Neuropsychological Triggering Factors in Musicians with Focal

Transcription

University of Veterinary Medicine Hannover
Institute of Music Physiology and Musicians’ Medicine
Hannover University of Music, Drama and Media
Centre for Systems Neuroscience (ZSN)
Neuropsychological Triggering Factors in Musicians
with Focal Dystonia
THESIS
Submitted in partial fulfilment of the requirements for the degree
DOCTOR OF PHILOSOPHY
(PhD)
awarded by the University of Veterinary Medicine Hannover
by
Christos I. Ioannou
Born in Paphos, Cyprus
Hannover, Germany, 2015
Centre for Systems Neuroscience (ZSN)
Neuropsychological Triggering Factors in Musicians
with Focal Dystonia
THESIS
Submitted in partial fulfilment of the requirements for the degree
DOCTOR OF PHILOSOPHY
(PhD)
awarded by the University of Veterinary Medicine Hannover
by
Christos I. Ioannou
Born in Paphos, Cyprus
Supervisor:
Prof. Dr. med. Eckart Altenmüller, MD, MA
Supervision Group:
Prof. Dr. med. Reinhard Dengler, MD
Prof. Dr. rer. nat. Claudia Grothe
1st Evaluation:
Prof. Dr. med. Eckart Altenmüller, MD, MA
Prof. Dr. med. Reinhard Dengler, MD
Department of Neurology
Hannover Medical School
Prof. Dr. rer. nat. Claudia Grothe
Institute of Neuroanatomy
Hannover Medical Schoolon:
2nd Evaluation:
Prof. Dr. med. Harald Gündel
Department of Psychosomatic Medicine and Psychotherapy
University of Ulm
Date of final exam:
06.11.2015
Parts of the thesis have been published previously in:
Ioannou, C. I., & Altenmüller, E. (2014). Psychological characteristics in musician's dystonia: a new diagnostic classification. Neuropsychologia, 61, 80-88.
Ioannou, C. I., Furuya, S., & Altenmüller, E. (in press). Objective evaluation of performance stress in musicians with focal dystonia: a case study. Journal of Motor Behavior.
Ioannou, C. I., Furuya, S., & Altenmüller, E. (2016). The impact of stress on motor
performance in skilled musicians suffering from focal dystonia: physiological and psychological characteristics. Neuropsychologia, 58, 226-236.
Sponsorship: The whole project was funded by the German Research Foundation (DFG),
(AL269/8-1).
To my dear parents Xenia and Yiannis
for their support, encouragement
and unconditional love…
Thank you!
Table of Contents
INTRODUCTION.................................................................................................................... 5
1 Dystonia ........................................................................................................................................ 7
1.1 Historical overview ............................................................................................................................ 7
1.2 Clinical characteristics ....................................................................................................................... 7
1.3 Classification ..................................................................................................................................... 8
1.4 Epidemiology and pathophysiology .................................................................................................. 9
2 Focal dystonia in musicians ........................................................................................................ 10
2.1 Clinical features and classification .................................................................................................. 10
2.2 Epidemiology and aetiology ............................................................................................................ 11
2.3 Genetics and heredity ...................................................................................................................... 12
2.4 Pathophysiology .............................................................................................................................. 12
2.4.1 Structural and functional abnormalities ............................................................................... 12
2.4.2 Dysfunction of the Basal Ganglia ........................................................................................ 14
2.4.3 Loss of inhibition ................................................................................................................. 15
2.4.4 Maladaptive plasticity and sensory dysfunction .................................................................. 16
2.5 Treatment methods .......................................................................................................................... 17
3 Psycho-psychiatric features ......................................................................................................... 19
3.1 Psychopathology in primary focal dystonia .................................................................................... 19
3.2 Psychopathology in Musician’s Dystonia ....................................................................................... 21
4 Aims ............................................................................................................................................ 24
CHAPTERS ............................................................................................................................ 25
Psychological Characteristics in Musician's Dystonia: A New Diagnostic Classification .......... 27
Objective Evaluation of Performance Stress in Musicians with Focal Dystonia:
A Case series ...................................................................................................................................... 29
The Impact of Stress on Motor Performance in Skilled Musicians Suffering from Focal
Dystonia: Physiological and Psychological Characteristics ........................................................... 31
CONCLUSIONS AND OUTLOOK ..................................................................................... 33
Conclusions .................................................................................................................................... 35
Future aspects ................................................................................................................................. 37
Definition ....................................................................................................................................... 37
REFERENCES ....................................................................................................................... 39
AFFIDAVIT ........................................................................................................................... 53
ACKNOWLEDGEMENTS .................................................................................................. 55
i
List of abbreviations
A
AA
ARI
active avoidance subscale of the SCQ
adjusted rand index
B
BL1
BL2
BLA
BMI
bpm
BTX
1st baseline
2nd baseline
basolateral amygdala
body mass index
beats per minute
botulinum toxin
C
CI
CM
CNS
CTAI
CTAIcp
CTAIsa
CTAIsdc
CV
co-activation index
concern over mistakes subscale of the FMPS
central nervous system
Competitive Trait Anxiety Inventory
concentration problems subscale of the CTAI
somatic anxiety subscale of the CTAI
self-doubt concern subscale of the CTAI
coefficient of variance
D
D
DA
DSM-IV
distraction subscale of the SCQ
doubts about actions subscale of the FMPS
Diagnostic and Statistical Manual of Mental disorders, 4th
edition
E
ECG
ECLIA
ED
EMG
electrocardiography
electrochemiluminescence immunoassay
embouchure dystonia
electromyography
F
FDM
FH–
FH+
FHD
FMPS
fMRI
FPI-R
FT
focal dystonia in musicians
no family history
positive family history
focal hand dystonia
Frost Multidimensional Perfectionism Scale
functional magnetic resonance imaging
Freiburg Personality Inventory
flight tendency subscale of the SCQ
G
GABA
GD
GPe
GPi
GZ
γ-Aminobutyric acid
guilt denial subscale of the SCQ
external globus pallidus
internal globus pallidus
grey zone
H
HM
HPA axis
HPE
IMMM
healthy musicians
hypothalamic-pituitary-adrenal axis
high psychological effects subgroup
I
IOI
inter-onset interval
ii
L
LPE
low psychological effects subgroup
M
max
MEG
min
MP
MRI
MRS
MVC
maximum
magneto-encephalography
minimum
mental perseveration subscale of the SCQ
magnetic resonance imaging
magnetic resonance spectroscopy
maximum voluntary contraction
N
NEO-FFI
nmol/L
NSC
O
OCD
NEO Five-Factor Inventory
nanomoles per litre
need for social support subscale of the SCQ
organisation subscale of the FMPS
obsessive compulsive symptoms
P
PC
PD
PE
PET
PM
PS
PSI
PT
parental criticism subscale of the FMPS
play down subscale of the SCQ
parental expectations subscale of the FMPS
positron emission tomography
premotor cortex
personal standards subscale of the FMPS
positive self-instruction subscale of the SCQ
post treatment
Q
Q
QCC
quartile
Competence and Control Orientation inventory
R
R
RC
RI
RP
resignation subscale of the SCQ
reaction control subscale of the SCQ
Rand index
recovery period
S
s-STAI
S1
SC
SCQ
SCQ-NEG
SCQ-POS
SI
SMA
SNc
SS
STAI
STN
Stress-NR
Stress-R
state anxiety scale of the STAI
somatosensory cortex
situation control subscale of the SCQ
Stress Coping Questionnaire
negative stress coping subscales of the SCQ
positive stress coping subscales of the SCQ
self-incrimination subscale of the SCQ
supplementary motor area
substantia nigra pars compacta
substitutional satisfaction subscale of the SCQ
State-Trait Anxiety Inventory
subthalamic nucleus
stress non-responders
stress-responders
T
TDCS
TMS
TSST
transcranial direct-current stimulation
transcranial magnetic stimulation
Trier Social Stress Test
W
WP1
WP2
WU
1st waiting period
2nd waiting period
warm-up
iii
List of figures and tables
Introduction
Fig. 1 Typical dystonic postures in musicians .................................................................................. 11
Fig. 2 Triggering factors contributing to the manifestation of FDM ................................................ 17
Fig. 3 Emotionally-induced memory consolidation in FDM patients with psychopathology .......... 23
iv
Summary
Neuropsychological Triggering Factors in Musicians with Focal Dystonia
Christos I. Ioannou
Focal dystonia is a neurological movement disorder which affects the fine motor control of a
specific body location. In professional musicians, a limb or the embouchure involved in
playing a musical instrument may be impacted. Focal dystonia in musicians (FDM) is
characterised by a loss of voluntary motor control and can be a career-ending condition. The
pathophysiology of focal dystonia, which remains incompletely understood, is mainly
associated with dysfunction of basal ganglia-thalamo-cortical circuits, with impaired
inhibition and dysfunctions of sensorimotor pathways. FDM is triggered by various
neuropsychological and environmental factors. However the existence of psycho-psychiatric
comorbidities and their possible impact on and/or contribution to the manifestation of FDM
remains under-investigated. Recent studies have revealed that motor function can be altered
as a result of psychological or psychiatric conditions, suggesting common neurobiological
networks. Studies conducted in other forms of focal dystonia have uncovered psychiatric or
other psychological comorbidities such as obsessions, phobias, anxieties and depression,
whereas a limited number of investigations with FDM patients have mainly indicated elevated
levels of anxiety and perfectionism. The aim of the current thesis was to provide new insights
into the psychopathology of focal dystonia and its possible consequences for motor
performance in affected musicians. The investigation was divided into three different studies
(chapters), each exploring a different aspect of the overall topic.
The first chapter comprises a comprehensive exploratory analysis of the psychological profile
of FDM patients based on standardised psycho-diagnostic instruments. Findings indicate that
in comparison to healthy controls, half of the FDM patients exhibited elevated instances of
psychological traits related to anxiety, perfectionism and dysfunctional stress-coping features.
