair-Desoyer
IJ,. Lesser MR (1979)
In December 1984, the Australian cochlear implant was approved by the United States Food and Drug
Administration to be implanted into adults in the United States. In 1990 the FDA lowered the approved age for
implantation to 2 years, then 18 months in 1998, and finally 12 months in 2002, although off label use has occurred
in babies as young as 6 months in the United States and 4 months internationally.
Throughout the 1990s, the large external components which had been worn strapped to the body grew smaller and
smaller thanks to developments in miniature electronics. By 2006, most school-age children and adults used a small
behind-the-ear (BTE) speech processor about the size of a power hearing aid. Younger children have small ears and
might mishandle behind-the-ear speech processors, therefore, they often wear the sound processor on their hip in a
pack or small harness, or wear the BTEs pinned to their collar, barrette or elsewhere.
On October 5, 2005, the first of 3 recipients was implanted with Cochlear's TIKI device, a totally implantable
cochlear implant, in Melbourne, Australia.[11] This was part of a research project conducted by Cochlear Ltd. and the
University of Melbourne Department of Otolaryngology under the umbrella of CRC HEAR to be the first cochlear
implant system capable of functioning for sustained periods with no external components. The system is capable of
providing hearing via the TIKI device in standalone mode (invisible hearing), or via an external sound processor.
Although these recipients continue to use their devices successfully today, it will be many years before a commercial
product becomes available.[12]
Since hearing in two ears allows people to localize sounds (given synchronised AGC's) and to hear better in noisy
environments, bilateral (both ear) implants are currently being investigated and utilized. Users generally report better
hearing with two implants, and tests show that bilateral implant users are better at localizing sounds and hearing in
noise.[13] Nearly 3000 people worldwide are bilateral cochlear implant users, including 1600 children. As of 2006,
the world's youngest recipient of a bilateral implant was just over 5 months old (163 days) in Germany (2004).[14]
Parts of the cochlear implant
The implant is surgically placed under the skin behind the ear. The basic parts of the device include:
External:
• a microphone which picks up sound from the environment
• a speech processor which selectively filters sound to prioritize audible speech and sends the electrical sound
signals through a thin cable to the transmitter,
• a transmitter, which is a coil held in position by a magnet placed behind the external ear, and transmits the
processed sound signals to the internal device by electromagnetic induction,
Internal:
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Cochlear implant
• a receiver and stimulator secured in bone beneath the skin, which
converts the signals into electric impulses and sends them through
an internal cable to electrodes,
• an array of up to 22 electrodes wound through the cochlea, which
send the impulses to the nerves in the scala tympani and then
directly to the brain through the auditory nerve system. There are 4
manufacturers for Cochlear implants, and each one produces a
different implant with a different number of electrodes. Advanced
Bionics produces implants with 16 electrodes and use a technique
The internal part of a cochlear implant (model
called current steering in which two electrodes are stimulated
Cochlear Freedom 24 RE)
simultaneously with different current levels to produce intermediate
virtual channels. The number of channels is not a primary factor upon which a manufacturer is chosen; the signal
processing algorithm is also another important block.
Candidates
There are a number of factors that determine the degree of success to expect from the operation and the device itself.
Cochlear implant centers determine implant candidacy on an individual basis and take into account a person's
hearing history, cause of hearing loss, amount of residual hearing, speech recognition ability, health status, and
family commitment to aural habilitation/rehabilitation.
A prime candidate is described as:
•
•
•
•
•
•
•
•
•
•
having severe to profound sensorineural hearing impairment in both ears.
having a functioning auditory nerve
having lived at least a short amount of time without hearing (approximately 70+ decibel hearing loss, on average)
having good speech, language, and communication skills, or in the case of infants and young children, having a
family willing to work toward speech and language skills with therapy
not benefitting enough from other kinds of hearing aids
having no medical reason to avoid surgery
living in or desiring to live in the "hearing world"
having realistic expectations about results
having the support of family and friends
having appropriate services set up for post-cochlear implant aural rehabilitation (through a speech language
pathologist, deaf educator, or auditory verbal therapist).
Type of hearing impairment
People with mild or moderate sensorineural hearing loss are generally not candidates for cochlear implantation. After
the implant is put into place, sound no longer travels via the ear canal and middle ear but will be picked up by a
microphone and sent through the device's speech processor to the implant's electrodes inside the cochlea. Thus, most
candidates have been diagnosed with profound sensorineural hearing loss.
The presence of auditory nerve fibres is essential to the functioning of the device: if these are damaged to such an
extent that they cannot receive electrical stimuli, the implant will not work. A small number of individuals with
severe auditory neuropathy may also benefit from cochlear implants.
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Cochlear implant
Age of recipient
Post-lingually deaf adults, pre-lingually deaf children and post-lingually impaired people (usually children) who
have lost hearing due to diseases such as meningitis, form three distinct groups of potential users of cochlear
implants with different needs and outcomes. Those who have lost their hearing as adults were the first group to find
cochlear implants useful, in regaining some comprehension of speech and other sounds. If an individual has been
deaf for a long period of time, the brain may begin using the area of the brain typically used for hearing for other
functions. If such a person receives a cochlear implant, the sounds can be very disorienting, and the brain often will
struggle to readapt to sound.
The risk of surgery in the older patient must be weighed against the improvement in quality of life. As the devices
improve, particularly the sound processor hardware and software, the benefit is often judged to be worth the surgical
risk, particularly for the newly deaf elderly patient.[15]
Another group of customers are parents of children born deaf who want to ensure that their children grow up with
good spoken language skills. Research shows that congenitally deaf children who receive cochlear implants at a
young age (less than 2 years) have better success with them than congenitally deaf children who first receive the
implants at a later age, though the critical period for utilizing auditory information does not close completely until
adolescence. Additionally, a 2010 study into bilateral implantation showed that children who receive their first
cochlear implant before the age of 1½ responded well to the second one, even if the second one was implanted as
late as 9 years old. In contrast, children who got their implants at age 2½ years or later did not respond as well to the
later second implant, regardless of when they received it.[16] One doctor has said "There is a time window during
which they can get an implant and learn to speak. From the ages of two to four, that ability diminishes a little bit.
And by age nine, there is zero chance that they will learn to speak properly. So it’s really important that they get
recognized and evaluated early."[17]
The third group who will benefit substantially from cochlear implantation are post-lingual subjects who have lost
hearing: a common cause is childhood meningitis. Young children (under five years) in these cases often make
excellent progress after implantation because they have learned how to form sounds, and only need to learn how to
interpret the new information in their brains.
Number of users
It was estimated in 2002 that around 10,000 children in the US and an additional 49,000 people worldwide had
received Cochlear implants. By the end of 2008, the total number of cochlear implant recipients has grown to an
estimated 150,000 worldwide.[18] A story in 2000 stated that one in ten deaf children in the United States had a
cochlear implant, and that the projection was the ratio would rise to one in three in ten years.[19]
Mexico had performed only 55 cochlear implant operations by the year 2000 (Berruecos 2000). China will be having
15,000 cochlear implant surgeries on children, which are being paid for by a Taiwanese philanthropist. There is
concern that the follow-up services in China are not adequate to meet the needs of cochlear implanted children.[20]
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Cochlear implant
The operation, post-implantation therapy and ongoing effects
The device is surgically implanted under a general
anaesthetic, and the operation usually takes from 1½ to
5 hours. First a small area of the scalp directly behind
the ear is shaven and cleaned. Then a small incision is
made in the skin just behind the ear and the surgeon
drills into the mastoid bone and the inner ear where the
electrode array is inserted into the cochlea. The patient
normally goes home the same day as or the day after
the surgery, although some cochlear implant recipients
stay in the hospital for 1 to 2 days. It is considered
outpatient surgery. As with every medical procedure,
the surgery involves a certain amount of risk; in this
Cochlear implant as worn by user
case, the risks include skin infection, onset of (or
change in) tinnitus, damage to the vestibular system,
and damage to facial nerves that can cause muscle weakness, impaired facial sensation, or, in the worst cases,
disfiguring facial paralysis. There is also the risk of device failure, usually where the incision does not heal properly.
This occurs in 2% of cases and the device must be removed. The operation also destroys any residual hearing the
patient may have in the implanted ear; as a result, some doctors advise single-ear implantation, saving the other ear
in case a biological treatment becomes available in the future.
After 1–4 weeks of healing (the wait is usually longer for children than adults) during which the wound must be kept
dry, the implant is turned on or "activated". Results are typically not immediate, and post-implantation therapy is
required as well as time for the brain to adapt to hearing new sounds. In the case of congenitally deaf children,
audiological training and speech therapy typically continue for years, though infants can become age appropriate able to speak and understand at the same level as a hearing child of the same age in a matter of months; however it is
far more common for the process to take years. The participation of the child's family in working on spoken
language development is considered to be even more important than therapy, because the family can aid
development by participating actively - and continually - in the child's therapy, making hearing and listening
interesting, talking about objects and actions, and encouraging the child to make sounds and form words.
In 2003, the CDC and FDA announced that children with cochlear implants are at a slightly increased risk of
bacterial meningitis (Reefhuis 2003). Though this risk is very small, it is still 30 times higher than children in the
general population, without proper immunizations. The CDC and other national health organisations (such as the
UK) now follow the practice of providing prophylactic vaccination against pneumococcal meningitis [21]CDC page
Many users, audiologists, and surgeons also report that when there is an ear infection causing fluid in the middle ear,
it can affect the cochlear implant, leading to temporarily reduced hearing.
The implant has a few effects unrelated to hearing. Manufacturers have cautioned against scuba diving due to the
pressures involved, but the depths found in normal recreational diving appear to be safe. The external components
must be turned off and removed prior to swimming or showering. Some brands of cochlear implant are unsafe in
areas with strong magnetic fields, and thus cannot be used with certain diagnostic tests such as magnetic resonance
imaging (MRI), but some are now FDA approved for use with certain strengths of MRI machine. Large amounts of
static electricity can cause the device's memory to reset. For this reason, children with cochlear implants are also
advised to avoid plastic playground slides.[22] The electronic stimulation the implant creates appears to have a
positive effect on the nerve tissue that surrounds it.[23]
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Cochlear implant
Cost
In the United States, medical costs run from US$45,000 to US$105,000; this includes evaluation, the surgery itself,
hardware (device), hospitalization and rehabilitation. Some or all of this may be covered by health insurance. In the
United Kingdom, the NHS covers cochlear implants in full, as does Medicare in Australia and Israel. According to
the US National Institute on Deafness and Other Communication Disorders, the estimated total cost is $60,000 per
person implanted.
A John Hopkins study determined that for a three-year-old child who receives cochlear implants can save $30,000 to
$50,000 in special-education costs for elementary and secondary schools as they are more likely to be mainstreamed
in school and thus use fewer support services than similarly deaf children.[24]
Efficacy
A cochlear implant will not cure deafness or hearing impairment, but is a prosthetic substitute for hearing. Some
recipients find them very effective, others somewhat effective and some feel worse overall with the implant than
without.[25] For people already functional in spoken language who lose their hearing, cochlear implants can be a
great help in restoring functional comprehension of speech, especially if they have only lost their hearing for a short
time.
Individuals who have acquired deafblindness (loss of hearing and vision combined) may find cochlear implants a
radical improvement in their daily life. It may provide them with more information for safety, communication,
balance, orientation and mobility and promote interaction within their environment and with other people, reducing
isolation. Having more auditory information that they may be familiar with may provide them with sensory
information that will help them become more independent.
British Member of Parliament Jack Ashley received a cochlear implant in 1994 at age 70 after 25 years of deafness,
and reported that he has no trouble speaking to people he knows; whether one on one or even on the telephone,
although he might have difficulty with a new voice or with a busy conversation, and still had to rely to some extent
on lipreading. He described the robotic sound of human voices perceived through the cochlear implant as "a croaking
dalek with laryngitis". Another recipient described the initial sounds as similar to radio static and voices as being
cartoonish, though after a year with the implant she said everything sounded right.[26] Even modern cochlear
implants have at most 24 electrodes to replace the 16,000 delicate hair cells that are used for normal hearing.
However, the sound quality delivered by a cochlear implant is often good enough that many users do not have to rely
on lipreading.
Adults who have grown up deaf can find the implants ineffective or irritating. This relates to the specific pathology
of deafness and the time frame. Adults who are born with normal hearing and who have had normal hearing for their
early years and who have then progressively lost their hearing tend to have better outcomes than adults who were
born deaf. This is due to the neural patterns laid down in the early years of life - which are crucially important to
speech perception. Cochlear implants cannot overcome such a problem. Some who were orally educated and used
amplifying hearing aids have been more successful with cochlear implants, as the perception of sound was
maintained through use of the hearing aid.
Children without a working auditory nerve may be helped with a cochlear implant, although the results may not be
optimal. Patients without a viable auditory nerve are usually identified during the candidacy process. Fewer than 1%
of deaf individuals have a missing or damaged auditory nerve, which today can be treated with an auditory brainstem
implant. Recent research has suggested that children and adults can benefit from bilateral cochlear implants in order
to aid in sound localization and speech understanding. (See Offeciers et al. 2005)
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Cochlear implant
Risks and disadvantages
Some effects of implantation are irreversible; while the device promises to provide new sound information for a
recipient, the implantation process inevitably results in damage to nerve cells within the cochlea, which often results
in a permanent loss of most residual natural hearing. While recent improvements in implant technology, and
implantation techniques, promise to minimize such damage, the risk and extent of damage still varies.
In addition, while the device can help the recipient better hear and understand sounds in their environment, it is not
as good as the quality of sound processed by a natural cochlea. The main problem is with the age of recipient. While
cochlear implants restore physical ability to hear, this does not mean the brain can learn to process and distinguish
speech if the recipient has passed the critical period of adolescence. As a result, those born deaf who receive an
implant as an adult can only distinguish simple sounds, such as a ringing phone vs a doorbell, while others who
receive implant early can clearly understand speech. The success rate depends on a variety of factors, most critically
the age of recipient but also the technology used and the condition of the recipient's cochlea.
The United States Food and Drug Administration reports that cochlear implant recipients may be at higher risk for
meningitis.[27] A study of 4,265 American children who received implants between 1997 and 2002 concluded that
recipient children had a risk of pneumococcal meningitis more than 30 times greater than that for children in the
general population.[28] A later, UK-based, study found that while the incidence of meningitis in implanted adults was
significantly higher than the general population, the incidence in children was no different than the general
population.[29] As a result, the Centers for Disease Control and Prevention and the Food and Drug Administration
both recommend that would-be implant recipients be vaccinated against meningitis prior to surgery.[30]
Necrosis has been observed in the skin flaps surrounding cochlear implants.[31] [32] Hyperbaric oxygen has been
shown to be a useful adjunctive therapy in the management of cochlear implant flap necrosis.[33]
As the location of the cochlear is close to the facial nerve, there is a risk that the nerve may be damaged during the
operation. The incidence of the damage is infrequent.[34]
There are strict protocols in choosing candidates to avoid risks and disadvantages. A battery of tests are performed to
make the decision of candidacy easier. For example, some patients suffer from deafness medial to the cochlea typically acoustic neuromas. Implantation into the cochlea has a low success rate with these people, as the artificial
signal does not have a healthy nerve to travel along.
With careful selection of candidates, the risks of implantation are minimized.
The Big Controversy
Discussions within the Deaf community continue to fuel controversy and emotional personal debates about health,
rights of the individual citizen, language, ethics, and the effects of the device on Deaf culture. For some in the Deaf
community, CIs are an affront to their culture, which as they view it, is a minority threatened by the hearing
majority.[35] This is an old problem for the Deaf community, going back as far as the 18th century with the argument
of manualism vs. oralism. Another part of the controversy concerns the basic right of an individual to choose a
language versus an individual as a young child having a mode of communication and language chosen for them. In
the past, many adults whose first language is a sign language endured policies created by medical and educational
governing bodies that enforced the use of spoken languages and use of hearing aids on them. In response, Deaf
individuals have successfully advocated change to improve human rights for individuals, and they continue to work
to advocate for change that will help children who are born with loss of hearing.
Cochlear implants for congenitally deaf children are often considered to be most effective when implanted at a
young age, during the critical period in which the brain is still learning to interpret sound. Hence they are implanted
before the recipients can decide for themselves. Critics question the ethics of such invasive elective surgery on
children. They point out that manufacturers and specialists have exaggerated the efficacy and downplayed the risks
of a procedure that they stand to gain from. On the other hand, Andrew Solomon of the New York Times states that
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Cochlear implant
"Much National Association of the Deaf propaganda about the danger of implants is alarmist; some of it is positively
inaccurate."[36]
Much of the strongest objection to cochlear implants has come from the Deaf community, which consists largely of
pre-lingually deaf people whose first language is a signed language. Regardless of the fact that to be deaf is to lack
the ability to hear, many individuals who are deaf and the Deaf community do not share the view of deafness held by
many hearing parents of deaf children, who regard deafness as a disability to be "fixed". On the other hand, many
people feel that refusing to implant deaf children is unethical, comparable to refusal to treat any other handicap or
disease that can be effectively alleviated. Many individuals who can hear or who have become deaf due to injury or
illness are not comfortable with the thought of a child who lacks the sense most commonly associated with human
language.
The conflict over these opposing models of deafness has raged since the 18th century, and cochlear implants are the
latest in a history of medical interventions promising to turn a deaf child into a hearing child — or, more accurately,
into a child with a mild or moderate hearing impairment.
Critics argue that the cochlear implant and the subsequent therapy often become the focus of the child's identity at
the expense of a Deaf identity and ease of communication in sign language. Measuring the child's success only by
their mastery of hearing and speech will lead to a poor self-image as "disabled" (because the implants do not produce
normal hearing) rather than having the healthy self-concept of a proud deaf person.[37]
Some writers have noted that children with cochlear implants are more likely to be educated orally and without
access to sign language (Spencer et al. 2003). Also, children with implants are often isolated from other deaf children
and from sign language (Spencer 2003). Instead they are 'married' to a team of hearing experts who will monitor
their cochlear implant and adjust the speech processor, at great expense. Children do not always receive support in
the educational system to fulfill their needs as they may require special education environments and Educational
Assistants. According to Johnston (2004), cochlear implants have been one of the technological and social factors
implicated in the decline of sign languages in the developed world. Some of the more extreme responses from Deaf
activists have labelled the widespread implantation of children as "cultural genocide".[19] As cochlear implants began
to be implanted into deaf children in the mid to late 1980s, the Deaf community responded with protests in the US,
UK, Germany, Finland, France and Australia.
Opposition continues today but is softening. As the trend for cochlear implants in children grows, deaf-community
advocates have tried to counter the "either or" formulation of oralism vs manualism with a "both and" approach;
some schools now are successfully integrating cochlear implants with sign language in their educational programs.
However, some opponents of sign language education argue that the most successfully implanted children are those
who are encouraged to listen and speak rather than overemphasize their visual sense.
Parents and children alike have been interviewed to discuss their opinions on cochlear implants. Many children
discuss the fact that many of their parents never asked them or discussed the idea of a cochlear implant with them.
While some discuss the fact that their parents asked them about it and discussed it with them and that made it better.
Young adults seem to have the worst experiences mainly for cosmetic reasons, but for some the cochlear implants
just do not work for them. If a child is placed into a mainstream setting it makes it difficult for them because they
feel like they do not fit in with their peers and cannot fully identify with the Deaf community. One interviewee in the
Christiansen and Leigh study states “In high school it was the worst time for me with the cochlear implant because I
was really trying to find my identity with the cochlear implant…I never accepted my deafness. And the cochlear
implant in some ways showed me that no matter what, the moment I take it off I’m deaf. I’ll never be hearing 24
hours.” [38]
A 2007 study about attitudes of young, implanted people shows that although they are aware of the negative effects,
their feelings about the implantation are overwhelmingly positive. None of the teenagers participating in the study
criticised their parents for making the decision. They developed a positive identity and felt that they belonged to both
the hearing and Deaf worlds although only some of them use both spoken and sign language.[39] A later 2010 study
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Cochlear implant
revealed that children with cochlear implants rated their quality of life as being as high as those with normal
hearing;[40] this contrasts to deaf children who prior studies have shown that they have more difficulty in making
friends and often feel less socially accepted than normally hearing children of the same age.[41]
Functionality
The implant works by using the tonotopic organization of the basilar membrane of the inner ear. "Tonotopic
organization", also referred to as a "frequency-to-place" mapping, is the way the ear sorts out different frequencies so
that our brain can process that information. In a normal ear, sound vibrations in the air lead to resonant vibrations of
the basilar membrane inside the cochlea. High-frequency sounds (i.e. high pitched sounds) do not pass very far along
the membrane, but low frequency sounds pass farther in. The movement of hair cells, located all along the basilar
membrane, creates an electrical disturbance that can be picked up by the surrounding nerve cells. The brain is able to
interpret the nerve activity to determine which area of the basilar membrane is resonating, and therefore what sound
frequency is being heard.
In individuals with sensorineural hearing loss, hair cells are often fewer in number and damaged. Hair cell loss or
absence may be caused by a genetic mutation or an illness such as meningitis. Hair cells may also be destroyed
chemically by an ototoxic medication, or simply damaged over time by excessively loud noises. The cochlear
implant bypasses the hair cells and stimulates the cochlear nerves directly using electrical impulses. This allows the
brain to interpret the frequency of sound as it would if the hair cells of the basilar membrane were functioning
properly (see above).
Processing
Sound received by the microphone must next be processed to determine how the electrodes should be activated.
Filterbank strategies use Fast Fourier Transforms to divide the signal into different frequency bands. The algorithm
chooses a number of the strongest outputs from the filters, the exact number depending on the number of implanted
electrodes and other factors. These strategies emphasize transmission of the spectral aspects of speech. Although
coarse temporal information is presented, the fine timing aspects are as yet poorly perceived and this is the focus of
much current research.
Feature extraction strategies used features which are common to all vowels. Each vowel has a fundamental
frequency (the lowest frequency peak) and formants (peaks with higher frequencies). The pattern of the fundamental
and formant frequencies is specific for different vowel sounds. These algorithms try to recognize the vowel and then
emphasize its features. These strategies emphasize the transmission of spectral aspects of speech. Feature extraction
strategies are no longer widely used. Each Cochlear implant manufacturer tries to use a different strategy, Cochlear 70% market share- for example uses the Speak-ACE strategy, ACE is mainly used; in which number of maxima (n)
from the available maxima in sound are selected, Advanced bionics uses other techniques like CIS, SAS and HiRes,
they stimulate the full spectrum. The processing strategy is a main block upon which one has to choose the implant
manufacturer, research shows that patients can understand speech with as at least 4 electrodes, but the obstacle is in
music perception, where it returns that fine structure stimulation is an important issue. Some strategies used in
Advanced Bionics and Medel strategies make use of fine structure presentation by implementing the Hilbert
Transform in the signal processing path, while ACE strategies depends mainly on the Short Time Fourier Transform.
181
Cochlear implant
Transmitter
This is used to transmit the processed sound information over a radio frequency link to the internal portion of the
device. Radio frequency is used so that no physical connection is needed, which reduces the chance of infection and
pain. The transmitter attaches to the receiver using a magnet that holds through the skin.
Receiver
This component receives directions from the speech processor by way of magnetic induction sent from the
transmitter. (The receiver also receives its power through the transmission.) The receiver is also a sophisticated
computer that translates the processed sound information and controls the electrical current sent to the electrodes in
the cochlea. It is embedded in the skull behind the ear.
Electrode array
The electrode array is made from a type of silicone rubber, while the electrodes are platinum or a similarly highly
conductive material. It is connected to the internal receiver on one end and inserted into the cochlea deeper in the
skull. (The cochlea winds its way around the auditory nerve, which is tonotopically organized just as the basilar
membrane is). When an electrical current is routed to an intracochlear electrode, an electrical field is generated and
auditory nerve fibers are stimulated.
In the devices manufactured by Cochlear Ltd, two electrodes sit outside the cochlea and acting as grounds-- one is a
ball electrode that sits beneath the skin, while the other is a plate on the device. This equates to 24 electrodes in the
Cochlear-brand 'nucleus' device, 22 array electrodes within the cochlea and 2 extra-cochlear electrodes.
Insertion depth is another important factor. The mean length of human being cochlea is 33–36 mm, due to some
physical limitation, the implants don't reach to the apical tip when inserted but it may reach up to 25 mm which
corresponds to a tonotopical frequency of 400–6000 Hz. Medel produced once a deep inserted implant that can get
inserted up to a tonotopical frequency of 100 Hz (according to Greenwood frequency to position formula in normal
hearing), but the distance between the electrodes is about 2.5 mm, while in the Nucleus Freedom from Cochlear Ltd
is about 0.7 mm. There is a strong research in this direction and the best sounding implant can be subjective from
patient to patient.
Speech processors
Speech processors are the component of the cochlear implant that transforms the sounds picked up by the
microphone into electronic signals capable of being transmitted to the internal receiver. The coding strategies
programmed by the user's audiologist are stored in the processor, where it codes the sound accordingly. The signal
produced by the speech processor is sent through the coil to the internal receiver, where it is picked up by radio
signal and sent along the electrode array in the cochlea.
There are primarily two forms of speech processors available. The most common kind is called the "behind-the-ear"
processor, or BTE. It is a small processor that is kept worn on the ear, typically together with the microphone. This is
the kind of processor used by most adults and older children. Babies and small children wear either a "baby" BTE
(pinned or clipped to the collar) or the body-worn processor, which was more common in previous years. Today's
tiny processors can often take the place of bulky body-worn processors. Med-el and Cochlear brands both carry a
"baby BTE" configurations.
182
Cochlear implant
183
Programming the speech processor
The cochlear implant must be programmed individually for each user. The programming is performed by an
audiologist trained to work with cochlear implants. The audiologist sets the minimum and maximum current level
outputs for each electrode in the array based on the user's reports of loudness. The audiologist also selects the
appropriate speech processing strategy and program parameters for the user.
Differences between Cochlear implants and hearing aids
Cochlear implants
Hearing aids
consonants and vowels are understandable
Only vowels
Unlimited possibilities for signal coding
Limited signal coding
Surgically implanted
No surgery needed
3 batteries or charged battery
1 battery
Battery life: 1 to 3 days
Battery life: 1 to 2 weeks
Success is individual and unpredictable
Success is individual and unpredictable
Rechargeable
Non- rechargeable
Scientific and technical advances
Professor Graeme Clark A.C. of La Trobe University, Melbourne, Australia, in 2008, announced beginning the
development of a prototype "hi fi" cochlear implant featuring 50 electrodes. The increased number of electrodes is
hoped to enable users to perceive music and discern specific voices in noisy rooms.[42]
Researchers at Northwestern University have used infrared light to directly stimulate the neurons in the inner ear of
deaf guinea pigs while recording electrical activity in the inferior colliculus, an area of the midbrain that acts as a
bridge between the inner ear and the auditory cortex. The laser stimulation produced more precise signals in that
brain region than the electrical stimulation commonly used in cochlear implants.[43] Laser stimulation is a promising
technology for improving the auditory resolution of implants but further research using fibre optics to stimulate the
neurons of the inner ear is required before products using the technology can be developed.
Cochlear implants are rarely used in ears that have a functional level of residual hearing. However, Electric Acoustic
Stimulation (EAS) devices, including the Hybrid "short-electrode" cochlear implant, have been developed that
combine a cochlear implant with a sound amplifying hearing aid.[44] [45] EAS devices have the potential to make
cochlear implants suitable for many people with partial hearing loss. The sound amplifying component helps users to
perceive lower frequency sounds through their residual natural hearing while the cochlear implant allows them to
hear middle and higher frequency sounds. The combination enhances speech perception in noisy environments[46] .
Manufacturers
Currently (as of 2007), the three cochlear implant devices approved for use in the U.S. are manufactured by Cochlear
Limited, Australia, MED-EL, Austria [47] and Advanced Bionics, US [48]. In the EU, an additional device
manufactured by Neurelec, of France [49] is available. Each manufacturer has adapted some of the successful
innovations of the other companies to their own devices. There is no clear-cut consensus that any one of these
implants is superior to the others. Users of all four devices display a wide range of performance after implantation.
Since the devices have a similar range of outcomes, other criteria are often considered when choosing a cochlear
implant: usability of external components, cosmetic factors, battery life, reliability of the internal and external
components, MRI compatibility, mapping strategies, customer service from the manufacturer, the familiarity of the
user's surgeon and audiologist with the particular device, and anatomical concerns.
Cochlear implant
There have been news reports of other organizations working to develop cochlear implants, in South Korea by the
Seoul National University Hospital[50] and in India by a branch of the Defence Research and Development
Organisation.[51]
See also
•
•
•
•
•
•
Brain implant
Electric Acoustic Stimulation
Neuroprosthetics
Noise health effects
Hearing Aid
Bone conduction
Resources
• Berruecos, Pedro. (2000). Cochlear implants: An international perspective - Latin American countries and Spain.
Audiology. Hamilton: Jul/Aug 2000. Vol. 39, 4:221-225
• House, W. F., Cochlear Implants. Ann Otol Rhinol Larynogol 1976; 85 (suppl 27): 1 – 93.
• Simmons, F. B., Electrical Stimulation of the Auditory Nerve in Man, Arch Otolaryng, Vol 84, July 1966
• Pialoux, P., Chouard, C. H. and MacLeod, P. 1976. Physiological and clinical aspects of the rehabilitation of total
deafness by implantation of multiple intracochlear electrodes. Acta Oto-Laryngologica 81: 436-441
• Chorost, Michael. (2005). Rebuilt: How Becoming Part Computer Made Me More Human. Boston: Houghton
Mifflin.
• Christiansen, John B., and Irene W. Leigh (2002,2005). Cochlear Implants in Children: Ethics and Choices.
Washington, DC: Gallaudet University Press.
• Cooper, Huw R. and Craddock, Louise C. (2006)Cochlear Implants A Practical Guide. London and Philadelphia:
Whurr Publishers.
• Djourno A, Eyriès C. (1957). 'Prothèse auditive par excitation électrique à distance du nerf sensoriel à l'aide d'un
bobinage inclus à demeure.' In: La Presse Médicale 65 no.63. 1957.
• Djourno A, Eyriès C, (1957) 'Vallencien B. De l'excitation électrique du nerf cochléaire chez l'homme, par
induction à distance, à l'aide d'un micro-bobinage inclus à demeure.' CR de la société.de biologie. 423-4. March 9,
1957.
• Eisen MD (2003), 'Djourno, Eyries, and the first implanted electrical neural stimulator to restore hearing.' in:
Otology and Neurotology. 2003 May;24(3):500-6.
• Grodin, M. (1997). Ethical Issues in Cochlear Implant Surgery: An Exploration into Disease, Disability, and the
Best Interests of the Child. Kennedy Institute of Ethics Journal 7:231-251.
• Johnston, Trevor. (2004). W(h)ither the deaf Community? In 'American Annals of the deaf' (volume 148 no. 5),
• Lane, H. and Bahan, B. (1998). Effects of Cochlear Implantation in Young Children: A Review and a Reply from
a DEAF-WORLD Perspective. Otolaryngology: Head and Neck Surgery 119:297-308.
• Lane, Harlan (1993), Cochlear Implants:Their Cultural and Historical Meaning. In 'deaf History Unveiled', ed.
J.Van Cleve, 272-291. Washington, D.C. Gallaudet University Press.
• Lane, Harlan (1994), The Cochlear Implant Controversy. World Federation of the deaf News 2 (3):22-28.
• Litovsky, Ruth Y., et al. (2006). "Bilateral Cochlear Implants in Children: Localization Acuity Measured with
Minimum Audible Angle." Ear & Hearing, 2006; 27; 43-59.
• Miyamoto, R.T.,K.I.Kirk, S.L.Todd, A.M.Robbins, and M.J.Osberger. (1995). Speech Perception Skills of
Children with Multichannel Cochlear Implants or Hearing Aids. Annals of Otology, Rhinology and Laryngology
105 (Suppl.):334-337
184
Cochlear implant
• Officiers, P.E., et. a. (2005). "International Consensus on bilateral cochlear implants and bimodal stimulation."
Acta Oto-Laryngologica, 2005; 125; 918-919.
• Osberger M.J. and Kessler, D. (1995). Issues in Protocol Design for Cochlear Implant Trials in Children: The
Clarion Pediatric Study. Annals of Otology, Rhinology and Laryngology 9 (Suppl.):337-339.
• Reefhuis J, et al. (2003) Risk of Bacterial Meningitis in Children with Cochlear Implants, USA 1997-2002. New
England Journal of Medicine, 2003; 349:435-445.
• Spencer, Patricia Elizabeth and Marc Marschark. (2003). Cochlear Implants: Issues and Implications. In 'Oxford
Handbook of deaf Studies, Language and Education', ed. Marc Marschark and Patricia Elizabeth Spencer,
434-450. Oxford: Oxford University Press, 2003.
• 3M Power Point Presentation on the Cochlear Implant [52].
External links
•
•
•
•
Cochlear Implant Online [53]
Cochlear Implants [54] at the Open Directory Project
Simulations for a CI [55]
Software for Cochlear Implant Simulation [56]
General
• Cochlear Implants [57] Information from the National Institutes of Health (NIH).
• NASA Spinoff article [58] on engineer Adam Kissiah's contribution to cochlear implants beginning in the 1970s.
News reports
• http://www.esquire.com/dont-miss/wifl/regainhearing0807 Esquire Magazine article about a cochlear implant
activation.
• NPR Story about improvements to improve the processing of music. [59] Includes simulations of what someone
with implants might hear.
• Tuning In [60] PBS article about advances in cochlear implant technology with simulations of what someone with
each type of implant would hear.
• My Bionic Quest for Boléro [61] (Wired, November 2005): Author Michael Chorost writes about his own implant
and trying the latest software from researchers in a quest to hear music better.
• Rationale for bilateral cochlear implantation (PDF) [62]
• "For Some Who Lost Their Hearing, Implants Help" [63], Jane E. Brody, New York Times, October 3, 2006.
References
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[4] W.F. House (May-June 1976). "Cochlear implants". Annals of Otology, Rhinology and Laryngology 85 (suppl 27): 1 – 93. PMID 779582.
[5] F. Blair Simmons (July 1966). "Electrical Stimulation of the Auditory Nerve in Man". Archives of Otolaryngology 84 (1): 2–54.
PMID 5936537.
[6] References: Michelson RP, Merzenich MM,Pettit, Schindler RAc A cochlear prosthesis: Further clinical observations; preliminary results of
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[7] Waltzman, SB, Roland, TJ, Cochlear Implants, 2nd Edition, Chapter 1, pp1-10
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[8] P. Pialoux‌, C. H. Chouard‌ and P. Macleod‌ (1976). "Physiological and Clinical Aspects of the Rehabilitation of Total Deafness By
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[13] Dave Tenenbaum (2010-01-11). "Study: Second cochlear implant can restore two important facets of binaural hearing" (http:/ / www. news.
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[15] Shapiro, Joseph (2005-12-20). "Elderly with Hearing Loss Turning to Cochlear Implants" (http:/ / www. npr. org/ templates/ story/ story.
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[20] "Cochlear Corp. News" (http:/ / www. cochlear. com/ News/ 1810. asp). .
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[31] Haberkamp TJ, Schwaber MK (January 1992). "Management of flap necrosis in cochlear implantation". Ann. Otol. Rhinol. Laryngol. 101
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[32] Stratigouleas ED, Perry BP, King SM, Syms CA (September 2006). "Complication rate of minimally invasive cochlear implantation" (http:/
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[39] Wheeler, A., Archbold, S., Gregory, S.: "Cochlear implants: young people's view" (http:/ / www. ndcs. org. uk/ document. rm?id=2302),
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[42] Cochlear implant maker says hi-fi bionic ear will help the deaf hear music. (http:/ / www. news. com. au/ technology/ story/
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[46] Turner, C.W., Gantz, B.J., Vidal, C., et al. (2004) Speech recognition in noise for cochlear implant listeners: Benefits of residual acoustic
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[50] Bae Ji-sook (2010-02-28). "Procedure Gives Hearing to Auditory Disabled" (http:/ / www. koreatimes. co. kr/ www/ news/ art/ 2010/ 02/
147_61550. html). The Korea Times. . Retrieved 2010-03-05.
