Neural correlates of emotional reactivity and regulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder

Abstract

Posttraumatic Stress Disorder (PTSD) is a debilitating condition often associated with difficulty in emotion regulation, including reappraising negative emotions. This study assessed neural mechanisms associated with emotion regulation in veterans prior to and following treatment for PTSD. Participants with PTSD and combat exposed controls (CC) completed diagnostic evaluation and underwent fMRI scanning while completing Emotion Regulation Task (ERT) and Emotional Faces Assessment Task (EFAT). Participants with PTSD were randomly assigned to Prolonged Exposure plus placebo (PE+PLB), Sertraline plus enhanced medication management (SERT+EMM), or PE plus SERT (PE+SERT) and repeated diagnostic evaluation and MRI scanning following treatment. The amygdala, dmPFC, and dlPFC were examined as regions of interest. On ERT, veterans with PTSD showed significantly less dmPFC activation than CCs during reappraisal vs emotional maintenance. Within the PTSD group, results demonstrated a significant association between less activation in the dmPFC during emotion reappraisal vs maintenance trials before treatment and greater reductions in symptoms from pre- to post-treatment. During the EFAT, there were no group differences between participants with PTSD and CCs in brain activation, and no relationships between brain function and PTSD symptoms. These findings suggest that less emotional reactivity might potentially reflect less need for recruitment of prefrontal regions when reappraising negative emotion, and is an individual factor associated with better treatment outcome.

Trial registration: ClinicalTrials.gov NCT01524133.

Keywords: Amygdala; Dorsomedial prefrontal cortex; Medial prefrontal cortex; Prolonged Exposure; SSRI; Veterans; fMRI.

Conflict of interest statement

Declaration of Competing Interest Dr. Duval reports in past 24 months funding from NIH, the Michigan Institute for Clinical Health Research, Cohen Veterans Bioscience, and One Mind Institute. Dr. King reports in past 24 months funding from NIH and the Michigan Institute for Clinica Health Research. Dr. Liberzon reports in past 24 months speaking or consulting with: Department of Defense, NIH, VA, Cohen Veteran Bioscience, ARMGO Pharma Inc., Sunovion Pharmaceuticals Inc. Aptinyx Inc., Heptares Therapeutics Ltd., Nobilis Therapeutics, Inc., Astrotide, Inc. Dr. Rauch reports in past 24 months speaking or consulting with Department of Defense, NIH, VA, Woodruff Foundation, McCormick Foundation, Wounded Warrior Project, Cohen Veteran Bioscience, and The Pennsylvania State University. Dr. Rauch receives royalties from Oxford University Press. Ms. Joshi and Drs. Sheynin, Phan, Martis, and Porter report no disclosures. The views expressed in this article are solely those of the authors and do not reflect an endorsement by or the official policy of the Department of Veterans Affairs, or the U.S. Government.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Fig. 1.

Timeline for administration of treatment in each treatment group (Rauch et al., 2018).

Fig. 2.

Task block designs of emotion regulation and appraisal tasks.

Fig. 3.

ROIs with coordinates (x, y, z), # of voxels (k), z statistics, and FWE corrected p-values for ERT and EFAT.

Fig. 4.

A. Pretreatment activation on Reappraise vs. Maintain trials was greater in the PTSD group compared to CC group. B. A further breakdown of average activation across Reappraise and Maintain trials for both PTSD and CC is provided to clarify direction of relationships. Error bars are based on standard error of the mean.

Fig. 5.

Less pretreatment neural activation for participants with PTSD in A. dmPFC, B. bilateral amygdala, and C. dlPFC was associated with greater symptom reduction over time. Reappraise vs. Maintain Contrast plotted against symptom change, with further breakdown of Reappraise and Maintain trials by symptom change to clarify direction of relationships.