A Multi-Symptom Circuit Architecture of Obsessive–Compulsive Disorder

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Abstract
Obsessive–compulsive disorder (OCD) manifests with diverse symptom constellations that likely arise from dysfunction in partially distinct neural circuits. Deep brain stimulation (DBS), paired with high-resolution connectomics, offers a unique window into these pathways in humans. Here, we analyzed clinical outcomes and stimulation sites from 77 treatment-refractory patients with OCD and 39 with Tourette’s syndrome (TS) exhibiting comorbid obsessive–compulsive behaviors (244 electrodes across 15 cohorts and eight targets). Engagement of the previously defined OCD response tract predicted global obsessive-compulsive symptom improvement across heterogeneous targets and diagnoses, spanning both OCD and TS. Beyond broad symptoms, obsessions, compulsions, anxiety, and depression mapped onto distinct yet overlapping subcircuits fragmenting the anterior limb of the internal capsule along a dorsoventral axis. This fine-scale architecture of OCD circuit dysfunction was reproducible across cross-validation schemes and patient subsets. Exploratory analyses identified additional subcircuits for cognitive control and flexibility. Global functional recovery was better explained by combined engagement of multiple symptom-specific rather than a single tract. Collectively, these findings illustrate how invasive neuromodulation can delineate a multi-symptom circuit taxonomy of compulsivity that may guide personalized neuromodulation.

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