Resting-State Functional Connectivity Differences Following Experimental Manipulation of the Orbitofrontal Cortex in Two Directions via Theta-Burst Stimulation.

Compulsive behaviors (CBs) have been linked to orbitofrontal cortex (OFC) function in animal and human studies. However, brain regions function not in isolation but as components of widely distributed brain networks-such as those indexed via resting-state functional connectivity (RSFC). Sixty-nine individuals with CB disorders were randomized to receive a single session of neuromodulation targeting the left OFC-intermittent theta-burst stimulation (iTBS) or continuous TBS (cTBS)-followed immediately by computer-based behavioral "habit override" training. OFC seeds were used to quantify RSFC following iTBS and following cTBS. Relative to cTBS, iTBS showed increased RSFC between right OFC (Brodmann's area 47) and other areas, including dorsomedial prefrontal cortex (dmPFC), occipital cortex, and a priori dorsal and ventral striatal regions. RSFC connectivity effects were correlated with OFC/frontopolar target engagement and with subjective difficulty during habit-override training. Findings help reveal neural network-level impacts of neuromodulation paired with a specific behavioral context, informing mechanistic intervention development.

A double-blind study assessing the impact of orbitofrontal theta burst stimulation on goal-directed behavior.

Patients with disorders of compulsivity show impairments in goal-directed behavior, which have been linked to orbitofrontal cortex (OFC) dysfunction. We recently showed that continuous theta burst stimulation (cTBS), which reduces OFC activity, had a beneficial effect on compulsive behaviors both immediately and at 1 week follow-up compared with inhibitory TBS (iTBS). In this same sample, we investigated whether two behavioral measures of goal-directed control (devaluation success on a habit override task; model-based planning on the two-step task) were also affected by acute modulation of OFC activity. Overall, model-based planning and devaluation success were significantly related to each other and (for devaluation success) to symptoms in our transdiagnostic clinical sample. These measures were moderately to highly stable across time. In individuals with low levels of model-based planning, active cTBS improved devaluation success. Analogous to previously reported clinical effects, this effect was specific to cTBS and not iTBS. Overall, results suggested that measures of goal directed behavior are reliable but less affected by cTBS than clinical self-report. Future research should continue to examine longitudinal changes in behavioral measures to determine their temporal relationship with symptom improvement after treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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

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.