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Cited by 48Obsessive-Compulsive Spectrum DisordersTranscranial Magnetic Stimulation StudiesNeurological disorders and treatments

Effect of Experimental Manipulation of the Orbitofrontal Cortex on Short-Term Markers of Compulsive Behavior: A Theta Burst Stimulation Study

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Price, Rebecca B., Gillan, Claire M., Hanlon, Colleen, Ferrarelli, Fabio, Kim, Tae, Karim, Helmet T., Renard, Marlee, Kaskie, Rachel +8 more·2021·American Journal of Psychiatry
DOI 10.1176/appi.ajp.2020.20060821PMC PMC8119344
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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.

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References 52 · Cited by 48

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Authors
Price, R. B., Gillan, C. M., Hanlon, C., Ferrarelli, F., Kim, T., Karim, H. T., Renard, M., Kaskie, R., Degutis, M., Wears, A., Vienneau, E. P., Peterchev, A. V., Brown, V., Siegle, G. J., Wallace, M. L., & Ahmari, S. E.
Affiliations
University of Pittsburgh (US)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2021-05-01
Volume
178
Issue
5
Pages
459-468
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.2020.20060821
PMC
PMC8119344
OpenAlex
W3137534105
Cited by
48
References
52
Citations by year
2026: 8 · 2025: 11 · 2024: 6 · 2023: 4 · 2022: 14 · 2021: 5
FWCI
4.95
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR001857)
  • National Institute of Mental Health (R21MH112770)
  • National Center for Advancing Translational Sciences
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
orbitofrontal cortex, compulsive behavior, obsessive-compulsive spectrum disorders, theta burst stimulation, continuous theta burst stimulation, intermittent theta burst stimulation, transcranial magnetic stimulation, stress response
MeSH terms
Adolescent, Adult, Compulsive Behavior, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Obsessive-Compulsive Disorder, Random Allocation, Theta Rhythm, Trichotillomania, Prefrontal Cortex, Transcranial Magnetic Stimulation, Young Adult, Body Dysmorphic Disorders, Functional Neuroimaging

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