area Fp1 - Big Brain

Two new cytoarchitectonic areas of the
human frontal pole
1,3,5
1
1
1
Sebastian Bludau , Simon Eickhoff
,
Axel
Schleicher,
Hartmut
Mohlberg
1,2,3
1,3,4
Karl Zilles , Katrin Amunts
1
Institute of Neuroscience and Medicine (INM-1, INM-2), Research Centre Jülich, Jülich, Germany
2
C. and O. Vogt Institute for Brain Research, University of Düsseldorf, Düsseldorf, Germany
Contact:
s.bludau@fz-juelich.de
3
JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany
4
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany
5
Institute for Clinical Neuroscience and Medical Psychology, University of Düsseldorf, Düsseldorf, Germany
INTRODUCTION
OBSERVER-INDEPENDENT BRAIN MAPPING
A)
10 fixed human postmortem brains were
MRI scanned, embedded in paraffin
sectioned at 20μm in coronal and
horizontal plane, stained for cell bodies.
Taken during autopsy from a body donor
program of the Department of Anatomy at
the University of Düsseldorf.
ŸArea 10 of the frontal pole of the human
brain occupies a larger proportion of
the brain than in any other species.
ŸArea 10 is involved in higher cognitive
functions such as planning of future
actions and the ability to draw
analogies.
B)
C)
59
GLI(%)
The bars at profile position 59 and 123
corresponds to the significant maxima of
the Mahalanobis distance function in the
following graph D) caused by
cytoarchitectonic differences.[3]
123
D)
profile area Fp1
18
Quantification of profiles by a vector of 10
features. Computation of distances
between neighbouring blocks of profiles
using Mahalanobis distance.
16
C)
14
Published cytoarchitectonic maps of the
human frontal pole.
- Korbinian Brodmann[1] (A,B)
- Ongur and colleagues [2] (C)
(subareas 10p, 10r, 10m)
Digitized ROI with contour lines and
superimposed numbered curvilinear
traverses (red lines) indicating where
profiles were extracted.
Regions of interest (ROI) were defined by
visual inspection and digitized in
microscopic resolution (1pixel = 1.02µm)
using a ZEISS Axiocam2.0 system
enviornment.
ŸIts localization in stereotaxic space and
intersubject variability, however, are
still unknown.
B)
12
(Layers labelled with roman numerals)
10
Mahalanobis distance
A)
Mahalanobis distance function
6
Observer-independent delineation of
cortical borders as significant local
maxima in the Mahalanobis distance
function.
59
123
4
area Fp1
In order to receive statistically reliable
results block sizes ranging from 10 to 24
were analysed.[3]
2
8
6
4
III
II
2
0
10
20
IV
30
40
VI
V
50
60
70
80
90
0
100
Position (%)
20
40
60
80
100
120
140
160
profile position
Individual brains and areas Fp1& Fp2 linear registered to T1-weighted
single-subject template[4] (n=10)
Fp1
Fp2
Mahalanobis distance
CYTOARCHITECTURE OF AREA Fp1 & Fp2 AND PROBABILISTIC MAPS
3D RECONSTRUCTION
3
Fp1
Fp2
2
1
100
Fp1
3
200
300
Fp1
Fp2
2
Areas Fp1 & Fp2 after nonlinear elastic registration to the MNI reference
brain[5](n=10)
Observer-independently
detected borders from the
right hemisphere of a
horizontally cut brain. The
black lines mark the sections'
locations within the brain. The
three graphs show the
corresponding Mahalanobis
distance functions. Red lines
mark the significant borders
between areas Fp1 and Fp2.