Furthermore, results suggest that these conditions pre-dated the onset of the disease and may
have contributed as aggravating risk factors to the development of FDM. We suggest that the
existence of FDM patients with and without psychopathology could reflect different maladaptive processes mediated via different circuits of the cortico-basal ganglia-thalamic loops.
Most of the features in the FDM patients diagnosed with psychopathology were related to
elevated levels of stress and anxiety. Therefore the second chapter focuses on the design of a
complex experimental paradigm which examines physiological parameters (electromyography [EMG] and fine motor performance) in relaxed and stressful conditions, in
combination with objective assessments (electrocardiography [ECG], cortisol) of the
hypothalamic-pituitary-adrenal (HPA) axis. Due to the fact that no similar paradigm has
previously been implemented for patients with focal dystonia, a pilot study with a small
number of patients was conducted. Findings suggest that the experimental design is feasible
and serves its purpose.
The final chapter encompasses a combined design derived from the first two chapters.
Possible electrophysiological differences were examined i) between FDM patients and
healthy controls, ii) among FDM patients before and after stress and iii) between patients with
and without psychopathology. Findings indicate that FDM patients are characterised by
increased sensitivity to psychosocial stressors, in comparison to healthy controls. The impact
of stress is expressed as an increase in muscular co-contraction of the affected hand, which
can be explained as a “natural” physiological response under stressful conditions. Finally, no
1
motor outcome differences are found between patients with and without psychopathology,
however results indicate that musicians with psychopathology had, on average, developed
dystonia around a decade earlier than the remainder of the patients, emphasising the
contribution of psycho-psychiatric conditions to the manifestation of dystonia.
Summarising, the current thesis suggests the existence of psychopathology in about 50% of
musicians with focal dystonia. FDM patients with and without psychopathology did not differ
in their motor performance, however there is clear evidence that psychopathology can be an
aggravating factor, which may accelerate or even trigger the manifestation of dystonia. The
current thesis supports the concept that motor and psycho-psychiatric features share common
neurobiological networks in patients with focal dystonia.
2
Zusammenfassung
Psychologische Faktoren als Auslöser der Musikerdystonie
Christos I. Ioannou
Die fokale Dystonie ist eine neurologische Krankheit, die sich in unwillkürlichen
Verkrampfungen, Fehlbewegungen und Verlust der feinmotorischen Kontrolle eines
umschriebenen Körperteils auswirkt. Bei Berufsmusikern tritt diese Erkrankung meist
aufgabenspezifisch als Handdystonie oder als Ansatzdystonie beim Spiel des Instrumentes auf.
Nicht selten bedroht die fokale Musikerdystonie (FDM) die Berufsfähigkeit. Die
Pathophysiologie der Erkrankung ist noch nicht völlig aufgeklärt. Einerseits werden
Dysfunktionen der Basalganglienschleife vermutet, andererseits ein Inhibitionsdefizit in
sensomotorischen Netzwerken und/oder maladaptive Plastizität auf allen Ebenen der
motorischen Systeme. Obwohl schon länger bekannt ist, dass verschiedene psychologische
Faktoren zur Auslösung der Musikerdystonie beitragen können, sind diese psychischen
Komorbiditäten bislang nicht ausreichend erforscht worden. Bereits seit längerem wird
angenommen, dass motorische Funktionen durch psychologische Faktoren und psychiatrische
Erkrankungen beeinflusst werden können, was für eine gemeinsame neurobiologischstrukturelle Verankerung spricht. So konnten in Studien zu anderen Dystonien psychiatrische
Begleiterkrankungen wie Zwangskrankheiten, Phobien, Angststörungen und Depressionen
überdurchschnittlich häufig nachgewiesen werden. Untersuchungen zur Musikerdystonie
ergaben vor allem Hinweise auf erhöhte Angstbereitschaft und auf perfektionistische
Charakterstrukturen. Das Ziel dieser These war, neue Einsichten hinsichtlich
psychopathologischer Auslöser und Begleiterscheinungen der Musikerdystonie zu gewinnen
und mögliche Auswirkungen dieser Komorbiditäten auf die Spielfertigkeit zu untersuchen.
Die Untersuchung dieser Fragen ist in drei verschiedenen Studien in jeweils separierten
Kapiteln dargestellt.
Das erste Kapitel widmet sich einer umfassenden explorativen Analyse der psychologischen
Profile gesunder Musiker und Musiker mit Musikerdystonie auf der Grundlage
standardisierter psychodiagnostischer Instrumente. Die Ergebnisse zeigen, dass im Vergleich
zu gesunden Musikern die Hälfte der Dystoniepatienten erhöhte Angstbereitschaft,
Perfektionismus und dysfunktionale Stress-Coping-Mechanismen aufwiesen. Darüberhinaus
deuten die Ergebnisse darauf hin, dass diese psychologischen Charakteristika bereits vor
Ausbruch der Dystonie nachweisbar waren und möglicherweise als Risikofaktoren zur
Auslösung der Dystonie beitrugen. Die Existenz von zwei unterschiedlichen Kategorien von
Musikerdystonien mit oder ohne psychopathologische Komorbiditäten könnte auf
unterschiedlichen maladaptiven Prozessen in spezifischen Segmenten der Basalganglienschleife beruhen.
Da die vorherrschenden psychopathologischen Befunde mit erhöhter Stress- und
Angstbereitschaft einhergingen, konzentrierte sich die zweite Studie auf ein experimentelles
Design, das unter experimentellen Bedingungen Stressreagibilität, motorische Leistung und
psychophysiologische Parameter (Elektromyographie, Elektrokardiographie, Cortisolspiegel
im Speichel) objektiv unter Ruhebedingungen und unter Stress erfasste. Da bislang kein
derartiges experimentelles Paradigma bei Musikern mit Dystonie existierte, wurde zunächst
an wenigen Probanden eine Pilotstudie durchgeführt. Die Ergebnisse dieser Studie zeigten,
dass das Experiment in der geplanten Art und Weise durchführbar war.
3
Das dritte Kapitel umfasst eine große Untersuchung, in der die experimentellen Designs
beider Studien kombiniert wurden. Unterschiede in psychophysiologischen Parametern und in
der motorischen Leistung wurden a.) zwischen gesunden Musikern und Musikern mit
Dystonien und b.) bei Musikern mit Dystonie vor und nach Stress, und c.) bei Musikern mit
Dystonie und unterschiedlichen psychopathologischen Profilen erfasst. Die Studie ergab, dass
Musiker mit Dystonie im Vergleich zu gesunden Musikern eine deutlich erhöhte
Stressbereitschaft haben. Stress wirkte sich bei gesunden und bei erkrankten Musikern vor
allem in einer muskulären Kokontraktion bei feinmotorischen Leistungen, etwa dem
Tonleiterspiel, aus. Dies kann als eine physiologische Reaktion auf psychische Anspannung
aufgefasst werden. Das Tonleiterspiel unterschied sich nicht bei Patienten mit oder ohne
psychischen Komorbiditäten. Ein interessantes Nebenergebnis war, dass Musiker mit
psychopathologischen Komorbiditäten im Durchschnitt etwa 10 Jahre früher eine Dystonie
entwickelten als Musikern ohne derartige Begleiterkrankungen. Dies weist auf die wichtige
Rolle psychopathologischer Faktoren als Trigger der Musikerdystonie hin.
Zusammenfassend belegt die vorliegende These das Vorliegen psychopathologischer Befunde
bei ca. 50% der Musiker mit Dystonien. Patienten mit oder ohne psychiatrische
Komorbiditäten unterschieden sich zwar nicht in der motorischen Performanz beim Spielen
des Instruments, aber die Ergebnisse zeigen, dass psychopathologische Faktoren die
Entwicklung einer Dystonie auslösen oder zumindest beschleunigen können. Die vorliegende
These unterstützt das Konzept gemeinsamer neurobiologischer Netzwerke für motorische und
psychopathologische Symptome bei der Musikerdystonie.
4
INTRODUCTION
Introduction
7
1 DYSTONIA
1.1 Historical overview
The term “dystonia” was firstly used in 1911, by the German neurologist Hermann
Oppenheim. 1 It derives from the Greek word δυσ-τονία (δυσ-/dys- = bad, abnormal,
misfortune, dysfunctional, and τόνος/tonos = tone, tension), which means impairment of
muscle tone or abnormal tonicity. Before Oppenheim, terminology such as “athetosis”
(Barraquer Roviralta, 1897), “tonic cramps” (Schwalbe, 1907), “torsion neurosis” (Ziehen,
1911) and “progressive torsion spasm” (Flatau & Sterling, 1911) had been used for
diagnosing dystonic symptoms. Oppenheim’s initial term was “dystonia musculorum
deformans” (Oppenheim, 1911). However as dystonia is not characterised by muscle
disorders the shortened term was preferred (Flatau & Sterling, 1911; Stacy, 2007). Since the
beginning of the 20th century neurologists have theorised about a possible genetic
predisposition for the condition, and a link between dystonic symptoms and psychiatric
diseases (Schwalbe, 1907). Finally, Ziehen (1911) emphasised the organic origin of dystonia
and argued that dystonic symptoms are exacerbated during action or emotional excitement.
Records of focal task-specific dystonias, the main topic of the current work, date back to the
beginning of 18th century. A detailed description of writer’s cramp was given in Ramazzini’s
treatise in 1713 (Ramazzini, 1964). Writer’s cramp was initially termed “scrivener’s palsy” by
Solly in 1864 (Frucht, 2014; Pearce, 2005), whereas in the late 19th century terms such as
“functional” or “neuroses” were also used, as neurologists believed that focal task-specific
dystonias were not purely psychologically-based (Frucht, 2014; Marsden & Sheehy, 1990;
Torres-Russotto & Perlmutter, 2008).
