Genetic influences on sociability: heightened amygdala reactivity and event-related responses to positive social stimuli in Williams syndrome

Abstract

Williams syndrome (WS) is a genetic disorder caused by a hemizygous microdeletion on chromosome 7q11.23. WS is associated with a compelling neurocognitive profile characterized by relative deficits in visuospatial function, relative strengths in face and language processing, and enhanced drive toward social engagement. We used a combined functional magnetic resonance imaging (fMRI) and event-related potential (ERP) approach to examine the neural basis of social responsiveness in WS participants to two types of social stimuli, negative (fearful) and positive (happy) emotional facial expressions. Here, we report a double dissociation consistent across both methods such that WS participants exhibited heightened amygdala reactivity to positive (happy) social stimuli and absent or attenuated amygdala reactivity to negative (fearful) social stimuli, compared with controls. The fMRI findings indicate that atypical social processing in WS may be rooted in altered development of disparate amygdalar nuclei that subserve different social functions. The ERP findings suggest that abnormal amygdala reactivity in WS may possibly function to increase attention to and encoding of happy expressions and to decrease arousal to fearful expressions. This study provides the first evidence that the genetic deletion associated with WS influences the function of the amygdala to be particularly responsive to socially appetitive stimuli.

Figure 1.

Right amygdala activation to happy (left) and fearful (right) facial expressions compared with neutral between groups. Bars represent percentage signal change of clusters localized by means of direct comparisons between the TD and WS groups. Error bars represent SEM.

Figure 2.

Areas of greater right amygdala reactivity to fearful and happy facial expressions (compared with neutral) within the WS and TD samples. A, These clusters were not overlapping. We reduced the threshold to p < 0.05 uncorrected to visualize the distinct location for each cluster. No voxels within the right amygdala were found to be significantly activated in response to fear versus neutral in the WS group or happy versus neutral in the TD group at the same statistical threshold. Clusters are overlaid onto three coronal slices (Montreal Neurological Institute coordinates: y = −2, 0, 2) of a representative TD brain normalized into standard stereotactic space. Voxels of greater activation in response to happy versus neutral facial expressions in the WS group are designated by cool colors (blue). Voxels of greater activation in response to fearful versus neutral facial expressions in the TD group are designated by warm colors (orange). Extracted time course of percentage signal change for peak voxels within the clusters displayed in A are shown in B for WS participants and in C for TD participants. Data were extracted and converted to percentage signal change using a moving average (200 s) by a standardized method (xjview toolbox in SPM2). Lines denoted with open circles represent BOLD response to happy faces. Lines denoted with filled circles represent BOLD response to fearful faces. Error bars represent SEM. R, Right.

Figure 3.

Direct comparison between groups for the P300–500 during happy relative to neutral facial expressions and the N200 and P500–700 during fearful relative to neutral facial expressions. A, The P300–500 difference for happy − neutral was larger for WS than TD or DD groups. B, For the N200, the WS group showed a larger N200 difference to neutral − fearful than TD or DD groups. C, The P500–700 difference to fearful − neutral was larger for TD than WS or DD groups.

Figure 4.

Event-related potentials and topographical maps comparing responses to different emotional expressions for the TD (left), WS (center), and DD (right) groups. Note that negative voltage is plotted up in all ERP plots. Topographical maps (top of each panel) illustrate the distribution of the difference in activity between conditions. Amplitude is plotted as a function of color with the most negative voltage as purple and most positive voltage as red. A, ERPs to happy (blue lines) compared with neutral (black lines) expressions depicted at site 42 (P2). For the WS group, the P300–500 (boxed area) was larger to happy than neutral expressions. The P300–500 did not differ by emotional expression for the other two groups. The posterior central distribution of the happy − neutral difference wave at 350 ms is shown in the topographical map. B, ERPs to neutral (black lines) compared with fearful (red lines) expressions shown at electrode 12 (AF3). The N200 amplitudes to fearful compared with neutral expressions are decreased in the WS group, and increased in the DD group. The topographical maps illustrate the anterior distribution of the N200 difference to fearful − neutral expressions at 240 ms. A larger N200 to fearful than neutral expression results in a positive difference that is represented in red as in the DD group (right side). In contrast, a smaller N200 to fearful than neutral expression results in a difference that is negative in voltage represented in purple as for the WS group. C, ERPs to neutral (black lines) and fearful (red lines) expressions are shown at the bottom half of the figure shown at electrode 57 (next to FC4). The anterior positivity from 500 to 700 ms, P500–700 (boxed area), was larger to fearful than neutral expression for the TD controls (left) and did not differ for the WS group. For the DD group, the P500–700 appears to be larger to neutral than fearful expressions at this site, but the effect was not significant at this or other sites. The anterior distribution of the P500–700 difference wave to fearful − neutral expression at 520 ms is illustrated in the topographical maps.