No abstract

Objective Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients will not respond. Brain functions governing treatment outcome are not well characterized. Here, we examined brain systems relevant to emotional reactivity and regulation, constructs thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. Methods Individuals with PTSD underwent functional magnetic resonance imaging (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomized to immediate prolonged exposure treatment (N=36) or waitlist (N=30). A random subset of treatment-randomized individuals (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine if predictive activation patterns reflect causal influence within circuits. Linear mixed effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the treatment effect on PTSD symptoms. Results Individuals with larger treatment-related symptom reductions (compared to waitlist) showed at baseline: 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. Conclusions Capacity to benefit from prolonged exposure for PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.