1.2 Clinical characteristics
Dystonia is a neurological movement disorder characterised by muscular overflow, and by
sustained and repetitive involuntary co-contractions of agonist and antagonist pairs of muscles.
Prolonged symptoms lead to abnormal, frequently stereotyped body postures often
accompanied by tremor and pain. However, phenomenology and severity vary: symptoms
may affect the entire body (generalised) or a single body part (focal) and can appear either at
rest or during the execution of specific motor tasks. Symptoms in some focal dystonias are
frequently reduced when using sensory tricks (“geste antagoniste”), e.g. touching the affected
body area (Hallett, 2011; Lin & Hallett, 2009; Tanabe et al., 2009).
1
Hermann Oppenheim (1 January 1858 - 5 May 1919) was a pioneering neurologist in Germany. He completed his medical
studies at the Universities of Berlin, Göttingen and Bonn. In 1891 Oppenheim established a private hospital in Berlin, and in
1894 he wrote a textbook titled Lehrbuch der Nervenkrankheiten für Ärzte und Studierende, which became a standard
resource in the field of neurology.
8
Introduction
Definition
Over the last three decades, a single definition established by the Dystonia Medical Research
Foundation has been used: “Dystonia is a syndrome of sustained muscle contractions,
frequently causing twisting and repetitive movements, or abnormal postures” (Fahn, 1988).
However, an updated definition has been recently introduced by Albanese et al. (2013):
“Dystonia is a movement disorder characterised by sustained or intermittent muscle
contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic
movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated
or worsened by voluntary action and associated with overflow muscle activation”.
1.3 Classification
Dystonia is traditionally classified along three main axes: aetiology, age at onset and body
distribution (Albanese et al., 2011; Fahn, 2011). Aetiology of dystonia is mainly subclassified as primary (idiopathic) and secondary (symptomatic). Primary dystonia is
diagnosed when symptoms occur spontaneously and no other clinical signs (apart from
tremor) or associated diseases are identifiable. In primary dystonia no structural abnormalities
of the central nervous system (CNS) are observed, and its cause is mainly unknown. However
in some forms, genetic predispositions are involved (Klein, 2014). Secondary dystonia is the
occurrence of dystonic symptoms as a consequence of certain neurological conditions (e.g.
brain injury, tumour, drug side-effect) or psychological disturbances (i.e. psychogenic
dystonia) (Quartarone et al., 2009). Age at onset, which is sub-classified mainly as early- and
late-onset, provides information about the cause and the prognostics (Greene et al., 1995). For
example, a childhood diagnosis of focal dystonia is more likely to be associated with the
condition spreading to multiple parts of the body. In contrast, late-onset or adult-onset focal
dystonia (in patients mainly over the age of 25) may involve only limited progression to
neighbouring body regions (Fahn et al., 1998).
Body distribution indicates the affected body locations. Focal dystonia, which is the most
common form, affects only one region (e.g. blepharospasm, cervical, writer’s cramp,
musician’s cramp). Segmental dystonia applies when two or more related parts are affected
(e.g. cranial dystonia, bi-brachial dystonia). Hemidystonia involves one side of the body and
generalised dystonia affects the trunk together with the upper or the lower limbs. An updated
classification based on two axes (clinical features and aetiology) has recently been proposed
(see Albanese et al., 2013). However, due to the fact that the updated terminology has not yet
been widely adapted, the traditional classification has been used throughout the present work.
Introduction
9
1.4 Epidemiology and pathophysiology
A recent meta-analysis by Steeves et al. (2012) revealed a prevalence of primary dystonia of
16.4 per 100,000 and a prevalence for focal and segmental dystonia specifically of 15.4 per
100,000 people. The authors suggested that the prevalence of dystonia increases with age
whereas other studies have also indicated that men may develop dystonia at an earlier age
(ESDE, 2000; Marras et al., 2007; Matsumoto et al., 2003). Interestingly, different
epidemiological studies have found variability across populations. For instance, the
prevalence of primary dystonia in Iceland was reported at 37.1 (Asgeirsson et al., 2006)
compared to 15.2 per 100,000 people (Sugawara et al., 2006) in Northern Japan. Differences
across populations have also been found in terms of the break-down across different subtypes
of dystonia. For example, in Japan a higher prevalence has been reported for blepharospasm
in comparison to cervical dystonia, whereas the opposite has been reported in Europe
(Matsumoto et al., 2003). In order to clarify the underlying causes of these reported
population differences (e.g. genetics, diagnostic criteria), further studies should be conducted
based on common methodological approaches.
The pathophysiology of dystonia is multifactorial and still not fully understood. It is related to
impaired inhibition of motor and sensory pathways (Defazio et al., 2007; Garibotto et al.,
2011; Hallett, 2011; Quartarone et al., 2008; Tinazzi et al., 2009), however the main
pathogenic mechanism seems to consist of an imbalance between direct and indirect pathways
of the basal ganglia (Berardelli et al., 1998; Defazio et al., 2007; Hallett, 2006; Neychev et al.,
2011; Quartarone & Hallett, 2013). The pathogenesis of dystonia has also been associated
with sensory dysfunction (Fiorio et al., 2007, 2008; Ghilardi et al., 2003; Molloy et al., 2003;
Peller et al., 2006), structural abnormalities of the basal ganglia (Black et al., 1998; Defazio et
al., 2007; Draganski et al., 2003; Etgen et al., 2006; Garraux et al., 2004; Peller et al., 2006)
and abnormalities of the cerebellothalamocortical circuit (Argyelan et al., 2009; Eidelberg et
al., 1998; Tanabe et al., 2009), among other factors. Finally, some forms of dystonia are
associated with genetic abnormalities classified as DYT loci, or with a failure of dopamine
synthesis caused by mutations in specific genes (Klein, 2014; Malek et al., 2015). Further
details of the pathophysiology of focal dystonia, the main topic of the current work, are
provided in section 2.4.
10 Introduction
2 FOCAL DYSTONIA IN MUSICIANS
As well as enjoying the magical world of emotions evoked by listening to a Liszt etude, a
Paganini caprice, or the flute sonata by Prokofiev, it is always impressive to observe the
incredible fine motor abilities of accomplished musicians. The development of such motor
skills requires long-term learning and practice from early childhood. As a result, life-long
adaptations of the nervous system render musicians to be one of the best models for
investigating motor learning effects and their consequences (Münte et al., 2002). However,
pushing motor functions to their limits is not always without cost. One of the most severe
motor disorders which can affect musicians’ fine motor control is focal dystonia. Focal
dystonia in musicians (FDM), also known as musician’s dystonia or musician’s cramp, has
been described since the beginning of 19th century. One of the most famous cases was the
Romantic-era pianist and composer Robert Schumann (1810-1856), who developed dystonia
in the middle finger of his right hand (Altenmüller, 2005).
2.1 Clinical features and classification
FDM is, in most cases, a primary dystonia developing without pain and characterised by
muscular incoordination and loss of voluntary motor control whilst playing an instrument.
Prolonged symptoms lead to abnormal posture, which can be accompanied by co-contraction
of the antagonistic muscle pairs while playing the instrument. It mostly affects one region
(focal) of the body, and is largely characterised by two features: i) task specificity, which
means that symptoms are triggered during the execution of specific activities (i.e. while
playing a musical instrument) and ii) the presence of an effective sensory trick, an immediate
improvement of the symptoms by changing the sensory input to the affected region (e.g.
wearing a glove on an affected hand) (Altenmüller & Janusch, 2009, 2010; Aránguiz et al.,
2011; Conti et al., 2008). FDM is mainly sub-classified as limb dystonia or embouchure
dystonia (Altenmüller, 2003; Frucht et al., 2004; Lederman, 1991). In limb dystonia the most
affected body regions are the upper limbs (e.g. finger[s], hand, wrist or arm). However, there
are also rare reports of musicians affected in the lower limbs, for example a death metal
drummer in the right thigh (Lee & Altenmüller, 2014). Hand dystonia is frequently
characterised by an involuntary flexion of the affected finger(s). However, extension or a
combination of flexion and extension may occur as well. Dystonia affecting only one finger is
more likely to spread to adjacent fingers than to a more distant one (Conti et al., 2008; Frucht,
2009). In embouchure dystonia, facial, cervical and tongue muscles are affected; lip- and/or
breathing incoordination are also common. Early symptoms are characterised by a lack of fine
motor control in already well-trained movements while performing (Figure 1).
Introduction
11
Fig. 1. Typical dystonic postures in musicians with hand and embouchure
dystonia. Figure from Jabusch & Altenmüller, (2006a). Reprinted with permission
from the authors.
2.2 Epidemiology and aetiology
The prevalence of FDM is estimated as 1% of musicians. It affects mostly male musicians
(male to female ratio is 4:1) and the age at onset varies from 18 to 60 years with a mean age
in the mid-30s (Altenmüller 2003; Altenmüller & Jabusch, 2010; Jabusch & Altenmüller
2006b; Lim et al., 2003). According to a recent investigation, about one fifth of affected
musicians tend to change profession (Lee et al., 2015). Alternatively, less severely affected
musicians often either select repertoire that does not trigger their dystonia or switch from solo
performance to instrumental teaching. Other epidemiological studies have shown that several
environmental factors can further explain the aetiology of dystonia. For example, professional
classical musicians are found to be at much higher risk than jazz, rock, pop or other
improvising musicians. The classical repertoire requires reproduction of predefined temporospatial fine motor patterns with temporal accuracy in a range of milliseconds. In contrast,
other musical genres such as jazz, rock or folk require a more free-style improvised manner of
performance and interpretation. Furthermore, musicians playing high-registered instruments
(e.g. violin) are more frequently affected than those playing instruments with a lower register
(e.g. double bass) (Jabusch & Altenmüller, 2006a, 2006b). With respect to localisation,
pianists and guitarists are more frequently affected on the right hand whereas violinists tend
to suffer on the left hand. These findings suggest that the higher the temporo-spatial
sensorimotor performance demands for a body region, the higher the risk of developing
dystonia (Altenmüller & Jabusch, 2010). Finally, a few studies focusing on the
psychopathology of musicians with dystonia have reported elevated levels of anxiety and
perfectionism (Altenmüller & Jabusch, 2009; Enders et al., 2011; Jabusch et al., 2004b). The
authors suggested that abnormal psychological features could additionally contribute to the
12 Introduction
manifestation of dystonia in musicians (for more details concerning psychological conditions
associated with FDM see section 3.2).
