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

Background: Compulsive behaviors (CBs) are core features 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 CBs, but human studies have largely been limited by correlational designs (e.g., cross-sectional comparisons). Methods: Following a baseline assessment, 69 individuals with CB disorders were randomized 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% target RMT). 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/ decrease. Pre-post assessments of target engagement (fMRI) and CBs performed in response to an idiographically designed stressful laboratory probe were acquired. Results: cTBS and iTBS modulated OFC activation in expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of CBs at +90min post-TBS. Following cTBS, these acute behavioral effects persisted at +1-week. Correspondence concerning this article should be addressed to Rebecca B. Price, University of Pittsburgh Department of Psychiatry, 3811 O’Hara St., Pittsburgh, PA 15213, Phone: 412-648-6445, Fax: 412-631-8947, rebecca.price@stanfordalumni.org. Financial Disclosures. All authors reported no biomedical financial interests or potential conflicts of interest. HHS Public Access Author manuscript Am J Psychiatry. Author manuscript; available in PMC 2022 May 01. Published in final edited form as: Am J Psychiatry. 2021 May 01; 178(5): 459–468. doi:10.1176/appi.ajp.2020.20060821. A uhor M anscript