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, 43 (3), 592-604

Prefrontal Social Cognition Network Dysfunction Underlying Face Encoding and Social Anxiety in Fragile X Syndrome

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Prefrontal Social Cognition Network Dysfunction Underlying Face Encoding and Social Anxiety in Fragile X Syndrome

Laura M Holsen et al. Neuroimage.

Abstract

Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.

Figures

Figure 1
Figure 1
Representative images of face stimuli.
Figure 2
Figure 2
Average fixation duration for eye, mouth, and face fixation by group. Error bars indicate the standard error of the mean.
Figure 3
Figure 3
Regions of interest in the FXS vs. control comparison of the Dm effect in which the control group showed greater activation than the FXS group (after accounting for variance associated with age and IQ). A: Left Superior Frontal gyrus (BA 10; -20,48,15), B: Left Medial Frontal gyrus (BA 8; -11,45,38) (images presented according to radiological convention, in which the right hemisphere is depicted on the left side of the coronal image). Averaged MR time series are presented below for each region for the 20 seconds following stimulus onset: FXS group - subsequently remembered (blue solid line), FXS group - subsequently forgotten (blue dashed line), Control group - subsequently remembered (green solid line), Control group - subsequently forgotten (green dashed line). Shaded portion of averaged time series indicates the section of the time series for which the percent signal change (for the Dm effect: subsequently remembered - subsequently forgotten) was extracted for graphing below.
Figure 4
Figure 4
Regions of interest in the regression of eye fixation duration on brain activation in response to successfully remembered faces in the FXS and control groups (after accounting for variance associated with age and IQ). A: Left Angular gyrus [-51,-65,36; Vol(mm3)=1000], B: Left Insula [-29,-19,18; Vol(mm3)=672], C: Left Posterior Cingulate gyrus [-15,-51,6; Vol(mm3)=880] (images presented according to radiological convention, in which the right hemisphere is depicted on the left side of the coronal image). Scatterplots of the correlations between eye fixation duration and percent signal change in each region are shown below.
Figure 5
Figure 5
Regions of interest in the regression of SPAI z-score on brain activation in response to successfully remembered faces in the FXS and control groups (after accounting for variance associated with age and IQ). A: Right Superior Frontal gyrus (25,51,6), B: Right Medial Frontal gyrus (11,47,-8), C: Left Inferior Frontal gyrus (-39,1,32), D: Left Hippocampus (-27,-39,-2) (images presented according to radiological convention, in which the right hemisphere is depicted on the left side of the coronal image). Scatterplots of the correlations between SPAI z-score and percent signal change in each region are shown below.

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