2.3 Genetics and heredity
Genetic predispositions have been found to be associated mainly with non-focal primary
forms of dystonia such as early onset, dopa-responsiveness, myoclonus, and paroxysmal
dystonias. These disorders have been labelled as “DYT” loci followed by a number indicating
the chronological order of the discovery and the phenotype (e.g. DYT1 - early-onset torsion
dystonia). Recently Marras et al. (2012) proposed an updated coding system which combined
the main clinical feature (“DYT”) and the gene name or chromosome locus (e.g. DYTTOR1A for early-onset generalised dystonia). This system, which provides a more
comprehensive classification, is divided mainly into isolated dystonias (early-onset
generalised dystonia, adolescent-onset dystonia of mixed type and adult-onset cranial-cervical
dystonia) and into combined dystonias (dystonia plus parkinsonism or myoclonus, or
paroxysmal dystonia plus other dyskinesia).
In contrast, to the above forms of dystonia, focal task-specific dystonias such as FDM or
writer’s cramp are much more rarely related to genetic abnormalities. However, investigations
support the argument that hereditary factors could contribute to the development of focal
dystonia in a considerable proportion of patients. A study by Stojanović et al. (1995)
investigated first-degree relatives of 43 patients with focal dystonia including torticollis,
blepharospasm and writer’s cramp. The authors found that 23% of patients had relatives
affected by related disorders. A similar study, which investigated 56 patients with
blepharospasm, found a positive family history in 27% of cases (Defazio et al., 2006). The
manifestation of FDM also seems to have a hereditary link. Altenmüller (2003) reported a
positive family history in about 10% of affected musicians. A more recent investigation,
focusing on genetic predisposition, investigated 28 families of musicians with dystonia. Half
of those patients reported positive family history (FH+) whereas the rest reported no family
history at all (FH-). Surprisingly, the study indicated that 36% of the FH- patients also had
relatives affected by focal dystonia. Finally, the same authors suggested that in at least some
cases, FDM may have a shared underlying genetic cause with other forms of task-specific
dystonia (Schmidt et al., 2009).
2.4 Pathophysiology
2.4.1 Structural and functional abnormalities
The pathophysiology of focal dystonia remains not fully understood. There are some
contradictory results which could be explained either by methodological or interpretational
differences, or by the different subtypes of dystonia being investigated. Most imaging studies
Introduction
13
find functional abnormalities of the basal ganglia-cortical loops. However a number of studies
have suggested structural abnormalities in different brain regions as well (Bhatia & Marsden,
1994; Fross et al., 1987; Prell at el., 2013; Rondot et al., 2001; Rutledge et al., 1988; Zoons et
al., 2011). Magnetic resonance imaging (MRI) studies in patients with cranial or hand
dystonia revealed a 10% increase in size of the putamen (Black et al., 1998) whereas Garraux
et al. (2004) found a bilateral grey matter increase in the hand area of primary sensorimotor
cortex in patients with hand dystonia. These findings are in contrast to the study of Delmaire
et al. (2007), which found a reduced volume in the same areas in patients with writer’s cramp.
In addition, Delmaire et al. (2007) reported a grey matter decrease in the thalamus and
cerebellum. A reduction in grey matter, which was more pronounced after a 5-year follow up,
was also found in the left caudate head and putamen, and in the premotor and primary
sensorimotor cortices bilaterally in patients with cervical dystonia (Pantano et al., 2011).
Egger et al. (2007) examined different types of primary dystonia (generalised, cervical, and
hand dystonia) and suggested that a common pattern of grey matter alterations exists in
patients with dystonia.
One of the very few imaging studies of pianists with right hand dystonia indicated an increase
in grey matter volume in the ipsilateral middle putamen in comparison to healthy pianists.
The authors further concluded that the lower the timing precision in piano execution, the
higher the grey matter volume in the middle putamen bilaterally (Granert et al., 2011). Finally,
increasing evidence suggests that abnormal activity of the cerebellum could also be involved
in the pathophysiology of dystonia (Avanzino & Abbruzzese, 2012; Lee et al., 2013;
Sadnicka et al., 2012). For instance, a transcranial magnetic stimulation (TMS) study found
reduced cerebellar modulation of the motor cortex excitability in patients with focal dystonia
(Brighina et al., 2009).
In addition to investigation of structural abnormalities, several functional neuroimaging
studies have been conducted in order to probe neuronal activity in specific brain regions.
Early positron emission tomography (PET) measurements demonstrated functional
abnormalities of the putamen and other components of basal ganglia-cortical circuits (Karbe
et al., 1992; Magyar-Lehmann et al., 1997; Perlmutter & Raichle, 1984; Stoessl et al., 1986).
A functional magnetic resonance imaging (fMRI) study conducted in patients with writer’s
cramp revealed bilateral enhanced activity of the putamen, caudate nucleus, internal globus
pallidus and lateral thalamus during the discrimination of tactile stimuli (Peller et al., 2006).
Two PET studies have shown deficient activity in the sensorimotor cortex in writer’s cramp
patients during a motor task paradigm (Ibáñez et al., 1999) and during sensory stimulation
(Tempel & Perlmutter, 1993). The first study additionally reported a reduced correlation
between premotor cortex and putamen activity, whereas the second found a reduced response
in the supplementary motor area. Lower signals in sensorimotor cortices have also been
reported in patients with laryngeal dystonia (Haslinger et al., 2005), whereas in patients with
14 Introduction
hand dystonia a persistent abnormal signal in the striatum has been observed immediately
following the end of a specific finger task (Blood et al., 2004). Another fMRI study in
writer’s cramp patients showed greater ipsilateral cerebellar activation, and an increased
activation of basal ganglia output via thalamus to motor and premotor cortical regions during
writing. The authors argued that this was evidence for the existence of dysfunctional
inhibition of the motor cortex leading to dystonic symptoms (Preibisch et al., 2001).
Finally, fMRI studies have also been conducted in musicians with focal dystonia. For instance,
affected guitarists revealed greater activation of the contralateral primary sensorimotor cortex
while performing with their musical instruments (Pujol et al., 2000). The authors concluded
that there is an abnormal recruitment of cortical areas during control of task-induced
movements. Recent investigations have also revealed an over-activation of somatotopic face
representations of primary sensorimotor and premotor cortex bilaterally in musicians with
embouchure dystonia (Haslinger et al., 2010), whereas guitarists with hand dystonia exhibited
irregular activation patterns in the motor-association system, with dysfunction primarily in
premotor regions and cerebellum (Kadota et al., 2010).
2.4.2 Dysfunction of the Basal Ganglia
The basal ganglia are subcortical nuclei located bilaterally in the forebrain. They comprise the
striatum (which consists of the caudate nucleus, the putamen, and the ventral striatum, which
also includes the nucleus accumbens), the globus pallidus, the substantia nigra (pars reticulata
and pars compacta) and the subthalamic nucleus (Kandel et al., 2000). The basal ganglia have
been associated with the tuning of fine motor control of voluntary movements, motor learning,
initiation and termination of voluntary movements and behavioural and emotional functions
(Helie et al., 2013; Hikosaka et al., 1995; Mink, 1996). The origin of focal dystonia has been
suggested to be an over-activity of the direct striatopallidal pathway of the basal ganglia
(Berardelli et al., 1998; Defazio et al., 2007; Hallett, 2004, 2006; Zeuner et al., 2015). As a
consequence, a reduced output of the internal globus pallidus (GPi) results in over-excitation
of the thalamic input to the cortical regions (Defazio et al., 2007).
Several studies have shown that the dopaminergic system may be affected in patients with
focal dystonia. The dopaminergic projection from the substantia nigra pars compacta (SNc) to
the striatum differentially affects the two striatal outputs (direct and indirect pathways).
Striatal neurons involved in the direct pathway (from putamen to GPi) have D1 dopamine
receptors responsible for facilitating transition, whereas striatal neurons involved in the
indirect pathway (from putamen to external globus pallidus [GPe]) have D2 receptors
involved in the reduction of transition (Kandel et al., 2000). A PET study has shown that
patients with focal dystonia have decreased (29%) dopamine D2 receptors in the putamen
(Perlmutter et al., 1997). Similar findings have also been reported by Naumann (1998) in
Introduction
15
patients with idiopathic cervical dystonia. The authors concluded that dystonia resulted from
disturbances of the indirect pathway of the basal ganglia. A reduced striatal D2 receptor in the
caudate and putamen has also been reported in patients with idiopathic torsion dystonia
(Asanuma et al., 2005).
2.4.3 Loss of inhibition
Movement excitability, muscular overflow of activity in adjacent muscles, and muscular cocontractions in patients with focal dystonia have been explained as consequences of loss of
inhibition. However, it remains unclear whether loss of inhibition indicates another cause of
dystonia, or is rather an adaptive reaction to the already-manifested dystonic symptoms
(Hallett, 2006; Quartarone & Hallett, 2013; Torres-Rossotto & Perlmutter, 2008).
