COMPUTATIONAL TOOLS 63
Box 4.2
The International Consortium for Brain Mapping (ICBM):
A Probabilistic Atlas and Reference System for the Human Brain
In the human population, the brain varies structurally and functionally in currently undefined ways. It is clear
that the size, shape, symmetry, folding pattern, and structural relationships of the systems in the human brain
vary from individual to individual. This has been a source of considerable consternation and difficulty in
research and clinical evaluations of the human brain from both the structural and the functional perspective.
Current atlases of the human brain do not address this problem. Cytoarchitectural and clinical atlases typically
use a single brain or even a single hemisphere as the reference specimen or target brain to which other brains
are matched, typically with simple linear stretching and compressing strategies. In 1992, John Mazziotta and
Arthur Toga proposed the concept of developing a probabilistic atlas from a large number of normal subjects
between the ages of 18 and 90. This data acquisition has now been completed, and the value of such an atlas
is being realized for both research and clinical purposes. The mathematical and software machinery required
to develop this atlas of normal subjects is now also being applied to patient populations including individuals
with Alzheimer’s disease, schizophrenia, autism, multiple sclerosis, and others.
Talairach Atlas
To date, more than 7,000 normal subjects have been entered into the Talairach atlas project and a wide range
of datasets. These datasets contain detailed demographic histories of the subjects, results of general medical
and neurological examinations, neuropsychiatric and neuropsychological evaluations, quantitative “handed-
ness measurements”, and imaging studies. The imaging studies include multispectra 1 mm^3 voxel-size mag-
netic resonance imaging (MRI) evaluations of the entire brain (T 1 , T 2 , and proton density pulse sequences). A
subset of individuals also undergo functional MRI, cerebral blood flow position emission tomography (PET)
and electroencephalogram (EEG) examinations (evoked potentials). Of these subjects, 5,800 individuals have
also had their DNA collected and stored for future genotyping. As such, this database represents the most
comprehensive evaluation of the structural and functional imaging phenotypes of the human brain in the
normal population across a wide age span and very diverse social, economic, and racial groups. Participating
laboratories are widely distributed geographically from Asia to Scandinavia, and include eight laboratories, in
seven countries, on four continents.
World Map of Sites
A component of the World Map of Sites project involves the post mortem MRI imaging of individuals who
have willed their bodies to science. Subsequent to MRI imaging, the brain is frozen and sectioned at a reso-
lution of approximately 100 microns. Block face images are stored, and the sectioned tissue is stained for
cytoarchitectural, chemoarchitectural, and differential myelin to produce microscopic maps of cellular anat-
omy, neuroreceptor or transmitter systems, and white matter tracts. These datasets are then incorporated into
a target brain to which the in vivo brain studies are warped in three dimensions and labeled automatically.
The 7,000 datasets are then placed in the standardized space, and probabilistic estimates of structural bound-
aries, volumes, symmetries, and shapes are computed for the entire population or any subpopulation (e.g.,
age, gender, race). In the current phase of the program, information is being added about in vivo chemoarchi-
tecture (5-HT2A [5-hydroxytryptamine-2A] in vivo PET receptor imaging), in vivo white matter tracts (MRI-
diffusion tensor imaging), vascular anatomy (magnetic resonance angiography and venography), and cerebral
connections (transcranial magnetic stimulation-PET cerebral blood flow measurements).
Target Brain
The availability of 342 twin pairs in the dataset (half monozygotic and half dizygotic) along with DNA for
genotyping provides the opportunity to understand structure-function relationships related to genotype and,
therefore, provides the first large-scale opportunity to relate phenotype-genotype in behavior across a wide
range of individuals in the human population.
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