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[52] http:/ / webpages. csom. umn. edu/ smo/ avandeven/ MGT6050/ CIP%20Team%204%20Slides. ppt
[53] http:/ / cochlearimplantonline. com
[54] http:/ / www. dmoz. org/ Business/ Healthcare/ Products_and_Services/ Disability/ Hearing_and_Listening_Aids/ Cochlear_Implants/ /
[55] http:/ / www. healthaffairs. uci. edu/ hesp/ Simulations/ simulationsmain. htm
[56] http:/ / www. ugr. es/ ~atv/ web_ci_SIM/ en/ ci_sim_en. htm
[57] http:/ / www. nidcd. nih. gov/ health/ hearing/ coch. htm
[58] http:/ / ntrs. nasa. gov/ archive/ nasa/ casi. ntrs. nasa. gov/ 20030099659_2003114614. pdf
[59] http:/ / www. npr. org/ templates/ story/ story. php?storyId=4961269
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[61] http:/ / www. wired. com/ wired/ archive/ 13. 11/ bolero. html?tw=wn_tophead_4
[62] http:/ / web. archive. org/ web/ 20070928000726/ http:/ / cochlearimplants. dallasoto. com/ facts/ Rationale+ for+ Bilateral+ Cochlear+
Implantation+ Final. pdf
[63] http:/ / www. nytimes. com/ 2006/ 10/ 03/ health/ 03brody. html?ref=science
187
Magnetic resonance imaging
188
Magnetic resonance imaging
Magnetic resonance imaging (MRI), or nuclear magnetic resonance
imaging (NMRI), is primarily a medical imaging technique most
commonly used in radiology to visualize detailed internal structure and
limited function of the body. MRI provides much greater contrast
between the different soft tissues of the body than computed
tomography (CT) does, making it especially useful in neurological
(brain), musculoskeletal, cardiovascular, and oncological (cancer)
imaging. Unlike CT, it uses no ionizing radiation, but uses a powerful
magnetic field to align the nuclear magnetization of (usually) hydrogen
atoms in water in the body. Radio frequency (RF) fields are used to
systematically alter the alignment of this magnetization, causing the
hydrogen nuclei to produce a rotating magnetic field detectable by the
scanner. This signal can be manipulated by additional magnetic fields
to build up enough information to construct an image of the body.[1] :36
Sagittal MR image of the knee
Magnetic resonance imaging is a relatively new technology. The first
MR image was published in 1973[2] [3] and the first cross-sectional
image of a living mouse was published in January 1974.[4] The first
studies performed on humans were published in 1977.[5] [6] By
comparison, the first human X-ray image was taken in 1895.
Magnetic resonance imaging was developed from knowledge gained in
the study of nuclear magnetic resonance. In its early years the
technique was referred to as nuclear magnetic resonance imaging
(NMRI). However, because the word nuclear was associated in the
public mind with ionizing radiation exposure it is generally now
referred to simply as MRI. Scientists still use the term NMRI when
discussing non-medical devices operating on the same principles. The
term magnetic resonance tomography (MRT) is also sometimes used.
Para-sagittal MRI of the head, with aliasing
artifacts (nose and forehead appear at the back of
the head)
How MRI works
The body is largely composed of water molecules which each contain two hydrogen nuclei or protons. When a
person goes inside the powerful magnetic field of the scanner, the magnetic moments of some of these protons align
with the direction of the field.
A radio frequency transmitter is then briefly turned on, producing an electromagnetic field. In simple terms, the
photons of this field have just the right energy, known as the resonance frequency, to flip the spin of the aligned
protons. As the intensity and duration of the field increases, more aligned spins are affected. After the field is turned
off, the protons decay to the original spin-down state and the difference in energy between the two states is released
as a photon. It is these photons that produce the signal which can be detected by the scanner. The frequency at which
the protons resonate depends on the strength of the magnetic field. As a result of conservation of energy, this also
dictates the frequency of the released photons.
It is this relationship between field-strength and frequency that allows the use of nuclear magnetic resonance for
imaging. Additional magnetic fields are applied during the scan in order to make the magnetic field strength depend
Magnetic resonance imaging
on the position within the patient, providing a straightforward method to control where the protons are excited by the
radio photons. These fields are created by passing electric currents through solenoids, known as gradient coils. Since
these coils are within the bore of the scanner, there will be large forces between them and the main field coils,
producing most of the noise that is heard during operation. Without efforts to dampen this noise, it can approach 130
decibels (the human pain threshold) with strong fields [7] .
An image can be constructed because the protons in different tissues return to their equilibrium state at different
rates. By changing the parameters on the scanner this effect is used to create contrast between different types of body
tissue or between other properties, as in fMRI and diffusion MRI.
Contrast agents may be injected intravenously to enhance the appearance of blood vessels, tumors or inflammation.
Contrast agents may also be directly injected into a joint in the case of arthrograms, MRI images of joints. Unlike
CT, MRI uses no ionizing radiation and is generally a very safe procedure. Nonetheless the strong magnetic fields
and radio pulses can affect metal implants, including cochlear implants and cardiac pacemakers. In the case of
cardiac pacemakers, the results can sometimes be lethal[8] , so patients with such implants are generally not eligible
for MRI.
MRI is used to image every part of the body, and is particularly useful for tissues with many hydrogen nuclei and
little density contrast, such as the brain, muscle, connective tissue and most tumors.
Applications
In clinical practice, MRI is used to distinguish pathologic tissue (such as a brain tumor) from normal tissue. One
advantage of an MRI scan is that it is believed to be harmless to the patient. It uses strong magnetic fields and
non-ionizing radiation in the radio frequency range, unlike CT scans and traditional X-rays which both use of
ionizing radiation.
While CT provides good spatial resolution (the ability to distinguish two structures an arbitrarily small distance from
each other as separate), MRI provides comparable resolution with far better contrast resolution (the ability to
distinguish the differences between two arbitrarily similar but not identical tissues). The basis of this ability is the
complex library of pulse sequences that the modern medical MRI scanner includes, each of which is optimized to
provide image contrast based on the chemical sensitivity of MRI.
For example, with particular values of the echo time (TE) and the repetition time (TR), which are basic parameters of
image acquisition, a sequence will take on the property of T2-weighting. On a T2-weighted scan, water- and
fluid-containing tissues are bright (most modern T2 sequences are actually fast T2 sequences) and fat-containing
tissues are dark. The reverse is true for T1-weighted images. Damaged tissue tends to develop edema, which makes a
T2-weighted sequence sensitive for pathology, and generally able to distinguish pathologic tissue from normal tissue.
With the addition of an additional radio frequency pulse and additional manipulation of the magnetic gradients, a
T2-weighted sequence can be converted to a FLAIR sequence, in which free water is now dark, but edematous
tissues remain bright. This sequence in particular is currently the most sensitive way to evaluate the brain for
demyelinating diseases, such as multiple sclerosis.
The typical MRI examination consists of 5–20 sequences, each of which are chosen to provide a particular type of
information about the subject tissues. This information is then synthesized by the interpreting physician.
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Magnetic resonance imaging
Basic MRI scans
T1-weighted MRI
T1-weighted scans use a gradient echo (GRE) sequence, with short TE and short TR. This is one of the basic types of
MR contrast and is a commonly run clinical scan. The T1 weighting can be increased (improving contrast) with the
use of an inversion pulse as in an MP-RAGE sequence. Due to the short repetition time (TR) this scan can be run
very fast allowing the collection of high resolution 3D datasets. A T1 reducing gadolinium contrast agent is also
commonly used, with a T1 scan being collected before and after administration of contrast agent to compare the
difference. In the brain T1-weighted scans provide good gray matter/white matter contrast.
T2-weighted MRI
T2-weighted scans use a spin echo (SE) sequence, with long TE and long TR. They have long been the clinical
workhorse as the spin echo sequence is less susceptible to inhomogeneities in the magnetic field. They are
particularly well suited to edema as they are sensitive to water content (edema is characterized by increased water
content).
T*2-weighted MRI
T*2 (pronounced "T 2 star") weighted scans use a gradient echo (GRE) sequence, with long TE and long TR. The
gradient echo sequence used does not have the extra refocusing pulse used in spin echo so it is subject to additional
losses above the normal T2 decay (referred to as T2′), these taken together are called T*2. This also makes it more
prone to susceptibility losses at air/tissue boundaries, but can increase contrast for certain types of tissue, such as
venous blood.
Spin density weighted MRI
Spin density, also called proton density, weighted scans try to have no contrast from either T2 or T1 decay, the only
signal change coming from differences in the amount of available spins (hydrogen nuclei in water). It uses a spin
echo or sometimes a gradient echo sequence, with short TE and long TR.
Specialized MRI scans
Diffusion MRI
Diffusion MRI measures the diffusion of water molecules in biological
tissues.[9] In an isotropic medium (inside a glass of water for example) water
molecules naturally move randomly according to turbulence and Brownian
motion. In biological tissues however, where the Reynold's number is low
enough for flows to be laminar, the diffusion may be anisotropic. For
example a molecule inside the axon of a neuron has a low probability of
crossing the myelin membrane. Therefore the molecule will move principally
along the axis of the neural fiber. If we know that molecules in a particular
voxel diffuse principally in one direction we can make the assumption that
the majority of the fibers in this area are going parallel to that direction.
The recent development of diffusion tensor imaging (DTI)[3] enables
diffusion to be measured in multiple directions and the fractional anisotropy
in each direction to be calculated for each voxel. This enables researchers to
make brain maps of fiber directions to examine the connectivity of different
regions in the brain (using tractography) or to examine areas of neural degeneration and demyelination in diseases
like Multiple Sclerosis.
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Magnetic resonance imaging
Another application of diffusion MRI is diffusion-weighted imaging (DWI). Following an ischemic stroke, DWI is
highly sensitive to the changes occurring in the lesion.[10] It is speculated that increases in restriction (barriers) to
water diffusion, as a result of cytotoxic edema (cellular swelling), is responsible for the increase in signal on a DWI
scan. The DWI enhancement appears within 5–10 minutes of the onset of stroke symptoms (as compared with
computed tomography, which often does not detect changes of acute infarct for up to 4–6 hours) and remains for up
to two weeks. Coupled with imaging of cerebral perfusion, researchers can highlight regions of "perfusion/diffusion
mismatch" that may indicate regions capable of salvage by reperfusion therapy.
Like many other specialized applications, this technique is usually coupled with a fast image acquisition sequence,
such as echo planar imaging sequence.
Magnetization Transfer MRI
Magnetization transfer (MT) refers to the transfer of longitudinal magnetization from free water protons to hydration
water protons in NMR and MRI.
In magnetic resonance imaging of molecular solutions, such as protein solutions, two types of water molecules, free
(bulk) and hydration, are found. Free water protons have faster average rotational frequency and hence less fixed
water molecules that may cause local field inhomogeneity. Because of this uniformity, most free water protons have
resonance frequency lying narrowly around the normal proton resonance frequency of 63 MHz (at 1.5 teslas). This
also results in slower transverse magnetization dephasing and hence longer T2. Conversely, hydration water
molecules are slowed down by interaction with solute molecules and hence create field inhomogeneities that lead to
wider resonance frequency spectrum.
Fluid attenuated inversion recovery (FLAIR)
Fluid Attenuated Inversion Recovery (FLAIR)[11] is an inversion-recovery pulse sequence used to null signal from
fluids. For example, it can be used in brain imaging to suppress cerebrospinal fluid (CSF) so as to bring out the
periventricular hyperintense lesions, such as multiple sclerosis (MS) plaques. By carefully choosing the inversion
time TI (the time between the inversion and excitation pulses), the signal from any particular tissue can be
suppressed.
Magnetic resonance angiography
Magnetic resonance angiography (MRA) is used to generate
pictures of the arteries in order to evaluate them for stenosis
(abnormal narrowing) or aneurysms (vessel wall dilatations, at risk
of rupture). MRA is often used to evaluate the arteries of the neck
and brain, the thoracic and abdominal aorta, the renal arteries, and
the legs (called a "run-off"). A variety of techniques can be used to
generate the pictures, such as administration of a paramagnetic
contrast agent (gadolinium) or using a technique known as
"flow-related enhancement" (e.g. 2D and 3D time-of-flight
sequences), where most of the signal on an image is due to blood
which has recently moved into that plane, see also FLASH MRI.
Techniques involving phase accumulation (known as phase
contrast angiography) can also be used to generate flow velocity
Magnetic Resonance Angiography
maps easily and accurately. Magnetic resonance venography
(MRV) is a similar procedure that is used to image veins. In this
method the tissue is now excited inferiorly while signal is gathered in the plane immediately superior to the
excitation plane, and thus imaging the venous blood which has recently moved from the excited plane[12] .
191
Magnetic resonance imaging
192
Magnetic resonance gated intracranial CSF dynamics (MR-GILD)
Magnetic resonance gated intracranial cerebrospinal fluid (CSF)or liquor dynamics (MR-GILD) technique is an MR
sequence based on bipolar gradient pulse used to demonstrate CSF pulsatile flow in ventricles, cisterns, aqueduct of
Sylvius and entire intracranial CSF pathway. It is a method for analyzing CSF circulatory system dynamics in
patients with CSF obstructive lesions such as normal pressure hydrocephalus. It also allows visualization of both
arterial and venous pulsatile blood flow in vessels without use of contrast agents.[13] [14] .
Diastolic time data acquisition (DTDA). Systolic time data acquisition (STDA).
Magnetic resonance spectroscopy
Magnetic resonance spectroscopy (MRS) is used to measure the levels of different metabolites in body tissues. The
MR signal produces a spectrum of resonances that correspond to different molecular arrangements of the isotope
being "excited". This signature is used to diagnose certain metabolic disorders, especially those affecting the
brain,[15] and to provide information on tumor metabolism.[16]
Magnetic resonance spectroscopic imaging (MRSI) combines both spectroscopic and imaging methods to produce
spatially localized spectra from within the sample or patient. The spatial resolution is much lower (limited by the
available SNR), but the spectra in each voxel contains information about many metabolites. Because the available
signal is used to encode spatial and spectral information, MRSI requires high SNR achievable only at higher field
strengths (3 T and above).
Functional MRI
Functional MRI (fMRI) measures signal changes in the brain that are
due to changing neural activity. The brain is scanned at low resolution
but at a rapid rate (typically once every 2–3 seconds). Increases in
neural activity cause changes in the MR signal via T*2 changes;[17] this
mechanism is referred to as the BOLD (blood-oxygen-level dependent)
effect. Increased neural activity causes an increased demand for
oxygen, and the vascular system actually overcompensates for this,
increasing the amount of oxygenated hemoglobin relative to
deoxygenated hemoglobin. Because deoxygenated hemoglobin
attenuates the MR signal, the vascular response leads to a signal
increase that is related to the neural activity. The precise nature of the
relationship between neural activity and the BOLD signal is a subject
of current research. The BOLD effect also allows for the generation of
high resolution 3D maps of the venous vasculature within neural tissue.
A fMRI scan showing regions of activation in
orange, including the primary visual cortex (V1,
BA17).
While BOLD signal is the most common method employed for neuroscience studies in human subjects, the flexible
nature of MR imaging provides means to sensitize the signal to other aspects of the blood supply. Alternative
techniques employ arterial spin labeling (ASL) or weight the MRI signal by cerebral blood flow (CBF) and cerebral
blood volume (CBV). The CBV method requires injection of a class of MRI contrast agents that are now in human
Magnetic resonance imaging
clinical trials. Because this method has been shown to be far more sensitive than the BOLD technique in preclinical
studies, it may potentially expand the role of fMRI in clinical applications. The CBF method provides more
quantitative information than the BOLD signal, albeit at a significant loss of detection sensitivity.
Interventional MRI
The lack of harmful effects on the patient and the operator make MRI well-suited for "interventional radiology",
where the images produced by a MRI scanner are used to guide minimally-invasive procedures. Of course, such
procedures must be done without any ferromagnetic instruments.
A specialized growing subset of interventional MRI is that of intraoperative MRI in which the MRI is used in the
surgical process. Some specialized MRI systems have been developed that allow imaging concurrent with the
surgical procedure. More typical, however, is that the surgical procedure is temporarily interrupted so that MR
images can be acquired to verify the success of the procedure or guide subsequent surgical work.
Radiation therapy simulation
Because of MRI's superior imaging of soft tissues, it is now being utilized to specifically locate tumors within the
body in preparation for radiation therapy treatments. For therapy simulation, a patient is placed in specific,
reproducible, body position and scanned. The MRI system then computes the precise location, shape and orientation
of the tumor mass, correcting for any spatial distortion inherent in the system. The patient is then marked or tattooed
with points which, when combined with the specific body position, will permit precise triangulation for radiation
therapy.
Current density imaging
Current density imaging (CDI) endeavors to use the phase information from images to reconstruct current densities
within a subject. Current density imaging works because electrical currents generate magnetic fields, which in turn
affect the phase of the magnetic dipoles during an imaging sequence. To date no successful CDI has been performed
using biological currents, but several studies have been published which involve currents applied through a pair of
electrodes.
Magnetic resonance guided focused ultrasound
In MRgFUS therapy, ultrasound beams are focused on a tissue—guided and controlled using MR thermal
imaging—and due to the significant energy deposition at the focus, temperature within the tissue rises to more than
65 °C (150 °F), completely destroying it. This technology can achieve precise "ablation" of diseased tissue. MR
imaging provides a three-dimensional view of the target tissue, allowing for precise focusing of ultrasound energy.
The MR imaging provides quantitative, real-time, thermal images of the treated area. This allows the physician to
ensure that the temperature generated during each cycle of ultrasound energy is sufficient to cause thermal ablation
within the desired tissue and if not, to adapt the parameters to ensure effective treatment.
Multinuclear imaging
Hydrogen is the most frequently imaged nucleus in MRI because it is present in biological tissues in great
abundance. However, any nucleus which has a net nuclear spin could potentially be imaged with MRI. Such nuclei
include helium-3, carbon-13, fluorine-19, oxygen-17, sodium-23, phosphorus-31 and xenon-129. 23Na, 31P and 17O
are naturally abundant in the body, so can be imaged directly. Gaseous isotopes such as 3He or 129Xe must be
hyperpolarized and then inhaled as their nuclear density is too low to yield a useful signal under normal conditions.
17
O, 13C and 19F can be administered in sufficient quantities in liquid form (e.g. 17O-water, 13C-glucose solutions or
perfluorocarbons) that hyperpolarization is not a necessity.
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Magnetic resonance imaging
Multinuclear imaging is primarily a research technique at present. However, potential applications include functional
imaging and imaging of organs poorly seen on 1H MRI (e.g. lungs and bones) or as alternative contrast agents.
Inhaled hyperpolarized 3He can be used to image the distribution of air spaces within the lungs. Injectable solutions
containing 13C or stabilized bubbles of hyperpolarized 129Xe have been studied as contrast agents for angiography
and perfusion imaging. 31P can potentially provide information on bone density and structure, as well as functional
imaging of the brain.
Susceptibility weighted imaging (SWI)
Susceptibility weighted imaging (SWI), is a new type of contrast in MRI different from spin density, T1, or T2
imaging. This method exploits the susceptibility differences between tissues and uses a fully velocity compensated,
three dimensional, RF spoiled, high-resolution, 3D gradient echo scan. This special data acquisition and image
processing produces an enhanced contrast magnitude image very sensitive to venous blood, hemorrhage and iron
storage. It is used to enhance the detection and diagnosis of tumors, vascular and neurovascular diseases (stroke and
hemorrhage, multiple sclerosis, Alzheimer's), and also detects traumatic brain injuries that may not be diagnosed
using other methods.[18] [19]
Other specialized MRI techniques
MRI is a new and active field of research and new methods and variants are often published when they are able to
get better results in specific fields. Examples of these recent improvements are T*2-weighted turbo spin-echo (T2
TSE MRI), double inversion recovery MRI (DIR-MRI) or phase-sensitive inversion recovery MRI (PSIR-MRI), all
of them able to improve imaging of the brain lesions[20] [21] . Another example is MP-RAGE
(magnetization-prepared rapid acquisition with gradient echo)[22] , which improves images of multiple sclerosis
cortical lesions[23] .
Portable instruments
Portable magnetic resonance instruments are available for use in education and field research. Using the principles of
Earth's field NMR, they have no powerful polarizing magnet, so that such instruments can be small and inexpensive.
Some can be used for both EFNMR spectroscopy and MRI imaging[24] . The low strength of the Earth's field results
in poor signal to noise ratios, requiring long scan times to capture spectroscopic data or build up MRI images.
Research with atomic magnetometers have discussed the possibility for cheap and portable MRI instruments without
the large magnet.[25] [26]
MRI versus CT
A computed tomography (CT) scanner uses X-rays, a type of ionizing radiation, to acquire its images, making it a
good tool for examining tissue composed of elements of a higher atomic number than the tissue surrounding them,
such as bone and calcifications (calcium based) within the body (carbon based flesh), or of structures (vessels,
bowel). MRI, on the other hand, uses non-ionizing radio frequency (RF) signals to acquire its images and is best
suited for non-calcified tissue, though MR images can also be acquired from bones and teeth[27] as well as fossils.[28]
CT may be enhanced by use of contrast agents containing elements of a higher atomic number than the surrounding
flesh such as iodine or barium. Contrast agents for MRI are those which have paramagnetic properties, e.g.
gadolinium and manganese.
Both CT and MRI scanners can generate multiple two-dimensional cross-sections (slices) of tissue and
three-dimensional reconstructions. Unlike CT, which uses only X-ray attenuation to generate image contrast, MRI
has a long list of properties that may be used to generate image contrast. By variation of scanning parameters, tissue
contrast can be altered and enhanced in various ways to detect different features. (See Applications above.)
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Magnetic resonance imaging
MRI can generate cross-sectional images in any plane (including oblique planes). In the past, CT was limited to
acquiring images in the axial (or near axial) plane. The scans used to be called Computed Axial Tomography scans
(CAT scans). However, the development of multi-detector CT scanners with near-isotropic resolution, allows the CT
scanner to produce data that can be retrospectively reconstructed in any plane with minimal loss of image quality.
For purposes of tumor detection and identification in the brain, MRI is generally superior.[29] [30] [31] However, in the
case of solid tumors of the abdomen and chest, CT is often preferred due to less motion artifact. Furthermore, CT
usually is more widely available, faster, less expensive, and may be less likely to require the person to be sedated or
anesthetized.
MRI is also best suited for cases when a patient is to undergo the exam several times successively in the short term,
because, unlike CT, it does not expose the patient to the hazards of ionizing radiation.
Economics of MRI
MRI equipment is expensive. 1.5 tesla scanners often cost between $1 million and $1.5 million USD. 3.0 tesla
scanners often cost between $2 million and $2.3 million USD. Construction of MRI suites can cost up to $500,000
USD, or more, depending on project scope.
MRI scanners have been significant sources of revenue for healthcare providers in the US. This is because of
favorable reimbursement rates from insurers and federal government programs. Insurance reimbursement is provided
in two components, an equipment charge for the actual performance of the MRI scan and professional charge for the
radiologist's review of the images and/or data. In the US Northeast, an equipment charge might be $3,500 and a
professional charge might be $350 [32] although the actual fees received by the equipment owner and interpreting
physician are often quite less and depend on the rates negotiated with insurance companies or determined by
governmental action as in the Medicare Fee Schedule. For example, an orthopedic surgery group in Illinois billed a
charge of $1,116 for a knee MRI in 2007 but the Medicare reimbursement in 2007 was only $470.91 [33] . Many
insurance companies require preapproval of an MRI procedure as a condition for coverage.
In the US, the 2007 Deficit Reduction Act (DRA) significantly reduced reimbursement rates paid by federal
insurance programs for the equipment component of many scans, shifting the economic landscape. Many private
insurers have followed suit.
195
Magnetic resonance imaging
196
Installation of the MRI unit
An MRI unit is a rather large item, typically requiring heavy
equipment (such as cranes) to move the unit to its final location. Once
the MRI unit is in place, the room that houses it is usually "built up"
around the unit itself. See this page [34] for an example of the
complexity involved in installing an MRI unit in a clinical setting. [35]
Safety
Heavy lifting equipment is used to install the
MRI unit.
Death and injuries have occurred from projectiles created by the
magnetic field, although few compared to the millions of examinations
administered.[36] [37] MRI makes use of powerful magnetic fields
which, though they have not been demonstrated to cause direct
biological damage, can interfere with metallic and electromechanical
devices. Additional (small) risks are presented by the radio frequency
systems, components or elements of the MRI system's operation,
elements of the scanning procedure and medications that may be
administered to facilitate MRI imaging.
Of great concern is the dramatic increase in the number of reported MRI accidents to the U.S. Food and Drug
Administration (FDA). Since 2004, the last year in which a decline in the number of MRI accidents was reported, the
full spectrum of MRI accidents has increased significantly in the following years. The 2008 FDA accident report
data [38] culminates in a 277% increase over the 2004 rate.
There are many steps that the MRI patient and referring physician can take to help reduce the remaining risks,
including providing a full, accurate and thorough medical history to the MRI provider.
Several of the specific MRI safety considerations are identified below:
Implants and foreign bodies
Pacemakers are generally considered an absolute contraindication towards MRI scanning, though highly specialized
protocols have been developed to permit scanning of select pacing devices. Several cases of arrhythmia or death
have been reported in patients with pacemakers who have undergone MRI scanning without appropriate precautions.
Other electronic implants have varying contraindications, depending upon scanner technology, and implant
properties, scanning protocols and anatomy being imaged.
Many other forms of medical or biostimulation implants may be contraindicated for MRI scans. These may include
vagus nerve stimulators, implantable cardioverter-defibrillators, loop recorders, insulin pumps, cochlear implants,
deep brain stimulators, and many others. Medical device patients should always present complete information
(manufacturer, model, serial number and date of implantation) about all implants to both the referring physician and
to the radiologist or technologist before entering the room for the MRI scan.
While these implants pose a current problem, scientists and manufacturers are working on improved designs which
will further minimize the risks that MRI scans pose to medical device operations. One such development in the
works is a nano-coating for implants intended to screen them from the radio frequency waves, helping to make MRI
exams available to patients currently prohibited from receiving them. The current article [39] for this is from New
Scientist.
Ferromagnetic foreign bodies (e.g. shell fragments), or metallic implants (e.g. surgical prostheses, aneurysm clips)
are also potential risks, and safety aspects need to be considered on an individual basis. Interaction of the magnetic
Magnetic resonance imaging
197
and radio frequency fields with such objects can lead to trauma due to movement of the object in the magnetic field,
thermal injury from radio-frequency induction heating of the object, or failure of an implanted device. These issues
are especially problematic when dealing with the eye. Most MRI centers require an orbital x-ray to be performed on
anyone suspected of having metal fragments in their eyes, something not uncommon in metalworking.
Because of its non-ferromagnetic nature and poor electrical conductivity, titanium and its alloys are useful for long
term implants and surgical instruments intended for use in image-guided surgery. In particular, not only is titanium
safe from movement from the magnetic field, but artifacts around the implant are less frequent and less severe than
with more ferromagnetic materials e.g. stainless steel. Artifacts from metal frequently appear as regions of empty
space around the implant—frequently called 'black-hole artifact'. E.g. a 3 mm titanium alloy coronary stent may
appear as a 5 mm diameter region of empty space on MRI, whereas around a stainless steel stent, the artifact may
extend for 10–20 mm or more.
In 2006, a new classification system for implants and ancillary clinical devices has been developed by ASTM
International and is now the standard supported by the US Food and Drug Administration:
MR-Safe — The device or implant is completely non-magnetic,
non-electrically conductive, and non-RF reactive, eliminating all of the
primary potential threats during an MRI procedure.
MR Safe sign
MR-Conditional — A device or implant that may contain magnetic,
electrically conductive or RF-reactive components that is safe for
operations in proximity to the MRI, provided the conditions for safe
operation are defined and observed (such as 'tested safe to 1.5 teslas' or
'safe in magnetic fields below 500 gauss in strength').
MR Conditional sign
Magnetic resonance imaging
198
MR-Unsafe — Nearly self-explanatory, this category is reserved for
objects that are significantly ferromagnetic and pose a clear and direct
threat to persons and equipment within the magnet room.
Though the current classification system was originally developed for
regulatory-approved medical devices, it is being applied to all manner
of items, appliances and equipment intended for use in the MR
environment.
In the case of pacemakers, the risk is thought to be primarily RF
induction in the pacing electrodes/wires causing inappropriate pacing
of the heart, rather than the magnetic field affecting the pacemaker
itself. Much research and development is being undertaken, and many
tools are being developed in order to predict the effects of the RF fields
inside the body.
MR Unsafe sign
Patients who have been prescribed MRI exams who are concerned about safety may be interested in the 10
Questions To Ask Your MRI Provider [40].
MRI providers who wish to measure the degree to which they have effectively addressed the safety issues for
patients and staff may be interested in the MRI Suite Safety Calculator [41] provided through a radiology website.
Projectile or missile effect
As a result of the very high strength of the magnetic field needed to produce scans (frequently up to 60,000 times the
Earth's own magnetic field effects), there are several incidental safety issues addressed in MRI facilities.
Missile-effect accidents, where ferromagnetic objects are attracted to the center of the magnet, have resulted in injury
and death.[36] [37] A video simulation of a fatal projectile effect accident [42] illustrates the extreme power that
contemporary MRI equipment can exert on ferromagnetic objects.
In order to help reduce the risks of projectile accidents, ferromagnetic objects and devices are typically prohibited in
proximity to the MRI scanner, with non-ferromagnetic versions of many tools and devices typically retained by the
scanning facility. Patients undergoing MRI examinations are required to remove all metallic objects, often by
changing into a gown or scrubs.
New ferromagnetic-only detection devices are proving highly effective in supplementing conventional screening
techniques in many leading hospitals and imaging centers and are now recommended by the American College of
Radiology's Guidance Document for Safe MR Practices: 2007 [43], the United States' Veterans Administration's
Design Guide [44] and the Joint Commission's Sentinel Event Alert #38 [45].
The magnetic field and the associated risk of missile-effect accidents remains a permanent hazard — as
superconductive MRI magnets retain their magnetic field, even in the event of a power outage.
Radio frequency energy
A powerful radio transmitter is needed for excitation of proton spins. This can heat the body to the point of risk of
hyperthermia in patients, particularly in obese patients or those with thermoregulation disorders. Several countries
have issued restrictions on the maximum specific absorption rate that a scanner may produce.
Peripheral nerve stimulation (PNS)
The rapid switching on and off of the magnetic field gradients is capable of causing nerve stimulation. Volunteers
report a twitching sensation when exposed to rapidly switched fields, particularly in their extremities. The reason the
peripheral nerves are stimulated is that the changing field increases with distance from the center of the gradient
coils (which more or less coincides with the center of the magnet). Note however that when imaging the head, the
Magnetic resonance imaging
heart is far off-center and induction of even a tiny current into the heart must be avoided at all costs. Although PNS
was not a problem for the slow, weak gradients used in the early days of MRI, the strong, rapidly switched gradients
used in techniques such as EPI, fMRI, diffusion MRI, etc. are indeed capable of inducing PNS. American and
European regulatory agencies insist that manufacturers stay below specified dB/dt limits (dB/dt is the change in field
per unit time) or else prove that no PNS is induced for any imaging sequence. As a result of dB/dt limitation,
commercial MRI systems cannot use the full rated power of their gradient amplifiers.
Acoustic noise
Switching of field gradients causes a change in the Lorentz force experienced by the gradient coils, producing
minute expansions and contractions of the coil itself. As the switching is typically in the audible frequency range, the
resulting vibration produces loud noises (clicking or beeping). This is most marked with high-field machines and
rapid-imaging techniques in which sound intensity can reach 120 dB(A) (equivalent to a jet engine at take-off) [46] .
Appropriate use of ear protection is essential for anyone inside the MRI scanner room during the examination.[47]
Cryogens
As described above in #Scanner construction and operation, many MRI scanners rely on cryogenic liquids to enable
superconducting capabilities of the electromagnetic coils within. Though the cryogenic liquids most frequently used
are non-toxic, their physical properties present specific hazards.
An emergency shut-down of a superconducting electromagnet, an operation known as "quenching", involves the
rapid boiling of liquid helium from the device. If the rapidly expanding helium cannot be dissipated through an
external vent, sometimes referred to as 'quench pipe', it may be released into the scanner room where it may cause
displacement of the oxygen and present a risk of asphyxiation.[48]
Liquid helium, the most commonly used cryogen in MRI, undergoes near explosive expansion as it changes from
liquid to a gaseous state. Rooms built in support of superconducting MRI equipment should be equipped with
pressure relief mechanisms[49] and an exhaust fan, in addition to the required quench pipe.
Since a quench results in rapid loss of all cryogens in the magnet, recommissioning the magnet is extremely
expensive and time-consuming. Spontaneous quenches are uncommon, but may also be triggered by equipment
malfunction, improper cryogen fill technique, contaminants inside the cryostat, or extreme magnetic or vibrational
disturbances.
Contrast agents
The most commonly used intravenous contrast agents are based on chelates of gadolinium. In general, these agents
have proved safer than the iodinated contrast agents used in X-ray radiography or CT. Anaphylactoid reactions are
rare, occurring in approx. 0.03–0.1%.[50] Of particular interest is the lower incidence of nephrotoxicity, compared
with iodinated agents, when given at usual doses—this has made contrast-enhanced MRI scanning an option for
patients with renal impairment, who would otherwise not be able to undergo contrast-enhanced CT.[51]
Although gadolinium agents have proved useful for patients with renal impairment, in patients with severe renal
failure requiring dialysis there is a risk of a rare but serious illness, nephrogenic systemic fibrosis, that may be linked
to the use of certain gadolinium-containing agents. The most frequently linked is gadodiamide, but other agents have
been linked too.[52] Although a causal link has not been definitively established, current guidelines in the United
States are that dialysis patients should only receive gadolinium agents where essential, and that dialysis should be
performed as soon as possible after the scan is complete, in order to remove the agent from the body promptly.[53] In
Europe, where more gadolinium-containing agents are available, a classification of agents according to potential
risks has been released.[54] [55] Recently a new contrast agent named gadoxetate, brand name Eovist (US) or
Primovist (EU), was approved for diagnostic use: this has the theoretical benefit of a dual excretion path.[56]
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Pregnancy
No effects of MRI on the fetus have been demonstrated.[57] In particular, MRI avoids the use of ionizing radiation, to
which the fetus is particularly sensitive. However, as a precaution, current guidelines recommend that pregnant
women undergo MRI only when essential. This is particularly the case during the first trimester of pregnancy, as
organogenesis takes place during this period. The concerns in pregnancy are the same as for MRI in general, but the
fetus may be more sensitive to the effects—particularly to heating and to noise. However, one additional concern is
the use of contrast agents; gadolinium compounds are known to cross the placenta and enter the fetal bloodstream,
and it is recommended that their use be avoided.
Despite these concerns, MRI is rapidly growing in importance as a way of diagnosing and monitoring congenital
defects of the fetus because it can provide more diagnostic information than ultrasound and it lacks the ionizing
radiation of CT. MRI without contrast agents is the imaging mode of choice for pre-surgical, in-utero diagnosis and
evaluation of fetal tumors, primarily teratomas, facilitating open fetal surgery, other fetal interventions, and planning
for procedures (such as the EXIT procedure) to safely deliver and treat babies whose defects would otherwise be
fatal.
Claustrophobia and discomfort
Due to the construction of some MRI scanners, they can be potentially unpleasant to lie in. Older models of closed
bore MRI systems feature a fairly long tube or tunnel. The part of the body being imaged needs to lie at the center of
the magnet which is at the absolute center of the tunnel. Because scan times on these older scanners may be long
(occasionally up to 40 minutes for the entire procedure), people with even mild claustrophobia are sometimes unable
to tolerate an MRI scan without management. Modern scanners may have larger bores (up to 70 cm) and scan times
are shorter. This means that claustrophobia is less of an issue, and many patients now find MRI an innocuous and
easily tolerated procedure.