Fp2
1
100
200
Fp1
3
Fp1
Fp2
Fp2
2
1
50
area Fp1
100
profile position
area Fp2
Individual areas of 10
brains were
integrated into one
probability map
10%
100%
[6]
META-ANALYTIC CONNECTIVITY MODELLING
• Investigation of functional connectivity by
coordinate-based metaanalysis of task-related activations
• Database driven approach(Brainmap.org)
GLI(%)
Regions that are co-activated above chance
with areas Fp1 & Fp2 as seed regions
V IV
III
II
I
200µm
[7,8]
• Delineation of concurrent activation patterns
Mitglied der Helmholtz-Gemeinschaft
VI
Comparison of the cytoarchitecture of areas Fp1 and Fp2
The lateral area Fp1 shows a broader layer II with a higher cell density, a higher
cell density in lower parts of layer III, and a broader layer IV than the medial area
Fp2. In addition to that, there was a higher cell density in upper layer V of area
Fp2, which could not be seen in area Fp1.
Probabilistic maps of areas Fp1 & Fp2 projected onto MNI reference brain.
Frontal A), medial B) C) view onto the probabilistic maps of the delineated areas Fp1 & Fp2.
Visualized as overlays on the MNI reference brain. The resulting cytoarchitectonic probabilistic
maps were thus registered in the “anatomical” MNI space[5]. The number of overlapping brains
for each voxel is color coded; e.g., green means that approximately 6 of 10 brains overlapped in
this voxel.
CONCLUSIONS
- Our probabilistic map represents the first stereotaxic map of the frontal pole.
- Area Fp2 shows a significantly smaller extent than described in a previous study [2], which was based on pure visual
architectonic analyses.
- The map provides an anatomical basis for comparison with in vivo neuroimaging data for studying structure-function
relationships.
- For the first time, an observer-independent subdivision into two distinct areas was demonstrated.
- The meta-analysis showed that areas Fp1 and Fp2 do not only differ with respect to their cytoarchitecture, but also
functionally.
References:
[1] Brodmann, K., 1909. Vergleichende Lokalisationslehre der Großhirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Verlag von Johann Ambrosius Barth, Leipzig.
[2] Ongur, D., Ferry, A.T., Price, J.L., 2003. Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 460, 425-449.
[3] Zilles, K., Schleicher, A., Palomero-Gallagher, N., Amunts, K., 2002. Quantitative analysis of cyto- and receptorarchitecture of the human brain. In: Toga, A., Mazziotta, J. (Eds.), Brain mapping: the methods. 2nd ed.
Academic Press, San Diego (CA), pp. 573--602.
[4] Evans, A.C., Marrett, S., Neelin, P., Collins, L., Worsley, K., Dai, W., Milot, S., Meyer, E., Bub, D., 1992. Anatomical mapping of functional activation in stereotactic coordinate space. Neuroimage 1, 43-53.
[5]
[6] Eickhoff, S.B., Bzdok, D., Laird, A.R., Kurth, F., Fox, P.T., 2011. Activation likelihood estimation meta-analysis revisited. Neuroimage.
[7] Laird A.R., Lancaster J.L., Fox P.T. (2005). BrainMap: The social evolution of a functional neuroimaging database. Neuroinformatics 3, 65-78.
[8] Fox P.T., Lancaster J.L. Mapping context and content: The BrainMap model. Nature Rev Neurosci 3, 319-321, 2002.
[9] Amunts, K., Kedo, O., Kindler, M., Pieperhoff, P., Mohlberg, H., Shah, N.J., Habel, U., Schneider, F., Zilles, K., 2005. Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex:
intersubject variability and probability maps. Anat Embryol (Berl) 210, 343-352.
Acknowledgments:
This study was supported by the BMBF project „Research collaboration on cognitive
performance and relevant disorders in humans”.Title: “Social gaze”: Phenomenology
and neurobiology of dysfunctions in high-functioning autism (HFA); Sub-project 4:
Cytoarchitectonic correlates of frontal lobe function and dysfunction (01GW0612,
K.A.).
Further funding was granted by the Helmholtz Alliance for Mental Health in an Aging
Society (HelMA; K.Z., K.A.) and by the Helmholtz Alliance on Systems Biology
(Human Brain Model; S.B.E.) and the NIH (R01-MH074457; S.B.E.).