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The Journal of Neuroscience, May 17, 2006, 26(20):5470-5483; doi:10.1523/JNEUROSCI.4154-05.2006

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Neurobiology of Disease
Symmetry of Cortical Folding Abnormalities in Williams Syndrome Revealed by Surface-Based Analyses

David C. Van Essen,¹ Donna Dierker,¹ A. Z. Snyder,² Marcus E. Raichle,² Allan L. Reiss,³ and Julie Korenberg⁴

Departments of ¹Anatomy and Neurobiology and ²Radiology and Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, ³Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, and ⁴Cedars-Sinai Medical Center, Los Angeles, California 90048

Correspondence should be addressed to Dr. David C. Van Essen, Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. Email: vanessen{at}brainvis.wustl.edu

We analyzed folding abnormalities in the cerebral cortex of subjects with Williams syndrome (WS), a genetically based developmental disorder, using surface-based analyses applied to structural magnetic resonance imaging data. Surfaces generated from each individual hemisphere were registered to a common atlas target (the PALS-B12 atlas). Maps of sulcal depth (distance from the cerebral hull) were combined across individuals to generate maps of average sulcal depth for WS and control subjects, along with depth-difference maps and t-statistic maps that accounted for within-group variability. Significant structural abnormalities were identified in 33 locations, arranged as 16 bilaterally symmetric pairs plus a lateral temporal region in the right hemisphere. Discrete WS folding abnormalities extended across a broad swath from dorsoposterior to ventroanterior regions of each hemisphere, in cortical areas associated with multiple sensory modalities as well as regions implicated in cognitive and emotional behavior. Hemispheric asymmetry in the temporal cortex is reduced in WS compared with control subjects. These findings provide insights regarding possible developmental mechanisms that give rise to folding abnormalities and to the spectrum of behavioral characteristics associated with WS.

Key words: cerebral cortex; morphometry; sulcus; gyrus; cognition; development; language; hemisphere; genetics; spatial cognition

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Received Sept. 29, 2005; revised Feb. 28, 2006; accepted March 3, 2006.

Correspondence should be addressed to Dr. David C. Van Essen, Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. Email: vanessen{at}brainvis.wustl.edu

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