Nervous patients may still find the following strategies helpful:
• Advance preparation
• visiting the scanner to see the room and practice lying on the table
• visualization techniques
• chemical sedation
• general anesthesia
• Coping while inside the scanner
•
•
•
•
holding a "panic button"
closing eyes as well as covering them (e.g. washcloth, eye mask)
listening to music on headphones or watching a movie with a Head-mounted display while in the machine
Scan Rooms with lighting, sound and images on the wall. Some rooms come with images on the walls or
ceiling.
Alternative scanner designs, such as open or upright systems, can also be helpful where these are available. Though
open scanners have increased in popularity, they produce inferior scan quality because they operate at lower
magnetic fields than closed scanners. However, commercial 1.5 tesla open systems have recently become available,
providing much better image quality than previous lower field strength open models[58] .
For babies and young children chemical sedation or general anesthesia are the norm, as these subjects cannot be
instructed to hold still during the scanning session. Obese patients and pregnant women may find the MRI machine
to be a tight fit. Pregnant women may also have difficulty lying on their backs for an hour or more without moving.
Acoustic noise associated with the operation of an MRI scanner can also exacerbate the discomfort associated with
the procedure.
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Guidance
Safety issues, including the potential for biostimulation device interference, movement of ferromagnetic bodies, and
incidental localized heating, have been addressed in the American College of Radiology's White Paper on MR Safety
which was originally published in 2002 and expanded in 2004. The ACR White Paper on MR Safety has been
rewritten and was released early in 2007 under the new title ACR Guidance Document for Safe MR Practices [43].
In December 2007, the Medicines in Healthcare product Regulation Agency (MHRA), a UK healthcare regulatory
body, issued their Safety Guidelines for Magnetic Resonance Imaging Equipment in Clinical Use [59].
In February 2008, the Joint Commission, a US healthcare accrediting organization, issued a Sentinel Event Alert #38
[45]
, their highest patient safety advisory, on MRI safety issues.
In July 2008, the United States Veterans Administration, a federal governmental agency serving the healthcare needs
of former military personnel, issued a substantial revision to their MRI Design Guide [60] which includes physical or
facility safety considerations.
The European Physical Agents Directive
The European Physical Agents (Electromagnetic Fields) Directive is legislation adopted in European legislature.
Originally scheduled to be required by the end of 2008, each individual state within the European Union must
include this directive in its own law by the end of 2012. Some member nations passed complying legislation and are
now attempting to repeal their state laws in expectation that the final version of the EU Physical Agents Directive
will be substantially revised prior to the revised adoption date.
The directive applies to occupational exposure to electromagnetic fields (not medical exposure) and was intended to
limit workers’ acute exposure to strong electromagnetic fields, as may be found near electricity substations, radio or
television transmitters or industrial equipment. However, the regulations impact significantly on MRI, with separate
sections of the regulations limiting exposure to static magnetic fields, changing magnetic fields and radio frequency
energy. Field strength limits are given which may not be exceeded for any period of time. An employer may commit
a criminal offense by allowing a worker to exceed an exposure limit if that is how the Directive is implemented in a
particular Member State.
The Directive is based on the international consensus of established effects of exposure to electromagnetic fields,
and in particular the advice of the European Commissions's advisor, the International Commission on Non-Ionizing
Radiation Protection (ICNIRP). The aims of the Directive, and the ICNIRP guidelines upon which it is based, are to
prevent exposure to potentially harmful fields. The actual limits in the Directive are very similar to the limits advised
by the Institute of Electrical and Electronics Engineers, with the exception of the frequencies produced by the
gradient coils, where the IEEE limits are significantly higher.
Many Member States of the EU already have either specific EMF regulations or (as in the UK) a general requirement
under workplace health and safety legislation to protect workers against electromagnetic fields. In almost all cases
the existing regulations are aligned with the ICNIRP limits so that the Directive should, in theory, have little impact
on any employer already meeting their legal responsibilities.
The introduction of the Directive has brought to light an existing potential issue with occupational exposures to MRI
fields. There are at present very few data on the number or types of MRI practice that might lead to exposures in
excess of the levels of the Directive.[61] [62] There is a justifiable concern amongst MRI practitioners that if the
Directive were to be enforced more vigorously than existing legislation, the use of MRI might be restricted, or
working practices of MRI personnel might have to change.
In the initial draft a limit of static field strength to 2 T was given. This has since been removed from the regulations,
and whilst it is unlikely to be restored as it was without a strong justification, some restriction on static fields may be
reintroduced after the matter has been considered more fully by ICNIRP. The effect of such a limit might be to
restrict the installation, operation and maintenance of MRI scanners with magnets of 2 T and stronger. As the
increase in field strength has been instrumental in developing higher resolution and higher performance scanners,
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Magnetic resonance imaging
this would be a significant step back. This is why it is unlikely to happen without strong justification.
Individual government agencies and the European Commission have now formed a working group to examine the
implications on MRI and to try to address the issue of occupational exposures to electromagnetic fields from MRI.
Three-dimensional (3D) image reconstruction
The principle
Because contemporary MRI scanners offer isotropic, or near isotropic, resolution, display of images does not need to
be restricted to the conventional axial images. Instead, it is possible for a software program to build a volume by
'stacking' the individual slices one on top of the other. The program may then display the volume in an alternative
manner.
3D rendering techniques
Surface rendering
A threshold value of greyscale density is chosen by the operator (e.g. a level that corresponds to fat). A
threshold level is set, using edge detection image processing algorithms. From this, a 3-dimensional model can
be constructed and displayed on screen. Multiple models can be constructed from various different thresholds,
allowing different colors to represent each anatomical component such as bone, muscle, and cartilage.
However, the interior structure of each element is not visible in this mode of operation.
Volume rendering
Surface rendering is limited in that it will only display surfaces which meet a threshold density, and will only
display the surface that is closest to the imaginary viewer. In volume rendering, transparency and colors are
used to allow a better representation of the volume to be shown in a single image - e.g. the bones of the pelvis
could be displayed as semi-transparent, so that even at an oblique angle, one part of the image does not
conceal another.
Image segmentation
Where different structures have similar threshold density, it can become impossible to separate them simply by
adjusting volume rendering parameters. The solution is called segmentation, a manual or automatic procedure that
can remove the unwanted structures from the image.
2003 Nobel Prize
Reflecting the fundamental importance and applicability of MRI in the medical field, Paul Lauterbur of the
University of Illinois at Urbana-Champaign and Sir Peter Mansfield of the University of Nottingham were awarded
the 2003 Nobel Prize in Physiology or Medicine for their "discoveries concerning magnetic resonance imaging". The
Nobel Prize committee acknowledged Lauterbur's insight of using magnetic field gradients to introduce spatial
localization, a discovery that allowed rapid acquisition of 2D images. Mansfield was credited with introducing the
mathematical formalism and developing techniques for efficient gradient utilization and fast imaging. The actual
research for which the prize was awarded was done almost 30 years ago, while Paul Lauterbur was at Stony Brook
University in New York.
The award was vigorously protested by Raymond Vahan Damadian, founder of FONAR Corporation, who claimed
that he was the inventor of MRI,[3] and that Lauterbur and Mansfield had merely refined the technology.[63] An ad
hoc group, called "The Friends of Raymond Damadian", took out full-page advertisements in the New York Times
and The Washington Post entitled "The Shameful Wrong That Must Be Righted", demanding that he be awarded at
least a share of the Nobel Prize.[64] Also, even earlier, in the Soviet Union, Vladislav Ivanov filed (in 1960) a
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Magnetic resonance imaging
203
document with the USSR State Committee for Inventions and Discovery at Leningrad for a Magnetic Resonance
Imaging device[65] , although this was not approved until the 1970s.[66] In a letter to Physics Today, Herman Carr
pointed out his own even earlier use of field gradients for one-dimensional MR imaging.[67]
See also
•
Earth's field NMR (EFNMR)
Magnetic Resonance Imaging (journal) •
Nuclear magnetic resonance (NMR)
•
Electron-spin resonance (spin physics) •
•
Magnetic resonance microscopy
•
2D-FT NMRI and Spectroscopy
•
History of brain imaging
•
Magnetic Particle Imaging (MPI)
•
Relaxation
•
Medical imaging
•
Magnetic resonance elastography
•
Robinson oscillator
•
Magnetic immunoassay
•
Neuroimaging software
•
Rabi cycle
•
Jemris (open source MRI simulator)
•
Nephrogenic fibrosing dermopathy
•
Virtopsy
•
Nobel Prize controversies
References
• Simon, Merrill; Mattson, James S (1996). The pioneers of NMR and magnetic resonance in medicine: The story of
MRI. Ramat Gan, Israel: Bar-Ilan University Press. ISBN 0-9619243-1-4.
• Haacke, E Mark; Brown, Robert F; Thompson, Michael; Venkatesan, Ramesh (1999). Magnetic resonance
imaging: Physical principles and sequence design. New York: J. Wiley & Sons. ISBN 0-471-35128-8.
External links
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Listing of MRI Types [68] - All Inclusive Listing of MRI Types
www.mri-tutorial.com [69]- MRI-TUTORIAL.COM | A free learning repository about neuroimaging
mri.startkabel.nl [70]- Grote verzameling MRI-gerelateerde links
BIGS-animation [71] - Physics of MRI like spin, modification of spin or pulse sequences
MDCT [72] - Free Radiology Resource For Radiographers, Radiologists and Technical Assistants
A Guided Tour of MRI: An introduction for laypeople [73] National High Magnetic Field Laboratory
Joseph P. Hornak, Ph.D. The Basics of MRI [74]. Underlying physics and technical aspects.
Video: What to Expect During Your MRI Exam [75] from the Institute for Magnetic Resonance Safety, Education,
and Research (IMRSER)
Interactive Flash Animation on MRI [76] - Online Magnetic Resonance Imaging physics and technique course
International Society for Magnetic Resonance in Medicine [77]
Article on helium scarcity and potential effects on NMR and MRI communities [78]
Danger of objects flying into the scanner [79]
Video compiled of MRI scans showing arachnoid cyst [80]
JEMRIS [81] - Parallel and single-core general MRI Simulator
Professor Laurance Hall [82] - Daily Telegraph obituary
mri-physics.com [83]- Online MRI physics textbook.
Magnetic resonance imaging
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[69] http:/ / www. mri-tutorial. com
[70] http:/ / mri. startkabel. nl
[71] http:/ / www. bigs. de/ BLH/ en/ index. php?option=com_content& view=category& layout=blog& id=100& Itemid=268
[72] http:/ / www. mdct. com. au
[73] http:/ / www. magnet. fsu. edu/ education/ tutorials/ magnetacademy/ mri/
[74] http:/ / www. cis. rit. edu/ htbooks/ mri/
[75] http:/ / www. imrser. org/ PatientVideo. html
[76]
[77]
[78]
[79]
[80]
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http:/ / www. youtube. com/ watch?v=PF_mDsdxSsg
http:/ / www. jemris. org
http:/ / www. telegraph. co. uk/ news/ obituaries/ medicine-obituaries/ 6252025/ Professor-Laurance-Hall. html
http:/ / www. mri-physics. com/ html/ textuk. html
206
Long-term video-EEG monitoring
Long-term video-EEG monitoring
Long-term video-EEG monitoring, also known as video telemetry, is a diagnostic technique used in certain
patients with epilepsy or seizures. It involves the inpatient hospitalization of the patient for a period of time, typically
days to weeks, during which they are continuously monitored and recorded with a video camera and an
electroencephalograph.
The recording is periodically monitored and analyzed by a neurologist. Typically one trained in clinical
neurophysiology, the neurologist determines when the monitoring is finished and issues the final report.
The purposes of long-term video-EEG monitoring include:
• discovering where in the brain a given person's seizures begin
• distinguishing epileptic seizures from psychogenic non-epileptic seizures
• evaluating a person who is a candidate for surgery to treat epilepsy
Brain–computer interface
A brain–computer interface (BCI), sometimes called a direct neural interface or a brain–machine interface, is
a direct communication pathway between a brain and an external device. BCIs are often aimed at assisting,
augmenting or repairing human cognitive or sensory-motor functions.
Research on BCIs began in the 1970s at the University of California Los Angeles (UCLA) under a grant from the
National Science Foundation, followed by a contract from DARPA.[1] [2] The papers published after this research
also mark the first appearance of the expression brain–computer interface in scientific literature.
The field of BCI has since blossomed spectacularly, mostly toward neuroprosthetics applications that aim at
restoring damaged hearing, sight and movement. Thanks to the remarkable cortical plasticity of the brain, signals
from implanted prostheses can, after adaptation, be handled by the brain like natural sensor or effector channels.[3]
Following years of animal experimentation, the first neuroprosthetic devices implanted in humans appeared in the
mid-nineties.
BCI versus neuroprosthetics
Neuroprosthetics is an area of neuroscience concerned with neural prostheses—using artificial devices to replace the
function of impaired nervous systems or sensory organs. The most widely used neuroprosthetic device is the
cochlear implant, which, as of 2006, has been implanted in approximately 100,000 people worldwide.[4] There are
also several neuroprosthetic devices that aim to restore vision, including retinal implants.
The differences between BCIs and neuroprosthetics are mostly in the ways the terms are used: neuroprosthetics
typically connect the nervous system to a device, whereas BCIs usually connect the brain (or nervous system) with a
computer system. Practical neuroprosthetics can be linked to any part of the nervous system—for example,
peripheral nerves—while the term "BCI" usually designates a narrower class of systems which interface with the
central nervous system.
The terms are sometimes used interchangeably, and for good reason. Neuroprosthetics and BCIs seek to achieve the
same aims, such as restoring sight, hearing, movement, ability to communicate, and even cognitive function. Both
use similar experimental methods and surgical techniques.
207
Brain–computer interface
208
Animal BCI research
Several laboratories have managed to record signals from monkey and
rat cerebral cortices in order to operate BCIs to carry out movement.
Monkeys have navigated computer cursors on screen and commanded
robotic arms to perform simple tasks simply by thinking about the task
and without any motor output[5] . In May 2008 photographs that
showed a monkey operating a robotic arm with its mind at the
Pittsburgh University Medical Center were published in a number of
well known science journals and magazines.[6] Other research on cats
has decoded visual signals.
Rats implanted with BCIs in Theodore Berger's
experiments
Early work
The operant conditioning studies of Fetz and colleagues first demonstrated that monkeys could learn to control the
deflection of a biofeedback meter arm with neural activity [7] . Such work in the 1970s established that monkeys
could quickly learn to voluntarily control the firing rates of individual and multiple neurons in the primary motor
cortex if they were rewarded for generating appropriate patterns of neural activity.[8]
Studies that developed algorithms to reconstruct movements from
motor cortex neurons, which control movement, date back to the
1970s. In the 1980s, Apostolos Georgopoulos at Johns Hopkins
University found a mathematical relationship between the electrical
responses of single motor-cortex neurons in rhesus macaque monkeys
and the direction that monkeys moved their arms (based on a cosine
function). He also found that dispersed groups of neurons in different
areas of the brain collectively controlled motor commands but was
only able to record the firings of neurons in one area at a time because
of technical limitations imposed by his equipment.[9]
Monkey operating a robotic arm with
brain–computer interfacing
There has been rapid development in BCIs since the mid-1990s.[10] Several groups have been able to capture
complex brain motor centre signals using recordings from neural ensembles (groups of neurons) and use these to
control external devices, including research groups led by Richard Andersen, John Donoghue, Phillip Kennedy,
Miguel Nicolelis, and Andrew Schwartz.
Brain–computer interface
209
Prominent research successes
Phillip Kennedy and colleagues built the first intracortical brain–computer interface by implanting
neurotrophic-cone electrodes into monkeys.
In 1999, researchers led by Yang Dan at University of California,
Berkeley decoded neuronal firings to reproduce images seen by cats.
The team used an array of electrodes embedded in the thalamus (which
integrates all of the brain’s sensory input) of sharp-eyed cats.
Researchers targeted 177 brain cells in the thalamus lateral geniculate
nucleus area, which decodes signals from the retina. The cats were
shown eight short movies, and their neuron firings were recorded.
Using mathematical filters, the researchers decoded the signals to
generate movies of what the cats saw and were able to reconstruct
recognizable scenes and moving objects.[11] Similar results in humans
have been since then achieved by researchers in Japan (see below).
Yang Dan and colleagues' recordings of cat
vision using a BCI implanted in the lateral
geniculate nucleus (top row: original image;
bottom row: recording)
Miguel Nicolelis has been a prominent proponent of using multiple electrodes spread over a greater area of the brain
to obtain neuronal signals to drive a BCI. Such neural ensembles are said to reduce the variability in output produced
by single electrodes, which could make it difficult to operate a BCI.
After conducting initial studies in rats during the 1990s, Nicolelis and his colleagues developed BCIs that decoded
brain activity in owl monkeys and used the devices to reproduce monkey movements in robotic arms. Monkeys have
advanced reaching and grasping abilities and good hand manipulation skills, making them ideal test subjects for this
kind of work.
By 2000, the group succeeded in building a BCI that reproduced owl monkey movements while the monkey
operated a joystick or reached for food.[12] The BCI operated in real time and could also control a separate robot
remotely over Internet protocol. But the monkeys could not see the arm moving and did not receive any feedback, a
so-called open-loop BCI.
Later experiments by Nicolelis using rhesus monkeys, succeeded in
closing the feedback loop and reproduced monkey reaching and
grasping movements in a robot arm. With their deeply cleft and
furrowed brains, rhesus monkeys are considered to be better models for
human neurophysiology than owl monkeys. The monkeys were trained
to reach and grasp objects on a computer screen by manipulating a
joystick while corresponding movements by a robot arm were
hidden.[13] [14] The monkeys were later shown the robot directly and
learned to control it by viewing its movements. The BCI used velocity
predictions to control reaching movements and simultaneously
predicted hand gripping force.
Diagram of the BCI developed by Miguel
Nicolelis and colleagues for use on Rhesus
monkeys
Other labs that develop BCIs and algorithms that decode neuron signals include John Donoghue from Brown
University, Andrew Schwartz from the University of Pittsburgh and Richard Andersen from Caltech. These
researchers were able to produce working BCIs even though they recorded signals from far fewer neurons than
Nicolelis (15–30 neurons versus 50–200 neurons).
Donoghue's group reported training rhesus monkeys to use a BCI to track visual targets on a computer screen with or
without assistance of a joystick (closed-loop BCI).[15] Schwartz's group created a BCI for three-dimensional tracking
in virtual reality and also reproduced BCI control in a robotic arm.[16] The group created headlines when they
demonstrated that a monkey could feed itself pieces of zucchini using a robotic arm controlled by the animal's own
brain signals.[17] [18]
Brain–computer interface
Andersen's group used recordings of premovement activity from the posterior parietal cortex in their BCI, including
signals created when experimental animals anticipated receiving a reward.[19]
In addition to predicting kinematic and kinetic parameters of limb movements, BCIs that predict electromyographic
or electrical activity of muscles are being developed.[20] Such BCIs could be used to restore mobility in paralyzed
limbs by electrically stimulating muscles.
Miguel Nicolelis worked with John Chapin, Johan Wessberg, Mark Laubach, Jose Carmena, Mikhail Lebedev,
Antonio Pereira, Jr., Sidarta Ribeiro and other colleagues showed that activity of large neural ensembles can predict
arm position. This work made possible creation of brain–machine interfaces — electronic devices that read arm
movement intentions and translate them into movements of artificial actuators. Carmena et al. (2003) programmed
the neural coding in a brain–machine interface allowed a monkey to control reaching and grasping movements by a
robotic arm, and Lebedev et al. (2005) argued that brain networks reorganize to create a new representation of the
robotic appendage in addition to the representation of the animal's own limbs.
The biggest impediment of BCI technology at present is the lack of a sensor modality that provides safe, accurate,
and robust access to brain signals. It is conceivable or even likely that such a sensor will be developed within the
next twenty years. The use of such a sensor should greatly expand the range of communication functions that can be
provided using a BCI.
Development and implementation of a Brain–Computer Interface (BCI) system is complex and time consuming. In
response to this problem, Dr. Gerwin Schalk has been developing a general-purpose system for BCI research, called
BCI2000. BCI2000 has been in development since 2000 in a project led by the Brain–Computer Interface R&D
Program at the Wadsworth Center of the New York State Department of Health in Albany, New York, USA.
A new 'wireless' approach uses light-gated ion channels such as Channelrhodopsin to control the activity of
genetically defined subsets of neurons in vivo. In the context of a simple learning task, illumination of transfected
cells in the somatosensory cortex influenced the decision making process of freely moving mice.[21]
Human BCI research
Invasive BCIs
Invasive BCI research has targeted repairing damaged sight and providing new functionality to persons with
paralysis. Invasive BCIs are implanted directly into the grey matter of the brain during neurosurgery. As they rest in
the grey matter, invasive devices produce the highest quality signals of BCI devices but are prone to scar-tissue
build-up, causing the signal to become weaker or even lost as the body reacts to a foreign object in the brain.
In vision science, direct brain implants have been used to treat
non-congenital (acquired) blindness. One of the first scientists to come
up with a working brain interface to restore sight was private
researcher William Dobelle.
Dobelle's first prototype was implanted into "Jerry", a man blinded in
adulthood, in 1978. A single-array BCI containing 68 electrodes was
implanted onto Jerry’s visual cortex and succeeded in producing
phosphenes, the sensation of seeing light. The system included cameras
mounted on glasses to send signals to the implant. Initially, the implant
Jens Naumann, a man with acquired blindness,
allowed Jerry to see shades of grey in a limited field of vision at a low
being interviewed about his vision BCI on CBS's
The Early Show
frame-rate. This also required him to be hooked up to a two-ton
mainframe, but shrinking electronics and faster computers made his
artificial eye more portable and now enable him to perform simple tasks unassisted.[22]
210
Brain–computer interface
211
In 2002, Jens Naumann, also blinded in adulthood, became the first in
a series of 16 paying patients to receive Dobelle’s second generation
implant, marking one of the earliest commercial uses of BCIs. The
second generation device used a more sophisticated implant enabling
better mapping of phosphenes into coherent vision. Phosphenes are
spread out across the visual field in what researchers call the
starry-night effect. Immediately after his implant, Jens was able to use
his imperfectly restored vision to drive slowly around the parking area
of the research institute.
BCIs focusing on motor neuroprosthetics aim to either restore
movement in individuals with paralysis or provide devices to assist
them, such as interfaces with computers or robot arms.
Researchers at Emory University in Atlanta led by Philip Kennedy and
Roy Bakay were first to install a brain implant in a human that
produced signals of high enough quality to simulate movement. Their
patient, Johnny Ray (1944-2002), suffered from ‘locked-in syndrome’
after suffering a brain-stem stroke in 1997. Ray’s implant was installed
in 1998 and he lived long enough to start working with the implant,
eventually learning to control a computer cursor; he died in 2002 of a
brain aneurysm.[23]
Dummy unit illustrating the design of a
BrainGate interface
Tetraplegic Matt Nagle became the first person to control an artificial hand using a BCI in 2005 as part of the first
nine-month human trial of Cyberkinetics Neurotechnology’s BrainGate chip-implant. Implanted in Nagle’s right
precentral gyrus (area of the motor cortex for arm movement), the 96-electrode BrainGate implant allowed Nagle to
control a robotic arm by thinking about moving his hand as well as a computer cursor, lights and TV.[24] One year
later, professor Jonathan Wolpaw received the prize of the Altran Foundation for Innovation to develop a Brain
Computer Interface with electrodes located on the surface of the skull, instead of directly in the brain.
Partially-invasive BCIs
Partially invasive BCI devices are implanted inside the skull but rest outside the brain rather than within the grey
matter. They produce better resolution signals than non-invasive BCIs where the bone tissue of the cranium deflects
and deforms signals and have a lower risk of forming scar-tissue in the brain than fully-invasive BCIs.
Electrocorticography (ECoG) measures the electrical activity of the brain taken from beneath the skull in a similar
way to non-invasive electroencephalography (see below), but the electrodes are embedded in a thin plastic pad that is
placed above the cortex, beneath the dura mater.[25] ECoG technologies were first trialed in humans in 2004 by Eric
Leuthardt and Daniel Moran from Washington University in St Louis. In a later trial, the researchers enabled a
teenage boy to play Space Invaders using his ECoG implant.[26] This research indicates that control is rapid, requires
minimal training, and may be an ideal tradeoff with regards to signal fidelity and level of invasiveness.
(Note: These electrodes were not implanted in the patients for BCI experiments. Implanting foreign objects into
people's brains solely for experimental purposes would be unethical. The patient was suffering from severe epilepsy
and had the electrodes temporarily implanted to help his physicians localize seizure foci; the researchers simply took
advantage of this.)
Light Reactive Imaging BCI devices are still in the realm of theory. These would involve implanting a laser inside
the skull. The laser would be trained on a single neuron and the neuron's reflectance measured by a separate sensor.
When the neuron fires, the laser light pattern and wavelengths it reflects would change slightly. This would allow
researchers to monitor single neurons but require less contact with tissue and reduce the risk of scar-tissue build-up.
Brain–computer interface
This signal can be either subdural or epidural, but is not taken from within the brain parenchyma itself. It has not
been studied extensively until recently due to the limited access of subjects. Currently, the only manner to acquire
the signal for study is through the use of patients requiring invasive monitoring for localization and resection of an
epileptogenic focus.
ECoG is a very promising intermediate BCI modality because it has higher spatial resolution, better signal-to-noise
ratio, wider frequency range, and lesser training requirements than scalp-recorded EEG, and at the same time has
lower technical difficulty, lower clinical risk, and probably superior long-term stability than intracortical
single-neuron recording. This feature profile and recent evidence of the high level of control with minimal training
requirements shows potential for real world application for people with motor disabilities.
Non-invasive BCIs
As well as invasive experiments, there have also been experiments in humans using non-invasive neuroimaging
technologies as interfaces. Signals recorded in this way have been used to power muscle implants and restore partial
movement in an experimental volunteer. Although they are easy to wear, non-invasive implants produce poor signal
resolution because the skull dampens signals, dispersing and blurring the electromagnetic waves created by the
neurons. Although the waves can still be detected it is more difficult to determine the area of the brain that created
them or the actions of individual neurons.
EEG
Electroencephalography (EEG) is the most studied potential
non-invasive interface, mainly due to its fine temporal resolution, ease
of use, portability and low set-up cost. But as well as the technology's
susceptibility to noise, another substantial barrier to using EEG as a
brain–computer interface is the extensive training required before users
can work the technology. For example, in experiments beginning in the
mid-1990s, Niels Birbaumer of the University of Tübingen in Germany
trained severely paralysed people to self-regulate the slow cortical
potentials in their EEG to such an extent that these signals could be
Recordings of brainwaves produced by an
used as a binary signal to control a computer cursor.[27] (Birbaumer
electroencephalogram
had earlier trained epileptics to prevent impending fits by controlling
this low voltage wave.) The experiment saw ten patients trained to
move a computer cursor by controlling their brainwaves. The process was slow, requiring more than an hour for
patients to write 100 characters with the cursor, while training often took many months.
Another research parameter is the type of waves measured. Birbaumer's later research with Jonathan Wolpaw at New
York State University has focused on developing technology that would allow users to choose the brain signals they
found easiest to operate a BCI, including mu and beta rhythms.
A further parameter is the method of feedback used and this is shown in studies of P300 signals. Patterns of P300
waves are generated involuntarily (stimulus-feedback) when people see something they recognize and may allow
BCIs to decode categories of thoughts without training patients first. By contrast, the biofeedback methods described
above require learning to control brainwaves so the resulting brain activity can be detected.
Lawrence Farwell and Emanuel Donchin developed an EEG-based brain–computer interface in the 1980s.[28] Their
"mental prosthesis" used the P300 brainwave response to allow subjects, including one paralyzed Locked-In
syndrome patient, to communicate words, letters, and simple commands to a computer and thereby to speak through
a speech synthesizer driven by the computer. A number of similar devices have been developed since then. In 2000,
for example, research by Jessica Bayliss at the University of Rochester showed that volunteers wearing virtual reality
helmets could control elements in a virtual world using their P300 EEG readings, including turning lights on and off
212
Brain–computer interface
213
and bringing a mock-up car to a stop.[29]
In 1999, researchers at Case Western Reserve University led by Hunter Peckham, used 64-electrode EEG skullcap to
return limited hand movements to quadriplegic Jim Jatich. As Jatich concentrated on simple but opposite concepts
like up and down, his beta-rhythm EEG output was analysed using software to identify patterns in the noise. A basic
pattern was identified and used to control a switch: Above average activity was set to on, below average off. As well
as enabling Jatich to control a computer cursor the signals were also used to drive the nerve controllers embedded in
his hands, restoring some movement.[30]
Electronic neural networks have been deployed which shift the learning phase from the user to the computer.
Experiments by scientists at the Fraunhofer Society in 2004 using neural networks led to noticeable improvements
within 30 minutes of training.[31]
Experiments by Eduardo Miranda aim to use EEG recordings of mental activity associated with music to allow the
disabled to express themselves musically through an encephalophone.[32]
The Emotiv company plans to produce a commercial video game controller (known as the Epoc) in December 21,
2009, which uses electromagnetic sensors.[33]
MEG and MRI
Magnetoencephalography (MEG) and functional magnetic resonance
imaging (fMRI) have both been used successfully as non-invasive
BCIs.[34] In a widely reported experiment, fMRI allowed two users
being scanned to play Pong in real-time by altering their
haemodynamic response or brain blood flow through biofeedback
techniques.[35]
fMRI measurements of haemodynamic responses in real time have also
been used to control robot arms with a seven second delay between
thought and movement.[36]
ATR Labs' reconstruction of human vision using
fMRI (top row: original image; bottom row:
More
recently,
research
developed
in
the
Advanced
reconstruction
from mean of combined readings)
Telecommunications Research (ATR) Computational Neuroscience
Laboratories in Kyoto, Japan allowed the scientists to reconstruct
images directly from the brain and display them on a computer. The article announcing these achievements was the
cover story of the journal Neuron of 10 December 2008,[37] While the early results are limited to black and white
images of 10x10 squares (pixels), according to the researchers further development of the technology may make it
possible to achieve color images, and even view or record dreams.[38] [39]
Commercialization and companies
John Donoghue and fellow researchers founded Cyberkinetics. Now listed on a US stock exchange and known as
Cyberkinetic Neurotechnology Inc, the company markets its electrode arrays under the BrainGate product name and
has set the development of practical BCIs for humans as its major goal. The BrainGate is based on the Utah Array
developed by Dick Normann.
Philip Kennedy founded Neural Signals [40] in 1987 to develop BCIs that would allow paralysed patients to
communicate with the outside world and control external devices. As well as an invasive BCI, the company also
sells an implant to restore speech. Neural Signals' Brain Communicator BCI device uses glass cones containing
microelectrodes coated with proteins to encourage the electrodes to bind to neurons.
Although 16 paying patients were treated using William Dobelle's vision BCI, new implants ceased within a year of
Dobelle's death in 2004. A company controlled by Dobelle, Avery Biomedical Devices [41], and Stony Brook
University are continuing development of the implant, which has not yet received Food and Drug Administration
Brain–computer interface
approval in the United States for human implantation.[42]
Ambient, at a TI developers conference in early 2008, demoed a product they have in development call The Audeo.
The Audeo is being developed to create a human–computer interface for communication without the need of
physical motor control or speech production. Using signal processing, unpronounced speech representing the thought
of the mind can be translated from intercepted neurological signals.[43]
Mindball is a product developed and commercialized by Interactive Productline in which players compete to control
a ball's movement across a table by becoming more relaxed and focused.[44] Interactive Productline is a Swedish
company whose objective is to develop and sell easy understandable EEG products that train the ability to relax and
focus.[45]
An Austrian company, Guger Technologies[46] , g.tec [47], has been offering Brain Computer Interface systems since
1999. The company provides base BCI models as development platforms for the research community to build upon,
including the P300 Speller, Motor Imagery, and mu-rhythm. They commercialized a Steady State Visual Evoked
Potiential BCI solution in 2008 with 4 degrees of machine control.
A Spanish company, Starlab [48], has entered this market in 2009 with a wireless 4-channel system called ENOBIO.
Designed for research purposes the system provides a platform for application development. [49]
There are three main consumer-devices commercial-competitors in this area (expected launch date mentioned in
brackets) which are going to launch such devices primarily for gaming- and PC-users:
• Neural Impulse Actuator (April - 2008)
• Emotiv Systems (December - 2009)
• NeuroSky (MindSet - June 2009, Uncle Milton Force Trainer - Fall 2009, Mattel MindFlex - Summer 2009)
Military applications
The United States military has been exploring applications for BCIs, to enhance troop performance as well as
develop systems to interfere with the communications of adversaries.[50] As one report concluded,
The most successful implementation of invasive interfaces has occurred in medical applications in
which nerve signals are used as the mechanism for information transfer.[51]
The DARPA budget for the fiscal year 2009 to 2010 includes $4 million for a program named Silent Talk, which
aims to "allow user-to-user communication on the battlefield without the use of vocalized speech through analysis of
neural signals."[52] A further $4 million was allocated by the Army to the University of California to investigate
computer-mediated "synthetic telepathy".[52] The research aims to detect and analyze the word-specific neural
signals, using EEG, which occur before speech is vocalized, and to see if the patterns are generalizable.[52] The
research is part of a wider $70 million project that began in 2000 which aims to develop hardware capable of
adapting to the behavior of its user.[53]
Cell-culture BCIs
Researchers have built devices to interface with neural cells and entire neural networks in cultures outside animals.
As well as furthering research on animal implantable devices, experiments on cultured neural tissue have focused on
building problem-solving networks, constructing basic computers and manipulating robotic devices. Research into
techniques for stimulating and recording from individual neurons grown on semiconductor chips is sometimes
referred to as neuroelectronics or neurochips.[54]
214
Brain–computer interface
215
Development of the first working neurochip was claimed by a Caltech
team led by Jerome Pine and Michael Maher in 1997.[55] The Caltech
chip had room for 16 neurons.
In 2003, a team led by Theodore Berger at the University of Southern
California started work on a neurochip designed to function as an
artificial or prosthetic hippocampus. The neurochip was designed to
function in rat brains and is intended as a prototype for the eventual
development of higher-brain prosthesis. The hippocampus was chosen
because it is thought to be the most ordered and structured part of the
brain and is the most studied area. Its function is to encode experiences
for storage as long-term memories elsewhere in the brain.[56]
World first: Neurochip developed by Caltech
researchers Jerome Pine and Michael Maher
Thomas DeMarse at the University of Florida used a culture of 25,000
neurons taken from a rat's brain to fly a F-22 fighter jet aircraft simulator.[57] After collection, the cortical neurons
were cultured in a petri dish and rapidly began to reconnect themselves to form a living neural network. The cells
were arranged over a grid of 60 electrodes and used to control the pitch and yaw functions of the simulator. The
study's focus was on understanding how the human brain performs and learns computational tasks at a cellular level.
Ethical considerations
There has not been a vigorous debate about the ethical implications of BCIs, even though there are several
commercially available systems such as brain pacemakers used to treat neurological conditions, and could
theoretically be used to modify other behaviours.
Emory University neuroscience professor Michael Crutcher has expressed concern about BCIs, specifically ear and
eye implants: "If only the rich can afford it, it puts everyone else at a disadvantage."[58]
Theme in fiction
The prospect of BCIs and brain implants of all kinds have been important themes in science fiction. See brain
implants in fiction and philosophy for a review of this literature.
See also
• Simulated reality
• Telepresence
• Whole brain emulation
Brain–computer interface
External links
Portals
• The open-source Electroencephalography project [46] and Programmable chip version [47], Sourceforge open
source EEG projects
• BCI database [59], Team PhyPA's public hub for BCI data exchange
Articles
Machine Translates Thoughts into Speech in Real Time [60] PhysOrg.com, by Lisa Zyga, December 21 2009.
