An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome

Abstract

Williams syndrome (WS) is a neurogenetic-neurodevelopmental disorder characterized by a highly variable and enigmatic profile of cognitive and behavioral features. Relative to overall intellect, affected individuals demonstrate disproportionately severe visual-spatial deficits and enhanced emotionality and face processing. In this study, high-resolution magnetic resonance imaging data were collected from 43 individuals with WS and 40 age- and gender-matched healthy controls. Given the distinct cognitive-behavioral dissociations associated with this disorder, we hypothesized that neuroanatomical integrity in WS would be diminished most in regions comprising the visual-spatial system and most "preserved" or even augmented in regions involved in emotion and face processing. Both volumetric analysis and voxel-based morphometry were used to provide convergent approaches for detecting the hypothesized WS neuroanatomical profile. After adjusting for overall brain volume, participants with WS showed reduced thalamic and occipital lobe gray matter volumes and reduced gray matter density in subcortical and cortical regions comprising the human visual-spatial system compared with controls. The WS group also showed disproportionate increases in volume and gray matter density in several areas known to participate in emotion and face processing, including the amygdala, orbital and medial prefrontal cortices, anterior cingulate, insular cortex, and superior temporal gyrus. These findings point to specific neuroanatomical correlates for the unique topography of cognitive and behavioral features associated with this disorder.

Figure1.

a shows the subdivisions of the prefrontal cortex as specified by a coronal delimiting plane corresponding to the most anterior extent of the genu of the corpus callosum and three axial planes coincident with or parallel to a line passing through the anterior and posterior commissures. Each axial plane was determined at the same location for each participant after fitting the Talairach proportional grid system (Talairach, 1988) to a positionally normalized 3D dataset (D, dorsal; MS, middle-superior; MI, middle-inferior; O, orbital). b shows the four measured segments of the cingulate gyrus. Similar to the prefrontal components, cingulate subdivisions were determined for each participant from coronal planes corresponding to specific Talairach atlas landmarks (VA, ventral anterior; DA, dorsal anterior; M, middle; P, posterior).

Figure 2.

Distribution of brain volumes (calculated in cubic centimeters) in WS and control (Con) groups. Total brain and occipital gray volumes are significantly reduced in WS, whereas amygdala and ventral prefrontal gray volumes are significantly increased compared with controls.

Figure 3.

a, b, Representative parasagittal images (at the same anatomic location) from a young adult control participant (a) and an age- and gender-matched participant with Williams syndrome (b). Horizontal line on each image shows the location of the plane defined by the AC and PC. Arrows point to the location of parietal-occipital fissure. Note the relatively greater amount of ventral prefrontal tissue inferior to the AC-PC plane and the disproportionately small occipital lobe (posterior and inferior to the parietal-occipital fissure) in the participant with Williams syndrome.

Figure 4.

Results of voxel-based morphometry analyses. a, Regions where controls showed greater gray matter density compared with WS. b, Regions where WS participants showed greater gray matter density compared with controls.