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

Abstract

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.

Similar patterns of cortical expansion during human development and evolution

“…To futher address this issue, we performed an interhemispheric correlation analysis that provides greater sensitivity in some regions based on symmetry between the two hemispheres (20). Figure 2C shows clusters that expanded significantly more (black outlines) or less (white outlines) than average in both hemispheres.…”

“…Interhemispheric symmetry test. The interhemispheric symmetry analysis tests for significant clusters present in corresponding locations in both hemispheres (20,57). This method is the same as the two-sample t test described above, except that both left and right hemispheres were examined and a t correlation map was generated after each permutation by multiplying the two-sample t statistic at each surface node in the left hemisphere by the corresponding node in the right hemisphere.…”

Cortical Folding Abnormalities in Autism Revealed by Surface-Based Morphometry

“…For each group comparison, a t-statistic value (assuming unequal variance) was computed at each node using the individual depth values within each group (see also Van Essen et al, 2006). Two statistical methods, a cluster-size analysis and an interhemispheric correlation analysis, were used to test for significant differences in sulcal depth across groups.…”

“…Levitt et al (2003), using manually traced threedimensional (3-D) sulcal trajectories, reported an anterior and superior shift in the Sylvian fissure, superior temporal sulcus, and inferior frontal sulcus in children with high-functioning autism. Here, using a surface-based approach involving sulcal depth maps that previously revealed dozens of folding abnormalities in Williams Syndrome (Van Essen et al, 2006), we identify and characterize significant folding abnormalities in each autism spectrum subgroup.…”

Cortical mapping of genotype–phenotype relationships in schizophrenia

“…Using identical cortical thickness mapping methods to those described here, Thompson et al [2005] observed a failure of cortical maturation in patients with WS, involving a zone of right hemisphere perisylvian cortex that was 5-10% thicker in WS than in matched controls, despite pervasive gray and white matter deficits, but with corresponding deficits in the adjacent dorsal stream, including superior parietal brain regions. Recently developed image analysis methods have revealed increased gyrification bilaterally in occipital regions and over the cuneus in WS subjects [Gaser et al, 2006;Tosun et al, 2006], as well as numerous cortical folding abnormalities in brain regions associated with multiple sensory modalities, as well as cognitive and emotional behavior [Van Essen et al, 2006]. Using functional brain imaging during visual processing tasks, Meyer-Lindenberg et al [2004] identified a pattern of hypoactivation in subjects with WS in the parietal portion of the dorsal stream, concomitant with gray matter volume reduction in the immediately adjacent parieto-occipital/intraparietal sulcus.…”