Monkey Neural Interfacing [61], Monkeys Consciously Control A Robot Arm Using Only Brain Signals
The Next Brainiacs [62] Wired Magazine, August 2001, article on Jim Jatich’s implant
Controlling robots with the mind [63], Scientific American, 16 September 2002, article on Miguel Nicolelis
Vision quest [64], Wired Magazine, September 2002, article on artificial vision
'Brain' in a dish flies flight simulator [65], CNN, 4 November 2004, article on cell-culture BCI
How to talk when you can't speak [66], Slate, 10 February 2005, article on using EEG to communicate with
minimally conscious patients
• Mind Control [67], Wired Magazine, March 2005, article on Matt Nagle
•
•
•
•
•
•
•
• ...a step towards neuron-based functional chips [68], Biosens Bioelectron, January 2006, academic paper on a
cell-culture BCI
• Functional alignment of feedback effects from visual cortex to thalamus [69] Nature Neuroscience 9, 1330-1336
(2006), 17 September 2006, recent advances in decoding LGN visual signals
• The Memory Hacker [70], PopSci.com, April 2007, article on Theodore Berger, retrieved 10 April 2007
• Lymnaea stagnalis and the development of neuroelectronic technologies [71], Journal of Neuroscience Research,
2004, academic paper on a cell-culture BCI
• Evolution of brain-computer interfaces: going beyond classic motor physiology [72], Journal of Neurosurgery,
July 2009, a survey
Lectures and videos
• "Brain–Computer Interfaces" video lecture [73] by Krishna Shenoy (Stanford University)
• "Brain–Computer Interfaces" video lecture [74] by Brendan Allison (now with the Brain–Computer Interfaces
Laboratory at the Technical University of Graz)
References
[1] J. Vidal, "Toward Direct Brain–Computer Communication", in Annual Review of Biophysics and Bioengineering, L.J. Mullins, Ed., Annual
Reviews, Inc., Palo Alto, Vol. 2, 1973, pp. 157-180.
[2] J. Vidal, "Real-Time Detection of Brain Events in EEG", in IEEE Proceedings, May 1977, 65-5:633-641.
[3] S. P. Levine, J. E. Huggins, S. L. BeMent, R. K. Kushwaha, L. A. Schuh, M. M. Rohde, E. A. Passaro, D. A. Ross, K. V. Elisevich, and B. J.
Smith, "A direct brain interface based on event-related potentials," IEEE Trans Rehabil Eng, vol. 8, pp. 180-5, 2000
[4] Laura Bailey. "University of Michigan News Service" (http:/ / www. umich. edu/ news/ index. html?Releases/ 2006/ Feb06/ r020606a). .
Retrieved February 6, 2006.
[5] Miguel Nicolelis et al. (2001) Duke neurobiologist has developed system that allows monkeys to control robot arms via brain signals (http:/ /
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218
Artificial limb
219
Artificial limb
An artificial limb is a type of prosthesis
that replaces a missing extremity, such as
arms or legs. The type of artificial limb used
is determined largely by the extent of an
amputation or loss and location of the
missing extremity. Artificial limbs may be
needed for a variety of reasons, including
disease, accidents, and congenital defects. A
congenital defect can create the need for an
artificial limb when a person is born with a
missing or damaged limb. Industrial,
vehicular, and war related accidents are the
leading cause of amputations in developing
areas, such as large portions of Africa. In
A United States soldier demonstrates table football with two transradial prosthetic
more developed areas, such as North
limbs.
America and Europe, disease is the leading
[1]
cause of amputations. Cancer, infection
and circulatory disease are the leading diseases that may lead to amputation.[2]
History
An artificial limb is mythologically referred to in the Rigveda, the
"iron leg" given to Vishpala by the Ashvins. The first specimen
discovered archaeologically, known as the Roman Capua Leg, was
found in a tomb in Capua, Italy, dating to 300 BCE, and was made of
copper and wood.[3] Roman bronze crowns have also been found, but
their use could have been more aesthetic than medical[4] . Two
artificial toes found on Egyptian mummies are even older, dating to
1295–664 BCE; these are being tested (as of July 2007) to determine
whether they could have been used in life.[3] Armorers in the 15th and
16th centuries made artificial limbs out of iron for soldiers who lost
limbs. Over the next several centuries, craftsmen began to develop
artificial limbs from wood instead of metal because of the lighter
weight of the material.
An artificial toe from the Third Intermediate
Period. The big toe is carved from wood and is
attached to the foot by a sewn leather wrapping.
In the 19th century, limbs became more widespread due to the large number of amputees from wars such as the
Napoleonic Wars in Europe and the American Civil War. An artificial leg designed by London’s James Potts in 1800
and patented in 1805 became known as the Anglesey Leg. The prosthetic was named after the Marquess of Anglesey
who had lost his leg at Waterloo. James Potts fitted his prosthetic leg consisting of a wooden shaft and socket, steel
knee
joint,
and
an
articulated
foot
with
artificial
cords
or
catgut
tendons
that
Artificial limb
220
connected knee flexion with foot flexion. The Anglesey Leg
technology was brought to the United States in 1839 and became
known as the American Leg. During the American Civil War, a
Confederate soldier, J.E. Hanger, who had himself suffered the war's
first amputation (see Battle of Philippi) founded what was for a time
the world's largest artificial limb factory.
In England, Marcel Desoutter who was fitted with a wooden leg after
an aviation accident, and his brother Charles, designed the first light
metal limb to be manufactured. Their jointed Duralumin alloy leg was
half the weight of the standard wooden leg. Developments included a
frictional knee control, which allowed the wearer to control the speed
and length of step, and the Desoutter cushion-joint foot, which imitated
the natural action of the human foot. Desoutter Brothers, manufacturers
of artificial limbs, was established in 1914 in London.[5]
Technology improved primarily for two reasons: the availability of
government funding and the discovery of anesthetics. After World War
II, the Artificial Limb Program was started in 1945 by the National
Academy of Sciences. This program helped improve artificial limbs by
promoting and coordinating scientific research on prosthetic devices.
The iron prosthetic hand worn by Götz von
Berlichingen from 1508 (1861 etching).
In recent years, a great deal of emphasis has been placed on developing
artificial limbs that look and move more like actual human limbs.
Advances in biomechanical understanding, through the combined work
of doctors and engineers, the development of new plastics, and the use
of computer aided design and computer aided manufacturing have all
contributed in the development of more realistic artificial limbs.[2] [6]
Wooden leg of Gen. Józef Sowiński; from early
19th century
Lower extremity prosthetics
Lower extremity prosthetics describes artificially replaced limbs located at the hip level or lower. The two main
subcategories of lower extremity prosthetic devices are 1.trans-tibial (any amputation transecting the tibia bone or a
congenital anomaly resulting in a tibial deficiency) and 2.trans-femoral (any amputation transecting the femur bone
or a congenital anomaly resulting in a femural deficiency). In the prosthetic industry a trans-tibial prosthetic leg is
often referred to as a "BK" or below the knee prosthesis while the trans-femoral prosthetic leg is often referred to as
an "AK" or above the knee prosthesis.
Other, less prevalent lower extremity cases include the following:
1. Hip disarticulations - This usually refers to when an amputee or congenitally challenged patient has either an
amputation or anomaly at or in close proximity to the hip joint.
2. Knee disarticulations - This usually refers to an amputation through the knee disarticulating the femur from the
tibia.
3. Symes - This is an ankle disarticulation while preserving the heel pad.
Artificial limb
Lower extremity modern history
Socket technology for lower extremity limbs saw a revolution of advancement during the 1980s when Sabolich [7]
Prosthetics, John Sabolich C.P.O., invented the Contoured Adducted Trochanteric-Controlled Alignment Method
(CATCAM) socket, later to evolve into the Sabolich Socket. The advancement was due to the difference in the
socket to patient contact model. Prior, sockets were made in the shape of a square bucket with no specialized
containment for either the patient's bony prominences' or muscular tissue. Sabolich's design held the patient's limb
like a glove, locking it into place and distributing the weight evenly over the existing limb as well as the bone
structure of the patient. This was the first instance of ischial containment and led to an extreme advancement in
patient accomplishment. Because of Sabolich's dedication to research and development in lower extremity
prosthetics, Sabolich Prosthetics saw the first above the knee prosthetic patients walk and run step over step with
both one leg and two legs missing, walking down stairs, suction sockets, modern plastic and bio elastic sockets,
sense of feel technology, and numerous other inventions in the prosthetic field.
Types
There are four main types of artificial limbs. These include the
transtibial, transfemoral, transradial, and transhumeral prostheses. The
type of prosthesis depends on what part of the limb is missing.
Transtibial Prosthesis
A transtibial prosthesis is an artificial limb that replaces a leg missing
below the knee. Transtibial amputees are usually able to regain normal
movement more readily than someone with a transfemoral amputation,
due in large part to retaining the knee, which allows for easier
movement. In the prosthetic industry a trans-tibial prosthetic leg is
often referred to as an "BK" or below the knee prosthesis.
Transfemoral Prosthesis
A transfemoral prosthesis is an artificial limb that replaces a leg
missing above the knee. Transfemoral amputees can have a very
difficult time regaining normal movement. In general, a transfemoral
A United States Marine with bilateral prosthetic
amputee must use approximately 80% more energy to walk than a
[8]
legs leads a formation run.
person with two whole legs. This is due to the complexities in
movement associated with the knee. In newer and more improved
designs, after employing hydraulics, carbon fibre, mechanical linkages, motors, computer microprocessors, and
innovative combinations of these technologies to give more control to the user. In the prosthetic industry a
trans-femoral prosthetic leg is often referred to as an "AK" or above the knee prosthesis.[9]
Transradial Prosthesis
A transradial prosthesis is an artificial limb that replaces an arm missing below the elbow. Two main types of
prosthetics are available. Cable operated limbs work by attaching a harness and cable around the opposite shoulder
of the damaged arm. The other form of prosthetics available are myoelectric arms. These work by sensing, via
electrodes, when the muscles in the upper arm moves, causing an artificial hand to open or close. In the prosthetic
industry a trans-radial prosthetic arm is often referred to as a "BE" or below elbow prosthesis.
221
Artificial limb
Transhumeral Prosthesis
A transhumeral prosthesis is an artificial limb that replaces an arm missing above the elbow. Transhumeral amputees
experience some of the same problems as transfemoral amputees, due to the similar complexities associated with the
movement of the elbow. This makes mimicking the correct motion with an artificial limb very difficult. In the
prosthetic industry a trans-humeral prosthesis is often referred to as a "AE" or above the elbow prothesis.
Current Technology/Manufacturing
In recent years there have been significant advancements in artificial limbs. New plastics and other materials, such as
carbon fiber, have allowed artificial limbs to be stronger and lighter, limiting the amount of extra energy necessary to
operate the limb. This is especially important for transfemoral amputees. Additional materials have allowed artificial
limbs to look much more realistic, which is important to transradial and transhumeral amputees because they are
more likely to have the artificial limb exposed.[6]
In addition to new materials, the use of electronics has become very common in artificial limbs. Myoelectric limbs,
which control the limbs by converting muscle movements to electrical signals, have become much more common
than cable operated limbs. Myoelectric limbs allow the amputees to more directly control the artificial limb.
Computers are also used extensively in the manufacturing of limbs. Computer Aided Design and Computer Aided
Manufacturing are often used to assist in the design and manufacture of artificial limbs.[6]
Most modern artificial limbs are attached to the stump of the amputee by belts and cuffs or by suction. The stump
usually fits into a socket on the prosthetic. The socket is custom made to create a better fit between the leg and the
artificial limb, which helps reduce wear on the stump. The custom socket is created by taking a plaster cast of the
stump and then making a mold from the plaster cast. Newer methods include laser guided measuring which can be
input directly to a computer allowing for a more sophisticated design.
One of the biggest problems with the stump and socket attachment is that there is a large amount of rubbing between
the stump and socket. This can be painful and can cause breakdown of tissue.[8]
Artificial limbs are typically manufactured using the following steps:[6]
1.
2.
3.
4.
5.
6.
Measurement of the stump
Measurement of the body to determine the size required for the artificial limb
Creation of a model of the stump
Formation of thermoplastic sheet around the model of the stump – This is then used to test the fit of the prosthetic
Formation of permanent socket
Formation of plastic parts of the artificial limb – Different methods are used, including vacuum forming and
injection molding
7. Creation of metal parts of the artificial limb using die casting
8. Assembly of entire limb
Emerging Technology
There are several areas of technology that have advanced significantly in recent years and are showing considerable
potential. Robotic limbs and direct bone attachment are two new technologies that have made tremendous gains
recently.
Robotic Limbs
Advancements in the processors used in myoelectric arms has allowed for artificial limbs to make gains in fine tuned
control of the prosthetic. The Boston Digital Arm is a recent artificial limb that has taken advantage of these more
advanced processors. The arm allows movement in five axes and allows the arm to be programmed for a more
customized feel.[10]
222
Artificial limb
223
Recently the i-Limb hand, invented in Edinburgh, Scotland, by David Gow has become the first commercially
available hand prosthesis with five individually powered digits. The hand also possesses a manually rotatable thumb
which is operated passively by the user and allows the hand to grip in precision, power and key grip modes.
Raymond Edwards, Limbless Association Acting CEO, is the first amputee to be fitted with the i-LIMB by the
National Health Service in the UK[11] . The hand, manufactured by "Touch Bionics"[12] of Scotland (a Livingston
company), went on sale on 18 July 2007 in Britain.[13] . It was named alongside the Super Hadron Collider in Time
magazine's top 50 innovations [14] .
Targeted muscle reinnervation (TMR) is a technique in which motor nerves which previously controlled muscles on
an amputated limb are surgically rerouted such that they reinnervate a small region of a large, intact muscle, such as
the pectoralis major. As a result, when a patient thinks about moving the thumb of his missing hand, a small area of
muscle on his chest will contract instead. By placing sensors over the reinervated muscle, these contractions can be
made to control movement of an appropriate part of the robotic prosthesis.[15] [16]
An emerging variant of this technique is called targeted sensory reinnervation (TSR). This procedure is similar to
TMR, except that sensory nerves are surgically rerouted to skin on the chest, rather than motor nerves rerouted to
muscle. The patient then feels any sensory stimulus on that area of the chest, such as pressure or temperature, as if it
were occurring on the area of the amputated limb which the nerve originally innervated. In the future, artificial limbs
could be built with sensors on fingertips or other important areas. When a stimulus, such as pressure or temperature,
activated these sensors, an electrical signal would be sent to an actuator, which would produce a similar stimulus on
the "rewired" area of chest skin. The user would then feel that stimulus as if it were occurring on an appropriate part
of the artificial limb.[15]
Recently, robotic limbs have improved in their ability to take signals from the human brain and translate those
signals into motion in the artificial limb. DARPA, the Pentagon’s research division, is working to make even more
advancements in this area. Their desire is to create an artificial limb that ties directly into the nervous system.[17]
Cosmesis
A French mutilé in 1918 wearing a mask provided by the American Red Cross (left) and without mask (right)
Cosmetic prosthesis has long been used to disguise injuries and disfigurements. With advances in modern
technology, cosmesis, the creation of lifelike limbs made from silicone or PVC has been made possible. Such
prosthetics, such as artificial hands, can now be made to mimic the appearance of real hands, complete with freckles,
veins, hair, fingerprints and even tattoos. Custom-made cosmeses are generally more expensive (costing thousands
of US dollars, depending on the level of detail), while standard cosmeses come ready-made in various sizes,
although they are often not as realistic as their custom-made counterparts. Another option is the custom-made
silicone cover, which can be made to match a person's skin tone but not details such as freckles or wrinkles.
Cosmeses are attached to the body in any number of ways, using an adhesive, suction, form-fitting, stretchable skin,
or a skin sleeve.
Artificial limb
Cognition
Unlike neuromotor prostheses, neurocognitive prostheses would sense or modulate neural function in order to
physically reconstitute or augment cognitive processes such as executive function, attention, language, and memory.
No neurocognitive prostheses are currently available but the development of implantable neurocognitive
brain-computer interfaces has been proposed to help treat conditions such as stroke, traumatic brain injury, cerebral
palsy, autism, and Alzheimer's disease.[18] The recent field of Assistive Technology for Cognition [19] concerns the
development of technologies to augment human cognition. Scheduling devices such as Neuropage [20] remind users
with memory impairments when to perform certain activities, such as visiting the doctor. Micro-prompting devices
such as PEAT, AbleLink [21] and Guide [22] have been used to aid users with memory and executive function
problems perform activities of daily living.
Direct Bone Attachment / Osseointegration
Osseointegration is a new method of attaching the artificial limb to the body. The stump and socket method can
cause significant pain in the amputee, which is why the direct bone attachment has been explored extensively. The
method works by inserting a titanium bolt into the bone at the end of the stump. After several months the bone
attaches itself to the titanium bolt and an abutment is attached to the titanium bolt. The abutment extends out of the
stump and the artificial limb is then attached to the abutment. Some of the benefits of this method include:
• Better muscle control of the prosthetic.
• The ability to wear the prosthetic for an extended period of time; with the stump and socket method this is not
possible.
• The ability for transfemoral amputees to drive a car.
The main disadvantage of this method is that amputees with the direct bone attachment cannot have large impacts on
the limb, such as those experienced during jogging, because of the potential for the bone to break.[8]
224
Artificial limb
Prosthetic enhancement
In addition to the standard artificial limb for everyday use, many amputees or congenital patients have special limbs
and devices to aid in the participation of sports and recreational activities.
Within science fiction, and, more recently, within the scientific
community, there has been consideration given to using advanced
prostheses to replace healthy body parts with artificial mechanisms and
systems to improve function. The morality and desirability of such
technologies are being debated. Body parts such as legs, arms, hands,
feet, and others can be replaced.
The first experiment with a healthy individual appears to have been
that by the British scientist Kevin Warwick. In 2002, an implant was
interfaced directly into Warwick's nervous system. The electrode array,
which contained around a hundred electrodes, was placed in the
median nerve. The signals produced were detailed enough that a robot
arm was able to mimic the actions of Warwick's own arm and provide
a form of touch feedback again via the implant.[23]
In early 2008, Oscar Pistorius, the "Blade Runner" of South Africa,
was briefly ruled ineligible to compete in the 2008 Summer Olympics
because his prosthetic limbs were said to give him an unfair advantage
over runners who had ankles. One researcher found that his limbs used
twenty-five percent less energy than those of an able-bodied runner
In 2008, Oscar Pistorius was briefly ruled
ineligible for the 2008 Summer Olympics due to
moving at the same speed. This ruling was overturned on appeal, with
an alleged mechanical advantage over runners
the appellate court stating that the overall set of advantages and
who have ankles.
disadvantages of Pistorius' limbs had not been considered. Pistorius did
not qualify for the South African team for the Olympics, but went on to
sweep the 2008 Summer Paralympics, and has been ruled eligible to qualify for any future Olympics.
The "Luke arm" is an advanced prosthesis currently under trials as of 2008.[24]
Cost
Transradial and transtibial prostheses typically cost between US $6,000 and $8,000. Transfemoral and transhumeral
prosthetics cost approximately twice as much with a range of $10,000 to $15,000 and can sometimes reach costs of
$35,000. The cost of an artificial limb does recur because artificial limbs are usually replaced every 3–4 years due to
wear and tear. In addition, if the artificial limb has fit issues, the limb must be replaced within several months.[25] [26]
.
Jaipur Foot, an artificial limb from Jaipur, India, costs about US$ 40.
There is currently an open Prosthetics design forum known as the "Open Prosthetics Project". The group employs
collaborators and volunteers to advance Prosthetics technology while attempting to lower the costs of these
necessary devices. Visit their site at http://OpenProsthetics.org.
A plan for a low-cost artificial leg, designed by Sébastien Dubois, was featured at the 2007 International Design
Exhibition award show in Copenhagen, Denmark. It would be able to create an energy-return prosthetic leg for US
$8.00, composed primarily of fiberglass.[27]
225
Artificial limb
See also
•
•
•
•
•
•
•
Prosthetist
Amputation
Anaplastology
Artificial organ
Artificial knee
Machine
Cyborg
External links
• Chard Museum [28] Display of James Gillingham's work on post WW1 artificial limbs.
• OandPCare.org [29] has an extensive glossary of terms relating to artificial limbs, prostheses and the field of
prosthetics
• National Amputee Centre [30] — Information about artificial limbs
• O&PCare [29] has a complete glossary relating to the field of prosthetics
• How Stuff Works : Biomechatronics [31] - An overview of the field of biomechatronics, of which prosthetics is a
part
References
[1] "Science, Medicine, and the Future: Artificial Limbs" (http:/ / www. bmj. com/ cgi/ content/ full/ 323/ 7315/ 732#SEC2), BMJ, 29 September
2001. Retrieved 11 February 2007.
[2] "History of Prostheses" (http:/ / www. uihealthcare. com/ depts/ medmuseum/ wallexhibits/ body/ histofpros/ histofpros. html), University of
Iowa, 5 June 2006. Retrieved 11 February 2007.
[3] "Cairo toe earliest fake body bit" (http:/ / news. bbc. co. uk/ 2/ hi/ health/ 6918687. stm), BBC News, 27 July 2007. Retrieved 27 July 2007.
[4] "Bronze single crown-like prosthetic restorations of teeth from the Late Roman period = Des restaurations par prothèses identiques à des
couronnes en simple bronze de dents pendant la fin de la période romaine" (http:/ / cat. inist. fr/ ?aModele=afficheN& cpsidt=1557911).
Cat.inist.fr. . Retrieved 2009-11-03.
[5] OPnews The origins of De Soutter Medical (http:/ / www. opnews. com/ profiles. php?index=27& total=53)
[6] "Artificial Limb" (http:/ / www. madehow. com/ Volume-1/ Artificial-Limb. html), How Products are Made, 2007. Retrieved 11 February
2007.
[7] http:/ / www. scottsabolich. com/
[8] "Getting an Artificial Leg Up" (http:/ / www. abc. net. au/ science/ slab/ leg/ default. htm), Australian Broadcasting Corporation, 2000.
Retrieved 11 February 2007.
[9] Physics: A First Course. "Connections, designing a better prosthetic leg"
[10] Recently the i-Limb hand, invented in Edinburgh, Scotland, by David Gow has become the first commercially available hand prosthesis with
five individually powered digits. The hand also possesses a manually rotatable thumb which is operated passively by the user and allows the
hand to grip in precision, power and key grip modes. "Advanced Signal Processing Dramatically Improves Capability of Artificial Limbs"
(http:/ / www. sigmorobot. com/ technology/ news/ boston_digital_arm. htm), SIGMO Technology, 2005. Retrieved 11 February 2007.
[11] BBC NEWS | Science/Nature | Bionic hand wins top tech prize (http:/ / news. bbc. co. uk/ 1/ hi/ sci/ tech/ 7443866. stm)
[12] http:/ / www. touchbionics. com/ professionals. php?section=5
[13] Gripping stuff (http:/ / www. telegraph. co. uk/ motoring/ 2754644/ Gripping-stuff. html)
[14] http:/ / current. com/ items/ 89499345/ bionic_hand_makes_top_inventions_list. htm
[15] Kuiken TA, Miller LA, Lipschutz RD, Lock BA, Stubblefield K, Marasco PD, Zhou P, Dumanian GA (February 3, 2007). "Targeted
reinnervation for enhanced prosthetic arm function in a woman with a proximal amputation: a case study". Lancet 369 (9559): 371–80.
doi:10.1016/S0140-6736(07)60193-7. PMID 17276777.
[16] http:/ / www. technologyreview. com/ blog/ editors/ 22730/
[17] Defense Sciences Office (http:/ / www. darpa. mil/ dso/ solicitations/ sn07-43. htm)
[18] Serruya MD, Kahana MJ (2008). "Techniques and devices to restore cognition". Behav Brain Res 192: 149. doi:10.1016/j.bbr.2008.04.007.
PMID 18539345.
[19] http:/ / cat. inist. fr/ ?aModele=afficheN& cpsidt=15764275
[20] http:/ / www. neuropage. nhs. uk/ default. asp?id=
[21] http:/ / www. ablelinktech. com/
226
Artificial limb
[22] http:/ / stir. academia. edu/ AlexGillespie/ Papers/ 97289/
Simulating-naturalistic-instruction--The-case-for-a-voice-mediated-interface-for-assistive-technology-for-cognition
[23] Warwick,K, Gasson,M, Hutt,B, Goodhew,I, Kyberd,P, Andrews,B, Teddy,P and Shad,A. “The Application of Implant Technology for
Cybernetic Systems”, Archives of Neurology, 60(10), pp1369-1373, 2003
[24] "IEEE Spectrum: Dean Kamen's "Luke Arm" Prosthesis Readies for Clinical Trials" (http:/ / spectrum. ieee. org/ biomedical/ bionics/
dean-kamens-luke-arm-prosthesis-readies-for-clinical-trials). .
[25] "Cost of Prosthetics Stirs Debate" (http:/ / www. boston. com/ business/ globe/ articles/ 2005/ 07/ 05/ cost_of_prosthetics_stirs_debate/ ),
The Boston Globe, 5 July 2005. Retrieved 11 February 2007.
[26] [8]
[27] INDEX:2007 INDEX: AWARD (http:/ / www. indexaward. dk/ 2007/ default. asp?id=706& show=nomination& nominationid=163&
playmovie=wmv)
[28] http:/ / www. chardmuseum. co. uk/ Pioneers_in_Artifical_Limbs/
[29] http:/ / www. oandpcare. org/ public/ glossary. asp
[30] http:/ / www. waramps. ca/ nac/ limbs. html
[31] http:/ / health. howstuffworks. com/ biomechatronics. htm
X-ray computed tomography
Computed tomography (CT) is a medical
imaging method employing tomography
created by computer processing.[1] Digital
geometry processing is used to generate a
three-dimensional image of the inside of an
object
from
a
large
series
of
two-dimensional X-ray images taken around
a single axis of rotation.[2]
CT produces a volume of data which can be
manipulated, through a process known as
"windowing", in order to demonstrate
various bodily structures based on their
ability to block the X-ray beam. Although
historically the images generated were in the
A multi-slice CT scanner
axial or transverse plane, orthogonal to the
long axis of the body, modern scanners
allow this volume of data to be reformatted in various planes or even as volumetric (3D) representations of
structures. Although most common in medicine, CT is also used in other fields, such as nondestructive materials
testing. Another example is the DigiMorph project at the University of Texas at Austin which uses a CT scanner to
study biological and paleontological specimens.
Usage of CT has increased dramatically over the last two decades[3] . An estimated 72 million scans were performed
in the United States in 2007.[4]
227
X-ray computed tomography
228
Terminology
The word "tomography" is derived from the Greek tomos (slice) and graphein (to write). Computed tomography was
originally known as the "EMI scan" as it was developed at a research branch of EMI, a company best known today
for its music and recording business. It was later known as computed axial tomography (CAT or CT scan) and
body section röntgenography.
Although the term "computed tomography" could be used to describe positron emission tomography and single
photon emission computed tomography, in practice it usually refers to the computation of tomography from X-ray
images, especially in older medical literature and smaller medical facilities.
In MeSH, "computed axial tomography" was used from 1977–79, but the current indexing explicitly includes
"X-ray" in the title.[5]
History
In the early 1900s, the Italian radiologist Alessandro
Vallebona proposed a method to represent a single slice
of the body on the radiographic film. This method was
known as tomography. The idea is based on simple
principles
of
projective
geometry:
moving
synchronously and in opposite directions the X-ray
tube and the film, which are connected together by a
rod whose pivot point is the focus; the image created by
the points on the focal plane appears sharper, while the
images of the other points annihilate as noise. This is
only marginally effective, as blurring occurs only in the
"x" plane. There are also more complex devices which
can move in more than one plane and perform more
effective blurring.
The prototype CT scanner
Tomography had been one of the pillars of radiologic
diagnostics until the late 1970s, when the availability of
minicomputers and of the transverse axial scanning
method, this last due to the work of Godfrey
Hounsfield and South African-born Allan McLeod
Cormack, gradually supplanted it as the modality of
CT.
The first commercially viable CT scanner was invented
by Sir Godfrey Hounsfield in Hayes, United Kingdom
at EMI Central Research Laboratories using X-rays.
Hounsfield conceived his idea in 1967,[6] and it was
publicly announced in 1972. Allan McLeod Cormack
A historic EMI-Scanner
of Tufts University in Massachusetts independently
invented a similar process, and both Hounsfield and Cormack shared the 1979 Nobel Prize in Medicine.[7]
The original 1971 prototype took 160 parallel readings through 180 angles, each 1° apart, with each scan taking a
little over 5 minutes. The images from these scans took 2.5 hours to be processed by algebraic reconstruction
techniques on a large computer. The scanner had a single photomultiplier detector, and operated on the
Translate/Rotate principle.
X-ray computed tomography
It has been claimed that thanks to the success of The Beatles, EMI could fund research and build early models for
medical use.[8] The first production X-ray CT machine (in fact called the "EMI-Scanner") was limited to making
tomographic sections of the brain, but acquired the image data in about 4 minutes (scanning two adjacent slices), and
the computation time (using a Data General Nova minicomputer) was about 7 minutes per picture. This scanner
required the use of a water-filled Perspex tank with a pre-shaped rubber "head-cap" at the front, which enclosed the
patient's head. The water-tank was used to reduce the dynamic range of the radiation reaching the detectors (between
scanning outside the head compared with scanning through the bone of the skull). The images were relatively low
resolution, being composed of a matrix of only 80 x 80 pixels. The first EMI-Scanner was installed in Atkinson
Morley Hospital in Wimbledon, England, and the first patient brain-scan was made with it in 1972. In the U.S., the
first installation was at the Mayo Clinic. As a tribute to the impact of this system on medical imaging the Mayo
Clinic has an EMI scanner on display in the Radiology Department.
The first CT system that could make images of any part of the body and did not require the "water tank" was the
ACTA (Automatic Computerized Transverse Axial) scanner designed by Robert S. Ledley, DDS, at Georgetown
University. This machine had 30 photomultiplier tubes as detectors and completed a scan in only 9 translate/rotate
cycles, much faster than the EMI-scanner. It used a DEC PDP11/34 minicomputer both to operate the
servo-mechanisms and to acquire and process the images. The Pfizer drug company acquired the prototype from the
university, along with rights to manufacture it. Pfizer then began making copies of the prototype, calling it the
"200FS" (FS meaning Fast Scan), which were selling as fast as they could make them. This unit produced images in
a 256×256 matrix, with much better definition than the EMI-Scanner's 80×80.
Previous studies
Tomography
A form of tomography can be performed by moving the X-ray source and detector during an exposure. Anatomy at
the target level remains sharp, while structures at different levels are blurred. By varying the extent and path of
motion, a variety of effects can be obtained, with variable depth of field and different degrees of blurring of "out of
plane" structures.[9] :25
Although largely obsolete, conventional tomography is still used in specific situations such as dental imaging
(orthopantomography) or in intravenous urography.
Tomosynthesis
Digital tomosynthesis combines digital image capture and processing with simple tube/detector motion as used in
conventional radiographic tomography. Although there are some similarities to CT, it is a separate technique. In CT,
the source/detector makes a complete 360-degree rotation about the subject obtaining a complete set of data from
which images may be reconstructed. In digital tomosynthesis, only a small rotation angle (e.g., 40 degrees) with a
small number of discrete exposures (e.g., 10) are used. This incomplete set of data can be digitally processed to yield
images similar to conventional tomography with a limited depth of field. However, because the image processing is
digital, a series of slices at different depths and with different thicknesses can be reconstructed from the same
acquisition, saving both time and radiation exposure.
Because the data acquired is incomplete, tomosynthesis is unable to offer the extremely narrow slice widths that CT
offers. However, higher resolution detectors can be used, allowing very-high in-plane resolution, even if the Z-axis
resolution is poor. The primary interest in tomosynthesis is in breast imaging, as an extension to mammography,
where it may offer better detection rates with little extra increase in radiation exposure.
Reconstruction algorithms for tomosynthesis are significantly different from conventional CT, because the
conventional filtered back projection algorithm requires a complete set of data. Iterative algorithms based upon
expectation maximization are most commonly used, but are extremely computationally intensive. Some
229
X-ray computed tomography
manufacturers have produced practical systems using off-the-shelf GPUs to perform the reconstruction.
Diagnostic use
Since its introduction in the 1970s, CT has become an important tool in medical imaging to supplement X-rays and
medical ultrasonography. It has more recently begun to also be used for preventive medicine or screening for
disease, for example CT colonography for patients with a high risk of colon cancer. A number of institutions offer
full-body scans for the general population. However, this is a controversial practice, given its lack of proven benefit,
cost, radiation exposure, and the risk of finding 'incidental' abnormalities that may trigger additional investigations.
Head
CT scanning of the head is typically used to detect:
1. bleeding, brain injury and skull fractures
Chest
CT can be used for detecting both acute and chronic changes in the lung parenchyma, that is, the internals of the
lungs. It is particularly relevant here because normal two dimensional x-rays do not show such defects. A variety of
different techniques are used depending on the suspected abnormality. For evaluation of chronic interstitial processes
(emphysema, fibrosis, and so forth), thin sections with high spatial frequency reconstructions are used—often scans
are performed both in inspiration and expiration. This special technique is called High Resolution CT (HRCT).
HRCT is normally done with thin section with skipped areas between the thin sections. Therefore it produces a
sampling of the lung and not continuous images. Continuous images are provided in a standard CT of the chest.
For detection of airspace disease (such as pneumonia) or cancer, relatively thick sections and general purpose image
reconstruction techniques may be adequate. IV contrast may also be used as it clarifies the anatomy and boundaries
of the great vessels and improves assessment of the mediastinum and hilar regions for lymphadenopathy; this is
particularly important for accurate assessment of cancer.
CT angiography of the chest is also becoming the primary method for detecting pulmonary embolism (PE) and aortic
dissection, and requires accurately timed rapid injections of contrast (Bolus Tracking) and high-speed helical
scanners. CT is the standard method of evaluating abnormalities seen on chest X-ray and of following findings of
uncertain acute significance. Cardiac CTA is now being used to diagnose coronary artery disease.
According to the 2007 New England Journal of Medicine study, 19.2 million (31%) of the 62 million CTs done
every year are for lung CTs.
Pulmonary angiogram
CT pulmonary angiogram (CTPA) is a medical diagnostic test used to diagnose pulmonary embolism (PE). It
employs computed tomography to obtain an image of the pulmonary arteries.
It is a preferred choice of imaging in the diagnosis of PE due to its minimally invasive nature for the patient, whose
only requirement for the scan is a cannula (usually a 20G).
MDCT (multi detector CT) scanners give the optimum resolution and image quality for this test. Images are usually
taken on a 0.625 mm slice thickness, although 2 mm is sufficient. 50–100 mls of contrast is given to the patient at a
rate of 4 ml/s. The tracker/locator is placed at the level of the pulmonary arteries, which sit roughly at the level of the
carina. Images are acquired with the maximum intensity of radio-opaque contrast in the pulmonary arteries. This is
done using bolus tracking.
CT machines are now so sophisticated that the test can be done with a patient visit of 5 minutes with an approximate
scan time of only 5 seconds or less.
230
X-ray computed tomography
A normal CTPA scan will show the contrast
filling the pulmonary vessels, looking bright
white. Ideally the aorta should be empty of
contrast, to reduce any partial volume
artifact which may result in a false positive.
Any mass filling defects, such as an
embolus, will appear dark in place of the
contrast, filling / blocking the space where
blood should be flowing into the lungs.
Cardiac
With the advent of subsecond rotation
combined with multi-slice CT (up to
64-slice), high resolution and high speed can
be obtained at the same time, allowing
Example of a CTPA, demonstrating a saddle embolus (dark horizontal line)
excellent imaging of the coronary arteries
occluding the pulmonary arteries (bright white triangle)
(cardiac CT angiography). Images with an
even higher temporal resolution can be
formed using retrospective ECG gating. In this technique, each portion of the heart is imaged more than once while
an ECG trace is recorded. The ECG is then used to correlate the CT data with their corresponding phases of cardiac
contraction. Once this correlation is complete, all data that were recorded while the heart was in motion (systole) can
be ignored and images can be made from the remaining data that happened to be acquired while the heart was at rest
(diastole). In this way, individual frames in a cardiac CT investigation have a better temporal resolution than the
shortest tube rotation time.