Studies based on TMS have repeatedly indicated reduced cortical inhibitions in patients with
focal dystonia. For instance, a reduction in both sides (symptomatic and asymptomatic) of
intracortical inhibition has been reported by Ridding et al. (1995) and Rona et al. (1998). In
contrast, Chen et al. (1997) reported a reduction of intracortical inhibition only in the
symptomatic hemisphere during voluntary muscle activation in writer’s cramp. Impaired
modulation of intracortical inhibition during the performance of a phasic index finger flexion
task has also been reported by Stinear and Byblow (2004a) in patients with focal hand
dystonia (FHD). Magnetic resonance spectroscopy (MRS) indicated a reduction in γAminobutyric acid (GABA), a major inhibitory neurotransmitter, in the sensorimotor cortex
and lentiform nuclei in patients with focal dystonia. GABA was significantly decreased in the
contralateral side to the affected hand (Levy & Hallett, 2002). Finally, lack of inhibition in
patients with writer’s cramp has also been demonstrated based on elevated excitability at the
corticospinal level during stimulation (Quartarone et al., 2003).
Another factor found to be related to focal dystonia is the loss of surround inhibition. In
healthy subjects, neighbouring muscles not directly engaged in a specific movement task
become actively inhibited (Hallett, 2011; Sohn & Hallett, 2004b; Stinear & Byblow, 2004b).
Numerous studies have demonstrated that this function is abnormal in patients with focal
dystonia (Beck et al., 2008, 2009; Hallett, 2011; Quartarone et al., 2005; Sohn & Hallett,
2004a). Rosenkranz et al. (2005) investigated pathophysiological differences between
musician’s and writer’s cramp. The study involved the stimulation of a single muscle of one
hand with a vibration, while the corticospinal excitability of the stimulated and other muscles
of both hands were tested with TMS. In healthy non-musicians the sensory stimulus of the
vibrated muscle evoked potentials of greater amplitude and demonstrated a decrease in shortlatency intracortical inhibition. The pattern in muscles of the non-vibrated hand was exactly
the opposite. These effects were abnormal in both focal dystonia groups, and were explained
as being due to a loss of surround inhibition. The authors suggested that the extensive practice
16 Introduction
required for music performance may lead to FDM patients undergoing abnormal changes in
the organisation of the motor cortex.
2.4.4 Maladaptive plasticity and sensory dysfunction
Physiological investigations have indicated that abnormal plasticity, mainly in sensory and
motor areas, could contribute to the pathogenesis of focal dystonia (Hallett, 2006; Quartarone
& Hallett, 2013; Quartarone & Pisani, 2011; Quartarone et al., 2003, 2006). A pioneering
animal study in focal dystonia was conducted by Byl and Merzenitch (1996). Monkeys were
trained to perform a long repetitive stereotypical task until their movement accuracy declined
to a level typical of impairments seen in hand dystonia. As a result of the reduced fine motor
control, cortical recordings in the sensorimotor cortex showed a degradation of cortical digit
representations of sensory information. These findings strongly support the idea that
environmental factors related to repetitive movement activities can impair sensory receptive
fields and promote the manifestation of focal dystonia. A study combining TMS and
transcranial direct-current stimulation (TDCS) found impaired homeostatic control
(corticospinal imbalance between excitation and inhibition) in writer’s cramp patients. The
authors suggested maladaptive plasticity of the sensorimotor circuits as an explanatory
mechanism (Quartarone et al., 2006). The cause of abnormal plasticity in focal dystonia
patients is still debated. It could either be a consequence of the loss of inhibition as discussed
above (Hallett, 2011), or result from extensive repetitive tasks (Torres-Russoto & Perlmutter,
2008).
Investigations of sensory dysfunction indicated that focal dystonia is not only characterised
by motor deficits but is also a disorder involving sensory abnormalities (Hallett, 2011).
Magneto-encephalographic (MEG) studies found bilaterally abnormal somatotopic
organisation of the hand in patients with unilateral hand dystonia (Nelson et al., 2001).
Further studies focusing on FHD have also reported greater temporal and spatial
discrimination thresholds in both affected and unaffected body regions (Bara-Jimenez et al.,
2000; Bradley et al., 2010; Fiorio et al., 2003; Molloy et al., 2003; Sanger et al., 2001;
Scontrini et al., 2009; Tamura et al., 2008). Interestingly, Molloy et al. (2003) reported
increased spatial discrimination thresholds for focal dystonia patients (i.e. hand dystonia,
blepharospasm and cervical dystonia) but not for generalised DYT1 dystonia patients,
suggesting that alterations of sensory processing have a primary pathophysiological role in
the manifestation of focal dystonia. A magnetic source imaging study, which compared handaffected FDM patients with healthy musicians (HM), indicated that patients, in comparison to
HM, were characterised by an overlapping of the digit representations in the symptomatic
somatosensory cortex. This effect was less pronounced in the contralateral non-affected hand
(Elbert et al., 1998; Münte et al., 2002). Finally, more recent EEG studies reported that
Introduction
17
Fig. 2. Triggering factors contributing to the manifestation of FDM. (Figure from Altenmüller & Jabusch (2010). Original
source from Jabusch & Altenmüller (2006a). Reprinted with permission from the authors.
pianists with focal dystonia show deficient phase synchronisation between those cortical
regions involved in preparation of upcoming motor movements (Ruiz et al., 2009, 2011).
With regard to the many, partially contradictory pathophysiological findings, the extent to
which they contribute to the genesis of dystonia, as opposed to being consequences of it,
remains uncertain. Taking all the above epidemiological and pathophysiological findings
together, FDM is clearly a complex neurological movement disorder, characterised by a
multifactorial aetiology. Triggering factors contributing to the manifestation of dystonia are
schematically represented in Figure 2.
2.5 Treatment methods
Due to the multi-aetiological cause and the limited pathophysiological understanding of focal
dystonia, a range of treatment methods are used in clinical practice and only few randomised
prospective studies exist. Oral medications such as anticholinergics (e.g. trihexyphenidyl),
dopaminergic and GABAergic drugs (e.g. benzodiazepines or baclofen) are often used. In the
case of musician’s dystonia, trihexyphenidyl has been reported as one of the most effective
medications (Jabusch et al., 2005). However, sometimes these substances are not welltolerated, giving rise to side-effects. Another method used in FHD dystonia is the injection of
botulinum toxin (BTX) type A in the dystonic muscle(s) (Schuele et al., 2005). BTX reduces
muscular activity and alleviates cramping and abnormal postures (Filippi et al., 1993).
However, its effect is temporary, lasting from three to six months, and muscular weakness
18 Introduction
may cause deterioration of playing ability (Cole et al., 1995). Other effective treatments with
long-term effects include retraining of the sensorimotor system (Altenmüller & Jabusch,
2010; Byl & McKenzie, 2000; Candia et al., 2003). Retraining frequently involves prolonged
training periods which can last up to two years. These therapies focus on the restoration of
hand sensory function, disorders of which have been explained above. Retraining and BTX
injections have been reported as the most effective treatment approaches in musicians with
dystonia (Hallett et al., 2009; Schuele et al., 2005; van Vugt et al., 2014).
Further treatment approaches include the immobilisation of the affected limb with specially
designed splints, adjustment of performance demands (e.g. selection of a repertoire which
does not trigger dystonia), ergonomic adaptations (e.g. instrument modifications) and
psychological supervision (Altenmüller & Jabusch, 2010; Frucht, 2009; Pesenti et al., 2004;
Priori et al., 2001). Surgical treatments, such as a stereotactic nucleus ventrooralis
thalamotomy (Taira & Hori, 2003) or deep brain stimulation have also been used (Tisch et al.,
2006a, b). However, surgical approaches are rather rare and are mainly used in more disabling
generalised dystonias (Torres-Russotto & Perlmutter, 2008). In summary, treatment for focal
dystonia is mostly symptomatic and there is still an urgent need to improve treatment efficacy.
Introduction
19
3 PSYCHO-PSYCHIATRIC FEATURES
3.1 Psychopathology in primary focal dystonia
Since the historical division between neurology and psychiatry, the treatment of movement
disorders has fallen within the purview of neurologists. However, over the last two decades a
plethora of studies have revealed that common movement disorders such as Parkinson's
disease, idiopathic dystonia, and Huntington's disease are accompanied by non-motor features
such as depression, anxiety, specific phobias, various obsessions, and cognitive deficits in
certain domains (Aarsland et al., 1999; Cummins et al., 2015; Gündel et al., 2001, 2003;
Halstead et al., 1994; Lennox & Lennox, 2002; Paulsen et al., 2001; Schröder et al., 2006,
2010; Stamelou et al., 2012). Ron (2009) suggested that:
“Dysfunction of basal ganglia-thalamo-cortical connectivity extends to limbic loops involving the
amygdala and orbitofrontal cortex that elicit or suppress motor activity in response to emotions”.
As explained above, dysfunction of the cortico-striatal-thalamo-cortical (cortico-basal
ganglia-cortical) circuit form part of the pathophysiology of primary dystonia (Hallett, 2006;
Quartarone & Hallett, 2013). However, this circuit has also been reported to support nonmotor function, such as sensory, cognitive, learning and reward processing. The basal ganglia
in general are involved in many cognitive, behavioural and emotional functions (Everitt &
Robbins, 2005; Graybiel, 2005; Helie et al., 2013; Hikosaka et al., 1995; Mink, 1996; Shatner
et al., 2003; Stamelou et al., 2012; Yin & Knowlton, 2006). There is evidence that the corticostriatal-thalamo-cortical circuits and specifically cortical-limbic-striatal and basal ganglia
dysfunction play an originating role in depression (Alexander et al., 1990; Stefurak et al.,
2003). Cavallaro et al. (2002) hypothesised that disturbances of the striato-thalamo-cortical
circuitry may be commonly associated with idiopathic focal dystonia and obsessivecompulsive symptoms. A further neurobiological link between focal dystonia and various
psychiatric disorders may be the loss of inhibition. As is the case with focal dystonia,
neuroimaging studies have reported over-excitation in several cortical and subcortical brain
regions in patients with depression (Fitzgerald et al., 2008; Savitz & Drevets, 2009). Those
authors suggested that loss of inhibition could be associated with depression, which is an
argument supported by studies in animal models (Hasler & Northoff, 2011).
