Genetic Contributions to Human Gyrification: Sulcal Morphometry in Williams Syndrome

Abstract

Although gyral and sulcal patterns are highly heritable, and emerge in a tightly controlled sequence during development, very little is known about specific genetic contributions to abnormal gyrification or the resulting functional consequences. Williams syndrome (WS), a genetic disorder caused by hemizygous microdeletion on chromosome 7q11.23 and characterized by abnormal brain structure and striking cognitive (impairment in visuospatial construction) and behavioral (hypersocial/anxious) phenotypes, offers a unique opportunity to study these issues. We performed a detailed analysis of sulcal depth based on geometric cortical surface representations constructed from high-resolution magnetic resonance imaging scans acquired from participants with WS and from healthy controls who were matched for age, sex, and intelligence quotient, and compared between-group differences with those obtained from a voxel-based morphometry analysis. We found bilateral reductions in sulcal depth in the intraparietal/occipitoparietal sulcus (PS) in the brains of participants with WS, as well as in the collateral sulcus and the orbitofrontal region in the left hemisphere. The left-hemisphere PS in the WS group averaged 8.5 mm shallower than in controls. Sulcal depth findings in the PS corresponded closely to measures of reduced gray matter volume in the same area, providing evidence that the gray matter volume loss and abnormal sulcal geometry may be related. In the context of previous functional neuroimaging findings demonstrating functional alterations in the same cortical regions, our results further define the neural endophenotype underlying visuoconstructive deficits in WS, set the stage for defining the effects of specific genes, and offer insight into genetic mechanisms of cortical gyrification.

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

“…In a preliminary report using a surface-based approach, we described several abnormalities of cortical folding in WS, including bilateral differences in position and average depth of the intraparietal sulcus (IPS) (Van Essen et al, 2004). Kippenhan et al (2005) confirmed and extended these findings using a similar approach and reported bilateral abnormalities in the parietal cortex but unilateral abnormalities in two other regions. Here, we have applied more sensitive analyses to a slightly larger data set.…”

“…The surface-based analysis of Kippenhan et al (2005), using a different group of WS subjects (slightly smaller, n ϭ 14; better matched for age and IQ) revealed fewer folding abnormalities (4 vs 33 in the present study) and less symmetry (1 pair vs 16 pairs in the present study). The greater sensitivity of our analysis is mainly attributable to methodological factors.…”

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

“…These include the hippocampal formation, IPL, amygdala, and OFC (12,14,17,20,(23)(24)(25)(26)(27)(28)30). Such transmodal cortical systems (51) are composed of subregionally specialized and highly interconnected heteromodal, paralimbic, and limbic cortices (51)(52)(53).…”

“…These mouse studies also documented alterations in fear response [for both LIMK1 and GTF2IRD1 (20,22)] and reduced aggression [for GTF2IRD1 (22)]. In parallel with these preclinical observations, research on the neural mechanisms underlying WS-specific behavioral characteristics has identified functional and structural alterations of the intraparietal sulcus (12,(23)(24)(25)(26), hippocampal formation (27), amygdala, and orbitofrontal cortex (OFC) (12,17,28), and aberrant orbitofrontal circuitry has been associated with the syndrome's distinctive pattern of emotional processing: remarkable lack of social fear coupled with a high incidence of nonsocial anxieties and phobias (17,29,30).…”

Constraints on Multiple Object Tracking in Williams Syndrome: How Atypical Development Can Inform Theories of Visual Processing

“…The WS brain structurally differs from TD individuals in a number of ways, including reduced gray matter volume (Boddaert et al, 2005;Chiang et al, 2007;Eckert et al, 2005;Meyer-Lindenberg et al, 2004;Reiss et al, 2000), sulcal depth (Gaser et al, 2006;Jackowski & Schultz, 2005;Kippenhan et al, 2005;Van Essen et al, 2006), and atypical properties of white matter tracts (Faria et al, 2012;Hoeft et al, 2007;Marenco et al, 2007). Especially pertinent to MOT, the parietal lobe, which supports a variety of spatial functions, shows atypical functional properties (Boddeart et al, 2005;Meyer-Lindenburg et al, 2004, 2005Mobbs et al, 2004).…”