Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder

Elizabeth R Duval; Jony Sheynin; Anthony P King; K Luan Phan; Naomi M Simon; Brian Martis; Katherine E Porter; Sonya B Norman; Israel Liberzon; Sheila A M Rauch

doi:10.1002/da.23022

Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder

Depress Anxiety. 2020 Jul;37(7):670-681. doi: 10.1002/da.23022. Epub 2020 Apr 19.

Authors

Elizabeth R Duval^{1

2}, Jony Sheynin^{1

2

3}, Anthony P King^{1

2}, K Luan Phan⁴, Naomi M Simon^{5

6}, Brian Martis^{2

7

8}, Katherine E Porter^{1

2}, Sonya B Norman^{7

8

9}, Israel Liberzon^{1

2

3}, Sheila A M Rauch^{10

11}

Affiliations

¹ VA Ann Arbor Healthcare System, Ann Arbor, Michigan.
² Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
³ Department of Psychiatry, Texas A&M University Health Science Center, Bryan, Texas.
⁴ Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio.
⁵ Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
⁶ Department of Psychiatry, New York University School of Medicine, New York, New York.
⁷ Research Service, VA San Diego Healthcare System, San Diego, California.
⁸ Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, California.
⁹ Executive Division, National Center for PTSD, White River Junction, Vermont.
¹⁰ Mental Health Service Line, VA Atlanta Healthcare System, Decatur, Georgia.
¹¹ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.

Abstract

Background: Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD.

Method: We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053).

Results: Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement.

Conclusions: This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

Trial registration: ClinicalTrials.gov NCT01524133.

Keywords: Cognitive Behavioral Therapy; PTSD; functional MRI; pharmacotherapy; trauma.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amygdala / diagnostic imaging
Brain / diagnostic imaging
Emotions
Humans
Magnetic Resonance Imaging
Stress Disorders, Post-Traumatic* / therapy

Associated data

ClinicalTrials.gov/NCT01524133

Abstract

Publication types

MeSH terms

Associated data

Grants and funding