Numerous studies exploring the psychopathology of focal dystonia have reported psychiatric
disorders or psychological instabilities in a considerable proportion of patients (Kuyper et al.,
2011; Stamelou et al., 2012). Fabbrini et al. (2010) investigated psychiatric features in 89
patients diagnosed with primary focal dystonia. All patients were interviewed based on the
20 Introduction
DSM-IV2 and were therefore evaluated for possible obsessive-compulsive disorders (OCD),
anxiety and depression based on standardised psycho-diagnostic instruments. 57.3% of the
patients were diagnosed with additional psychiatric disorders such as depressive conditions.
Moreover, the authors proposed that these features were supplementary to the motor
dysfunction rather than a psychoreactive phenomenon. Psychiatric comorbidities have also
been examined in a large group of patients with spasmodic torticollis (n = 116). Social phobia
was reported in 41.3% of the patients, whereas depressive coping behaviour was found to be
the main predictor of this comorbidity (Gündel et al., 2001, 2003). Patients with spasmodic
torticollis revealed 3.7 times increased risk for psychiatric comorbidities related to anxiety
and depression. This investigation is remarkable since other patients (specifically diagnosed
with alopecia areata), with similar physical appearance and body image satisfaction, were
used as controls. Matched criteria associated with body image between patients and controls
ensured that any psychiatric comorbidity would not be a secondary effect after the onset of
the condition.
Further studies investigating psychopathology in patients with spasmodic torticollis reported
psychopathology in about half of the patients. The most frequently detected features were
depressive disorder and anxiety (Moraru et al., 2002; Wenzel et al., 1998). Anxious
personality disorders related to obsessive-compulsive and avoidant behaviour were also found
in 32.6% of 86 patients diagnosed with primary focal dystonia (Lencer et al., 2009). Finally,
one study by Scheidt et al. (1996), who found psychopathology in more than 50% of patients
with spasmodic torticollis, reported an exacerbation of psychopathology under stressful
psychosocial life events. Gündel et al. (2007), who detected psychiatric comorbidities in a
considerable proportion of patients suffering from spasmodic dysphonia, found a positive
correlation between the level of the psychiatric comorbidities (i.e. depression and anxiety) and
the severity of the disorder. These authors suggested that this correlation may be a result of a
strong interaction between the somatic complaints of the specific type of dystonia and the
psychiatric complaints. Only a few studies have reported an association between psychiatric
disorders and the severity of dystonia (Lewis et al., 2008; Naber et al., 1998; Scheidt et al.,
1996).
Cavallaro et al. (2002) examined 76 patients affected by idiopathic focal dystonia. 19.7% of
them were additionally affected by OCD with 13.8% having OCD-related family history. The
authors proposed a common pathophysiological mechanism in OCD and focal dystonia; other
studies have suggested that dystonia and OCD are derived from the same dysfunctional
circuits of the basal ganglia (McNeill, 2003). Recently, Lehn et al. (2014), who investigated
psychopathology in 103 patients with focal dystonia, found increased levels of OCD followed
2
The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), is a standardised classification manual
used by clinicians, therapists, researchers, and others for diagnosing mental health disorders in children and adults. The
DSM-IV is published by the American Psychiatric Association.
Introduction
21
by anxiety and depression. The authors also showed that anxiety features may have better
discriminatory power to distinguish patients with and without psychopathology. Higher
prevalence of OCD in patients with focal dystonia has been also reported by Bihari et al.
(1992), Barahona-Corrêa et al. (2011) and Mula et al. (2012).
Finally, in addition to the psychiatric conditions in patients with dystonia, several other mild
non-motor features, such as cognitive and emotional impairments (Aleman et al., 2009;
Bugalho et al., 2008; Jahanshahi et al., 2003; Nikolova et al., 2011) or sleep disturbances
(Avanzino et al., 2010; Trotti et al., 2009; Wein & Golubev, 1979) have been reported (for
reviews, see Kuyper et al. [2011] and Stamelou et al. [2012]). Taken together, the studies
mentioned above clearly reveal that a considerable proportion of patients with focal dystonia
(~50%) are additionally diagnosed with psychopathology. Depression, OCD, anxiety and
specific phobias seem to be the most frequent features accompanying motor symptoms
(Stamelou et al., 2012).
3.2 Psychopathology in Musician’s Dystonia
Only a few studies have focused on psychopathology in musician’s dystonia. Jabusch et al.
(2004b) examined psychological conditions in 20 FDM patients, 20 musicians with chronic
pain, and 30 HM. Personality features (e.g. somatic complains, emotionality, irritability) were
examined based on the Freiburg Personality Inventory (FPI-R) (Fahrenberg et al., 1994),
while features such as self-concept of abilities and control orientations were tested using the
Competence and Control Orientation (QCC) inventory (Krampen, 1991). Finally a selfdesigned questionnaire was constructed in order to assess perfectionism and anxiety. Both
patient groups revealed elevated levels of anxiety in comparison to healthy controls, with
FDM patients exhibiting more perfectionism. The authors speculated that psychological
conditions in musicians with dystonia and in those with chronic pain pre-dated the onset of
the main disease. Another study conducted by the same laboratory focused exclusively on
anxiety disorders (e.g. social phobia, agoraphobia) (Jabusch & Altenmüller, 2004). Again,
FDM (n = 20) and chronic pain (n = 20) groups were compared with healthy controls (n = 30).
All participants filled out an investigator-designed questionnaire. Findings indicated that
social phobias and specific phobias, which seemed to appear before the onset of dystonia,
were more prominent in FDM patients. Finally, a more recent investigation explored
psychopathology in musicians with dystonia by comparing 44 FDM patients with 45 HM and
44 healthy non-musicians (Enders et al., 2011). Anxiety and personality traits were examined
using the NEO Five-Factor Inventory (NEO-FFI) (Costa & McCrae, 1992) and the State-Trait
Anxiety Inventory (STAI) (Spielberger & Gorsuch, 1983). The FDM patients exhibited
increased levels of neuroticism and general state and trait anxiety in comparison to the two
control groups. As with previous studies, the authors suggested that these psychological
conditions were not psychoreactive phenomena.
22 Introduction
The above-mentioned studies suggest that FDM patients are characterised primarily by
elevated levels of anxiety, perfectionism and neuroticism. If we consider that neuroticism is a
personality trait largely involving anxiety, fear, worry, guilt, and depressed mood (Matthews
et al., 2003; Thompson, 2008) we can conclude that features related to anxiety and
perfectionism - which also seem to pre-date the onset of the disease - can be considered
psychiatric comorbidities in musicians with focal dystonia. Increased anxiety has also been
reported in many other forms of focal dystonia (Gündel et al., 2001, 2007; Lencer et al., 2009;
Moraru et al., 2002), whereas perfectionism may be more related to occupations such as
music and sports (Altenmüller & Jabusch, 2009; Gucciardi et al., 2012).
Musicians affected with focal dystonia are mostly classical performers. The classical
repertoire requires practising and interpreting with maximal temporal and pitch precision.
These demands minimise the error rate and consequently maximise the expectation of the
performers and audience. In addition, a successful performance often is the “ticket” to the
next job (performance). This concept is highly associated with income, carrier-development
and the social prestige of the musicians. These factors trigger psychosocial pressure in a
reward and punishment context, which may well lead to increased levels of anxiety and
perfectionism (Altenmüller & Jabusch, 2010). Jabusch & Altenmüller (2004) suggested that
pre-existing anxiety and perfectionism could contribute to the manifestation of dystonia. They
claimed that motor disturbances in musicians with increased psychological conditions may be
perceived as a threatening element (emotional stress) and therefore could impair emotionallyinduced memory consolidation. Emotional memory consolidation relies on noradrenergic
activation of the basolateral amygdala (BLA) (Clayton & Williams, 2000; Ferry & McGaugh,
2000; McGaugh, 2000; Packard et al., 1994; Williams et al., 1998), which projects to the
primary motor cortex (Sripanidkulchai et al., 1984). Based on animal studies, Bergado et al.
(2006) indicated that activation of the BLA also contributes to the reinforcement of neural
plasticity. Impairments of this circuit in combination with dysfunctional motor programs may
additionally contribute to the manifestation of dystonia (Figure 3). To summarise, the authors
suggested that emotionally-induced motor memory consolidation could contribute to the
development of dystonia (Altenmüller & Jabusch, 2009).
Animal model studies have similarly demonstrated that pathologies of the motor system could
be influenced by stress and glucocorticoids, whereas stress-associated anxiety or emotional
changes associated with stress can also affect skilled fine motor movements (Kirkland et al.,
2008; Metz, 2007; Metz et al., 2001; 2003, 2005; Smith et al., 2008; Zucchi et al., 2009).
Making music in professional contexts requires extreme fine motor skills under emotionally
charged conditions. Therefore exploring psychopathology in musicians with focal dystonia
may contribute to the understanding of the common neuro(psycho)biological links between
focal dystonia and various psychiatric disorders.
Introduction
23
Fig. 3. Emotionally-induced memory consolidation in FDM patients with elevated levels of anxiety and perfectionism.
Increased norepinephrine release of the basolateral amygdala (BLA), which projects to the primary motor cortex (M1), is a
prerequisite for memory-enhancing effects of glucocorticoids. It has been suggested that emotional memory consolidation
may contribute to the development of dystonia. However it remains unknown whether modulatory activity of the BLA also
has an effect on the basal ganglia circuit (Jabusch & Altenmüller, 2004). GPe = external globus pallidus; PM = premotor
cortex; S1 = somatosensory cortex; SMA = supplementary motor area; GPi = internal globus pallidus; STN = subthalamic
nucleus. Figure from Jabusch & Altenmüller (2004). Original source from McGaugh (2000). Reprinted with permission
from AAAS.
