Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry

Abstract

Social anxiety disorder (SAD) is characterized at a neurobiological level by disrupted activity in emotion regulation neural circuitry. Previous work has demonstrated amygdala hyperreactivity and disrupted prefrontal responses to social cues in individuals with SAD (Kim et al., 2011). While exposure-based psychological treatments effectively reduce SAD symptoms, not all individuals respond to treatment. Better understanding of the neural mechanisms involved offers the potential to improve treatment efficacy. In this study, we investigated functional connectivity in emotion regulation neural circuitry in a randomized controlled treatment trial for SAD. Participants with SAD underwent fMRI scanning while performing an implicit emotion regulation task prior to treatment (n=62). Following 12 weeks of cognitive behavioral therapy, acceptance and commitment therapy, or wait-list, participants completed a second scan (n=42). Psychophysiological interaction analyses using amygdala seed regions demonstrated differences between SAD and healthy control participants (HC; n=16) in right amygdala-vmPFC connectivity. SAD participants demonstrated more negative amygdala-to-vmPFC connectivity, compared to HC participants, an effect that was correlated with SAD symptom severity. Post-treatment symptom reduction was correlated with altered amygdala-to-vm/vlPFC connectivity, independent of treatment type. Greater symptom reduction was associated with more negative amygdala-to-vm/vlPFC connectivity. These findings suggest that effective psychological treatment for SAD enhances amygdala-prefrontal functional connectivity.

Keywords: ACT; Amygdala; CBT; FMRI; Prefrontal cortex; Psychophysiological interactions; Randomized controlled trial.

Figure 1

Differences between SAD patients and healthy controls (HC) in functional connectivity during implicit emotion regulation (affect labeling > gender labeling). A) Prior to treatment, there were differences in right amygdala functional connectivity between HC and SAD participants during affect labeling, including in the vmPFC. B) Right amygdala-to-vmPFC functional connectivity was positive in HC participants and negative in SAD participants during affect labeling, based on mean connectivity estimates across all voxels within the suprathreshold vmPFC cluster identified (* denotes significance at the whole brain level, as established during whole brain analysis, α = .05, p < .005, k > 40; error bars represent mean +/− standard error). C) Within the SAD group, symptom severity was correlated with amygdala-vmPFC functional connectivity, such that higher symptom levels were associated with more negative connectivity (r = −.29, n = 64, p = .02).

Figure 2

Treatment-related changes were observed in amygdala-prefrontal functional connectivity during affect labeling. Using the right amygdala as a seed region, greater symptom reduction was associated with more negative functional connectivity with right vlPFC from pre- to post-treatment (A). Similarly, using the left amygdala as a seed region, greater symptom reduction was associated with more negative functional connectivity with vmPFC from pre-to-post treatment (B). Together, results indicate that larger reductions in anxiety were associated with stronger negative amygdala-prefrontal connectivity at post- relative to pre-treatment. [Blue indicates changes in right amygdala functional connectivity; Red indicates changes in left amygdala functional connectivity; correlations are significant based on whole brain analyses, p < .005, clusters thresholded at k > 40]