Site maintenance Wednesday, November 13th, 2024. Please note that access to some content and account information will be unavailable on this date.
Skip to main content

Abstract

Objective:

Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors “stamped in” through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings.

Methods:

After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe.

Results:

cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS.

Conclusions:

Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.

Formats available

You can view the full content in the following formats:

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 459 - 468
PubMed: 33726523

History

Received: 9 June 2020
Revision received: 11 September 2020
Revision received: 19 October 2020
Accepted: 25 November 2020
Published online: 17 March 2021
Published in print: May 01, 2021

Keywords

  1. Theta Burst Stimulation
  2. Transcranial Magnetic Stimulation
  3. Compulsive Behaviors
  4. Obsessive-Compulsive Disorder
  5. Orbitofrontal Cortex
  6. Goal-Directed Behavior

Authors

Details

Rebecca B. Price, Ph.D. [email protected]
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Claire M. Gillan, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Colleen Hanlon, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Fabio Ferrarelli, M.D., Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Tae Kim, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Helmet T. Karim, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Marlee Renard, B.A.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Rachel Kaskie, B.S.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Michelle Degutis, B.S.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Anna Wears, B.A.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Emelina P. Vienneau, B.S.E.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Angel V. Peterchev, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Vanessa Brown, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Greg J. Siegle, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Meredith L. Wallace, Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Susanne E. Ahmari, M.D., Ph.D.
Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).

Notes

Send correspondence to Dr. Price ([email protected]).

Funding Information

Supported by NIMH grant R21MH112770 and by the Clinical and Translational Sciences Institute at the University of Pittsburgh (UL1-TR-001857).Dr. Peterchev is an inventor on patents and patent applications related to TMS, and he has received travel funds as well as patent royalties from Rogue Research; he has received research grants, travel funds, consulting fees, and equipment donation from Tal Medical/Neurex, research grant, hardware donations, and patent application support from Magstim, equipment loans and hardware donations from MagVenture, and consulting fees from Neuronetics and Advise Connect Inspire. Dr. Wallace has served as a statistical consultant for Noctem. The other authors report no financial relationships with commercial interests.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/EPUB

View PDF/EPUB

Full Text

View Full Text

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share