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Abstract

Objective:

Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms.

Method:

Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively.

Results:

Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum.

Conclusions:

Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1175 - 1184
PubMed: 28715907

History

Received: 25 September 2016
Revision received: 31 March 2017
Accepted: 20 April 2017
Published online: 18 July 2017
Published in print: December 01, 2017

Keywords

  1. Posttraumatic Stress Disorder
  2. Brain Imaging Techniques
  3. Psychotherapy
  4. Emotion Regulation
  5. Transcranial Magnetic Stimulation
  6. Frontopolar Cortex

Authors

Details

Gregory A. Fonzo, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Madeleine S. Goodkind, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Desmond J. Oathes, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Yevgeniya V. Zaiko, B.A.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Meredith Harvey, B.A.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Kathy K. Peng, M.A.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
M. Elizabeth Weiss, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Allison L. Thompson, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Sanno E. Zack, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Colleen E. Mills-Finnerty, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Benjamin M. Rosenberg, B.A.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Raleigh Edelstein, B.A.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Rachael N. Wright, B.S.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Carena A. Kole, B.S.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Steven E. Lindley, M.D., Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Bruce A. Arnow, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Booil Jo, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
James J. Gross, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Barbara O. Rothbaum, Ph.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.
Amit Etkin, M.D., Ph.D. [email protected]
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Department of Psychiatry, Emory University School of Medicine, Atlanta.

Notes

Address correspondence to Dr. Etkin ([email protected]).
Presented at the 54th annual meeting of the American College of Neuropsychopharmacology, Hollywood, Fla., Dec. 6–10, 2015.

Author Contributions

Drs. Fonzo and Goodkind contributed equally as first authors.

Funding Information

National Institute of Mental Health10.13039/100000025: R01 MH091860, T32 MH019938
Supported by NIMH grant R01 MH091860 to Dr. Etkin. Dr. Fonzo was partially supported by NIMH grant T32 MH019938.Dr. Rothbaum has received funding from the Wounded Warrior Project, the Department of Defense (Clinical Trial Grant W81XWH-10-1-1045), NIMH (grant 1R01MH094757-01), a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant, the McCormick Foundation, and Transcept Pharmaceuticals; she has served on an advisory board for Genentech, owns equity in Virtually Better, and has received royalties from Oxford University Press, Guilford, American Psychiatric Publishing, and Emory University. Dr. Etkin has served as a consultant for Takeda, Otsuka, and Acadia, has received a research grant from Brain Resource, Inc., and owns equity in Akili Interactive. The other authors report no financial relationships with commercial interests.

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