Anterior cingulate cortex and insula response during indirect and direct processing of emotional faces in generalized social anxiety disorder

Abstract

Background: Generalized social anxiety disorder (gSAD) is associated with a heightened neural sensitivity to signals that convey threat, as evidenced by exaggerated amygdala and/or insula activation when processing face stimuli that express negative emotions. Less clear in the brain pathophysiology of gSAD are cortical top down control mechanisms that moderate reactivity in these subcortical emotion processing regions. This study evaluated amygdala, insula, and anterior cingulate cortex (ACC) activity in gSAD with a novel "Emotional Faces Shifting Attention Task" (EFSAT), an adaptation of perceptual assessment tasks well-known to elicit amygdala response. In healthy volunteers, the task has been shown to engage the amygdala when attention is directed to emotional faces and the ACC when attention is directed to shapes, away from emotional faces.

Methods: During functional MRI, 29 participants with gSAD and 27 healthy controls viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio of geometric shapes (circles, rectangles, or triangles) within the same field of view. Participants were instructed to match faces or match shapes, effectively directing attention towards or away from emotional information, respectively.

Results: Participants with gSAD exhibited greater insula, but not amygdala, activation compared to controls when attending to emotional faces. In contrast, when attention was directed away from faces, controls exhibited ACC recruitment, which was not evident in gSAD. Across participants, greater ACC activation was associated with less insula activation.

Conclusions: Evidence that individuals with gSAD exhibited exaggerated insula reactivity when attending to emotional faces in EFSAT is consistent with other studies suggesting that the neural basis of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in controls than gSAD when sustained goal-directed attention is required to shift attention away from social signals, together with a negative relationship between ACC and bilateral insula activity, indicate the ACC may have served a regulatory role when the focus of attention was directed to shapes amidst emotional faces.

Keywords: Brain imaging; Emotional faces; Social anxiety; Threat processing; fMRI.

Figures

Figure 1

Schematic of an exemplar Match Faces and Match Shapes blocks in the Emotional Faces Shifting Attention Task (EFSAT).

Figure 2

A priori region of interest: Anterior insula. A) Voxel-wise main effect of group for the contrast Match Faces > Match Shapes, along with Match Angry > Match Shapes, Match Fear > Match Shapes, and Match Happy > Match Shapes, showing bilateral anterior insula (aINS) displayed on statistical F-map at p < 0.05; cluster size >10 contiguous voxels (family-wise error corrected for multiple comparisons across small volumes of interest). Color scale reflects F-score. B) Bar graphs depicting extracted parameter estimates of activation from the aINS ROI within each group showing Generalized Social Anxiety Disorder exhibited greater bilateral anterior insula activation than Healthy Controls (p < 0.05).

Figure 3

A priori region of interest: Anterior cingulate cortex. A) Voxel-wise main effect of group for the contrast Match Shapes > Match Faces, along with Match Shapes (Angry distractor) > Match Angry, Match Shapes (Fear distractor) > Match Fear, and Match Shapes (Happy distractor) > Match Happy, showing anterior cingulate cortex (ACC) displayed on statistical F-map at p < 0.05; cluster size >10 contiguous voxels (family-wise error corrected for multiple comparisons across small volumes of interest). Color scale reflects F-score. B) Bar graphs depicting extracted parameter estimates of activation from the ACC ROI activation within each group showing Healthy Controls exhibited ACC activation, whereas, Generalized Social Anxiety Disorder showed no ‘activation’.

Figure 4

Correlation between extent of activation from the anterior cingulate cortex (ACC) ROI and extent of activation in A) right anterior insula and B) left anterior insula ROIs across all subjects. Generalized Social Anxiety Disorder subjects are coded in red; Healthy Controls are coded in green.