- Brain folds virtually unfolded to study brain disorder
Caren B. Les
A computerized brain atlas
has enabled scientists to study brain structure changes in subjects who have Williams
syndrome. This unusual developmental disorder impairs visual, spatial and problem-solving
skills, while sparing such functions as social and musical abilities. Identifying
connections among genetic changes and alterations in brain structure and function
could help clinicians and teachers develop customized educational strategies for
children with the disorder.
To conduct their study, David C. van Essen and
his colleagues at Washington University School of Medicine in St. Louis, along with
a team from Stanford University School of Medicine in California used the Population-Average,
Landmark- and Surface-based (PALS) Atlas. The tool is an electronic mapping of
the cerebral cortex, the folded surface layer of the brain that plays a role in
the higher cognitive functions of human behavior.
“New methods in computerized
brain mapping have been key to making new discoveries about how the structure of
the brain is affected in a specific neurological disorder,” according to van
Developed by neuroscientists at Washington
University in 2005, the atlas links brain function to the various wrinkles in the
cortex. It was initially based on MRI scans of the brains of 12 healthy people.
Cortical surface reconstructions were generated for each hemisphere, and the surfaces
were inflated, flattened and made to standard spherical shapes using software. A
target sphere was generated by averaging selected landmark contours from each of
the 24 hemispheres, and each hemisphere was deformed to the target using surface
The “surface based” approach
is essential for viewing the entire cortical sheet at once despite deep convolutions,
van Essen said. This technique is particularly powerful in detecting interesting
structural differences that were missed by the conventional volume-based method,
which also is used in the atlas.
PALS also is based on a population,
rather than on an individual brain, which is essential for dealing with the tremendous
variability in the pattern of cortical folding, he said.
For their study on Williams syndrome,
the scientists obtained data from MRI brain scans of 16 individuals with the disorder.
They aligned or registered each brain to the PALS atlas, enabling them to identify
33 folds in the cerebral cortex.
An electronic “surface based” brain atlas reveals abnormal
folding patterns of the cerebral cortex in Williams syndrome, a rare brain disorder.
In a lateral view (left) and midline view (right) of the cortex, the blue and green
areas indicate where the cortex is deeper on average in subjects with the disorder,
while the red and yellow areas show where it is deeper on average in the control
group. Seventeen regions of abnormal folding in the syndrome are visible in the
right hemisphere. Images courtesy of Washington University School of Medicine.
They could observe several changes
against a background of normal variability in folding patterns provided by the atlas.
They found 16 changes on the left side of the brain and identified 16 changes in
corresponding regions on the right side. One abnormality was present only on the
right side of the brain.
They also noticed that the olfactory
sulcus, a structure above the olfactory tract, tended to be shallower on average
in those with the syndrome.
The team wants to extend the approach
to other neurological and psychiatric disorders, and a number of collaborations
are under way, according to van Essen. A study on autism, a more common developmental
disorder, is in progress with a group at the University of California-Davis, and
it is expected that several previously unrecognized abnormalities in the folding
of the cortex will be revealed.
Journal of Neuroscience, May 17, 2006, pp. 5470-5483.
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