PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation

• Type of Material: Article
• Authors: Gregory A. Fonzo, Stanford University; Madeleine S. Goodkind, New Mexico Veterans Affairs Healthcare System; Desmond J. Oathes, University of Pennsylvania; Yevgeniya V. Zaiko, Stanford University; Meredith Harvey, Stanford University; Kathy K. Peng, Stanford University; M. Elizabeth Weiss, Stanford University; Allison L. Thompson, Stanford University; Sanno E. Zack, Stanford University; Steven E. Lindley, Stanford University; Bruce A. Arnow, Stanford University; Booil Jo, Stanford University; James J. Gross, Stanford University; Barbara Rothbaum, Emory University; Amit Etkin, Stanford University
• Language: English
• Date: 2017-12-01
• Publisher: AMER PSYCHIATRIC PUBLISHING, INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Psychiatric Association
• Final Published Version (URL): http://dx.doi.org/10.1176/appi.ajp.2017.16091072
• Title of Journal or Parent Work: American Journal of Psychiatry
• Volume: 174
• Issue: 12
• Start Page: 1163
• End Page: 1174
• Grant/Funding Information: BOR has funding from Wounded Warrior Project, Department of Defense Clinical Trial Grant No. W81XWH-10-1-1045, “Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure with a Cognitive Enhancer”, National Institute of Mental Health Grant No. 1R01MH094757-01, “Prospective Determination of Psychobiological Risk Factors for Posttraumatic Stress,” Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant, “Optimal Dose of early intervention to prevent PTSD”, and McCormick Foundation “Brave Heart: MLB’s Welcome Back Veterans SouthEast Initiative.” BOR receives royalties from Oxford University Press, Guilford, APPI, and Emory University and received one advisory board payment from Genentech.; This study was funded by a grant from the National Institute of Mental Health R01 MH091860 to AE. GF was partially supported by a grant from the National Institute of Mental Health T32 MH019938.
• Keywords: AFGHANISTAN VETERANS; Life Sciences & Biomedicine; CONFLICT; METAANALYSIS; DORSOLATERAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; ANTERIOR CINGULATE CORTEX; EXPOSURE THERAPY; Psychiatry; FEAR EXTINCTION; ANXIETY; Science & Technology; MENTAL-HEALTH DIAGNOSES
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience; Psychology, Clinical

Abstract

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