Because the heart is effectively imaged more than once (as described above), cardiac CT angiography results in a
relatively high radiation exposure around 12 mSv. For the sake of comparison, a chest X-ray carries a dose of
approximately 0.02[10] to 0.2 mSv and natural background radiation exposure is around 0.01 mSv/day. Thus, cardiac
CTA is equivalent to approximately 100-600 chest X-rays or over 3 years worth of natural background radiation.
Methods are available to decrease this exposure, however, such as prospectively decreasing radiation output based
on the concurrently acquired ECG (aka tube current modulation.) This can result in a significant decrease in
radiation exposure, at the risk of compromising image quality if there is any arrhythmia during the acquisition. The
significance of radiation doses in the diagnostic imaging range has not been proven, although the possibility of
inducing an increased cancer risk across a population is a source of significant concern. This potential risk must be
weighed against the competing risk of not performing a test and potentially not diagnosing a significant health
problem such as coronary artery disease.
It is uncertain whether this modality will replace invasive coronary catheterization. Currently, it appears that the
greatest utility of cardiac CT lies in ruling out coronary artery disease rather than ruling it in. This is because the test
has a high sensitivity (greater than 90%) and thus a negative test result means that a patient is very unlikely to have
coronary artery disease and can be worked up for other causes of their chest symptoms. This is termed a high
negative predictive value. A positive result is less conclusive and often will be confirmed (and possibly treated) with
subsequent invasive angiography. The positive predictive value of cardiac CTA is estimated at approximately 82%
and the negative predictive value is around 93%.
Dual Source CT scanners, introduced in 2005, allow higher temporal resolution by acquiring a full CT slice in only
half a rotation, thus reducing motion blurring at high heart rates and potentially allowing for shorter breath-hold
time. This is particularly useful for ill patients who have difficulty holding their breath or who are unable to take
heart-rate lowering medication.
231
X-ray computed tomography
The speed advantages of 64-slice MSCT have rapidly established it as the minimum standard for newly installed CT
scanners intended for cardiac scanning. Manufacturers are now actively developing 256-slice and true 'volumetric'
scanners, primarily for their improved cardiac scanning performance.
The latest MSCT scanners acquire images only at 70-80% of the R-R interval (late diastole). This prospective gating
can reduce effective dose from 10-15mSv to as little as 1.2mSv in follow-up patients acquiring at 75% of the R-R
interval. Effective doses at a centre with well trained staff doing coronary imaging can average less than the doses
for conventional coronary angiography.
Abdominal and pelvic
CT is a sensitive method for diagnosis of abdominal diseases. It is used
frequently to determine stage of cancer and to follow progress. It is
also a useful test to investigate acute abdominal pain (especially of the
lower quadrants, whereas ultrasound is the preferred first line
investigation for right upper quadrant pain). Renal stones, appendicitis,
pancreatitis, diverticulitis, abdominal aortic aneurysm, and bowel
obstruction are conditions that are readily diagnosed and assessed with
CT. CT is also the first line for detecting solid organ injury after
trauma.
Oral and/or rectal contrast may be used depending on the indications
CT Scan of 11 cm Wilms' tumor of right kidney
for the scan. A dilute (2% w/v) suspension of barium sulfate is most
in 13 month old patient.
commonly used. The concentrated barium sulfate preparations used for
fluoroscopy e.g. barium enema are too dense and cause severe artifacts
on CT. Iodinated contrast agents may be used if barium is contraindicated (for example, suspicion of bowel injury).
Other agents may be required to optimize the imaging of specific organs, such as rectally administered gas (air or
carbon dioxide) or fluid (water) for a colon study, or oral water for a stomach study.
CT has limited application in the evaluation of the pelvis. For the female pelvis in particular, ultrasound and MRI are
the imaging modalities of choice. Nevertheless, it may be part of abdominal scanning (e.g. for tumors), and has uses
in assessing fractures.
CT is also used in osteoporosis studies and research alongside dual energy X-ray absorptiometry (DXA). Both CT
and DXA can be used to assess bone mineral density (BMD) which is used to indicate bone strength, however CT
results do not correlate exactly with DXA (the gold standard of BMD measurement). CT is far more expensive, and
subjects patients to much higher levels of ionizing radiation, so it is used infrequently.
Extremities
CT is often used to image complex fractures, especially ones around joints, because of its ability to reconstruct the
area of interest in multiple planes. Fractures, ligamentous injuries and dislocations can easily be recognised with a
0.2 mm resolution.
Advantages and hazards
Advantages over traditional radiography
There are several advantages that CT has over traditional 2D medical radiography. First, CT completely eliminates
the superimposition of images of structures outside the area of interest. Second, because of the inherent high-contrast
resolution of CT, differences between tissues that differ in physical density by less than 1% can be distinguished.
Finally, data from a single CT imaging procedure consisting of either multiple contiguous or one helical scan can be
232
X-ray computed tomography
viewed as images in the axial, coronal, or sagittal planes, depending on the diagnostic task. This is referred to as
multiplanar reformatted imaging.
CT is regarded as a moderate to high radiation diagnostic technique. While technical advances have improved
radiation efficiency, there has been simultaneous pressure to obtain higher-resolution imaging and use more complex
scan techniques, both of which require higher doses of radiation. The improved resolution of CT has permitted the
development of new investigations, which may have advantages; compared to conventional angiography for
example, CT angiography avoids the invasive insertion of an arterial catheter and guidewire; CT colonography (also
known as virtual colonoscopy or VC for short) may be as useful as a barium enema for detection of tumors, but may
use a lower radiation dose. CT VC is increasingly being used in the UK as a diagnostic test for bowel cancer and can
negate the need for a colonoscopy.
The greatly increased availability of CT, together with its value for an increasing number of conditions, has been
responsible for a large rise in popularity. So large has been this rise that, in the most recent comprehensive survey in
the United Kingdom, CT scans constituted 7% of all radiologic examinations, but contributed 47% of the total
collective dose from medical X-ray examinations in 2000/2001.[11] Increased CT usage has led to an overall rise in
the total amount of medical radiation used, despite reductions in other areas. In the United States and Japan for
example, there were 26 and 64 CT scanners per 1 million population in 1996. In the U.S., there were about 3 million
CT scans performed in 1980, compared to an estimated 62 million scans in 2006.[12]
The radiation dose for a particular study depends on multiple factors: volume scanned, patient build, number and
type of scan sequences, and desired resolution and image quality. Additionally, two helical CT scanning parameters
that can be adjusted easily and that have a profound effect on radiation dose are tube current and pitch.[13]
Computed tomography (CT) scan has been shown to be more accurate than radiographs in evaluating anterior
interbody fusion but may still over-read the extent of fusion.[14]
Safety concerns
The increased use of CT scans has been the greatest in two fields: screening of adults (screening CT of the lung in
smokers, virtual colonoscopy, CT cardiac screening and whole-body CT in asymptomatic patients) and CT imaging
of children. Shortening of the scanning time to around 1 second, eliminating the strict need for subject to remain still
or be sedated, is one of the main reasons for large increase in the pediatric population (especially for the diagnosis of
appendicitis).[12] CT scans of children have been estimated to produce non-negligible increases in the probability of
lifetime cancer mortality, leading to calls for the use of reduced current settings for CT scans of children.[15] These
calculations are based on the assumption of a linear relationship between radiation dose and cancer risk; this claim is
controversial, as some but not all evidence shows that smaller radiation doses are less harmful.[12] Estimated lifetime
cancer mortality risks attributable to the radiation exposure from a CT in a 1-year-old are 0.18% (abdominal) and
0.07% (head)—an order of magnitude higher than for adults—although those figures still represent a small increase
in cancer mortality over the background rate. In the United States, of approximately 600,000 abdominal and head CT
examinations annually performed in children under the age of 15 years, a rough estimate is that 500 of these
individuals might ultimately die from cancer attributable to the CT radiation.[16] The additional risk is still very low
(0.35%) compared to the background risk of dying from cancer (23%).[16] However, if these statistics are
extrapolated to the current number of CT scans, the additional rise in cancer mortality could be 1.5 to 2%.
Furthermore, certain conditions can require children to be exposed to multiple CT scans. Again, these calculations
can be problematic because the assumptions underlying them could overestimate the risk.[12]
In 2009 a number of studies appeared that further defined the risk of cancer that may be caused by CT scans.[17] One
study indicated that radiation by CT scans is often higher and more variable than cited and each of the 19,500 CT
scans that are daily performed in the US is equivalent to 30 to 442 chest x-rays in radiation. It has been estimated
that CT radiation exposure will result in 29,000 new cancer cases just from the CT scans performed in 2007.[17] The
most common cancers caused by CT are thought to be lung cancer, colon cancer and leukemia with younger people
233
X-ray computed tomography
234
and women more at risk. These conclusions, however, are criticized by the American College of Radiology (ACR)
that maintains that the life expectancy of CT scanned patients is not that of the general population and that the model
of calculating cancer is based on total body radiation exposure and thus faulty.[17]
CT scans can be performed with different settings for lower exposure in children, although these techniques are often
not employed. Surveys have suggested that currently, many CT scans are performed unnecessarily. Ultrasound
scanning or magnetic resonance imaging are alternatives (for example, in appendicitis or brain imaging) without the
risk of radiation exposure. Although CT scans come with an additional risk of cancer (it can be estimated that the
radiation exposure from a full body scan is the same as standing 2.4 km away from the WWII atomic bomb blasts in
Japan[18] ), especially in children, the benefits that stem from their use outweighs the risk in many cases.[16] Studies
support informing parents of the risks of pediatric CT scanning.[19]
Typical scan doses
Examination
Typical effective dose (mSv) (millirem)
Chest X-ray
0.1
Head CT
1.5
Screening mammography
3
Abdomen CT
5.3
Chest CT
5.8
10
[20]
[12]
150
300
[20]
530
[20]
580
CT colonography (virtual colonoscopy) 3.6–8.8
[20]
Chest, abdomen and pelvis CT
9.9
Cardiac CT angiogram
6.7-13
Barium enema
15
Neonatal abdominal CT
20
[21]
360–880
990
670–1300
[12]
1500
[12]
2000
For purposes of comparison, the average background exposure in the UK is 1-3 mSv per year.
Adverse reactions to contrast agents
Because contrast CT scans rely on intravenously administered contrast agents in order to provide superior image
quality, there is a low but non-negligible level of risk associated with the contrast agents themselves. Many patients
report nausea and discomfort, including warmth in the crotch which mimics the sensation of wetting oneself. Certain
patients may experience severe and potentially life-threatening allergic reactions to the contrast dye.
The contrast agent may also induce kidney damage. The risk of this is increased with patients who have preexisting
renal insufficiency, preexisting diabetes, or reduced intravascular volume. In general, if a patient has normal kidney
function, then the risks of contrast nephropathy are negligible. Patients with mild kidney impairment are usually
advised to ensure full hydration for several hours before and after the injection. For moderate kidney failure, the use
of iodinated contrast should be avoided; this may mean using an alternative technique instead of CT, e.g., MRI.
Perhaps paradoxically, patients with severe renal failure requiring dialysis do not require special precautions, as their
kidneys have so little function remaining that any further damage would not be noticeable and the dialysis will
remove the contrast agent.
X-ray computed tomography
Low-dose CT scan
The main issue within radiology today is how to reduce the radiation dose during CT examinations without
compromising the image quality. Generally, a high radiation dose results in high-resolution images, while a lower
dose leads to increased image noise and results in unsharp images. Unfortunately, as the radiation dose increases, so
does the associated risk of radiation induced cancer—a four phase CT abdomen gives the same radiation dose as 300
chest x-rays. However, there are several methods that can be used in order to lower the exposure to ionizing radiation
during a CT scan.
1. New software technology can significantly reduce the radiation dose. The software works as a filter that reduces
random noise and enhances structures. In this way, it is possible to get high-quality images and at the same time
lower the dose by as much as 30 to 70 percent.
2. Individualize the examination and adjust the radiation dose to the body type and body organ examined. Different
body types and organs require different amounts of radiation.
3. Prior to every CT examination, evaluate the appropriateness of the exam whether it is motivated or if another type
of examination is more suitable. Higher resolution is not always suitable for any given scenario, such as detection
of small pulmonary masses[22]
Computed tomography versus MRI
See the entries on paragraphs of the same name in the MRI and 2D-FT NMRI and Spectroscopy articles. The basic
mathematics of the 2D-Fourier transform in CT reconstruction is very similar to the 2D-FT NMRI, but the computer
data processing in CT does differ in detail, as for example in the case of the volume rendering or the artifacts
elimination algorithms that are specific to CT.
• guidelines for appropriate use of CT, some discussion of MR and Ultarsound as alternatives [23]
Process
X-ray slice data is generated using an X-ray source that rotates around the object; X-ray sensors are positioned on the
opposite side of the circle from the X-ray source. The earliest sensors were scintillation detectors, with
photomultiplier tubes excited by (typically) cesium iodide crystals. Cesium iodide was replaced during the 1980s by
ion chambers containing high pressure Xenon gas. These systems were in turn replaced by scintillation systems
based on photo diodes instead of photomultipliers and modern scintillation materials with more desirable
characteristics. Many data scans are progressively taken as the object is gradually passed through the gantry. They
are combined together by the mathematical procedures known as tomographic reconstruction. The data are arranged
in a matrix in memory, and each data point is convolved with its neighbours according with a seed algorithm using
Fast Fourier Transform techniques. This dramatically increases the resolution of each Voxel (volume element). Then
a process known as back projection essentially reverses the acquisition geometry and stores the result in another
memory array. This data can then be displayed, photographed, or used as input for further processing, such as
multi-planar reconstruction.
Newer machines with faster computer systems and newer software strategies can process not only individual cross
sections but continuously changing cross sections as the gantry, with the object to be imaged, is slowly and smoothly
slid through the X-ray circle. These are called helical or spiral CT machines. Their computer systems integrate the
data of the moving individual slices to generate three dimensional volumetric information (3D-CT scan), in turn
viewable from multiple different perspectives on attached CT workstation monitors. This type of data acquisition
requires enormous processing power, as the data are arriving in a continuous stream and must be processed in
real-time.
In conventional CT machines, an X-ray tube and detector are physically rotated behind a circular shroud (see the
image above right); in the electron beam tomography (EBT) the tube is far larger and higher power to support the
235
X-ray computed tomography
236
high temporal resolution. The electron beam is deflected in a hollow funnel-shaped vacuum chamber. X-rays are
generated when the beam hits the stationary target. The detector is also stationary. This arrangement can result in
very fast scans, but is extremely expensive.
The data stream representing the varying radiographic intensity sensed at the detectors on the opposite side of the
circle during each sweep is then computer processed to calculate cross-sectional estimations of the radiographic
density, expressed in Hounsfield units. Sweeps cover 360 or just over 180 degrees in conventional machines, 220
degrees in EBT.
CT is used in medicine as a diagnostic tool and as a guide for
interventional procedures. Sometimes contrast materials such as
intravenous iodinated contrast are used. This is useful to highlight
structures such as blood vessels that otherwise would be difficult to
delineate from their surroundings. Using contrast material can also
help to obtain functional information about tissues.
Pixels in an image obtained by CT scanning are displayed in terms of
relative radiodensity. The pixel itself is displayed according to the
mean attenuation of the tissue(s) that it corresponds to on a scale from
+3071 (most attenuating) to -1024 (least attenuating) on the Hounsfield
scale. Pixel is a two dimensional unit based on the matrix size and the
CT scanner with cover removed to show the
field of view. When the CT slice thickness is also factored in, the unit
principle of operation
is known as a Voxel, which is a three dimensional unit. The
phenomenon that one part of the detector cannot differentiate between
different tissues is called the "Partial Volume Effect". That means that a big amount of cartilage and a thin layer of
compact bone can cause the same attenuation in a voxel as hyperdense cartilage alone. Water has an attenuation of 0
Hounsfield units (HU) while air is -1000 HU, cancellous bone is typically +400 HU, cranial bone can reach 2000 HU
or more (os temporale) and can cause artifacts. The attenuation of metallic implants depends on atomic number of
the element used: Titanium usually has an amount of +1000 HU, iron steel can completely extinguish the X-ray and
is therefore responsible for well-known line-artifacts in computed tomograms. Artifacts are caused by abrupt
transitions between low- and high-density materials, which results in data values that exceed the dynamic range of
the processing electronics.
Artifacts
Although CT is a relatively accurate test, it is liable to produce artifacts, such as the following (for more details, see
Chapter 3 and 5 of ref.[2] ).
• Aliasing artifact or streaks
These appear as dark lines which radiate away from sharp corners. It
occurs because it is impossible for the scanner to "sample" or take
enough projections of the object, which is usually metallic. It can also
occur when an insufficient X-ray tube current is selected, and
insufficient penetration of the x-ray occurs. These artifacts are also
closely tied to motion during a scan. This type of artifact commonly
occurs in head images around the pituitary fossa area.
Example of beam hardening
• Partial volume effect
This appears as "blurring" over sharp edges. It is due to the scanner being unable to differentiate between a small
amount of high-density material (e.g. bone) and a larger amount of lower density (e.g., cartilage). The processor tries
to average out the two densities or structures, and information is lost. This can be partially overcome by scanning
X-ray computed tomography
237
using thinner slices.
• Ring artifact
Probably the most common mechanical artifact, the image of one or many "rings" appears within an image. This is
usually due to a detector fault.
• Noise artifact
This appears as graining on the image and is caused by a low signal to noise ratio. This occurs more commonly when
a thin slice thickness is used. It can also occur when the power supplied to the X-ray tube is insufficient to penetrate
the anatomy.
• Motion artifact
This is seen as blurring and/or streaking which is caused by movement of the object being imaged.
• Windmill
Streaking appearances can occur when the detectors intersect the reconstruction plane. This can be reduced with
filters or a reduction in pitch.
• Beam hardening
This can give a "cupped appearance". It occurs when there is more attenuation in the center of the object than around
the edge. This is easily corrected by filtration and software.
Three-dimensional (3D) image reconstruction
The principle
Because contemporary CT scanners offer isotropic or near isotropic, resolution, display of images does not need to
be restricted to the conventional axial images. Instead, it is possible for a software program to build a volume by
"stacking" the individual slices one on top of the other. The program may then display the volume in an alternative
manner.[24]
Multiplanar reconstruction
Multiplanar reconstruction (MPR) is the simplest method of
reconstruction. A volume is built by stacking the axial slices. The
software then cuts slices through the volume in a different plane
(usually orthogonal). Optionally, a special projection method, such as
maximum-intensity projection (MIP) or minimum-intensity projection
(mIP), can be used to build the reconstructed slices.
MPR is frequently used for examining the spine. Axial images through
the spine will only show one vertebral body at a time and cannot
reliably show the intervertebral discs. By reformatting the volume, it
becomes much easier to visualise the position of one vertebral body in
relation to the others.
Modern software allows reconstruction in non-orthogonal (oblique)
planes so that the optimal plane can be chosen to display an anatomical
structure. This may be particularly useful for visualising the structure
of the bronchi as these do not lie orthogonal to the direction of the scan.
Typical screen layout for diagnostic software,
showing one 3D and three MPR views
For vascular imaging, curved-plane reconstruction can be performed. This allows bends in a vessel to be
"straightened" so that the entire length can be visualised on one image, or a short series of images. Once a vessel has
been "straightened" in this way, quantitative measurements of length and cross sectional area can be made, so that
X-ray computed tomography
surgery or interventional treatment can be planned.
MIP reconstructions enhance areas of high radiodensity, and so are useful for angiographic studies. mIP
reconstructions tend to enhance air spaces so are useful for assessing lung structure.
3D rendering techniques
Surface rendering
A threshold value of radiodensity is chosen by the operator (e.g. a level that corresponds to bone). A threshold
level is set, using edge detection image processing algorithms. From this, a three-dimensional model can be
constructed and displayed on screen. Multiple models can be constructed from various different thresholds,
allowing different colors to represent each anatomical component such as bone, muscle, and cartilage.
However, the interior structure of each element is not visible in this mode of operation.
Volume rendering
Surface rendering is limited in that it will only display surfaces which meet a threshold density, and will only
display the surface that is closest to the imaginary viewer. In volume rendering, transparency and colors are
used to allow a better representation of the volume to be shown in a single image—e.g. the bones of the pelvis
could be displayed as semi-transparent, so that even at an oblique angle, one part of the image does not
conceal another.
Image segmentation
Where different structures have similar radiodensity, it can become impossible to separate them simply by adjusting
volume rendering parameters. The solution is called segmentation, a manual or automatic procedure that can remove
the unwanted structures from the image.
Example
Some slices of a cranial CT scan are shown below. The bones are whiter than the surrounding area. (Whiter means
higher attenuation.) Note the blood vessels (arrowed) showing brightly due to the injection of an iodine-based
contrast agent.
238
X-ray computed tomography
239
Computed tomography of human brain, from base of the skull to top. Taken with intravenous contrast medium.
A volume rendering of this volume clearly shows the high density bones.
Bone reconstructed in 3D
After using a segmentation tool to remove the bone, the previously concealed vessels can now be demonstrated.
X-ray computed tomography
240
Brain vessels reconstructed in 3D after bone has
been removed by segmentation
See also
• Virtopsy
• Xenon-enhanced CT scanning
External links
Open-source computed tomography simulator with educational tracing displays [25]
idoimaging.com: Free software for viewing CT and other medical imaging files [26]
CT Artefacts [27] by David Platten
DigiMorph [28] A library of 3D imagery based on CT scans of the internal and external structure of living and
extinct plants and animals.
• MicroCT and calcified tissues [29] A website dedicated to microCT in the microscopic analysis of calcified
tissues.
• Free Radiology Resource for Radiologists, Radiographers, and Technical Assistance [30]
•
•
•
•
•
•
•
•
•
Radiation Risk Calculator [31] Calculate cancer risk from CT scans and xrays.
CT scanner video - gantry [32]
CT in your clinical practice [33] by Gregory J. Kohs and Joel Legunn.
Coronary CT angiography by Eugene Lin [34]
CT physics lecture [35] excellent video lectures about physics in computed tomography
References
[1] "computed tomography—Definition from the Merriam-Webster Online Dictionary" (http:/ / www. merriam-webster. com/ dictionary/
computed+ tomography). . Retrieved 2009-08-18.
[2] Herman, G. T., Fundamentals of computerized tomography: Image reconstruction from projection, 2nd edition, Springer, 2009
[3] Smith-Bindman R, Lipson J, Marcus R, et al. (December 2009). "Radiation dose associated with common computed tomography
examinations and the associated lifetime attributable risk of cancer". Arch. Intern. Med. 169 (22): 2078–86.
doi:10.1001/archinternmed.2009.427. PMID 20008690.
[4] Berrington de González A, Mahesh M, Kim KP, et al. (December 2009). "Projected cancer risks from computed tomographic scans
performed in the United States in 2007". Arch. Intern. Med. 169 (22): 2071–7. doi:10.1001/archinternmed.2009.440. PMID 20008689.
[5] MeSH Tomography,+X-Ray+Computed (http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2009/ MB_cgi?mode=& term=Tomography,+ X-Ray+
Computed)
[6] Richmond, Caroline (September 18, 2004). "Obituary—Sir Godfrey Hounsfield" (http:/ / www. bmj. com/ cgi/ content/ full/ 329/ 7467/ 687).
BMJ (London, UK: BMJ Group) 2004:329:687 (18 September 2004). . Retrieved September 12, 2008.
X-ray computed tomography
[7] Filler, AG (2009): The history, development, and impact of computed imaging in neurological diagnosis and neurosurgery: CT, MRI, DTI:
Nature Precedings DOI: 10.1038/npre.2009.3267.5 (http:/ / precedings. nature. com/ documents/ 3267/ version/ 5).
[8] "The Beatles greatest gift... is to science" (http:/ / www. whittington. nhs. uk/ default. asp?c=2804& t=1). Whittington Hospital NHS Trust. .
Retrieved 2007-05-07.
[9] Novelline, Robert. Squire's Fundamentals of Radiology. Harvard University Press. 5th edition. 1997. ISBN 0674833392.
[10] Hart, D; Wall B F (2002). "Radiation exposure of the UK population from Medical and Dental X-ray examinations" (http:/ / www. hpa. org.
uk/ radiation/ publications/ w_series_reports/ 2002/ nrpb_w4. pdf) ( – Scholar search (http:/ / scholar. google. co. uk/ scholar?hl=en& lr=&
q=author:Hart+ intitle:Radiation+ exposure+ of+ the+ UK+ population+ from+ Medical+ and+ Dental+ X-ray+ examinations&
as_publication=NRPB+ report+ W-4& as_ylo=2002& as_yhi=2002& btnG=Search)). NRPB report W-4. .
[11] Hart, D.; Wall (2004). "UK population dose from medical X-ray examinations" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/
S0720048X03001785). European Journal of Radiology 50 (3): 285–291. doi:10.1016/S0720-048X(03)00178-5. PMID 15145489. .
[12] Brenner DJ, Hall EJ (November 2007). "Computed tomography—an increasing source of radiation exposure" (http:/ / content. nejm. org/
cgi/ pmidlookup?view=short& pmid=18046031& promo=ONFLNS19). N. Engl. J. Med. 357 (22): 2277–84. doi:10.1056/NEJMra072149.
PMID 18046031. .
[13] Donnelly, Lane F.; et al (1 February 2001). "Minimizing Radiation Dose for Pediatric Body Applications of Single-Detector Helical CT"
(http:/ / www. ajronline. org/ cgi/ reprint/ 176/ 2/ 303). American Journal of Roentgenology 176 (2): 303–6. PMID 11159061. .
[14] Brian R. Subach M.D., F.A.C.S 'Reliability and accuracy of fine-cut computed tomography scans to determine the status of anterior
interbody fusions with metallic cages' Spine J. 2008 Nov-Dec;8(6):998-1002. Epub February 14, 2008.http:/ / www. spinemd. com/
publications/ articles/
reliability-and-accuracy-of-fine-cut-computed-tomography-scans-to-determine-the-status-of-anterior-interbody-usions-with-metallic-cages
[15] Brenner, David J.; et al. (1 February 2001). "Estimated Risks of Radiation-Induced Fatal Cancer from Pediatric CT" (http:/ / www. ajronline.
org/ cgi/ content/ abstract/ 176/ 2/ 289). American Journal of Roentgenology 176 (176): 289–296. PMID 11159059. .
[16] Brenner D, Elliston C, Hall E, Berdon W (February 2001). "Estimated risks of radiation-induced fatal cancer from pediatric CT" (http:/ /
www. ajronline. org/ cgi/ pmidlookup?view=long& pmid=11159059). AJR Am J Roentgenol 176 (2): 289–96. PMID 11159059. .
[17] Roxanne Nelson (December 17, 2009). "Thousands of New Cancers Predicted Due to Increased Use of CT" (http:/ / www. medscape. com/
viewarticle/ 714025). Medscape. . Retrieved January 2, 2010.
[18] Khamsi, Roxanne (2007). New Scientist (http:/ / www. newscientist. com/ article/
dn11827-ct-scan-radiation-can-equal-nuclear-bomb-exposure-. html). 11 May 2007. .
[19] Larson DB, Rader SB, Forman HP, Fenton LZ (August 2007). "Informing parents about CT radiation exposure in children: it's OK to tell
them" (http:/ / www. ajronline. org/ cgi/ pmidlookup?view=long& pmid=17646450). AJR Am J Roentgenol 189 (2): 271–5.
doi:10.2214/AJR.07.2248. PMID 17646450. .
[20] Shrimpton, P.C; Miller, H.C; Lewis, M.A; Dunn, M. Doses from Computed Tomography (CT) examinations in the UK - 2003 Review
(http:/ / www. hpa. org. uk/ web/ HPAwebFile/ HPAweb_C/ 1194947420292)
[21] "Radiation Exposure during Cardiac CT: Effective Doses at Multi–Detector Row CT and Electron-Beam CT" (http:/ / radiology. rsnajnls.
org/ cgi/ content/ abstract/ 226/ 1/ 145). Radiology.rsnajnls.org. 2002-11-21. . Retrieved 2009-10-13.
[22] Simpson, Graham. 2009. "Thoracic computed tomography: principles and practice". Australian Prescriber, 32:4. Available at http:/ / www.
australianprescriber. com/ upload/ pdf/ articles/ 1036. pdf [accessed 25 September 2009]
[23] http:/ / www. cancer. gov/ ncicancerbulletin/ 012610/ page8|
[24] Udupa, J.K. and Herman, G. T., 3D Imaging in Medicine, 2nd Edition, CRC Press, 2000
[25] http:/ / ctsim. org
[26] http:/ / www. idoimaging. com
[27] http:/ / www. impactscan. org/ slides/ impactcourse/ artefacts/ img0. html
[28] http:/ / digimorph. org/
[29] http:/ / www. med. univ-angers. fr/ discipline/ lab_histo/ page_microCT. htm
[30] http:/ / www. mdct. com. au:
[31] http:/ / www. xrayrisk. com
[32] http:/ / www. radrounds. com/ video/ ct-scanner-gantry-full-speed
[33] http:/ / www. ajronline. org/ cgi/ data/ 183/ 3/ DC1/ 1
[34] http:/ / emedicine. medscape. com/ article/ 1603072-overview
[35] http:/ / www. radiolopolis. com/ index. php/ radiology-videos/ video-gallery. html?task=viewvideo& video_id=122
241
Preimplantation genetic diagnosis
Preimplantation genetic diagnosis
In medicine and (clinical) genetics preimplantation genetic diagnosis (PGD or PIGD) (also known as embryo
screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes
prior to fertilization. PGD is considered another way to prenatal diagnosis. Its main advantage is that it avoids
selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under
consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) to
obtain oocytes or embryos for evaluation.
The term preimplantation genetic screening (PGS) is used to denote procedures that do not look for a specific
disease but use PGD techniques to identify embryos at risk. PGD is a poorly chosen phrase because, in medicine, to
"diagnose" means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of
disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. To "screen" means to
test for anatomical, physiological, or genetic conditions in the absence of symptoms of disease. So both PGD and
PGS should be referred to as types of embryo screening.
Procedures performed on sex cells before fertilization may instead be referred to as fertilization, although the
methods and aims partly overlap with PGD.
History
In 1967, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first
steps towards PGD[1] . It was not until the 1980s that human IVF was fully developed, which coincided with the
breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first
successful attempts at testing were in October 1989 with the first births in 1990[2] though the preliminary
experiments had been published some years earlier[3] [4] . In these first cases, PCR was used for sex determination
for patients carrying X-linked diseases.
PGD and society
As with all medical interventions associated with human reproduction, PGD rise strong often conflicting the social
acceptability in particular due to its eugenic implications. For example, in Germany the use of PGD is prohibited by
the Embryo Protection Act of 1990 [5].
In other countries PGD is permitted in law but its operation is controlled by the state. In the UK, the use of PGD is
controlled by the HFEA ([6]) - the UK regulator for fertility treatment and embryo research. The HFEA only permits
the use of PGD where the clinic concerned has a licence from the HFEA and sets out the rules for this licensing in its
Code of Practice ([7]). Each clinic, and each medical condition, requires a separate application where the HFEA
check the suitability of the genetic test proposed and the staff skills and facilities of the clinic. Only then can PGD be
used for a patient.
Indications and applications
Currently, there are mainly two groups of patients for which PGD is being applied:
• In the first group PGD is used to look for a specific disorder in couples with a high risk of transmitting an
inherited condition. This can be a monogenic disorder, meaning the condition is due to a single gene only,
(autosomal recessive, autosomal dominant or X-linked disorders) or a chromosomal structural aberration (such as
a balanced translocation). PGD helps these couples identify embryos carrying a genetic disease or a chromosome
abnormality, thus avoiding the difficult choice of abortion. In addition, there are infertile couples who carry an
inherited condition and who opt for PGD as it can be easily combined with their IVF treatment.
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Preimplantation genetic diagnosis
• The second group consists of couples who undergo IVF treatment and whose embryos are screened for
chromosome aneuploidies. The technique is not used to obtaining a specific prenatal diagnosis but rather for
screening, properly referred to as preimplantation genetic screening (PGS), to increase the chances of an ongoing
pregnancy.
Specific disorders
PGD is available for a large number of monogenic disorders. The most frequently diagnosed autosomal recessive
disorders are cystic fibrosis, Beta-thalassemia, sickle cell disease and spinal muscular atrophy type 1. The most
common dominant diseases are myotonic dystrophy, Huntington's disease and Charcot-Marie-Tooth disease; and in
the case of the X-linked diseases, most of the cycles are performed for fragile X syndrome, haemophilia A and
Duchenne muscular dystrophy. Though it is quite infrequent, some centers report PGD for mitochondrial disorders
or two indications simultaneously.
In the case of chromosomal abnormalities, PGD is mainly carried out for reciprocal and Robertsonian translocations,
and few cases for other abnormalities such as chromosomal inversions or deletions. PGD is also now being
performed in a disease called Hereditary multiple exostoses(MHE / MO / HME) Aneuploidy screening is probably
the most frequent indication for PGD, mainly suggested to couples undergoing IVF with an advanced maternal age
and for patients with repetitive IVF failure. The principle behind it is that, since it is known that numerical
chromosomal abnormalities explain most of the cases of pregnancy loss, and a large proportion of the human
embryos are aneuploid, the selective replacement of euploid embryos should increase the chances of a successful
IVF treatment. Different studies provide indications that PGS increases the implantation rate[8] [9] [10] [11] and lowers
the spontaneous abortion rate [12] , though other studies indicate that there are no significant differences for patients
with an advanced maternal age [13] [14] , with a poor implantation rate [13] or with recurrent idiopathic miscarriages
[15]
. It is thus clear that large randomised-controlled studies are still necessary to measure the real impact of this
technique for the different indications. A recent systematic review on PGS can be found in the Cochrane database
[16]
.
General screening
The main purpose of preimplantation genetic screening (PGS) is to increase the chances of an ongoing pregnancy.
The main applications for PGS are an advanced maternal age, a history of recurrent miscarriages or repeated
unsuccessful implantation. As the results of PGS rely on the assessment of a single cell, PGS has inherent limitations
as the tested cell may not be representative of the embryo and embryo mosaicism may not be clinically
significant.[17] Further, studies have not shown that IVF success rates in terms of live births are better when PGS is
used, and there is some concern that a biopsy may lower success rates.[17] It has also been proposed for patients with
obstructive and non-obstructive azoospermia.
Other
Other indications include all of the ethically difficult cases, including the following situations:
HLA matching
Human leukocyte antigen (HLA) typing of embryos, so that the child's HLA matches a sick sibling, avaliling for
cord-blood stem cell donation (Pattinson 2003) [18]. LA typing has meanwhile become an important PGD indication
in those countries where the law permits it [19] . The HLA matching can be combined with the diagnosis for
monogenic diseases such as Fanconi anaemia or b-thalassemia in those cases where the ailing sibling is affected with
this disease, or it may be exceptionally performed on its own for cases such as children with leukaemia. The main
ethical argument against is the possible exploitation of the child, although some authors maintain that the Kantian
imperative is not breached since the future donor child will not only be a donor but also a loved individual within the
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Preimplantation genetic diagnosis
family.
Non-disclosure
Another problematic case is the non-disclosure PGD for Huntington's disease. It is applied when patients do not wish
to know their carrier status but want to ensure that they have offspring free of the disease. This procedure can place
practitioners in questionable ethical situations, e.g. when no healthy, unaffected embryos are available for transfer
and a mock transfer has to be carried out so that the patient does not suspect that he/she is a carrier. The ESHRE
ethics task force currently recommends using exclusion testing instead. Exclusion testing is based on a linkage
analysis with polymorphic markers, in which the parental and grandparental origin of the chromosomes can be
established. This way, only embryos are replaced that do not contain the chromosome derived from the affected
grandparent, avoiding the need to detect the mutation itself.
