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 Essen.

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 registration.

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.