24 Introduction
4 AIMS
Based on previous studies exploring psychopathology in FDM, several questions have been
derived for the present thesis:
•
Do musicians with dystonia suffer from performance-related trait anxiety and
perfectionistic tendencies more frequently than healthy musicians, when assessed with
standardised psycho-diagnostic instruments? Could stress-coping strategies also
contribute to the understanding of the psychopathology of FDM patients?
•
If psychopathology exists among FDM patients, is it associated with all patients or
only with a certain class of them?
•
If subgroups do indeed exist, are there any phenomenological or motor outcome
differences between patients with and without psychopathology?
•
How do patients with and without psychopathology respond to psychosocial stressors?
Is there any impact of psychosocially stressful events on the motor symptoms of FDM
patients?
The major aim of the current work was to investigate the psychopathology of musicians with
focal dystonia and its possible impact on motor function. The research questions above were
addressed in three different studies, each presented in a separate chapter with the following
specific objectives:
1. The first study presents an open design exploratory analysis, which investigates the
psychological profile of FDM patients. A range of psycho-diagnostic subscales
exploring performance-related trait anxiety, perfectionism and stress-coping strategies
were used.
2. The second study was conducted in order to assess the feasibility of a complex
experimental paradigm designed to examine the effect of stress on motor performance
of FDM patients.
3. Finally, the last study examines electrophysiological motor performance features of
FDM patients; firstly, before and after exposure to psychosocially stressful events, and
secondly in association with psychopathology.
CHAPTERS
1
PSYCHOLOGICAL CHARACTERISTICS IN MUSICIAN'S DYSTONIA
A NEW DIAGNOSTIC CLASSIFICATION*
Christos I. Ioannou, Eckart Altenmüller
Institute of Music Physiology and Musicians' Medicine, Hannover University of Music, Drama and Media,
Emmichplatz 1, 30175 Hannover, Germany
*
The current chapter corresponds to an article already published in the journal Neuropsychologia,
2014, Vol. 61, pp. 80-88.
(doi:10.1016/j.neuropsychologia.2014.05.014)
Author contributions: Experimental design: CII, EA; Clinical examination of patients: EA; Conducting the
experiments, Data acquisition and pre-processing, Statistical analysis: CII; Writing of manuscript: CII;
Contribution to the writing and revision of manuscript: EA.
Abstract: Numerous studies suggest that dysfunctional basal ganglia-thalamo-cortical
circuits are involved in both movement disorders and psychiatric impairments. The current
exploratory investigation explored possible psychological differences, firstly between 24
healthy musicians (HM) and 24 musicians diagnosed with focal dystonia (FDM) (Study I),
and secondly among 35 FDM patients only (Study II). Results revealed that FDM patients are
six times more likely to exhibit elevated anxiety, perfectionistic and stress characteristics than
HM. These psychological conditions might contribute as aggravating risk factors to the
development of FDM. However, half of the FDM patients did not demonstrate any signs of
anxiety, perfectionism or stress. The findings point to the clear existence of two different
psychological profiles among FDM patients. We suggest that this psychological distinction
might reflect two different maladaptive processes mediated via different circuits of the
cortico-basal ganglia-thalamicloops. The new classification of FDM patients will contribute
to the reinforcement of the diagnostic repertoire, necessary for the selection of more specific
treatment methods.
Keywords: Focal dystonia; musicians; psychological characteristics; diagnostic classifycation; cluster analysis
27
2
OBJECTIVE EVALUATION OF PERFORMANCE STRESS
IN MUSICIANS WITH FOCAL DYSTONIA
A CASE SERIES*
Christos I. Ioannoua, Shinichi Furuyaa, b, Eckart Altenmüllera
a
b
Department of Information and Communication Science Sophia University
4-4 Chiyodaku, Tokyo, Japan
*
The current chapter corresponds to an article already in press in the journal of Motor Behavior.
(doi: 10.1080/00222895.2016.1161590)
experiments, Data acquisition and pre-processing, Statistical analysis: CII; Electromyographic analysis: SF;
Writing of manuscript: CII; Contribution to the writing and revision of manuscript: SF, EA.
Abstract: Five musicians suffering from focal dystonia participated in a pilot study which
examined the feasibility of an experimental protocol designed to assess musicians’ motor
performance under stress. Electrocardiography (ECG), free cortisol levels and subjective
assessments were used to monitor alterations of the hypothalamic-pituitary-adrenal (HPA)
axis. As measures of motor outcome, temporal variability of finger movements and muscular
co-contraction (EMG) of the wrist flexor and extensor were assessed. Findings suggest that
the specific experimental design could be successfully applied. Several methodological issues
such as carryover effects, the use of free cortisol, the inclusion of a double baseline and the
classification of dystonic patients into stress responders and non-responders are analysed and
discussed.
Keywords: Focal dystonia; motor performance; EMG; ECG; free cortisol; Trier Social Stress
Test
29
3
THE IMPACT OF STRESS ON MOTOR PERFORMANCE IN
SKILLED MUSICIANS SUFFERING FROM FOCAL DYSTONIA
PHYSIOLOGICAL AND PSYCHOLOGICAL CHARACTERISTICS
Christos I. Ioannoua, Shinichi Furuyaa, b, Eckart Altenmüllera
a
b
Department of Information and Communication Science Sophia University
4-4 Chiyodaku, Tokyo, Japan
*
The current chapter corresponds to an article already published in the journal Neuropsychologia,
2016, Vol. 85, pp. 226-236.
(doi: 10.1016/j.neuropsychologia.2016.03.029)
experiments, Data acquisition and pre-processing, Statistical analysis: CII; Electromyographic analysis: SF;
Writing of manuscript: CII; Contribution to the writing and revision of manuscript: SF, EA.
Abstract: Recent investigations have suggested that stress can modulate motor function.
However, the impact of stress on motor performance of musicians suffering from focal
dystonia (FDM) remains unknown. The current study assessed motor performance in 20 FDM
patients and 16 healthy musicians (HM) before and under stress. Stress was manipulated
using the Trier Social Stress Test (TSST). Motor performance was evaluated based on
analysis of electromyographic (EMG) activity and temporal variability, while electrocardiography (ECG) and the level of free cortisol were used to test for objective alterations
of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, the psychological profiles of both
groups were analyzed using three psycho-diagnostic standardized questionnaires. Results
showed that patients' motor impairments did not change under acute stressful conditions.
However, an increase in muscular co-contractions was observed, reflecting a physiological
muscular response under stressful conditions. Psycho-diagnostic analysis revealed higher
levels of psychological traits related to elevated anxiety, stress and perfectionism in 40% of
the patients. Although the motor outcome between those patients and those with an opposing
psychological profile did not differ, patients characterized by stressful and perfectionistic
personalities had, on average, developed dystonia about ten years earlier than the rest of the
patients. The current study suggests that acute stress conditions may not have any direct
impact on fine motor control of FDM patients. However psychological traits associated with
increased stress, anxiety and perfectionism may have a long-lasting effect on the motor
function of affected musicians, by promoting the acceleration or even the triggering of
dystonia.
Keywords: Focal dystonia in musicians; motor outcome; temporal variability; stress; EMG;
ECG; cortisol; psycho-diagnostics
31
CONCLUSIONS AND OUTLOOK
Conclusions and Outlook
35
CONCLUSIONS
The current thesis explored psychological conditions and their possible impact on motor
performance in musicians suffering from focal dystonia. Limitations and questions derived
from previous studies exploring psychopathology in FDM patients (see section 4) were
investigated in three consecutive studies.
Summarising, the first study focused on the exploration of the psychological profile of FDM
patients. A cluster analysis indicated that based on specific psychological features related to
anxiety, perfectionism and stress, FDM patients can be classified into those with and those
without psychopathology (ratio about 1:1). The risk of exhibiting these psychological
comorbidities was about six times greater for patients than healthy controls. Most previous
studies exploring psychopathology in other forms of focal dystonia have indicated that it
occurs in a considerable proportion of, but not in all patients (for a review see Stamelou et al.
[2012]). Our results indicate that FDM patients are characterised by psychological
heterogeneity, leading to the suggestion that further exploration and diagnostic classification
is needed in FDM. We further conclude that psychological conditions could contribute to the
development of dystonia in musicians, and as previous studies also suggested (Enders et al.,
2011; Jabusch & Altenmüller, 2004; Stamelou et al., 2012) our findings indicate that
psychological conditions are not psychoreactive phenomena. In line with ideas set out by
Alexander (1990), Haber and Calzavara (2009), and Ron (2009), the first study suggests that
the two subgroups (FDM patients with and without psychopathology) might reflect two
different maladaptive processes mediated via different circuits of the cortico-basal gangliathalamic loops.
Furthermore, we proposed a heuristic model with which individuals could be psychologically
evaluated and classified. This model remains useful for experimental procedures and could be
further developed into a more comprehensive and standardised psycho-diagnostic protocol in
a clinical setting. Finally, the first study suggests that musicians suffering from focal dystonia
should be additionally submitted to neurological evaluation with respect to possible psychopsychiatric comorbidities. A broader neuropsychological diagnosis would help the selection
of appropriate therapeutic approaches. The establishment of standardised psycho-diagnostic
instruments, suitable for musicians suffering from dystonia, would reinforce the diagnostic
repertoire of physicians.
