Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material.

This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment.

Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement.

These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.