PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation
Open accessAbstract
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-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms. RESULTS: At baseline, individuals with larger treatment-related 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 by single 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 not when deliberately reducing negative emotionality.
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Fonzo et al. reported that at baseline, individuals with the greatest symptom improvement with prolonged exposure psychotherapy showed greater dorsal PFC and vmPFC activation during emotional conflict regulation.
“Fonzo et al. [167] reported on fMRI task-based assessment while completing three tasks assessing emotional reactivity and regulation prior to prolonged exposure psychotherapy for PTSD. At baseline, individuals with the greatest symptom improvement with therapy showed, among other findings, greater dorsal PFC and vmPFC activation during emotional conflict regulation.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [167]
The Abstract Results distinguish greater dorsal prefrontal activation during emotional reactivity from greater ventromedial prefrontal activation during emotional conflict regulation. The Results further describe the dorsal prefrontal finding in the emotional conflict task as a contrast that isolates valence in the absence of conflict. Thus, the claim incorrectly places both activation findings during conflict regulation. (LLM, conf=0.91)
Experimental — accuracy not yet measuredParticipants who are most likely to benefit from exposure therapy demonstrate spontaneous activity of PFC when superficially processing threat and adapting to emotional interference.
“They interpreted these findings to suggest that participants who are most likely to benefit from exposure therapy demonstrate spontaneous activity of PFC when superficially processing threat and adapting to emotional interference.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [167]
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- Authors
- Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M. E., Thompson, A. L., Zack, S. E., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., & Etkin, A.
- Affiliations
- VA Palo Alto Health Care System (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2017-12-01
- Volume
- 174
- Issue
- 12
- Pages
- 1163-1174
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5711543
- OpenAlex
- W2739325771
- Cited by
- 149
- References
- 43
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 14 · 2023: 13 · 2022: 18 · 2021: 16 · 2020: 23 · 2019: 18 · 2018: 17 · 2017: 2
- FWCI
- 20.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- McCormick Foundation
- American Psychiatric Publishing
- Emory University
- National Alliance for Research on Schizophrenia and Depression
- University of Oxford
- Genentech
- National Institute of Mental Health (R01MH094757, R01MH091860, T32MH019938)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- post-traumatic stress disorder, prolonged exposure therapy, treatment outcome prediction, emotional reactivity, emotion regulation, amygdala, dorsolateral prefrontal cortex, ventromedial prefrontal cortex, ventral striatum, single-pulse transcranial magnetic stimulation, cognitive reappraisal, emotional conflict
- MeSH terms
- Adolescent, Adult, Amygdala, Corpus Striatum, Emotions, Female, Humans, Implosive Therapy, Magnetic Resonance Imaging, Male, Middle Aged, Neural Inhibition, Stress Disorders, Post-Traumatic, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation, Young Adult, Functional Neuroimaging
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