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.
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.
Authors: Lior Carmi; Aron Tendler; Alexander Bystritsky; Eric Hollander; Daniel M Blumberger; Jeff Daskalakis; Herbert Ward; Kyle Lapidus; Wayne Goodman; Leah Casuto; David Feifel; Noam Barnea-Ygael; Yiftach Roth; Abraham Zangen; Joseph Zohar Journal: Am J Psychiatry Date: 2019-05-21 Impact factor: 18.112
Authors: Sung Wook Chung; Aron T Hill; Nigel C Rogasch; Kate E Hoy; Paul B Fitzgerald Journal: Neurosci Biobehav Rev Date: 2016-02-03 Impact factor: 8.989
Authors: Prantik Kundu; Noah D Brenowitz; Valerie Voon; Yulia Worbe; Petra E Vértes; Souheil J Inati; Ziad S Saad; Peter A Bandettini; Edward T Bullmore Journal: Proc Natl Acad Sci U S A Date: 2013-09-13 Impact factor: 11.205
Authors: Todd Lencz; Ashley Moyett; Miklos Argyelan; Anita D Barber; John Cholewa; Michael L Birnbaum; Juan A Gallego; Majnu John; Philip R Szeszko; Delbert G Robinson; Anil K Malhotra Journal: Neuropsychopharmacology Date: 2022-10-05 Impact factor: 8.294