Changes in functional connectivity with cognitive behavioral therapy for social anxiety disorder predict outcomes at follow-up

Abstract

Approximately half of individuals with Social Anxiety Disorder (SAD) treated with psychological intervention do not achieve clinically significant improvement or retain long-term gains. Neurobiological models of SAD propose that disruptions in functioning of amygdala-prefrontal circuitry is implicated in short-term treatment response. However, whether treatment-related changes in functional connectivity predict long-term well-being after psychotherapy is unknown. Patients with SAD completed an incidental emotion regulation task during fMRI before and after treatment with cognitive behavioral therapy or acceptance and commitment therapy (n = 23, collapsed across groups). Psychophysiological interaction analyses using amygdala seed regions were conducted to assess changes in functional connectivity from pre-to post-treatment that predicted symptom change from 6 to 12-month follow-up. Negative change (i.e., greater inverse/weaker positive) in amygdala connectivity with the dorsomedial prefrontal cortex (dmPFC) and dorsal anterior cingulate cortex (dACC) predicted greater symptom reduction during follow-up. Positive change in amygdala connectivity with the cerebellum, fusiform gyrus, and pre-central and post-central gyri predicted less symptom reduction (e.g., no change or worsening). Results suggest that strengthened amygdala connectivity with regulatory regions may promote better long-term outcomes, whereas changes with visual and sensorimotor regions may represent sensitization to emotion-related cues, conferring poorer outcomes. Clinical implications for treatment personalization are discussed, should effects replicate in larger samples.

Keywords: Amygdala; Emotion regulation; Long-term treatment response; Prefrontal cortex; fMRI.

Figure 1.

Patient flow chart with reasons for exclusion at each time point. CBT = cognitive behavioral therapy; ACT = acceptance and commitment therapy; 6MFU = 6-month follow-up; 12MFU = 12-month follow-up.

Figure 2.

Example stimuli from the contrast of interest (Affect Label > Gender Label) in the affect labeling task.

Figure 3.

Regions of interest for connectivity analyses, defined using Neurosynth displaying left and right vlPFC (red and yellow), vmPFC (blue), and dACC (green).

Figure 4.

Pre- to post-treatment changes in left amygdala functional connectivity during affect labeling were associated with changes in symptoms from 6 to 12-month follow-up, controlling for pre-treatment symptom severity. Lower symptom change scores reflect greater improvement in social anxiety symptom severity from 6 to 12-month follow-up. Red indicates changes in left amygdala connectivity with dmPFC and dACC; purple indicates left amygdala connectivity with mid- to posterior cingulate cortex, calcarine and precuneus; green indicates left amygdala connectivity with precuneus; light blue indicates left amygdala connectivity with the cerebellum; dark blue indicates left amygdala connectivity with the pre- and post-central gyrus. All p < 0.05, corrected (see Methods).