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The Journal of Neuroscience, April 20, 2005, 25(16):4146-4158; doi:10.1523/JNEUROSCI.0165-05.2005

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Neurobiology of Disease
Abnormal Cortical Complexity and Thickness Profiles Mapped in Williams Syndrome

Paul M. Thompson,¹ Agatha D. Lee,¹ Rebecca A. Dutton,¹ Jennifer A. Geaga,¹ Kiralee M. Hayashi,¹ Mark A. Eckert,² Ursula Bellugi,³ Albert M. Galaburda,⁴ Julie R. Korenberg,⁵ Debra L. Mills,⁶ Arthur W. Toga,¹ and Allan L. Reiss²

¹Laboratory of Neuroimaging, Brain Mapping Division, Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, California 90095, ²Stanford Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, ³Salk Institute Laboratory for Cognitive Neuroscience, La Jolla, California 92037, ⁴Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, ⁵Department of Pediatrics, University of California Los Angeles, Los Angeles, California 90095, and ⁶Department of Psychology, Emory University, Atlanta, Georgia 30322

We identified and mapped an anatomically localized failure of cortical maturation in Williams syndrome (WS), a genetic condition associated with deletion of 20 contiguous genes on chromosome 7. Detailed three-dimensional (3D) maps of cortical thickness, based on magnetic resonance imaging (MRI) scans of 164 brain hemispheres, identified a delimited zone of right hemisphere perisylvian cortex that was thicker in WS than in matched controls, despite pervasive gray and white matter deficits and reduced total cerebral volumes. 3D cortical surface models were extracted from 82 T1-weighted brain MRI scans (256 x 192 x 124 volumes) of 42 subjects with genetically confirmed WS (mean ± SD, 29.2 ± 9.0 years of age; 19 males, 23 females) and 40 age-matched healthy controls (27.5 ± 7.4 years of age; 16 males, 24 females). A cortical pattern-matching technique used 72 sulcal landmarks traced on each brain as anchors to align cortical thickness maps across subjects, build group average maps, and identify regions with altered cortical thickness in WS. Cortical models were remeshed in frequency space to compute their fractal dimension (surface complexity) for each hemisphere and lobe. Surface complexity was significantly increased in WS (p < 0.0015 and p < 0.0014 for left and right hemispheres, respectively) and correlated with temporoparietal gyrification differences, classified via Steinmetz criteria. In WS, cortical thickness was increased by 5-10% in a circumscribed right hemisphere perisylvian and inferior temporal zone (p < 0.002). Spatially extended cortical regions were identified with increased complexity and thickness; cortical thickness and complexity were also positively correlated in controls (p < 0.03). These findings visualize cortical zones with altered anatomy in WS, which merit additional study with techniques to assess function and connectivity.

Key words: Williams syndrome; brain imaging; genetics; MRI; cortex; fractal complexity; brain mapping

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Received Sep 8, 2004; revised March 14, 2005; accepted March 15, 2005.

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