Cancer predisposition
A more recent application of PGD is to diagnose late-onset diseases and (cancer) predisposition syndromes. It can be
argued that PGD for late-onset diseases is unethical since the individuals remain healthy until the onset of the
disease, usually in the fourth decade of life. On the other hand, the high probability or certainty of developing some
disorders, and their incurable nature, can lead to a stressful life, waiting for the first symptoms to occur and to an
early death. In the case of predisposition syndromes, such as BRCA1 mutations predisposing to breast cancer, it can
be argued that there is no certainty of getting the disease and that the disease can usually be treated. It is a fact that
although PGD is often regarded as an early form of prenatal diagnosis, the nature of the requests for PGD often
differs from those of prenatal diagnosis requests made when the mother is already pregnant. Some of the widely
accepted indications for PGD would not be acceptable for prenatal diagnosis.
Sex selection
Increasingly, PGD is also used for sex selection for non-medical reasons. A 2006 survey [20] found that 42 per cent
of clinics that offer PGD have provided it for this reason. Nearly half of these clinics perform it only for “family
balancing”, which is where a couple with two or more children of one sex desire a child of the other, but half do not
restrict sex selection to family balancing. In India, this practice has been used to select only male embryos although
this practice is illegal . Opinions on whether sex selection for non-medical reasons is ethically acceptable differ
widely, as exemplified by the fact that the ESHRE Task Force could not formulate a uniform recommendation.
Minor disabilities
A 2006 survey reveals that PGD has occasionally been used to select an embryo for the presence of a particular
disease or disability, such as deafness, in order that the child would share that characteristic with the parents.[21]
Technical aspects of preimplantation genetic diagnosis
PGD is a form of genetic diagnosis performed prior to implantation. This implies that the patient’s oocytes should be
fertilized in vitro and the embryos kept in culture until the diagnosis is established. It is also necessary to perform a
biopsy on these embryos in order to obtain material on which to perform the diagnosis. The diagnosis itself can be
carried out using several techniques, depending on the nature of the studied condition. Generally, PCR-based
methods are used for monogenic disorders and FISH for chromosomal abnormalities and for sexing those cases in
which no PCR protocol is available for an X-linked disease. These techniques need to be adapted to be performed on
blastomeres and need to be thoroughly tested on single-cell models prior to clinical use. Finally, after embryo
replacement, surplus good quality unaffected embryos can be cryopreserved, to be thawed and transferred back in a
next cycle.
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Preimplantation genetic diagnosis
Obtaining embryos for preimplantation genetic diagnosis
Currently, all PGD embryos are obtained by assisted reproductive technology, although the use of natural cycles and
in vivo fertilization followed by uterine lavage was attempted in the past and is now largely abandoned. In order to
obtain a large cohort of oocytes, the patients undergo controlled ovarian stimulation (COH). COH is carried out
either in an agonist protocol, using gonadotrophin-releasing hormone (GnRH) analogues for pituitary desensitisation,
combined with human menopausal gonadotrophins (hMG) or recombinant follicle stimulating hormone (FSH), or an
antagonist protocol using recombinant FSH combined with a GnRH antagonist according to clinical assessment of
the patient’s profile (age, body mass index (BMI), endocrine parameters). hCG is administered when at least three
follicles of more than 17 mm mean diameter are seen at transvaginal ultrasound scan. Transvaginal
ultrasound-guided oocyte retrieval is scheduled 36 hours after hCG administration. Luteal phase supplementation
consists of daily intravaginal administration of 600 µg of natural micronized progesterone.
Oocytes are carefully denudated from the cumulus cells, as these cells can be a source of contamination during the
PGD if PCR-based technology is used. In the majority of the reported cycles, intracytoplasmic sperm injection
(ICSI) is used instead of IVF. The main reasons are to prevent contamination with residual sperm adhered to the
zona pellucida and to avoid unexpected fertilization failure. The ICSI procedure is carried out on mature
metaphase-II oocytes and fertilization is assessed 16–18 hours after. The embryo development is further evaluated
every day prior to biopsy and until transfer to the woman’s uterus. During the cleavage stage, embryo evaluation is
performed daily on the basis of the number, size, cell-shape and fragmentation rate of the blastomeres. On day 4,
embryos were scored in function of their degree of compaction and blastocysts were evaluated according to the
quality of the throphectoderm and inner cell mass, and their degree of expansion.
Biopsy procedures
As PGD can be performed on cells from different developmental stages, the biopsy procedures vary accordingly.
Theoretically, the biopsy can be performed at all preimplantation stages, but only three have been suggested: on
unfertilised and fertilised oocytes (for polar bodies, PBs), on day three cleavage-stage embryos (for blastomeres) and
on blastocysts (for trophectoderm cells).
The biopsy procedure always involves two steps: the opening of the zona pellucida and the removal of the cell(s).
There are different approaches to both steps, including mechanical, chemical (Tyrode’s acidic solution) and laser
technology for the breaching of the zona pellucida, extrusion or aspiration for the removal of PBs and blastomeres,
and herniation of the trophectoderm cells.
Polar body biopsy
The first and second polar body of the oocyte are extruded at the time of the conclusion of the meiotic division,
normally the first polar body is noted after ovulation, and the second polar body after fertilization. PB biopsy is used
mainly by two PGD groups in the USA [22] [23] and by groups in countries where cleavage-stage embryo selection is
banned [24] . They have been used for diagnosing translocations and monogenic disorders of maternal origin, as well
as for PGS.
The first PB is removed from the unfertilised oocyte, and the second PB from the zygote, shortly after fertilization.
The main advantage of the use of PBs in PGD is that they are not necessary for successful fertilisation or normal
embryonic development, thus ensuring no deleterious effect for the embryo. One of the disadvantages of PB biopsy
is that it only provides information about the maternal contribution to the embryo, which is why cases of autosomal
dominant and X-linked disorders that are maternally transmitted can be diagnosed, and autosomal recessive disorders
can only partially be diagnosed. Another drawback is the increased risk of diagnostic error, for instance due to the
degradation of the genetic material or events of recombination that lead to heterozygous first PBs. It is generally
agreed that it is best to analyse both PBs in order to minimize the risk of misdiagnosis. This can be achieved by
sequential biopsy, necessary if monogenic diseases are diagnosed, to be able to differentiate the first from the second
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PB, or simultaneous biopsy if FISH is to be performed. In Germany, where the legislation bans the selection of
preimplantation embryos, PB analysis is the only possible method to perform PGD. The biopsy and analysis of the
first and second PBs can be completed before syngamy, which is the moment from which the zygote is considered an
embryo and becomes protected by the law.
Cleavage-stage biopsy (Blastomere biopsy)
Cleavage-stage biopsy is generally performed the morning of day three post-fertilization, when normally developing
embryos reach the eight-cell stage. The biopsy is usually performed on embryos with less than 50% of anucleated
fragments and at an 8-cell or later stage of development. A hole is made in the zona pellucida and one or two
blastomeres containing a nucleus are gently aspirated or extruded through the opening. The main advantage of
cleavage-stage biopsy over PB analysis is that the genetic input of both parents can be studied. On the other hand,
cleavage-stage embryos are found to have a high rate of chromosomal mosaicism, putting into question whether the
results obtained on one or two blastomeres will be representative for the rest of the embryo. It is for this reason that
some programs utilize a combination of PB biopsy and blastomere biopsy. Furthermore, cleavage-stage biopsy, as in
the case of PB biopsy, yields a very limited amount of tissue for diagnosis, necessitating the development of
single-cell PCR and FISH techniques. Although theoretically PB biopsy and blastocyst biopsy are less harmful than
cleavage-stage biopsy, this is still the prevalent method. It is used in approximately 94% of the PGD cycles reported
to the ESHRE PGD Consortium. The main reasons are that it allows for a safer and more complete diagnosis than
PB biopsy and still leaves enough time to finish the diagnosis before the embryos must be replaced in the patient’s
uterus, unlike blastocyst biopsy. Of all cleavage-stages, it is generally agreed that the optimal moment for biopsy is
at the eight-cell stage. It is diagnostically safer than the PB biopsy and, unlike blastocyst biopsy, it allows for the
diagnosis of the embryos before day 5. In this stage, the cells are still totipotent and the embryos are not yet
compacting. Although it has been shown that up to a quarter of a human embryo can be removed without disrupting
its development, it still remains to be studied whether the biopsy of one or two cells correlates with the ability of the
embryo to further develop, implant and grow into a full term pregnancy.
Blastocyst biopsy
In an attempt to overcome the difficulties related to single-cell techniques, it has been suggested to biopsy embryos
at the blastocyst stage, providing a larger amount of starting material for diagnosis. It has been shown that if more
than two cells are present in the same sample tube, the main technical problems of single-cell PCR or FISH would
virtually disappear. On the other hand, as in the case of cleavage-stage biopsy, the chromosomal differences between
the inner cell mass and the trophectoderm (TE) can reduce the accuracy of diagnosis, although this mosaicism has
been reported to be lower than in cleavage-stage embryos.
TE biopsy has been shown to be successful in animal models such as rabbits [25] , mice [26] and primates [27] . These
studies show that the removal of some TE cells is not detrimental to the further in vivo development of the embryo.
Human blastocyst-stage biopsy for PGD is performed by making a hole in the ZP on day three of in vitro culture.
This allows the developing TE to protrude after blastulation, facilitating the biopsy. On day five post-fertilization,
approximately five cells are excised from the TE using a glass needle or laser energy, leaving the embryo largely
intact and without loss of inner cell mass. After diagnosis, the embryos can be replaced during the same cycle, or
cryopreserved and transferred in a subsequent cycle.
There are two drawbacks to this approach, due to the stage at which it is performed. First, only approximately half of
the preimplantation embryos reach the blastocyst stage. This can restrict the number of blastocysts available for
biopsy, limiting in some cases the success of the PGD. Mc Arthur and coworkers [28] report that 21% of the started
PGD cycles had no embryo suitable for TE biopsy. This figure is approximately four times higher than the average
presented by the ESHRE PGD consortium data, where PB and cleavage-stage biopsy are the predominant reported
methods. On the other hand, delaying the biopsy to this late stage of development limits the time to perform the
genetic diagnosis, making it difficult to redo a second round of PCR or to rehybridize FISH probes before the
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embryos should be transferred back to the patient.
Genetic analysis techniques
Fluorescent in situ hybridization (FISH) and Polymerase chain reaction (PCR) are the two most commonly used
technologies in PGD, although other approaches have been proposed or are currently in development (such as whole
genome amplification and comparative genomic hybridization) . PCR is generally used to diagnose monogenic
disorders and FISH is used for the detection of chromosomal abnormalities (for instance, aneuploidy screening or
chromosomal translocations). Recently a method was developed allowing to fix metaphase plates from single
blastomeres. This technique in conjunction with FISH, m-FISH can produce more reliable results, since analysis is
done on whole metaphase plates[29]
FISH
FISH is the most commonly applied method to determine the chromosomal constitution of an embryo. In contrast to
karyotyping, it can be used on interphase chromosomes, so that it can be used on PBs, blastomeres and TE samples.
The cells are fixated on glass microscope slides and hybridised with DNA probes. Each of these probes are specific
for part of a chromosome, and are labelled with a fluorochrome. Currently, a large panel of probes are available for
different segments of all chromosomes, but the limited number of different fluorochromes confines the number of
signals that can be analysed simultaneously.
The type and number of probes that are used on a sample depends on the indication. For sex determination (used for
instance when a PCR protocol for a given X-linked disorder is not available), probes for the X and Y chromosomes
are applied along with probes for one or more of the autosomes as an internal FISH control. More probes can be
added to check for aneuploidies, particularly those that could give raise to a viable pregnancy (such as a trisomy 21).
The use of probes for chromosomes X, Y, 13, 14, 15, 16, 18, 21 and 22 has the potential of detecting 70% of the
aneuploidies found in spontaneous abortions.
In order to be able to analyse more chromosomes on the same sample, up to three consecutive rounds of FISH can be
carried out. In the case of chromosome rearrangements, specific combinations of probes have to be chosen that flank
the region of interest. The FISH technique is considered to have an error rate between 5 and 10%.
The main problem of the use of FISH to study the chromosomal constitution of embryos is the elevated mosaicism
rate observed at the human preimplantation stage. Sandalinas and collaborators found that up to 70% of the embryos
they studied by FISH were mosaic for some kind of chromosomal abnormality [30] . Li and co-workers[31] found that
40% of the embryos diagnosed as aneuploid on day 3 turned out to have a euploid inner cell mass at day 6. Staessen
and collaborators found that 17.5% of the embryos diagnosed as abnormal during PGS, and subjected to post-PGD
reanalysis, were found to also contain normal cells, and 8.4% were found grossly normal [32] . As a consequence, it
has been questioned whether the one or two cells studied from an embryo are actually representative of the complete
embryo, and whether viable embryos are not being discarded due to the limitations of the technique.
PCR
Kary Mullis conceived PCR in 1985 as an in vitro simplified reproduction of the in vivo process of DNA replication.
Taking advantage of the chemical properties of DNA and the availability of thermostable DNA polymerases, PCR
allows for the enrichment of a DNA sample for a certain sequence. PCR provides the possibility to obtain a large
quantity of copies of a particular stretch of the genome, making further analysis possible. It is a highly sensitive and
specific technology, which makes it suitable for all kinds of genetic diagnosis, including PGD. Currently, many
different variations exist on the PCR itself, as well as on the different methods for the posterior analysis of the PCR
products.
When using PCR in PGD, one is faced with a problem that is inexistent in routine genetic analysis: the minute
amounts of available genomic DNA. As PGD is performed on single cells, PCR has to be adapted and pushed to its
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physical limits, and use the minimum amount of template possible: one strand. This implies a long process of
fine-tuning of the PCR conditions and a susceptibility to all the problems of conventional PCR, but several degrees
intensified. The high number of needed PCR cycles and the limited amount of template makes single-cell PCR very
sensitive to contamination. Another problem specific to single-cell PCR is the allele drop out (ADO) phenomenon. It
consists of the random non-amplification of one of the alleles present in a heterozygous sample. ADO seriously
compromises the reliability of PGD as a heterozygous embryo could be diagnosed as affected or unaffected
depending on which allele would fail to amplify. This is particularly concerning in PGD for autosomal dominant
disorders, where ADO of the affected allele could lead to the transfer of an affected embryo.
Establishing a diagnosis
The establishment of a diagnosis in PGD is not always straightforward. The criteria used for choosing the embryos to
be replaced after FISH or PCR results are not equal in all centres. In the case of FISH, in some centres only embryos
are replaced that are found to be chromosomally normal (that is, showing two signals for the gonosomes and the
analysed autosomes) after the analysis of one or two blastomeres, and when two blastomeres are analysed, the results
should be concordant. Other centres argue that embryos diagnosed as monosomic could be transferred, because the
false monosomy (i.e. loss of one FISH signal in a normal dipoloid cell) is the most frequently occurring
misdiagnosis. In these cases, there is no risk for an aneuploid pregnancy, and normal diploid embryos are not lost for
transfer because of a FISH error. Moreover, it has been shown that embryos diagnosed as monosomic on day 3
(except for chromosomes X and 21), never develop to blastocyst, which correlates with the fact that these
monosomies are never observed in ongoing pregnancies.
Diagnosis and misdiagnosis in PGD using PCR have been mathematically modelled in the work of Navidi and
Arnheim and of Lewis and collaborators[33] [34] . The most important conclusion of these publications is that for the
efficient and accurate diagnosis of an embryo, two genotypes are required. This can be based on a linked marker and
disease genotypes from a single cell or on marker/disease genotypes of two cells. An interesting aspect explored in
these papers is the detailed study of all possible combinations of alleles that may appear in the PCR results for a
particular embryo. The authors indicate that some of the genotypes that can be obtained during diagnosis may not be
concordant with the expected pattern of linked marker genotypes, but are still providing sufficient confidence about
the unaffected genotype of the embryo. Although these models are reassuring, they are based on a theoretical model,
and generally the diagnosis is established on a more conservative basis, aiming to avoid the possibility of
misdiagnosis. When unexpected alleles appear during the analysis of a cell, depending on the genotype observed, it
is considered that either an abnormal cell has been analysed or that contamination has occurred, and that no
diagnosis can be established. A case in which the abnormality of the analysed cell can be clearly identified is when,
using a multiplex PCR for linked markers, only the alleles of one of the parents are found in the sample. In this case,
the cell can be considered as carrying a monosomy for the chromosome on which the markers are located, or,
possibly, as haploid. The appearance of a single allele that indicates an affected genotype is considered sufficient to
diagnose the embryo as affected, and embryos that have been diagnosed with a complete unaffected genotype are
preferred for replacement. Although this policy may lead to a lower number of unaffected embryos suitable for
transfer, it is considered preferable to the possibility of a misdiagnosis.
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Preimplantation genetic haplotyping
Preimplantation genetic haplotyping (PGH) is a new clinical method of Preimplantation genetic diagnosis (PGD).
PGH was first developed in 2006 at London's Guy's Hospital and greatly advances PGD by using DNA
fingerprinting rather than identifying the actual genetic signature (such as point mutations).
Embryo transfer and cryopreservation of surplus embryos
Embryo transfer is usually performed on day three or day five post-fertilization, the timing depending on the
techniques used for PGD and the standard procedures of the IVF centre where it is performed.
With the introduction in Europe of the single-embryo transfer policy, which aims at the reduction of the incidence of
multiple pregnancies after ART, usually one embryo or early blastocyst is replaced in the uterus. Serum hCG is
determined at day 12. If a pregnancy is established, an ultrasound examination at 7 weeks is performed to confirm
the presence of a fetal heartbeat. Couples are generally advised to undergo PND because of the, albeit low, risk of
misdiagnosis.
It is not unusual that after the PGD, there are more embryos suitable for transferring back to the woman than
necessary. For the couples undergoing PGD, those embryos are very valuable, as their current cycle may not lead to
an ongoing pregnancy. The cryopreservation and later thawing and replacement of these embryos would give them a
second chance to pregnancy without undergoing another time the cumbersome and expensive ART and PGD
procedures.
Ethical issues
PGD has raised ethical issues. The technique can be used to determine the gender of the embryo, and thus can be
used to select embryos of one gender in preference of the other in the context of “family balancing”. It may be
possible to make other "social selection" choices in the future. While controversial, this approach is less destructive
than fetal deselection during the pregnancy. At least one bioethicist, Jacob Appel, has argued that PGD should be
mandatory under certain circumstances.[35]
Costs are substantial and insurance coverage may not be available. Thus PGD widens the gap between people who
can afford the procedure versus a majority of patients who may benefit but cannot afford the service.
PGD has the potential to screen for genetic issues unrelated to medical necessity. The prospect of a “designer baby”
is closely related to the PGD technique.
By relying on the result of one cell from the multi-cell embryo, PGD operates under the assumption that this cell is
representative of the remainder of the embryo. This may not be the case as the incidence of mosaicism is often
relatively high.[36] On occasion, PGD may result in a false negative result leading to the acceptance of an abnormal
embryo, or in a false positive result leading to the deselection of a normal embryo.
Religious objections
Some religious organizations disapprove of this procedure. The Roman Catholic Church, for example, takes the
position that it involves the destruction of human life. [37] and besides that, opposes the necessary in vitro
fertilization of eggs as contrary to Aristotelian principles of nature.
References in popular culture
• PGD features prominently in the 1997 film Gattaca. The movie is set in a near-future world where PGD/IVF is
the most common form of reproduction. In the movie parents routinely use PGD to select desirable traits for their
children such as height, eye color and freedom from even the smallest of genetic predispositions to disease. The
ethical consequences of PGD are explored through the story of the main character who faces discrimination
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because he was conceived without such methods.
• PGD is mentioned in the 2004 novel My Sister's Keeper by the characters as the main character, Anna Fitzgerald,
was created through PGD to be a genetic match for her APL positive sister Kate so that she could donate blood
marrow at her birth to help Kate fight the APL. It is also mentioned in the book that her parents received criticism
for the act.
• PGD was also referenced in the video game CSI: Hard Evidence. In Case 2 : Double Down, PGD is used in an
attempt to ensure a male child is the end result of in vitro. Unfortunately, the procedure proves unsuccessful, and
a female fetus is conceived, much to the dismay of the payer of the expensive procedure.
Information on clinic websites
In an study of 135 IVF clinics, 88% had websites, 70% mentioned PGD and 27% of the latter were university- or
hospital-based and 63% were private clinics. Sites mentioning PGD also mentioned uses and benefits of PGD far
more than the associated risks. Of the sites mentioning PGD, 76% described testing for single-gene diseases, but
only 35% mentioned risks of missing target diagnoses, and only 18% mentioned risks for loss of the embryo. 14%
described PGD as new or controversial. Private clinics were more likely than other programs to list certain PGD
risks like for example diagnostic error, or note that PGD was new or controversial, reference sources of PGD
information, provide accuracy rates of genetic testing of embryos, and offer gender selection for social reasons.[38]
See also
• Bioethics
External links
• Preimplantation genetic diagnosis and sex selection- How does it work in the UK? [39]
• In Focus "Preimplantation Genetic Diagnosis: scientific, legal and moral aspects" (German Reference Centre for
Ethics in the Life Sciences ) [40]
• Fertility Trends Make Headline News [41] from Coastal Fertility Medical Center
• Huntington's Disease and PGD [42]
• List of diseases screened in the UK licensed by the HFEA [43]
• Screening Embryos for Disease by Joe Palca @ NPR.org [44]
• Preimplantation genetic diagnosis and sex selection [45]
• Religious views on PGD [46]
• List of some diseases that can be screened for - Australia [47]
• Preimplantation Genetic Diagnosis images. [48] Polar body and blastomere biopsy images. Normal and abnormal
FISH images.
• Saving Henry by Laurie Strongin, a non-fiction account of Strongin's pioneering, yet failed attempts at using PGD
to save the life of her son Henry [49]
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[32] Staessen C, Platteau P, Van Assche E, et al. (Dec 2004). "Comparison of blastocyst transfer with or without preimplantation genetic
diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial". Hum. Reprod. 19 (12):
2849–58. doi:10.1093/humrep/deh536. PMID 15471934.
[33] Navidi W, Arnheim N (Jul 1991). "Using PCR in preimplantation genetic disease diagnosis" (http:/ / humrep. oxfordjournals. org/ cgi/
pmidlookup?view=long& pmid=1757524). Hum. Reprod. 6 (6): 836–49. PMID 1757524. .
[34] Lewis CM, Pinêl T, Whittaker JC, Handyside AH (Jan 2001). "Controlling misdiagnosis errors in preimplantation genetic diagnosis: a
comprehensive model encompassing extrinsic and intrinsic sources of error" (http:/ / humrep. oxfordjournals. org/ cgi/
pmidlookup?view=long& pmid=11139534). Hum. Reprod. 16 (1): 43–50. doi:10.1093/humrep/16.1.43. PMID 11139534. .
[35] Appel, Jacob M. "Mandatory Genetic Testing isn't Eugenics, it's Smart Science" (http:/ / www. opposingviews. com/ articles/
opinion-mandatory-genetic-testing-isn-t-eugenics-it-s-smart-science)
[36] Sivitz, Laura (2000-10-28). "Its a boy! Its a girl! Its a mosaic embryo" (http:/ / sciencenews. org/ view/ generic/ id/ 993/ title/
Its_a_boy!_Its_a_girl!_Its_a_mosaic_embryo). Science News 158 (18): 276. . Retrieved 2009-09-01.
[37] ZENIT article (http:/ / www. zenit. org/ article-24541?l=english)
[38] Klitzman R, Zolovska B, Folberth W, Sauer MV, Chung W, Appelbaum P (October 2009). "Preimplantation genetic diagnosis on in vitro
fertilization clinic websites: presentations of risks, benefits and other information". Fertil. Steril. 92 (4): 1276–83.
doi:10.1016/j.fertnstert.2008.07.1772. PMID 18829009.
[39] http:/ / www. hfea. gov. uk/ PGD. html
[40] http:/ / www. drze. de/ themen/ blickpunkt/ pgd-en?la=en[41] http:/ / www. coastalfertility. com/ dr_werlin. htm
[42] http:/ / www. hdfreewithpgd. com/
[43] http:/ / www. hfea. gov. uk/ pgd-screening. html
[44] http:/ / www. npr. org/ templates/ story/ story. php?storyId=6653837
[45] http:/ / www. doctorslounge. com/ fertility/ articles/ pgd/ pgd_technique/ index. htm
[46] http:/ / www. religioustolerance. org/ abo_pgd. htm
[47] http:/ / www. sydneyivf. com/ PGDIVFforgeneticdisorders/ PGDforinheriteddisease/ tabid/ 368/ Default. aspx
[48] http:/ / www. ivf1. com/ PGD---Preimplantation-Genetic-Diagnosis/ 2/
[49] http:/ / www. savinghenry. com/
252
Multielectrode array
Multielectrode array
Multielectrode arrays (MEAs) or microelectrode arrays are devices that contain multiple plates or shanks through
which neural signals are obtained or delivered, essentially serving as neural interfaces that connect neurons to
electronic circuitry. There are two general classes of MEAs: implantable MEAs, used in vivo, and non-implantable
MEAs, used in vitro.
Theory
Neurons and muscle cells create ion currents through their membranes when excited, causing a change in voltage
both inside and outside the cell. When recording, the electrodes on an MEA transduce the change in voltage from the
environment carried by ions into currents carried by electrons (electronic currents). When stimulating, electrodes
transduce electronic currents into ionic currents through the media. This triggers the voltage-gated ion channels on
the membranes of the excitable cells, causing the cell to depolarize and trigger an action potential if it is a neuron or
a twitch if it is a muscle cell.
The size and shape of a recorded signal depend upon several factors: the nature of the medium in which the cell or
cells are located (e.g. the medium's electrical conductivity, capacitance, and homogeneity); the nature of contact
between the cells and the MEA electrode (e.g. area of contact and tightness); the nature of the MEA electrode itself
(e.g. its geometry, impedance, and noise); the analog signal processing (e.g. the system’s gain, bandwidth, and
behavior outside of cutoff frequencies); and the data sampling properties (e.g. sampling rate and digital signal
processing).[1] For the recording of a single cell that partially covers a planar electrode, the voltage at the contact pad
is approximately equal to the voltage of the overlapping region of the cell and electrode multiplied by the ratio the
surface area of the overlapping region to the area of the entire electrode, or:
assuming the area around an electrode is well-insulated and has a very small capacitance associated with it.[1] The
equation above, however, relies on modeling the electrode, cells, and their surroundings as an equivalent circuit
diagram. An alternative means of predicting cell-electrode behavior is by modeling the system using a
geometry-based finite element analysis in an attempt to circumvent the limitations of oversimplifying the system in a
lumped circuit element diagram.[2]
An MEA can be used to perform electrophysiological experiments on tissue slices or dissociated cell cultures. With
acute tissue slices, the connections between the cells within the tissue slices prior to extraction and plating are more
or less preserved, while the intercellular connections in dissociated cultures are destroyed prior to plating. With
dissociated neuronal cultures, the neurons spontaneously form networks.[3]
It can be seen that the voltage amplitude an electrode experiences is inversely related to the distance from which a
cell depolarizes.[4] Thus, it may be necessary for the cells to be cultured or otherwise placed as close to the electrodes
as possible. With tissue slices, a layer of electrically passive dead cells form around the site of incision due to
edema.[5] A way to deal with this is by fabricating an MEA with three-dimensional electrodes fabricated by masking
and chemical etching. These 3-D electrodes penetrate the dead cell layer of the slice tissue, decreasing the distance
between live cells and the electrodes.[6] In dissociated cultures, proper adherence of the cells to the MEA substrate is
important for getting robust signals.
253
Multielectrode array
254
History
The first implantable arrays were microwire arrays developed in the 1950s.[7] The first experiment involving the use
of an array of planar electrodes to record from cultured cells was conducted in 1972 by C.A. Thomas, Jr. and his
colleagues.[4] The experimental setup used a 2 x 15 array of gold electrodes plated with platinum black, each spaced
100 µm apart from each other. Myocytes harvested from embryonic chicks were dissociated and cultured onto the
MEAs, and signals up to 1 mV high in amplitude were recorded.[8] MEAs were constructed and used to explore the
electrophysiology of snail ganglia independently by G. Gross and his colleagues in 1977 without prior knowledge of
Thomas and his colleagues’ work.[4] In 1982, Gross observed spontaneous electrophysiological activity from
dissociated spinal cord neurons, and found that activity was very dependent on temperature. Below about 30˚C
signal amplitudes decrease rapidly to relatively small value at room temperature.[4]
Before the 1990’s, significant entry barriers existed for new laboratories that sought to conduct MEA research due to
the custom MEA fabrication and software they had to develop.[3] However, with the advent of affordable computing
power[1] and commercial MEA hardware and software,[3] many other laboratories were able to undertake research
using MEAs.
Types
Microelectrode arrays can be divided up into subcategories based on their potential use: in vitro and in vivo arrays.
In vitro arrays
The standard type of in vitro MEA comes in
a pattern of 8 x 8 or 6 x 10 electrodes.
Electrodes are typically composed of indium
tin oxide or titanium and have diameters
between 10 and 30 μm. These arrays are
normally used for single-cell cultures or
acute brain slices.[1]
One challenge among in vitro MEAs has
been imaging them with microscopes that
use high power lenses, requiring low
working distances on the order of
micrometers. In order to avoid this problem,
“thin”-MEAs have been created using cover
slip glass. These arrays are approximately
180 μm allowing them to be used with
high-power lenses.[1] [9] .
An in vitro MEA
In another special design, 60 electrodes are
split into 6 x 5 arrays separated by 500 μm. Electrodes within a group are separated by 30 um with diameters of 10
μm. Arrays such as this are used to examine local responses of neurons while also studying functional connectivity
of organotypic slices.[1] [10]
Spatial resolution is one of the key advantages of MEAs and allows signals sent over a long distance to be taken with
higher precision when a high-density MEA is used. These arrays usually have a square grid pattern of 256 electrodes
that cover an area of 2.8 by 2.8 mm.[1]
In order to obtain quality signals electrodes and tissue must be in close contact with one another. The perforated
MEA design applies negative pressure to openings in the substrate so that tissue slices can be positioned on the
Multielectrode array
electrodes to enhance contact and recorded signals.[1]
In vivo arrays
The three major categories of implantable
MEAs are microwire, silicon- based, and
flexible microelectrode arrays. Microwire
MEAs are largely made of stainless steel or
tungsten and they can be used to estimate
the position of individual recorded neurons
by
triangulation.
Silicon-based
microelectrode arrays include two specific
models: the Michigan and Utah arrays.
Michigan arrays allow a higher density of
sensors for implantation as well as a higher
spatial resolution than microwire MEAs.
They also allow signals to be obtained along
Schematic of the "Utah" "in vitro" electrode array
the length of the shank, rather than just at
the ends of the shanks. In contrast to
Michigan arrays, Utah arrays are 3-D, consisting of 100 conductive silicon needles. However, in a Utah array signals
are only received from the tips of each electrode, which limits the amount of information that can be obtained at one
time. Furthermore, Utah arrays are manufactured with set dimensions and parameters while the Michigan array
allows for more design freedom. Flexible arrays, made with polyimide, parylene, or benzocyclobutene, provide an
advantage over rigid microelectrode arrays because they provide a closer mechanical match, as the Young’s modulus
of silicon is much larger than that of brain tissue, contributing to shear-induced inflammation.[7]
Data Processing Methods
The fundamental unit of communication of neurons is, electrically, at least, the action potential. This all-or-nothing
phenomenon is believed to originate at the axon hillock,[11] resulting in a depolarization of the intracellular
environment which propagates down the axon. This ion flux through the cellular membrane generates a sharp change
in voltage in the extracellular environment, which is what the MEA electrodes ultimately detect. Thus, voltage spike
counting and sorting is often used in research to characterize network activity.
Advantages
In general, the major strengths of in vitro arrays when compared to more traditional methods such as patch clamping
include:[12]
• Allowing the placement of multiple electrodes at once rather than individually
• The ability to set up controls within the same experimental setup (by using one electrode as a control and others
as experimental)
• The ability to select different recordings sites within the array
• The ability to simultaneously receive data from multiple sites
Furthermore, in vitro arrays are non-invasive when compared to patch clamping because they do not require
breaching of the cell membrane.
With respect to in vivo arrays however, the major advantage over patch clamping is the high spatial resolution.
Implantable arrays allow signals to be obtained from individual neurons enabling information such as position or
velocity of motor movement that can be used to control a prosthetic device.
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Multielectrode array
Disadvantages
In vitro MEAs are less suited for recording and stimulating single cells due to their low spatial resolution compared
to patch clamp and dynamic clamp systems. The complexity of signals an MEA electrode could effectively transmit
to other cells is limited compared to the capabilities of dynamic clamps.
There are also several biological responses to implantation of a microelectrode array, particularly in regards to
chronic implantation. Most notable among these effects are neuronal cell loss, glial scarring, and a drop in the
number of functioning electrodes.[13] The tissue response to implantation is dependent among many factors including
size of the MEA shanks, distance between the shanks, MEA material composition, and time period of insertion. The
tissue response is typically divided into short term and long term response. The short term response occurs within
hours of implantation and begins with an increased population of astrocytes and glial cells surrounding the device.
The recruited microglia then initiate inflammation and a process of phagocytosis of the foreign material begins. Over
time, the astrocytes and microglia recruited to the device begin to accumulate, forming a sheath surrounding the
array that extends tens of micrometres around the device. This not only increases the space between electrode
probes, but also insulates the electrodes and increases impedance measurements. Problems with chronic implantation
of arrays have been a driving force in the research of these devices. One novel study examined the neurodegenerative
effects of inflammation caused by chronic implantation.[14] Immunohistochemical markers showed a surprising
presence of hyperphosphorylated tau, an indicator of Alzheimer’s disease, near the electrode recording site. The
phagocytosis of electrode material also brings to question the issue of a biocompatibility response, which research
suggests has been minor and becomes almost nonexistent after 12 weeks in vivo. Research to minimize the negative
effects of device insertion includes surface coating of the devices with proteins that encourage neuron attachment,
such as laminin, or drug eluting substances.[15]
Applications
In vitro Applications
The nature of dissociated neuronal
networks does not seem to change or
diminish the character of its
pharmacological
response
when
compared to in vivo models,
suggesting that MEAs can be used to
study pharmacological effects on
dissociated neuronal cultures in a more
simple, controlled environment.[16] A
number of pharmacological studies
using MEAs on dissociated neuronal
networks, e.g. studies with ethanol.[17]
In addition, a substantial body of work
on various biophysical aspects of
Schematic for a neurally controlled animat
network function was carried out by
reducing phenomena usually studied at
the behavioral level to the dissociated cortical network level. For example, the capacity of such networks to extract
spatial [18] and temporal [19] features of various input signals, dynamics of synchronization [20] , sensitivity to
neuromodulation [21] [22] [23] and kinetics of learning using closed loop regimes [24] [25] . Finally, combining MEA
256
Multielectrode array
technology with confocal microscopy allows for studying relationships between network activity and synaptic
remodeling [9] .
MEAs have been used to interface neuronal networks with non-biological systems as a controller. For example, a
neural-computer interface can be created using MEAs. Dissociated rat cortical neurons were integrated into a closed
stimulus-response feedback loop to control an animat in a virtual environment.[26] . A closed-loop stimulus-response
system has also been constructed using an MEA by Dr. Potter, Dr. Mandhavan, and Dr. DeMarse,[27] and by Mark
Hammond, Kevin Warwick, and Ben Whalley in the University of Reading. About 300,000 dissociated rat neurons
were plated on an MEA, which was connected to motors and ultrasound sensors on a robot, and was conditioned to
avoid obstacles when sensed.[28] Along these lines, Shimon Marom and colleagues in the Technion hooked
dissociated neuronal networks growing on MEAs to a Lego MindStorms robot; the visual field of the robot was
classified by the network, and commands were delivered to the robot wheels such that it completely avoids bumping
into obstacles .[18] link to movie [29]. Interestingly, this "Braitenberg Vehicle" was used to demonstrate the
indeterminacy of reverse neuro-engineering [30] showing that even in a simple setup with practically unlimited access
to every piece of relevant information, it was impossible to deduce with certainty the specific neural coding scheme
that was used to drive the robots behavior.