The second study was conducted in order to examine the feasibility of a complex
experimental paradigm designed to assess musicians’ motor performance before and after
stress. According to our knowledge this has never previously been investigated in FDM
patients, nor in patients with other forms of focal dystonia. A well-established protocol (TSST,
Kirschbaum et al., 1993) designed to induce stress in laboratory conditions, was adapted and
36 Conclusions and Outlook
alterations of the HPA axis were continuously assessed using physiological measurements
(ECG and cortisol analysis). The motor outcome of musicians was also evaluated using EMG
analysis and a MIDI-Analysis-System (Jabusch et al., 2004a) which examines the temporal
variability of precise finger strokes in scale playing. This pilot analysis indicated the stability
of the specific experimental design and provided further methodological insights such us the
effective application of a second baseline in order to eliminate carryover effects. On the basis
of the study, we suggest that the classification of dystonic patients (or any population which
may exhibit psychopathology) into stress responders and non-responders should be based on
objective rather than on subjective measurements. The novel experimental design, which was
successfully applied, could form a strong scientific tool for further examination of
psychophysiological factors in patients suffering from focal dystonia or other movement
disorders.
The final investigation comprised a combination of the psycho-diagnostic evaluation of the
first study and the experimental paradigm of the second study. The main goal was to explain
physiological (motor outcome) differences i) between FDM patients with and without
psychopathology and ii) under non-stressful versus stressful conditions. Findings showed that
FDM patients were characterised by impairments of fine motor control in comparison to HM
(Altenmüller & Jabusch, 2009, 2010; Jabusch et al., 2004a). The psycho-diagnostic analysis
replicated the results of the first study. However, no motor performance differences were
observed between patients with and without psychopathology, suggesting that abnormal
psychological conditions have no direct impact on the motor performance of affected
musicians. Similarly, FDM patients revealed no alterations of their fine motor control under
stress, although an increase in muscular co-contraction activity was observed, which was
explained as a normal physical reaction under stressful conditions. Finally, FDM patients
indicated greater sensitivity to psychosocial stressors compared to healthy musicians, which
could be explained by the increased levels of stress and anxieties in the former group.
Beside the fact that no motor outcome differences were found between patients with and
without psychopathology, a remarkable finding was that patients with psychopathological
comorbidities developed dystonia much earlier (by about ten years) than those without. This
could support the idea that common neurobiological networks interact during motor and
psychological control. Findings from animal model studies indicating that pathologies of the
motor system could be influenced by stress and glucocorticoids (Kirkland et al., 2008; Metz,
2007; Smith et al., 2008; Zucchi et al., 2009) may explain the acceleration of the
manifestation of dystonia in patients with psychopathology. The current result could also
provide further insights about the pathophysiology of focal dystonia. Our findings support the
theory that in patients with psychopathology, dysfunction of basal ganglia-thalamo-cortical
pathways could extend to limbic loops (Alexander et al., 1990; Cavallaro et al., 2002; Gündel
et al., 2003; Ron, 2009; Stefurak et al., 2003). Nevertheless, further studies focusing on
Conclusions and Outlook
37
structural and functional abnormalities between FDM patients with and without
psychopathology are needed. Concluding, and in line with previous findings from our
laboratory (Altenmüller & Jabusch, 2009; Enders et al., 2011; Jabusch & Altenmüller, 2004;
Jabusch et al., 2004b), the results of the current thesis provide support for psychopathology
constituting an aggravating risk factor in the development of FDM.
FUTURE ASPECTS
Based on the knowledge derived from the current thesis, new and related research questions
and directions arise:
•
Apart from psychological features related to anxiety, stress and perfectionism among
FDM patients, further comorbidities related to OCD and depression remain to be
examined.
•
Neuroimaging studies focusing on the structural and functional brain differences
between FDM patients with and without psychopathology may provide further
insights about the pathophysiology of focal dystonia.
•
Intervention studies based on the application of specific treatment approaches for
FDM patients with and without psychopathology may be informative about the
pathophysiology, and aid the development of new, more efficient treatments in the
field of focal dystonia.
DEFINITION
Finally, an additional suggestion concerns the classification and the definition of FDM. Until
now, and based on the traditional three-axis classification of dystonia: i) aetiology, ii) age at
onset and iii) body distribution (Albanese et al., 2011; Fahn, 2011), FDM has been classified
as primary (aetiology) and focal (body distribution). The age at onset is almost never reported
as the disorder always develops in adulthood (i.e. it is a late onset dystonia). Combining the
findings of the current investigation with the recently updated classification system of
dystonia introduced by Albanese et al. (2013), a new classification and definition of FDM is
essential. The system of Albanese et al. (2013) categorises dystonic conditions along two,
instead of three main axes: i) the clinical features and ii) the aetiology. The first axis is further
divided into five subgroups: i) age at onset, ii) body distribution, iii) temporal pattern, iv)
associated features and v) occurrence of other neurological manifestation. The fourth
subgroup is further broken down into isolated dystonia (when dystonic features are the only
38 Conclusions and Outlook
symptoms) and combined dystonia (when dystonic features occur alongside other movement
disorders such as myoclonus and parkinsonism). The word “isolated” was mainly introduced
to replace the term “primary”, which Albanese et al. (2013) deemed ambiguous. The fifth
subcategory (occurrence of other neurological manifestations) was included to cover the
existence of additional mainly non-motor (i.e. cognitive, psychological or psychiatric)
features. Therefore, according to the above classification and to the findings of the current
thesis we suggest that the following definition, partly based on the general dystonia definition,
(see section 1.2), would be most appropriate for FDM:
“Focal dystonia in musicians (FDM) is an isolated movement disorder characterised by
sustained or intermittent muscle contractions causing abnormal postures of the affected limb
or embouchure (focal). Symptoms are often initiated or worsened by voluntary actions
related to the playing of a musical instrument. FDM may occur with or without additional
non-motor neuropsychological conditions”.
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Zucchi, F. C., Kirkland, S. W., Jadavji, N. M., et al. (2009). Predictable stress versus
unpredictable stress: a comparison in a rodent model of stroke. Behav Brain Res,
205(1), 67-75.
AFFIDAVIT
I herewith declare that I autonomously carried out the PhD thesis entitled “Neuropsychological Triggering Factors in Musicians with Focal Dystonia”.
No third party assistance has been used.
I did not receive any assistance in return for payment by consulting agencies or any other
person. No one received any kind of payment for direct or indirect assistance in correlation to
the content of the submitted thesis.
I conducted the project at the following institution: Institute of Music Physiology and
Musicians’ Medicine, Hannover University of Music, Drama and Media.
The thesis has not been submitted elsewhere for an exam, as thesis or for evaluation in a
similar context.
I hereby affirm the above statements to be complete and true to the best of my knowledge.
04.12.2015
......................................................
date
Christos I. Ioannou
......................................................
signature
53
ACKNOWLEDGEMENTS
The current thesis would not have been possible to complete without the help and support of
many other people. First, I would like to express my gratitude and warmest thanks to my main
supervisor Prof. Dr. Eckart Altenmüller for the opportunity to work in his laboratory. His
supportive, creative, critical and constructive supervision, always accompanied by
friendliness, sensitivity and nice sense of humour were essential for the completion of the
project. Thanks are also extended to my co-supervisors, Prof. Dr. Reinhard Dengler and Prof.
Dr. Claudia Grothe, for their critical discussions and suggestions during our annual meetings.
A special thank you to the German Research Foundation (DFG) who funded the overall
project and to the Hannover University of Music, Drama and Media for its excellent facilities,
administration and continued assistance. Additional thanks also to the members (academic
and staff) of the Centre for Systems Neuroscience (ZSN) for the exciting and high-quality
courses, laboratory classes and scientific meetings during the PhD program.
Furthermore I would like to express my appreciation to all my collaborators in the Institute of
Music Physiology and Musicians’ Medicine (IMMM) for the friendly and supportive
atmosphere, their help in many different aspects during the last few years and their critical
discussions and encouragement (Dr. André Lee, Dr. Floris van Vugt, Dr. Shinichi Furuya,
Daniel Scholz, Martin Neubauer, Yousreya Pölkner, Dr. Erwin Schoonderwaldt, Dr. Felicia
Pei-Hsin Cheng and Dr. Maria C. van der Steen). A special thanks also to Dr. Michael
Großbach for his technical support, assistance, and critical and beneficial statistical
discussions. Finally, my great appreciation and thanks to all the internship students who
occasionally contributed to the project, to all the musicians who participated in the
experiments, to my assistant Mai Tran who helped me with the organisation and the
performance of the experiments, and to my great friend and colleague Alexander Billig for his
beneficial feedback on the improvement of scientific English.
The project was part of a larger investigation focusing on task-specific cramps in musicians
and athletes. During this project a great and continuing collaboration has been developed with
the German Sport University Cologne - Institute of Psychology, and specifically with my
great friends and colleagues Dr. Martin Klämpfl, and with Dr. Babett Helen Lobinger and
Prof. Markus Raab, who I would like to thank whole-heartedly for their critical feedback and
encouragement.
Furthermore, I would like to express my great thanks to all my friends but especially to Spiros
Pisinos for his great support and encouragement since the very beginning of my studies. He
has always stood by my side. Likewise, I would like to express my gratitude to my partner
Katerina Papachristou for her patience, love and support during the last few years.
Finally, my truly appreciation and deep thanks to my family: my mother Xenia and my father
Yiannis for their unconditional love, support, encouragement and trust, as well as my two
brothers Charis and Kyriacos with their wives Evdokia and Lilia respectively, for their love,
support, trust, critical discussions and encouragement during this magnificent academic and
life journey. Σας ευχαριστώ από τα βάθη της ψυχής µου!
55
Doctor of Philosophy (PhD) thesis submitted
by Christos I. Ioannou
Neuropsychological Triggering Factors in Musicians with Focal Dystonia
http://www.tiho-hannover.de/de/startseite/
Centre for Systems Neuroscience
http://www.tiho-hannover.de/forschung/zsn-hannover/
http://www.immm.hmtm-hannover.de/en/home/

Neuropsychological Triggering Factors in Musicians with Focal

Transcription

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