Prefrontal control and predictors of cognitive behavioral therapy response in social anxiety disorder

Generalized social anxiety disorder (gSAD) is associated with aberrant anterior cingulate cortex (ACC) response to threat distractors. Perceptual load has been shown to modulate ACC activity such that under high load, when demands on processing capacity is restricted, individuals with gSAD exhibit compensatory activation to threat distractors yet under low load, there is evidence of reduced activation. It is not known if neural predictors of response to cognitive behavioral therapy (CBT), based on such emotional conflict resolution, interact with demands on controlled processes. Prior to CBT, 32 patients with gSAD completed an fMRI task involving a target letter in a string of identical targets (low perceptual load) or a target letter in a mixed letter string (high perceptual load) superimposed on fearful, angry and neutral face distractors. Whole-brain voxel-wise analyses revealed better CBT outcome was predicted by more frontopartial activity that included dorsal ACC (dACC) and insula to threat (vs neutral) distractors during high, but not low, perceptual load. Psychophysiological interaction analysis with dACC as the seed region revealed less connectivity with dorsolateral prefrontal cortex to threat distractors during high load. Results indicate patients with less regulatory capability when demands on higher-order control are great may benefit more from CBT.