MEAs have been used to observe network firing in hippocampal slices.[31]
In vivo Applications
There are several implantable interfaces that are currently available for consumer use including deep brain
stimulators, cochlear implants, and cardiac pacemakers. Deep brain stimulation (DBS) has been effective at treating
movement disorders such as Parkinson’s disease,[32] and cochlear implants have helped many to improve their
hearing by assisting stimulation of the auditory nerve. Because of their remarkable potential, MEAs are a prominent
area of neuroscience research. Research suggests that MEAs may provide insight into processes such as memory
formation and perception and may also hold therapeutic value for conditions such as epilepsy, depression, and
obsessive-compulsive disorder. Clinical trials using interface devices for restoring motor control after spinal cord
injury or as treatment for ALS have been initiated in a project entitled BrainGate (see video demo: BrainGate [33]).
MEAs provide the high resolution necessary to record time varying signals, giving them the ability to be used to both
control and obtain feedback from prosthetic devices, as was shown by Kevin Warwick, Mark Gasson and Peter
Kyberd.[34] [35] Research suggests that MEA use may be able to assist in the restoration of vision by stimulating the
optic pathway.[7]
See also
•
•
•
•
Animat
Artificial pacemaker
Deep brain stimulation
Patch clamp
References
[1] Boven K-H, Fejtl M, Möller A, Nisch W, Stett A. On Micro-Electrode Array Revival. In: Baudry M, Taketani M, eds. Advances in Network
Electrophysiology Using Multi-Electrode Arrays. New York: Springer Press; 2006: 24-37.
[2] Buitenweg JR, Rutten WL, and Marani E. 2003. Geometry-based finite element modeling of the electrical contact between a cultured neuron
and a microelectrode. IEEE Trans Biomed Eng. 50: 501-509.
[3] Potter SM. 2001. Distributed processing in cultured neuronal networks. Prog Brain Res 130: 49-62.
[4] Pine J. A History of MEA Development. In: Baudry M, Taketani M, eds. Advances in Network Electrophysiology Using Multi-Electrode
Arrays. New York: Springer Press; 2006:3-23.
[5] Buisson B, Heuschkel MO,Steidl EM, Wirth C. Development of 3-D Multi-Electrode Arrays for Use with Acute Tissue Slices. In: Baudry M,
Taketani M, eds. Advances in Network Electrophysiology Using Multi-Electrode Arrays. New York: Springer Press; 2006:69-111.
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[6] Thiebaud P, deRooij NF, Koudelka-Hep M, Stoppini L. 1997. Microelectrode arrays for electrophysiological monitoring of hippocampal
organotypic slice cultures. IEEE Trans Biomed Eng. 44: 1159-63.
[7] Cheung KC. 2007. Implantable microscale neural interfaces. Biomedical Microdevices 9: 923-38
[8] Thomas CA, Springer PA, Loeb GE, Berwald-Netter Y, Okun LM. 1972. A miniature microelectrode array to monitor the bioelectric activity
of cultured cells. Exp Cell Res. 74: 61-66.
[9] Minerbi A, Kahana R, Goldfeld L, Kaufman M, Marom S, Ziv NE. 2009. Long-term relationships between synaptic tenacity, synaptic
remodeling, and network activity. PLoS Biol. 7(6):e1000136.
[10] Segev R, Berry II, MJ. 2003. Recording from all of the ganglion cells in the retina. Soc Neurosci Abstr. 264: 11.
[11] Angelides KJ, Elmer LW, Loftus D, Elson E. 1988. Distribution and lateral mobility of voltage-dependent sodium channels in neurons. J
Cell Biol. 106: 1911-25.
[12] Whitson J, Kubota D, Shimono K, Jia Y, Taketani M. Multi-Electrode Arrays: Enhancing Traditional Methods and Enabling Network
Physiology. In: Baudry M, Taketani M, eds. Advances in Network Electrophysiology Using Multi-Electrode Arrays. New York: Spring Press;
2006: 38-68
[13] Biran R, Martin DC, Tresco PA. 2005. Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon
microelectrode arrays. Experimental Neurology 195: 115-26
[14] McConnell GC, Rees HD, Levey AI, Gross RG, Bellamkonda RV. 2008. Chronic electrodes induce a local, neurodegenerative state:
Implications for chronic recording reliability. Society for Neuroscience, Washington, D.C
[15] He W, McConnell GC, Bellamkonda RV. 2006. Nanoscale laminin coating modulates cortical scarring response around implanted silicon
microelectrode arrays. Journal of Neural Engineering 3: 316-26
[16] Gopal KV, Gross GW. Emerging Histotypic Properties of Cultured Neuronal Networks. In: Baudry M, Taketani M, eds. Advances in
Network Electrophysiology Using Multi-Electrode Arrays. New York: Springer Press; 2006:193-214.
[17] Xia Y and Gross GW. 2003. Histotypic electrophysiological responses of cultured neuronal networks to ethanol. Alcohol 30: 167-74.
[18] Shahaf G, Eytan D, Gal A, Kermany E, Lyakhov V, Zrenner C, Marom S. 2008. Order-based representation in random networks of cortical
neurons. PLoS Comput Biol. 4(11):e1000228.
[19] Eytan D, Brenner N, Marom S. 2003. Selective adaptation in networks of cortical neurons.J Neurosci. 23, 9349-9356.
[20] Eytan D, Marom S. 2006. Dynamics and effective topology underlying synchronization in networks of cortical neurons. J Neurosci. 26,
8465-8476.
[21] Eytan D, Minerbi A, Ziv NE, Marom S. 2004. Dopamine-induced dispersion of correlations between action potentials in networks of
cortical neurons. J Neurophysiol. 92,1817-1824.
[22] Tateno T, Jimbo Y, Robinson HP. 2005. Spatio-temporal cholinergic modulation in cultured networks of rat cortical neurons: spontaneous
activity. Neuroscience. 134, 425-437
[23] Tateno T, Jimbo Y, Robinson HP. 2005. Spatio-temporal cholinergic modulation in cultured networks of rat cortical neurons: evoked
activity. Neuroscience. 134, 439-448
[24] Shahaf G, Marom S. 2001. Learning in networks of cortical neurons. J Neurosci. 21,8782-8788.
[25] Stegenga J, Le Feber J, Marani E, Rutten WL. 2009. The effect of learning on bursting. IEEE Trans Biomed Eng. 56,1220-1227.
[26] DeMarse TB, Wagenaar DA, Blau AW, Potter SM. 2001. The Neurally Controlled Animat: Biological Brains Acting with Simulated
Bodies. Autonomous Robots 11: 305-10.
[27] Potter, SM, Madhavan, R and DeMarse, TB. 2003. Long-term bidirectional neuron interfaces for robotic control, and in vitro learning
studies. Proc. 25th IEEE EMBS Annual Meeting.
[28] Marks P. 2008. Rise of the rat-brained robots. New Scientist 2669.
[29] http:/ / www. ncbi. nlm. nih. gov/ pmc/ articles/ PMC2580731/ bin/ pcbi. 1000228. s004. mov
[30] Marom S, Meir R, Braun E, Gal A, Kermany E, Eytan D. 2009. On the precarious path of reverse neuro-engineering. Front Comput
Neurosci. ;3:5.
[31] Colgin, L.L., Kramar, E.A., Gall, C.M., and Lynch, G. (2003). Septal modulation of excitatory transmission in hippocampus. J
Neurophysiol. 90: 2358-2366.
[32] Breit S, Schulz JB, Benabid AL. 2004. Deep Brain Stimulation. Cell Tissue Research 318: 275-288.
[33] http:/ / www. cyberkineticsinc. com/ video. htm
[34] Warwick, K, Gasson, M, Hutt, B, Goodhew, I, Kyberd, P, Andrews, B, Teddy, P and Shad, A:“The Application of Implant Technology for
Cybernetic Systems”, Archives of Neurology, 60(10), pp1369-1373, 2003
[35] Schwartz AB. 2004. Cortical Neural Prosthetics. Annual Review of Neuroscience 27: 487-507.
258
259
Surrounding Areas
Bioethics
Bioethics is the philosophical study of the ethical controversies brought about by advances in biology and medicine.
Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences,
biotechnology, medicine, politics, law, philosophy, and theology.
History
Terminology
The term Bioethics (Greek bios, life; ethos, behavior) was coined in 1927 by Fritz Jahr, who "anticipated many of the
arguments and discussions now current in biological research involving animals" in an article about the "bioethical
imperative," as he called it, regarding the scientific use of animals and plants.[1] [2] In 1970, the American biochemist
Van Rensselaer Potter also used the term with a broader meaning including solidarity towards the biosphere, thus
generating a "global ethics," a discipline representing a link between biology, ecology, medicine and human values
in order to attain the survival of both human beings and other animal species.[3] [4]
Development of a discipline
Although bioethical issues have been debated since ancient times, and public attention briefly focused on the role of
human subjects in biomedical experiments following the revelation of Nazi experiments conducted during World
War II, the modern field of bioethics first emerged as an academic discipline in Anglophone societies in the 1960s.
Technological advances in such diverse areas as organ transplantation and end-of-life care, including the
development of kidney dialysis and respirators, posed novel questions regarding when and how care might be
withdrawn. Furthermore, as philosophy in Britain and elsewhere moved away from the influences of logical
positivism and emotivism, the development of theories of ethics and their application to practical problems gained in
interest. These questions were often discussed by philosophers and religious scholars; in England, there were notable
contributions from GEM Anscombe and RM Hare. By the 1970s, bioethical think tanks and academic bioethics
programs had emerged. Among the earliest such institutions were the Hastings Center (originally known as The
Institute of Society, Ethics and the Life Sciences), founded in 1969 by philosopher Daniel Callahan and psychiatrist
Willard Gaylin, and the Kennedy Institute of Ethics, established at Georgetown University in 1971. The publication
of Principles of Biomedical Ethics by James F. Childress and Tom Beauchamp—the first American textbook of
bioethics—marked a transformative moment in the discipline.
During the subsequent three decades, bioethical issues gained widespread attention through the court cases
surrounding the deaths of Karen Ann Quinlan, Nancy Cruzan and Terri Schiavo. The field developed its own cadre
of widely-known advocates, such as Al Jonsen at the University of Washington, John Fletcher at the University of
Virginia, Jacob M. Appel at Brown University, Ruth Faden at Johns Hopkins University, and Arthur Caplan at the
University of Pennsylvania. In 1995, President Bill Clinton established the President's Council on Bioethics, a sign
that the field had finally reached an unprecedented level of maturity and acceptance in the United States of America.
President George W. Bush also relied upon a Council on Bioethics in rendering decisions in areas such as the public
funding of embryonic stem-cell research.
Bioethics
Purpose and scope
The field of bioethics has addressed a broad swath of human inquiry, ranging from debates over the boundaries of
life (e.g. abortion, euthanasia) to the allocation of scarce health care resources (e.g. organ donation, health care
rationing) to the right to turn down medical care for religious or cultural reasons. Bioethicists often disagree among
themselves over the precise limits of their discipline, debating whether the field should concern itself with the ethical
evaluation of all questions involving biology and medicine, or only a subset of these questions. Some bioethicists
would narrow ethical evaluation only to the morality of medical treatments or technological innovations, and the
timing of medical treatment of humans. Others would broaden the scope of ethical evaluation to include the morality
of all actions that might help or harm organisms capable of feeling fear and pain, and include within bioethics all
such actions of a bear in relation to medicine and biology. However, most bioethicists share a commitment to
discussing these complex issues in an honest, civil and intelligent way, using tools from the many different
disciplines that "feed" the field to produce meaningful frameworks for analysis.
Principles
One of the first areas addressed by modern bioethicists was that of human experimentation. The National
Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was initially established
in 1974 to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research
involving human subjects. However, the fundamental principles announced in the Belmont Report (1979)--namely,
autonomy, beneficence and justice--have influenced the thinking of bioethicists across a wide range of issues. Others
have added non-maleficence, human dignity and the sanctity of life to this list of cardinal values.
Medical ethics
Medical ethics is the study of moral values and judgments as they apply to medicine. As a scholarly discipline,
medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy,
theology, and sociology.
Medical ethics tends to be understood narrowly as an applied professional ethics, whereas bioethics appears to have
worked more expansive concerns, touching upon the philosophy of science and issues of biotechnology. Still, the
two fields often overlap and the distinction is more a matter of style than professional consensus. Medical ethics
shares many principles with other branches of healthcare ethics, such as nursing ethics.
Perspectives and methodology
Bioethicists come from a wide variety of backgrounds and have training in a diverse array of disciplines. The field
contains individuals trained in philosophy such as Peter Singer of Princeton University and Daniel Brock of Harvard
University, medically-trained clinician ethicists such as Mark Siegler of the University of Chicago and Joseph Fins
of Cornell University, lawyers such as Jacob Appel and Wesley J. Smith, political economists like Francis
Fukuyama, and theologians including James Childress. The field, once dominated by formally trained philosophers,
has become increasingly interdisciplinary, with some critics even claiming that the methods of analytic philosophy
have had a negative effect on the field's development. Leading journals in the field include the Hastings Center
Report, the Journal of Medical Ethics and the Cambridge Quarterly of Healthcare Ethics.
Many religious communities have their own histories of inquiry into bioethical issues and have developed rules and
guidelines on how to deal with these issues from within the viewpoint of their respective faiths. The Jewish,
Christian and Muslim faiths have each developed a considerable body of literature on these matters. In the case of
many non-Western cultures, a strict separation of religion from philosophy does not exist. In many Asian cultures,
for example, there is a lively discussion on bioethical issues. Buddhist bioethics, in general, is characterised by a
naturalistic outlook that leads to a rationalistic, pragmatic approach. Buddhist bioethicists include Damien Keown. In
260
Bioethics
261
India, Vandana Shiva is the leading bioethicist speaking from the Hindu tradition. In Africa, and partly also in Latin
America, the debate on bioethics frequently focusses on its practical relevance in the context of underdevelopment
and geopolitical power relations.
See also
•
•
•
•
•
Bioethics (journal)
Johns Hopkins Berman Institute of Bioethics
Linacre Quarterly
Medical law
Resources for clinical ethics consultation
Issues
Areas of health sciences that are the subject of published, peer-reviewed bioethical analysis include:
•
Abortion
•
Gene theft
•
Parthenogenesis
•
Animal rights
•
Gene therapy
•
Patients' Bill of Rights
•
Artificial insemination
•
Genetically modified food
•
Placebo
•
Artificial life
•
Genetically modified organism
•
Population control
•
Artificial womb
•
Genomics
•
Prescription drugs (prices in the US)
•
Assisted suicide
•
Great Ape Project
•
Procreative beneficence
•
Biopiracy
•
Human cloning
•
Professional ethics
•
Biorisk
•
Human enhancement
•
Psychosurgery
•
Blood/blood plasma (trade)
•
Human genetic engineering
•
Quality of Life (Healthcare)
•
Body modification
•
Iatrogenesis
•
Recreational drug use
•
Brain-computer interface
•
Infertility treatments
•
Reproductive rights
•
Chimeras
•
Life extension
•
Reprogenetics
•
Circumcision
•
Life support
•
Sperm and eggs (donation)
•
Cloning
•
Lobotomy
•
Spiritual drug use
•
Confidentiality (medical records)
•
Medical malpractice
•
Stem cell research
•
Consent
•
Medical research
•
Suicide
•
Contraception (birth control)
•
Medical torture
•
Surrogacy
•
Cryonics
•
Moral obligation
•
Three-parent babies
•
Disability
•
Nanomedicine
•
Transexuality
•
Eugenics
•
Organ donation (fair allocation, class and race biases) •
Transhumanism
•
Euthanasia (human, non-human animal) •
Pain management
•
Transplant trade
•
Feeding tube
•
Xenotransplantation
Further reading
General bioethics
• Andre, Judith (2002), Bioethics as Practice, Chapel Hill and London: University of North Carolina Press,
ISBN 0-8078-2733-9
• Appel, Jacob (2009), A Supreme Court for Bioethics [5]
• Aulisio, Mark; Arnold, Robert; Younger, Stuart (2003), Ethics Consultation; from theory to practice, Baltimore,
London: Johns Hopkins University Press, ISBN 0-8018-7165-4
• Faden, Ruth (2004), Bioethics: A field in transition, Journal of Law, Medicine & Ethics
• Caplan, Arthur Smart Mice Not So Smart People Rowman Littlefield 2006
Bioethics
• Glad, John (2008). Future Human Evolution: Eugenics in the Twenty-First Century [6]. Hermitage Press.
ISBN 1-55779-154-6.
• Emanuel, Ezekiel; Crouch, Robert; Arras, John; Moreno, Jonathan; Grady, Christine (2003), Ethical and
Regulatory Aspects of Clinical Research, Baltimore, London: Johns Hopkins University Press,
ISBN 0-8018-7813-6
• Crowley, Mary (ed) (2008), From Birth to Death and Bench to Clinic: The Hastings Center Bioethics Briefing
Book [7], Garrison, New York: The Hastings Center
• Beauchamp, Tom; Childress, James (2001), Principles of Biomedical Ethics, Oxford, New York: Oxford
University Press, ISBN 0-19-514332-9
• Jonsen, Albert; Veatch, Robert; Walters, leRoy (1998), SourceBook in Bioethics, Washington: Georgetown
University Press, ISBN 0-87840-685-9
• Jonathan, Baron (2006). Against Bioethics. The MIT Press. ISBN 978-0-262-02596-6.
• McGee, Glenn (2003), Pragmatic Bioethics, Cambridge: Massachusetts Institute of Technology Press,
ISBN 0-2626-3272-1
• Khushf, Tom (ed) (2004), Handbook of Bioethics: taking stock of the field from a philosophical perspective,
Dordrecht, Boston, London: Kluwer Academic Publishers, ISBN 1-4020-1893-2
• Korthals, Michiel; Robert J. Bogers (eds.) (2004). Ethics for Life Scientists [8]. Springer.
ISBN 978-1-4020-3178-6.
• Kuczewski, Mark G.; Ronald Polansky (eds.) (2002). Bioethics: Ancient Themes in Contemporary Issues. The
MIT Press. ISBN 978-0-262-61177-0.
• Murphy, Timothy (2004). Case Studies in Biomedical Research Ethics. The MIT Press.
ISBN 978-0-262-13437-8.
• Singer, Peter A.; Viens, A.M. (2008), Cambridge Textbook of Bioethics [9], Cambridge: Cambridge University
Press, ISBN 978-0-521-69443-8
• Sugarman, Jeremy; Sulmasy, Daniel (1999), Confessions of a Medicine Man, Cambridge: MIT Press,
ISBN 0-262-70072-7
• Tauber, Alfred I (2005), Patient Autonomy and the Ethics of Responsibility, Cambridge: MIT Press,
ISBN 0-262-70112-x
Christian bioethics
• Colson, Charles W. (ed.) (2004). Human Dignity in the Biotech Century: A Christian Vision for Public Policy.
Downers Grove, Illinois: InterVarsity Press. ISBN 0830827838
• Demy, Timothy J. and Gary P. Stewart. (1998). Suicide: A Christian Response: Crucial Considerations for
Choosing Life. Grand Rapids: Kregel. ISBN 0825423554
• Pope John Paul II. (1995). Evangelium Vitae: The Gospel of Life. New York: Random House. ISBN 0812926714
• Kilner, John et al. (1995). Bioethics and the Future of Medicine: A Christian Appraisal. Grand Rapids, Michigan:
Wm. B. Eerdmans Publishing Company. ISBN 0802840817
• Kilner, John F., Arlene B. Miller, and Edmund D. Pellegrino (eds.). (1996). Dignity and Dying: A Christian
Appraisal. Grand Rapids, MI: Eerdmans Publishing Co.; and Carlisle, United Kingdom: Paternoster Press. ISBN
0802842321
• Meilaender, Gilbert (2004). Bioethics: A Primer For Christians. Grand Rapids, Michigan: Wm. B. Eerdmans
Publishing Company. ISBN 0802842348
• Loudovikos, Nikolaos, Protopresbyter (2002). The Individualization of Death and Euthanasia [10], Holy Synod of
the Church of Greece, Committee of Bioethics, Scientific Conference on Euthanasia (Athens, May 17–18, 2002),
retrieved on February 27, 2009. (Article in Greek).
• Pope Paul VI. (1968). Humanae Vitae: Human Life. Vatican City.
262
Bioethics
• Smith, Wesley J. (2004). Consumer's Guide to A Brave New World. San Francisco: Encounter Books. ISBN
1893554996
• Smith, Wesley J. (2000). Culture of Death: The Assault on Medical Ethics in America. San Francisco: Encounter
Books. ISBN 1893554066
• Smith, Wesley J. (1997). Forced Exit: The Slippery Slope from Assisted Suicide to Murder. New York: Times
Books. ISBN 0812927907
• Stewart, Gary P. et al. (1998). Basic Questions on Suicide and Euthanasia: Are They Ever Right? BioBasics
Series. Grand Rapids: Kregel. ISBN 0825430720
• Stewart, Gary P. et al. (1998). Basic Questions on End of Life Decisions: How Do We Know What's Right? Grand
Rapids: Kregel. ISBN 0825430704
• Westphal, Euler Renato. O Oitavo dia – na era da seleção artificial (See The Eighth Day (book) Review) . 1. ed.
São Bento do Sul: União Cristã, 2004. v. 01. 125 p. ISBN 85-87485-18-0
Jewish bioethics
• Bleich, J. David. (1981). Judaism and Healing. New York: Ktav. ISBN 087068891X
• Dorff, Elliot N. (1998). Matters of Life and Death: A Jewish Approach to Modern Medical Ethics. Philadelphia:
Jewish Publication Society. ISBN 0827606478
• Feldman DM. (1974). Marital relations, birth control, and abortion in Jewish law. New York: Schocken Books.
• Freedman B. (1999). Duty and healing: foundations of a Jewish bioethic. New York: Routledge. ISBN
0415921791
• Jakobovits I. (1959). Jewish Medical Ethics. New York: Bloch Publishing.
• Mackler, Aaron L. (ed.) (2000). Life & Death Responsibilities in Jewish Biomedical Ethics. New York: JTS.
ISBN 0873340817.
• Maibaum M. "A 'progressive' Jewish medical ethics: notes for an agenda" in Journal of Reform Judaism
1986;33(3):27-33.
• Rosner, Fred. (1986). Modern medicine and Jewish ethics. New York: Yeshiva University Press. ISBN
0881250910
• Conservative Judaism Vol. 54(3), Spring 2002 (contains a set of six articles on bioethics)
• Zohar, Noam J. (1997). Alternatives in Jewish Bioethics. Albany: State University of New York Press. ISBN
0791432734
Muslim bioethics
• Al Khayat MH. "Health and Islamic behaviour" in: El Gindy AR, editor, Health policy, ethics and human values:
Islamic perspective. Kuwait: Islamic Organization of Medical Sciences; 1995. p. 447-50.
• Ebrahim, Abul Fadl Mohsin. (1989). Abortion, Birth Control and Surrogate Parenting. An Islamic Perspective.
Indianapolis. ISBN 0892590815
• Esposito, John. (ed.) (1995). "Surrogate Motherhood" in The Oxford Encyclopedia of the Modern Islamic World
(vol. 4). New York: Oxford University Press. ISBN 0195096150
• Karic, Enes. "The Ethics of Cloning [11]" in Islamica Magazine Fall/Winter 2004. Issue #11
263
Bioethics
Buddhist bioethics
• Florida, R. E. (1994) Buddhism and the Four Principles in Principles of Health Care Ethics, ed. R. Gillon and A.
Lloyd, Chichester: John Wiley & Sons, 105-16.
• Keown, Damien. (1995) Buddhism & Bioethics. London and New York: Macmillan/St. Martins Press.
Hindu bioethics
• Coward, H. G., J. J. Lipner, and K. K. Young. (1989) Hindu Ethics: Purity, Abortion, and Euthanasia. Albany:
State University of New York Press.
• Crawford, S. C. (2003) Hindu bioethics for the Twenty-first Century. Albany, NY: State University of New York
Press.
• Crawford, S. C. (1995) Dilemmas of Life and Death, Hindu Ethics in A North American Context 1995. Albany,
NY: State University of New York Press.
• Firth, S. (2005) End-of-life: a Hindu view. The Lancet. 366(9486): 682-686.
• Lakhan, Shaheen. (2008) Hinduism: life and death [12]. Student BMJ. 16(18):310-311.
References
[1] Lolas, F. (2008). Bioethics and animal research: A personal perspective and a note on the contribution of Fritz Jahr. Biol. Res., Santiago,
41(1), 119-123. Available in <http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000100013&lng=es&nrm=iso>,
accessed on Jan 15, 2010. doi: 10.4067/S0716-97602008000100013.
[2] Sass, H. M. (2007). Fritz Jahr's 1927 concept of bioethics. Kennedy Inst Ethics J, 17(4), Dec, 279-295.
[3] Lolas, F., op. cit.
[4] Goldim, J. R. (2009). Revisiting the beginning of bioethics: The contribution of Fritz Jahr (1927). Perspect Biol Med, Sum, 377-380.
[5] http:/ / www. huffingtonpost. com/ jacob-m-appel/ a-supreme-court-for-bioet_b_228967. html
[6] http:/ / www. whatwemaybe. org/ txt/ txt0000/ Glad. John. 2008. FHE. Meisenberg-abridgement. en. pdf
[7] http:/ / www. thehastingscenter. org/ Publications/ BriefingBook/ Default. aspx
[8] http:/ / library. wur. nl/ frontis/ ethics/ toc. html
[9] http:/ / www. cambridge. org/ catalogue/ catalogue. asp?isbn=9780521694438
[10] http:/ / www. bioethics. org. gr/ 03_dLoudo. html
[11] http:/ / www. islamicamagazine. com/ content/ view/ 181/ 63/
[12] http:/ / archive. student. bmj. com/ issues/ 08/ 09/ life/ 310. php
264
Transhumanism
265
Transhumanism
Part of Ideology series on
Transhumanism
Ideologies
Abolitionism · Democratic transhumanism
Extropianism · Immortalism
Libertarian transhumanism
Postgenderism · Singularitarianism
Technogaianism
Related articles
Transhumanism in fiction
Transhumanist art
Organizations
Applied Foresight Network
Alcor Life Extension Foundation
American Cryonics Society
Cryonics Institute · Foresight Institute
Humanity+ · Immortality Institute
Singularity Institute for Artificial Intelligence
Transhumanism Portal
Transhumanism is an international intellectual and cultural movement supporting the use of science and technology
to improve human mental and physical characteristics and capacities. The movement regards aspects of the human
condition, such as disability, suffering, disease, aging, and involuntary death as unnecessary and undesirable.
Transhumanists look to biotechnologies and other emerging technologies for these purposes. Dangers, as well as
benefits, are also of concern to the transhumanist movement.[1]
The term "transhumanism" is symbolized by H+ or h+ and is often used as a synonym for "human enhancement".[2]
Although the first known use of the term dates from 1957, the contemporary meaning is a product of the 1980s when
futurists in the United States began to organize what has since grown into the transhumanist movement.
Transhumanist thinkers predict that human beings may eventually be able to transform themselves into beings with
such greatly expanded abilities as to merit the label "posthuman".[1] Transhumanism is therefore sometimes referred
to as "posthumanism" or a form of transformational activism influenced by posthumanist ideals.[3]
The transhumanist vision of a transformed future humanity has attracted many supporters and detractors from a wide
range of perspectives. Transhumanism has been described by one critic, Francis Fukuyama, as the world's most
dangerous idea,[4] while one proponent, Ronald Bailey, counters that it is the "movement that epitomizes the most
daring, courageous, imaginative, and idealistic aspirations of humanity".[5]
Transhumanism
266
History
According to philosophers who have studied and written about the
history of transhumanist thought,[1] transcendentalist impulses have
been expressed at least as far back as in the quest for immortality in the
Epic of Gilgamesh, as well as historical quests for the Fountain of
Youth, Elixir of Life, and other efforts to stave off aging and death.
Transhumanist philosophy, however, is rooted in Renaissance
humanism and the Enlightenment. For example, Giovanni Pico della
Mirandola called on people to "sculpt their own statue", and the
Marquis de Condorcet speculated about the use of medical science to
indefinitely extend the human life span, while Benjamin Franklin
dreamed of suspended animation, and after Charles Darwin "it became
increasingly plausible to view the current version of humanity not as
the endpoint of evolution but rather as a possibly quite early phase."[1]
However, Friedrich Nietzsche is considered by some to be less of an
influence, despite his exaltation of the "overman", due to his emphasis
on self-actualization rather than technological transformation.[1]
[6]
Cover of the first issue of H+ Magazine , a
web-based quarterly publication that focuses on
transhumanism, covering the scientific,
technological, and cultural developments that are
challenging and overcoming human limitations.
Nikolai Fyodorov, a 19th-century Russian philosopher, advocated
radical life extension, physical immortality and even resurrection of the
dead using scientific methods.[7] In the 20th century, a direct and influential precursor to transhumanist concepts was
geneticist J.B.S. Haldane's 1923 essay Daedalus: Science and the Future, which predicted that great benefits would
come from applications of advanced sciences to human biology—and that every such advance would first appear to
someone as blasphemy or perversion, "indecent and unnatural". J. D. Bernal speculated about space colonization,
bionic implants, and cognitive enhancement, which have been common transhumanist themes since then.[1] Biologist
Julian Huxley, brother of author Aldous Huxley (a childhood friend of Haldane's), appears to have been the first to
use the actual word "transhumanism". Writing in 1957, he defined transhumanism as "man remaining man, but
transcending himself, by realizing new possibilities of and for his human nature".[8] This definition differs, albeit not
substantially, from the one commonly in use since the 1980s.
Computer scientist Marvin Minsky wrote on relationships between human and artificial intelligence beginning in the
1960s.[9] Over the succeeding decades, this field continued to generate influential thinkers, such as Hans Moravec
and Raymond Kurzweil, who oscillated between the technical arena and futuristic speculations in the transhumanist
vein.[10] [11] The coalescence of an identifiable transhumanist movement began in the last decades of the 20th
century. In 1966, FM-2030 (formerly F.M. Esfandiary), a futurist who taught "new concepts of the Human" at the
The New School in New York City, began to identify people who adopt technologies, lifestyles and world views
transitional to "posthumanity" as "transhuman" (short for "transitory human").[12] In 1972, Robert Ettinger
contributed to the conceptualization of "transhumanity" in his book Man into Superman.[13] [14] FM-2030 published
the Upwingers Manifesto in 1973 to stimulate transhumanly conscious activism.[15]
The first self-described transhumanists met formally in the early 1980s at the University of California, Los Angeles,
which became the main center of transhumanist thought. Here, FM-2030 lectured on his "Third Way" futurist
ideology. At the EZTV Media venue frequented by transhumanists and other futurists, Natasha Vita-More presented
Breaking Away, her 1980 experimental film with the theme of humans breaking away from their biological
limitations and the Earth's gravity as they head into space.[16] [17] FM-2030 and Vita-More soon began holding
gatherings for transhumanists in Los Angeles, which included students from FM-2030's courses and audiences from
Vita-More's artistic productions. In 1982, Vita-More authored the Transhumanist Arts Statement,[18] and, six years
later, produced the cable TV show TransCentury Update on transhumanity, a program which reached over 100,000
Transhumanism
viewers.
In 1986, Eric Drexler published Engines of Creation: The Coming Era of Nanotechnology,[19] which discussed the
prospects for nanotechnology and molecular assemblers, and founded the Foresight Institute. As the first non-profit
organization to research, advocate for, and perform cryonics, the Southern California offices of the Alcor Life
Extension Foundation became a center for futurists. In 1988, the first issue of Extropy Magazine was published by
Max More and Tom Morrow. In 1990, More, a strategic philosopher, created his own particular transhumanist
doctrine, which took the form of the Principles of Extropy,[20] and laid the foundation of modern transhumanism by
giving it a new definition:[21]
Transhumanism is a class of philosophies that seek to guide us towards a posthuman condition.
Transhumanism shares many elements of humanism, including a respect for reason and science, a commitment
to progress, and a valuing of human (or transhuman) existence in this life. […] Transhumanism differs from
humanism in recognizing and anticipating the radical alterations in the nature and possibilities of our lives
resulting from various sciences and technologies […].
In 1992, More and Morrow founded the Extropy Institute, a catalyst for networking futurists and brainstorming new
memeplexes by organizing a series of conferences and, more importantly, providing a mailing list, which exposed
many to transhumanist views for the first time during the rise of cyberculture and the cyberdelic counterculture. In
1998, philosophers Nick Bostrom and David Pearce founded the World Transhumanist Association (WTA), an
international non-governmental organization working toward the recognition of transhumanism as a legitimate
subject of scientific inquiry and public policy.[22] In 1999, the WTA drafted and adopted The Transhumanist
Declaration.[23] The Transhumanist FAQ, prepared by the WTA, gave two formal definitions for transhumanism:[24]
1. The intellectual and cultural movement that affirms the possibility and desirability of fundamentally
improving the human condition through applied reason, especially by developing and making widely available
technologies to eliminate aging and to greatly enhance human intellectual, physical, and psychological
capacities.
2. The study of the ramifications, promises, and potential dangers of technologies that will enable us to overcome
fundamental human limitations, and the related study of the ethical matters involved in developing and using
such technologies.
A number of similar definitions have been collected by Anders Sandberg, an academic and prominent
transhumanist.[25]
In possible contrast with other transhumanist organizations, WTA officials considered that social forces could
undermine their futurist visions and needed to be addressed.[26] A particular concern is the equal access to human
enhancement technologies across classes and borders.[27] In 2006, a political struggle within the transhumanist
movement between the libertarian right and the liberal left resulted in a more centre-leftward positioning of the WTA
under its former executive director James Hughes.[] [28] In 2006, the board of directors of the Extropy Institute
ceased operations of the organization, stating that its mission was "essentially completed".[29] This left the World
Transhumanist Association as the leading international transhumanist organization. In 2008, as part of a rebranding
effort, the WTA changed its name to "Humanity+" in order to project a more humane image.[30] Humanity Plus and
Betterhumans publish h+ Magazine, a periodical edited by R. U. Sirius which disseminates transhumanist news and
ideas.[31] [32]
267
Transhumanism
Theory
It is a matter of debate whether transhumanism is a branch of "posthumanism" and how posthumanism should be
conceptualised with regard to transhumanism. The latter is often referred to as a variant or activist form of
posthumanism by its conservative,[4] Christian[33] and progressive[34] [35] critics, but also by pro-transhumanist
scholars who, for example, characterise it as a subset of "philosophical posthumanism".[3] A common feature of
transhumanism and philosophical posthumanism is the future vision of a new intelligent species, into which
humanity will evolve, which will supplement humanity or supersede it. Transhumanism stresses the evolutionary
perspective, including sometimes the creation of a highly intelligent animal species by way of cognitive
enhancement (i.e. biological uplift),[26] but clings to a "posthuman future" as the final goal of participant
evolution.[36]
Nevertheless, the idea to create intelligent artificial beings, proposed, for example, by roboticist Hans Moravec, has
influenced transhumanism.[10] Moravec's ideas and transhumanism have also been characterised as a "complacent"
or "apocalyptic" variant of posthumanism and contrasted with "cultural posthumanism" in humanities and the
arts.[37] While such a "cultural posthumanism" would offer resources for rethinking the relations of humans and
increasingly sophisticated machines, transhumanism and similar posthumanisms are, in this view, not abandoning
obsolete concepts of the "autonomous liberal subject" but are expanding its "prerogatives" into the realm of the
posthuman.[38] Transhumanist self-characterisations as a continuation of humanism and Enlightenment thinking
correspond with this view.
Some secular humanists conceive transhumanism as an offspring of the humanist freethought movement and argue
that transhumanists differ from the humanist mainstream by having a specific focus on technological approaches to
resolving human concerns and on the issue of mortality.[39] However, other progressives have argued that
posthumanism, whether it be its philosophical or activist forms, amount to a shift away from concerns about social
justice, from the reform of human institutions and from other Enlightenment preoccupations, toward narcissistic
longings for a transcendence of the human body in quest of more exquisite ways of being.[40] In this view,
transhumanism is abandoning the goals of humanism, the Enlightenment, and progressive politics.
Aims
While many transhumanist theorists and advocates seek to apply reason, science and technology for the purposes of
reducing poverty, disease, disability, and malnutrition around the globe, transhumanism is distinctive in its particular
focus on the applications of technologies to the improvement of human bodies at the individual level. Many
transhumanists actively assess the potential for future technologies and innovative social systems to improve the
quality of all life, while seeking to make the material reality of the human condition fulfill the promise of legal and
political equality by eliminating congenital mental and physical barriers.
Transhumanist philosophers argue that there not only exists a perfectionist ethical imperative for humans to strive for
progress and improvement of the human condition but that it is possible and desirable for humanity to enter a
transhuman phase of existence, in which humans are in control of their own evolution. In such a phase, natural
evolution would be replaced with deliberate change.
Some theorists, such as Raymond Kurzweil, think that the pace of technological innovation is accelerating and that
the next 50 years may yield not only radical technological advances but possibly a technological singularity, which
may fundamentally change the nature of human beings.[41] Transhumanists who foresee this massive technological
change generally maintain that it is desirable. However, some are also concerned with the possible dangers of
extremely rapid technological change and propose options for ensuring that advanced technology is used
responsibly. For example, Bostrom has written extensively on existential risks to humanity's future welfare,
including risks that could be created by emerging technologies.[42]
268
Transhumanism
Ethics
Transhumanists engage in interdisciplinary approaches to understanding and evaluating possibilities for overcoming
biological limitations. They draw on futurology and various fields of ethics such as bioethics, infoethics, nanoethics,
neuroethics, roboethics, and technoethics mainly but not exclusively from a philosophically utilitarian, socially
progressive, politically and economically liberal perspective. Unlike many philosophers, social critics, and activists
who place a moral value on preservation of natural systems, transhumanists see the very concept of the specifically
"natural" as problematically nebulous at best, and an obstacle to progress at worst.[43] In keeping with this, many
prominent transhumanist advocates refer to transhumanism's critics on the political right and left jointly as
"bioconservatives" or "bioluddites", the latter term alluding to the 19th century anti-industrialisation social
movement that opposed the replacement of human manual labourers by machines.[44]
Currents
There is a variety of opinion within transhumanist thought. Many of the leading transhumanist thinkers hold views
that are under constant revision and development.[45] Some distinctive currents of transhumanism are identified and
listed here in alphabetical order:
• Abolitionism, an ethical ideology based upon a perceived obligation to use technology to eliminate involuntary
suffering in all sentient life.[46]
• Democratic transhumanism, a political ideology synthesizing liberal democracy, social democracy, radical
democracy and transhumanism.[47]
• Extropianism, an early school of transhumanist thought characterized by a set of principles advocating a proactive
approach to human evolution.[20]
• Immortalism, a moral ideology based upon the belief that technological immortality is possible and desirable, and
advocating research and development to ensure its realization.[48]
• Libertarian transhumanism, a political ideology synthesizing libertarianism and transhumanism.[44]
• Postgenderism, a social philosophy which seeks the voluntary elimination of gender in the human species through
the application of advanced biotechnology and assisted reproductive technologies.[49]
• Singularitarianism, a moral ideology based upon the belief that a technological singularity is possible, and
advocating deliberate action to effect it and ensure its safety.[41]
• Technogaianism, an ecological ideology based upon the belief that emerging technologies can help restore Earth's
environment, and that developing safe, clean, alternative technology should therefore be an important goal of
environmentalists.[47]
Spirituality
Although some transhumanists report a strong sense of secular spirituality, they are for the most part atheists.[22] A
minority of transhumanists, however, follow liberal forms of Eastern philosophical traditions such as Buddhism and
Yoga[50] or have merged their transhumanist ideas with established Western religions such as liberal Christianity[51]
or Mormonism[52] . Despite the prevailing secular attitude, some transhumanists pursue hopes traditionally espoused
by religions, such as "immortality",[48] while several controversial new religious movements, originating in the late
20th century, have explicitly embraced transhumanist goals of transforming the human condition by applying
technology to the alteration of the mind and body, such as Raëlism.[53] However, most thinkers associated with the
transhumanist movement focus on the practical goals of using technology to help achieve longer and healthier lives;
while speculating that future understanding of neurotheology and the application of neurotechnology will enable
humans to gain greater control of altered states of consciousness, which were commonly interpreted as "spiritual
experiences", and thus achieve more profound self-knowledge.[50]
The majority of transhumanists are materialists who do not believe in a transcendent human soul. Transhumanist
personhood theory also argues against the unique identification of moral actors and subjects with biological humans,
269
Transhumanism
judging as speciesist the exclusion of non-human and part-human animals, and sophisticated machines, from ethical
consideration.[54] Many believe in the compatibility of human minds with computer hardware, with the theoretical
implication that human consciousness may someday be transferred to alternative media, a speculative technique
commonly known as "mind uploading".[55] One extreme formulation of this idea may be found in Frank Tipler's
proposal of the Omega point. Drawing upon ideas in digitalism, Tipler has advanced the notion that the collapse of
the Universe billions of years hence could create the conditions for the perpetuation of humanity in a simulated
reality within a megacomputer, and thus achieve a form of "posthuman godhood". Tipler's thought was inspired by
the writings of Pierre Teilhard de Chardin, a paleontologist and Jesuit theologian who saw an evolutionary telos in
the development of an encompassing noosphere, a global consciousness.[56]
The idea of uploading personality to a non-biological substrate and the underlying assumptions are criticised by a
wide range of scholars, scientists and activists, sometimes with regard to transhumanism itself, sometimes with
regard to thinkers such as Marvin Minsky or Hans Moravec, who are often seen as its originators. Relating the
underlying assumptions, for example, to the legacy of cybernetics, some have argued that this materialist hope
engenders a spiritual monism, a variant of philosophical idealism.[57] Viewed from a conservative Christian
perspective, the idea of mind uploading is asserted to represent a denigration of the human body characteristic of
gnostic belief.[58] Transhumanism and its presumed intellectual progenitors have also been described as neo-gnostic
by non-Christian and secular commentators.[59] [60]
The first dialogue between transhumanism and faith was the focus of an academic seminar held at the University of
Toronto in 2004.[61] Because it might serve a few of the same functions that people have traditionally sought in
religion, religious and secular critics maintained that transhumanism is itself a religion or, at the very least, a
pseudoreligion. Religious critics alone faulted the philosophy of transhumanism as offering no eternal truths nor a
relationship with the divine. They commented that a philosophy bereft of these beliefs leaves humanity adrift in a
foggy sea of postmodern cynicism and anomie. Transhumanists responded that such criticisms reflect a failure to
look at the actual content of the transhumanist philosophy, which far from being cynical, is rooted in optimistic,
idealistic attitudes that trace back to the Enlightenment.[62] Following this dialogue, William Sims Bainbridge
conducted a pilot study, published in the Journal of Evolution and Technology, suggesting that religious attitudes
were negatively correlated with acceptance of transhumanist ideas, and indicating that individuals with highly
religious worldviews tended to perceive transhumanism as being a direct, competitive (though ultimately futile)
affront to their spiritual beliefs.[63]
Practice
While some transhumanists take an abstract and theoretical approach to the perceived benefits of emerging
technologies, others have offered specific proposals for modifications to the human body, including heritable ones.
Transhumanists are often concerned with methods of enhancing the human nervous system. Though some propose
modification of the peripheral nervous system, the brain is considered the common denominator of personhood and
is thus a primary focus of transhumanist ambitions.[64]
As proponents of self-improvement and body modification, transhumanists tend to use existing technologies and
techniques that supposedly improve cognitive and physical performance, while engaging in routines and lifestyles
designed to improve health and longevity.[65] Depending on their age, some transhumanists express concern that they
will not live to reap the benefits of future technologies. However, many have a great interest in life extension
strategies, and in funding research in cryonics in order to make the latter a viable option of last resort rather than
remaining an unproven method.[66] Regional and global transhumanist networks and communities with a range of
objectives exist to provide support and forums for discussion and collaborative projects.
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271
Technologies of interest
Transhumanists support the emergence and convergence of
technologies such as nanotechnology, biotechnology, information
technology and cognitive science (NBIC), and hypothetical future
technologies such as simulated reality, artificial intelligence,
superintelligence, mind uploading, and cryonics. They believe that
humans can and should use these technologies to become more than
human.[68] They therefore support the recognition and/or protection of
cognitive liberty, morphological freedom, and procreative liberty as
civil liberties, so as to guarantee individuals the choice of using human
enhancement technologies on themselves and their children.[69] Some
speculate that human enhancement techniques and other emerging
technologies may facilitate more radical human enhancement by the
midpoint of the 21st century.[41]
[67]
Converging Technologies
, a 2002 report
exploring the potential for synergy among nano-,
bio-, info- and cogno-technologies, has become a
landmark in near-future technological
speculation.
A 2002 report, Converging Technologies for Improving Human
Performance, commissioned by the National Science Foundation and
US Department of Commerce, contains descriptions and commentaries on the state of NBIC science and technology
by major contributors to these fields. The report discusses potential uses of these technologies in implementing
transhumanist goals of enhanced performance and health, and ongoing work on planned applications of human
enhancement technologies in the military and in the rationalization of the human-machine interface in industry.[70]
While international discussion of the converging technologies and NBIC concepts includes strong criticism of their
transhumanist orientation and alleged science fictional character,[71] [72] [73] research on brain and body alteration
technologies has accelerated under the sponsorship of the US Department of Defense, which is interested in the
battlefield advantages they would provide to the "supersoldiers" of the United States and its allies.[74] There has
already been a brain research program to "extend the ability to manage information" while military scientists are now
looking at stretching the human capacity for combat to a maximum 168 hours without sleep.[75]
Arts and culture
Transhumanist themes have become increasingly prominent in various literary forms during the period in which the
movement itself has emerged. Contemporary science fiction often contains positive renditions of technologically
enhanced human life, set in utopian (especially techno-utopian) societies. However, science fiction's depictions of
enhanced humans or other posthuman beings frequently come with a cautionary twist. The more pessimistic
scenarios include many horrific or dystopian tales of human bioengineering gone wrong. In the decades immediately
before transhumanism emerged as an explicit movement, many transhumanist concepts and themes began appearing
in the speculative fiction of authors such as Robert A. Heinlein (Lazarus Long series, 1941–87), A. E. van Vogt
(Slan, 1946), Isaac Asimov (I, Robot, 1950), Arthur C. Clarke (Childhood's End, 1953) and Stanislaw Lem
(Cyberiad, 1967).[26]
The cyberpunk genre, exemplified by William Gibson's Neuromancer (1984) and Bruce Sterling's Schismatrix
(1985), has particularly been concerned with the modification of human bodies. Other novels dealing with
transhumanist themes that have stimulated broad discussion of these issues include Blood Music (1985) by Greg
Bear, The Xenogenesis Trilogy (1987–1989) by Octavia Butler; The Beggar's Trilogy (1990–94) by Nancy Kress;
much of Greg Egan's work since the early 1990s, such as Permutation City (1994) and Diaspora (1997); The Culture
novels of Iain M. Banks; The Bohr Maker (1995) by Linda Nagata; Oryx and Crake (2003) by Margaret Atwood;
The Elementary Particles (Eng. trans. 2001) and The Possibility of an Island (Eng. trans. 2006) by Michel
Houellebecq; Mindscan (2005) by Robert J. Sawyer; and Glasshouse (2005) by Charles Stross. Many of these works
Transhumanism
are considered part of the cyberpunk genre or its postcyberpunk offshoot.
Fictional transhumanist scenarios have also become popular in other media during the late twentieth and early
twenty first centuries. Such treatments are found in comic books (Captain America, 1941; Transmetropolitan, 1997;
The Surrogates, 2006), films (2001: A Space Odyssey, 1968; Blade Runner, 1982; Gattaca, 1997; Repo! The Genetic
Opera, 2008), television series (the Cybermen of Doctor Who, 1966; The Six Million Dollar Man, 1973; the Borg of
Star Trek: The Next Generation, 1989; manga and anime (Galaxy Express 999, 1978; Appleseed, 1985; Ghost in the
Shell, 1989; Neon Genesis Evangelion, 1995; and Gundam Seed, 2002), computer games (Metal Gear Solid, 1998;
Deus Ex, 2000; Half-Life 2, 2004; and BioShock, 2007), and role-playing games (Shadowrun, 1989, Transhuman
Space, 2002).
In addition to the work of Natasha Vita-More, curator of the Transhumanist Arts & Culture center, transhumanist
themes appear in the visual and performing arts.[76] Carnal Art, a form of sculpture originated by the French artist
Orlan, uses the body as its medium and plastic surgery as its method.[77] Commentators have pointed to American
performer Michael Jackson as having used technologies such as plastic surgery, skin-lightening drugs and hyperbaric
oxygen therapy over the course of his career, with the effect of transforming his artistic persona so as to blur
identifiers of gender, race and age.[78] The work of the Australian artist Stelarc centers on the alteration of his body
by robotic prostheses and tissue engineering.[79] Other artists whose work coincided with the emergence and
flourishing of transhumanism and who explored themes related to the transformation of the body are the
Yugoslavian performance artist Marina Abramovic and the American media artist Matthew Barney. A 2005 show,
Becoming Animal, at the Massachusetts Museum of Contemporary Art, presented exhibits by twelve artists whose
work concerns the effects of technology in erasing boundaries between the human and non-human.
Controversy
Transhumanist thought and research depart significantly from the mainstream and often directly challenge orthodox
theories. The very notion and prospect of human enhancement and related issues also arouse public controversy.[80]
[81]
Criticisms of transhumanism and its proposals take two main forms: those objecting to the likelihood of
transhumanist goals being achieved (practical criticisms); and those objecting to the moral principles or world view
sustaining transhumanist proposals or underlying transhumanism itself (ethical criticisms). However, these two
strains sometimes converge and overlap, particularly when considering the ethics of changing human biology in the
face of incomplete knowledge.
Critics or opponents often see transhumanists' goals as posing threats to human values. Some also argue that strong
advocacy of a transhumanist approach to improving the human condition might divert attention and resources from
social solutions. As most transhumanists support non-technological changes to society, such as the spread of civil
rights and civil liberties, and most critics of transhumanism support technological advances in areas such as
communications and health care, the difference is often a matter of emphasis. Sometimes, however, there are strong
disagreements about the very principles involved, with divergent views on humanity, human nature, and the morality
of transhumanist aspirations. At least one public interest organization, the U.S.-based Center for Genetics and
Society, was formed, in 2001, with the specific goal of opposing transhumanist agendas that involve
transgenerational modification of human biology, such as full-term human cloning and germinal choice technology.
The Institute on Biotechnology and the Human Future of the Chicago-Kent College of Law critically scrutinizes
proposed applications of genetic and nanotechnologies to human biology in an academic setting.
Some of the most widely known critiques of the transhumanist program refer to novels and fictional films. These
works of art, despite presenting imagined worlds rather than philosophical analyses, are used as touchstones for
some of the more formal arguments.
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Transhumanism
Infeasibility (Futurehype argument)
In his 1992 book Futurehype: The Tyranny of Prophecy, sociologist Max Dublin points out many past failed
predictions of technological progress and argues that modern futurist predictions will prove similarly inaccurate. He
also objects to what he sees as scientism, fanaticism, and nihilism by a few in advancing transhumanist causes, and
writes that historical parallels exist to millenarian religions and Communist doctrines.[82] Several notable
transhumanists have predicted that death-defeating technologies will arrive (usually late) within their own
conventionally-expected lifetimes. Wired magazine founding executive editor Kevin Kelly has argued these
transhumanists have overly optimistic expectations of when dramatic technological breakthroughs will occur
because they hope to be saved from their own deaths by those developments.[83] Despite his sympathies for
transhumanism, in his 2002 book Redesigning Humans: Our Inevitable Genetic Future, public health professor
Gregory Stock is skeptical of the technical feasibility and mass appeal of the cyborgization of humanity predicted by
Raymond Kurzweil, Hans Moravec and Kevin Warwick. He believes that throughout the 21st century, many humans
will find themselves deeply integrated into systems of machines, but will remain biological. Primary changes to their
own form and character will arise not from cyberware but from the direct manipulation of their genetics, metabolism,
and biochemistry.[84]
In his 2006 book Future Hype: The Myths of Technology Change, computer scientist and engineer Bob Seidensticker
argues that today's technological achievements are not unprecedented. Exposing major myths of technology and
examining the history of high tech hype, he aims to uncover inaccuracies and misunderstandings that may
characterise the popular and transhumanist views of technology, to explain how and why these views have been
created, and to illustrate how technological change in fact proceeds.[85]
Those thinkers who defend the likelihood of massive technological change within a relatively short timeframe
emphasize what they describe as a past pattern of exponential increases in humanity's technological capacities. This
emphasis appears in the work of popular science writer Damien Broderick, notably his 1997 book, The Spike, which
contains his speculations about a radically changed future. Kurzweil develops this position in much detail in his 2005
book, The Singularity Is Near. Broderick points out that many of the seemingly implausible predictions of early
science fiction writers have, indeed, come to pass, among them nuclear power and space travel to the moon. He also
claims that there is a core rationalism to current predictions of very rapid change, asserting that such observers as
Kurzweil have a good track record in predicting the pace of innovation.[86]
Hubris (Playing God argument)
There are two distinct categories of criticism, theological and secular, that have been referred to as "playing god"
arguments:
The first category is based on the alleged inappropriateness of humans substituting themselves for an actual god.
This approach is exemplified by the 2002 Vatican statement Communion and Stewardship: Human Persons Created
in the Image of God,[87] in which it is stated that, "Changing the genetic identity of man as a human person through
the production of an infrahuman being is radically immoral", implying, as it would, that "man has full right of
disposal over his own biological nature". At the same time, this statement argues that creation of a superhuman or
spiritually superior being is "unthinkable", since true improvement can come only through religious experience and
"realizing more fully the image of God". Christian theologians and lay activists of several churches and
denominations have expressed similar objections to transhumanism and claimed that Christians already enjoy,
however post mortem, what radical transhumanism promises such as indefinite life extension or the abolition of
suffering. In this view, transhumanism is just another representative of the long line of utopian movements which
seek to immanentize the eschaton i.e. try to create "heaven on earth".[88] [89]
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Transhumanism
The second category is aimed mainly at "algeny", which Jeremy Rifkin
defined as "the upgrading of existing organisms and the design of
wholly new ones with the intent of 'perfecting' their performance",[90]
and, more specifically, attempts to pursue transhumanist goals by way
of genetically modifying human embryos in order to create "designer
babies". It emphasizes the issue of biocomplexity and the
unpredictability of attempts to guide the development of products of
biological evolution. This argument, elaborated in particular by the
biologist Stuart Newman, is based on the recognition that the cloning
The biocomplexity spiral is a depiction of the
and germline genetic engineering of animals are error-prone and
multileveled complexity of organisms in their
inherently disruptive of embryonic development. Accordingly, so it is
environments, which is seen by many critics as
argued, it would create unacceptable risks to use such methods on
the ultimate obstacle to transhumanist ambition.
human embryos. Performing experiments, particularly ones with
permanent biological consequences, on developing humans, would thus be in violation of accepted principles
governing research on human subjects (see the 1964 Declaration of Helsinki). Moreover, because improvements in
experimental outcomes in one species are not automatically transferable to a new species without further
experimentation, there is claimed to be no ethical route to genetic manipulation of humans at early developmental
stages.[91]
As a practical matter, however, international protocols on human subject research may not present a legal obstacle to
attempts by transhumanists and others to improve their offspring by germinal choice technology. According to legal
scholar Kirsten Rabe Smolensky, existing laws would protect parents who choose to enhance their child's genome
from future liability arising from adverse outcomes of the procedure.[92]
Religious thinkers allied with transhumanist goals, such as the theologians Ronald Cole-Turner and Ted Peters,
reject the first argument, holding that the doctrine of "co-creation" provides an obligation to use genetic engineering
to improve human biology.[93] [94]
Transhumanists and other supporters of human genetic engineering do not dismiss the second argument out of hand,
insofar as there is a high degree of uncertainty about the likely outcomes of genetic modification experiments in
humans. However, bioethicist James Hughes suggests that one possible ethical route to the genetic manipulation of
humans at early developmental stages is the building of computer models of the human genome, the proteins it
specifies, and the tissue engineering he argues that it also codes for. With the exponential progress in bioinformatics,
Hughes believes that a virtual model of genetic expression in the human body will not be far behind and that it will
soon be possible to accelerate approval of genetic modifications by simulating their effects on virtual humans.[26]
Public health professor Gregory Stock points to artificial chromosomes as an alleged safer alternative to existing
genetic engineering techniques.[84] Transhumanists therefore argue that parents have a moral responsibility called
procreative beneficence to make use of these methods, if and when they are shown to be reasonably safe and
effective, to have the healthiest children possible. They add that this responsibility is a moral judgment best left to
individual conscience rather than imposed by law, in all but extreme cases. In this context, the emphasis on freedom
of choice is called procreative liberty.[26]
Contempt for the flesh (Fountain of Youth argument)
Philosopher Mary Midgley, in her 1992 book Science as Salvation, traces the notion of achieving immortality by
transcendence of the material human body (echoed in the transhumanist tenet of mind uploading) to a group of male
scientific thinkers of the early 20th century, including J.B.S. Haldane and members of his circle. She characterizes
these ideas as "quasi-scientific dreams and prophesies" involving visions of escape from the body coupled with
"self-indulgent, uncontrolled power-fantasies". Her argument focuses on what she perceives as the pseudoscientific
speculations and irrational, fear-of-death-driven fantasies of these thinkers, their disregard for laymen, and the
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Transhumanism
remoteness of their eschatological visions.[95] Many transhumanists see the 2006 film The Fountain's theme of
necrophobia and critique of the quixotic quest for eternal youth as depicting some of these criticisms.[96]
What is perceived as contempt for the flesh in the writings of Marvin Minsky, Hans Moravec, and some
transhumanists, has also been the target of other critics for what they claim to be an instrumental conception of the
human body.[38] Reflecting a strain of feminist criticism of the transhumanist program, philosopher Susan Bordo
points to "contemporary obsessions with slenderness, youth, and physical perfection", which she sees as affecting
both men and women, but in distinct ways, as "the logical (if extreme) manifestations of anxieties and fantasies
fostered by our culture.”[97] Some critics question other social implications of the movement's focus on body
modification. Political scientist Klaus-Gerd Giesen, in particular, has asserted that transhumanism's concentration on
altering the human body represents the logical yet tragic consequence of atomized individualism and body
commodification within a consumer culture.[59]
Nick Bostrom asserts that the desire to regain youth, specifically, and transcend the natural limitations of the human
body, in general, is pan-cultural and pan-historical, and is therefore not uniquely tied to the culture of the 20th
century. He argues that the transhumanist program is an attempt to channel that desire into a scientific project on par
with the Human Genome Project and achieve humanity's oldest hope, rather than a puerile fantasy or social trend.[1]
Trivialization of human identity (Enough argument)
In his 2003 book Enough: Staying Human in an Engineered Age,
environmental ethicist Bill McKibben argued at length against many of
the technologies that are postulated or supported by transhumanists,
including germinal choice technology, nanomedicine and life extension
strategies. He claims that it would be morally wrong for humans to
tamper with fundamental aspects of themselves (or their children) in an
attempt to overcome universal human limitations, such as vulnerability
to aging, maximum life span, and biological constraints on physical
In the US, the Amish are a religious group
and cognitive ability. Attempts to "improve" themselves through such
probably most known for their avoidance of
certain modern technologies. Transhumanists
manipulation would remove limitations that provide a necessary
draw a parallel by arguing that in the near-future
context for the experience of meaningful human choice. He claims that
there will probably be "Humanish", people who
human lives would no longer seem meaningful in a world where such
choose to "stay human" by not adopting human
limitations could be overcome technologically. Even the goal of using
enhancement technologies, whose choice they
[98]
believe must be respected and protected.
germinal choice technology for clearly therapeutic purposes should be
relinquished, since it would inevitably produce temptations to tamper
with such things as cognitive capacities. He argues that it is possible for societies to benefit from renouncing
particular technologies, using as examples Ming China, Tokugawa Japan and the contemporary Amish.[99]
Transhumanists and other supporters of technological alteration of human biology, such as science journalist Ronald
Bailey, reject as extremely subjective the claim that life would be experienced as meaningless if some human
limitations are overcome with enhancement technologies. They argue that these technologies will not remove the
bulk of the individual and social challenges humanity faces. They suggest that a person with greater abilities would
tackle more advanced and difficult projects and continue to find meaning in the struggle to achieve excellence.
Bailey also claims that McKibben's historical examples are flawed, and support different conclusions when studied
more closely.[100] For example, few groups are more cautious than the Amish about embracing new technologies, but
though they shun television and use horses and buggies, some are welcoming the possibilities of gene therapy since
inbreeding has afflicted them with a number of rare genetic diseases.[84]
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Transhumanism
Genetic divide (Gattaca argument)
Some critics of libertarian transhumanism have focused on its likely socioeconomic consequences in societies in
which divisions between rich and poor are on the rise. Bill McKibben, for example, suggests that emerging human
enhancement technologies would be disproportionately available to those with greater financial resources, thereby
exacerbating the gap between rich and poor and creating a "genetic divide".[99] Lee M. Silver, a biologist and science
writer who coined the term "reprogenetics" and supports its applications, has nonetheless expressed concern that
these methods could create a two-tiered society of genetically-engineered "haves" and "have nots" if social
democratic reforms lag behind implementation of enhancement technologies.[101] Critics who make these arguments
do not thereby necessarily accept the transhumanist assumption that human enhancement is a positive value; in their
view, it should be discouraged, or even banned, because it could confer additional power upon the already powerful.
The 1997 film Gattaca's depiction of a dystopian society in which one's social class depends entirely on genetic
modifications is often cited by critics in support of these views.[26]
These criticisms are also voiced by non-libertarian transhumanist advocates, especially self-described democratic
transhumanists, who believe that the majority of current or future social and environmental issues (such as
unemployment and resource depletion) need to be addressed by a combination of political and technological
solutions (such as a guaranteed minimum income and alternative technology). Therefore, on the specific issue of an
emerging genetic divide due to unequal access to human enhancement technologies, bioethicist James Hughes, in his
2004 book Citizen Cyborg: Why Democratic Societies Must Respond to the Redesigned Human of the Future, argues
that progressives or, more precisely, techno-progressives must articulate and implement public policies (such as a
universal health care voucher system that covers human enhancement technologies) in order to attenuate this
problem as much as possible, rather than trying to ban human enhancement technologies. The latter, he argues, might
actually worsen the problem by making these technologies unsafe or available only to the wealthy on the local black
market or in countries where such a ban is not enforced.[26]
Threats to morality and democracy (Brave New World argument)
Various arguments have been made to the effect that a society that adopts human enhancement technologies may
come to resemble the dystopia depicted in the 1932 novel Brave New World by Aldous Huxley. Sometimes, as in the
writings of Leon Kass, the fear is that various institutions and practices judged as fundamental to civilized society
would be damaged or destroyed.[102] In his 2002 book Our Posthuman Future and in a 2004 Foreign Policy
magazine article, political economist and philosopher Francis Fukuyama designates transhumanism the world's most
dangerous idea because he believes that it may undermine the egalitarian ideals of democracy in general and liberal
democracy in particular, through a fundamental alteration of "human nature".[4] Social philosopher Jürgen Habermas
makes a similar argument in his 2003 book The Future of Human Nature, in which he asserts that moral autonomy
depends on not being subject to another's unilaterally imposed specifications. Habermas thus suggests that the human
"species ethic" would be undermined by embryo-stage genetic alteration.[103] Critics such as Kass, Fukuyama, and a
variety of Christian authors hold that attempts to significantly alter human biology are not only inherently immoral
but also threats to the social order. Alternatively, they argue that implementation of such technologies would likely
lead to the "naturalizing" of social hierarchies or place new means of control in the hands of totalitarian regimes. The
AI pioneer Joseph Weizenbaum criticizes what he sees as misanthropic tendencies in the language and ideas of some
of his colleagues, in particular Marvin Minsky and Hans Moravec, which, by devaluing the human organism per se,
promotes a discourse that enables divisive and undemocratic social policies.[104]
In a 2004 article in Reason, science journalist Ronald Bailey has contested the assertions of Fukuyama by arguing
that political equality has never rested on the facts of human biology. He asserts that liberalism was founded not on
the proposition of effective equality of human beings, or de facto equality, but on the assertion of an equality in
political rights and before the law, or de jure equality. Bailey asserts that the products of genetic engineering may
well ameliorate rather than exacerbate human inequality, giving to the many what were once the privileges of the
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Transhumanism
few. Moreover, he argues, "the crowning achievement of the Enlightenment is the principle of tolerance". In fact, he
argues, political liberalism is already the solution to the issue of human and posthuman rights since, in liberal
societies, the law is meant to apply equally to all, no matter how rich or poor, powerful or powerless, educated or
ignorant, enhanced or unenhanced.[5] Other thinkers who are sympathetic to transhumanist ideas, such as philosopher
Russell Blackford, have also objected to the appeal to tradition, and what they see as alarmism, involved in Brave
New World-type arguments.[105]
Dehumanization (Frankenstein argument)
Biopolitical activist Jeremy Rifkin and biologist Stuart Newman accept
that biotechnology has the power to make profound changes in
organismal identity. They argue against the genetic engineering of
human beings, because they fear the blurring of the boundary between
human and artifact.[91] [106] Philosopher Keekok Lee sees such
developments as part of an accelerating trend in modernization in
Australian artist Patricia Piccinini's concept of
what human-animal hybrids might look like are
which technology has been used to transform the "natural" into the
provocative creatures which are part of a
"artifactual".[107] In the extreme, this could lead to the manufacturing
sculpture entitled The Young Family, produced to
and enslavement of "monsters" such as human clones, human-animal
address the reality of such possible parahumans
chimeras or bioroids, but even lesser dislocations of humans and
in a compassionate way. Transhumanists would
call for the recognition of self-aware parahumans
non-humans from social and ecological systems are seen as
as persons.
problematic. The film Blade Runner (1982), the novels The Boys From
Brazil (1978) and The Island of Dr. Moreau (1896) depict elements of
such scenarios, but Mary Shelley's 1818 novel Frankenstein is most often alluded to by critics who suggest that
biotechnologies could create objectified and socially-unmoored people and subhumans. Such critics propose that
strict measures be implemented to prevent what they portray as dehumanizing possibilities from ever happening,
usually in the form of an international ban on human genetic engineering.[108]
Writing in Reason magazine, Ronald Bailey has accused opponents of research involving the modification of
animals as indulging in alarmism when they speculate about the creation of subhuman creatures with human-like
intelligence and brains resembling those of Homo sapiens. Bailey insists that the aim of conducting research on
animals is simply to produce human health care benefits.[109]
A different response comes from transhumanist personhood theorists who object to what they characterize as the
anthropomorphobia fueling some criticisms of this research, which science writer Isaac Asimov termed the
"Frankenstein complex". They argue that, provided they are self-aware, human clones, human-animal chimeras and
uplifted animals would all be unique persons deserving of respect, dignity, rights and citizenship. They conclude that
the coming ethical issue is not the creation of so-called monsters but what they characterize as the "yuck factor" and
"human-racism" that would judge and treat these creations as monstrous.[22] [54]
Specter of coercive eugenicism (Eugenics Wars argument)
Some critics of transhumanism allege an ableist bias in the use of such concepts as "limitations", "enhancement" and
"improvement". Some even see the old eugenics, social Darwinist and master race ideologies and programs of the
past as warnings of what the promotion of eugenic enhancement technologies might unintentionally encourage.
Some fear future "eugenics wars" as the worst-case scenario: the return of coercive state-sponsored genetic
discrimination and human rights violations such as compulsory sterilization of persons with genetic defects, the
killing of the institutionalized and, specifically, segregation from, and genocide of, "races" perceived as inferior.[110]
Health law professor George Annas and technology law professor Lori Andrews are prominent advocates of the
position that the use of these technologies could lead to such human-posthuman caste warfare.[108] [111]
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Transhumanism
For most of its history, eugenics has manifested itself as a movement to sterilize against their will the "genetically
unfit" and encourage the selective breeding of the genetically fit. The major transhumanist organizations strongly
condemn the coercion involved in such policies and reject the racist and classist assumptions on which they were
based, along with the pseudoscientific notions that eugenic improvements could be accomplished in a practically
meaningful time frame through selective human breeding. Most transhumanist thinkers instead advocate a "new
eugenics", a form of egalitarian liberal eugenics.[112] In their 2000 book From Chance to Choice: Genetics and
Justice, (non-transhumanist) bioethicists Allen Buchanan, Dan Brock, Norman Daniels and Daniel Wikler have
argued that liberal societies have an obligation to encourage as wide an adoption of eugenic enhancement
technologies as possible (so long as such policies do not infringe on individuals' reproductive rights or exert undue
pressures on prospective parents to use these technologies) in order to maximize public health and minimize the
inequalities that may result from both natural genetic endowments and unequal access to genetic enhancements.[113]
Most transhumanists holding similar views nonetheless distance themselves from the term "eugenics" (preferring
"germinal choice" or "reprogenetics")[101] to avoid having their position confused with the discredited theories and
practices of early-20th-century eugenic movements.[114]
Existential risks (Terminator argument)
Struck by a passage from Unabomber Theodore Kaczynski's anarcho-primitivist manifesto (quoted in Ray
Kurzweil's 1999 book, The Age of Spiritual Machines[11] ), computer scientist Bill Joy became a notable critic of
emerging technologies.[115] Joy's 2000 essay "Why the future doesn't need us" argues that human beings would
likely guarantee their own extinction by developing the technologies favored by transhumanists. It invokes, for
example, the "grey goo scenario" where out-of-control self-replicating nanorobots could consume entire ecosystems,
resulting in global ecophagy.[116] Joy's warning was seized upon by appropriate technology organizations such as the
ETC Group. Related notions were also voiced by self-described neo-luddite Kalle Lasn, a culture jammer who
co-authored a 2001 spoof of Donna Haraway's 1985 Cyborg Manifesto as a critique of the techno-utopianism he
interpreted it as promoting.[117] Lasn argues that high technology development should be completely relinquished
since it inevitably serves corporate interests with devastating consequences on society and the environment.[118]
In his 2003 book Our Final Hour, British Astronomer Royal Martin Rees argues that advanced science and
technology bring as much risk of disaster as opportunity for progress. However, Rees does not advocate a halt to
scientific activity; he calls for tighter security and perhaps an end to traditional scientific openness.[119] Advocates of
the precautionary principle, such as the Green movement, also favor slow, careful progress or a halt in potentially
dangerous areas. Some precautionists believe that artificial intelligence and robotics present possibilities of
alternative forms of cognition that may threaten human life.[120] The Terminator franchise's doomsday depiction of
the emergence of an A.I. that becomes a superintelligence - Skynet, a malignant computer network which initiates a
nuclear war in order to exterminate the human species, has often been cited by some involved in this debate.[121]
Transhumanists do not necessarily rule out specific restrictions on emerging technologies so as to lessen the prospect
of existential risk. Generally, however, they counter that proposals based on the precautionary principle are often
unrealistic and sometimes even counter-productive, as opposed to the technogaian current of transhumanism which
they claim is both realistic and productive. In his television series Connections, science historian James Burke
dissects several views on technological change, including precautionism and the restriction of open inquiry. Burke
questions the practicality of some of these views, but concludes that maintaining the status quo of inquiry and
development poses hazards of its own, such as a disorienting rate of change and the depletion of our planet's
resources. The common transhumanist position is a pragmatic one where society takes deliberate action to ensure the
early arrival of the benefits of safe, clean, alternative technology rather than fostering what it considers to be
anti-scientific views and technophobia.[122]
One transhumanist solution proposed by Nick Bostrom is differential technological development, in which attempts
would be made to influence the sequence in which technologies developed. In this approach, planners would strive to
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Transhumanism
retard the development of possibly harmful technologies and their applications, while accelerating the development
of likely beneficial technologies, especially those that offer protection against the harmful effects of others.[42] An
argument for an "anti-progressionist and pessimistic version of transhumanism" has also been presented by Philippe
Verdoux [123] .
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