A Multi-Symptom Circuit Architecture of Obsessive-Compulsive Disorder.

Area of Science:

• Neuroscience
• Psychiatry
• Neuromodulation

Background:

• Obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS) involve complex neural circuit dysfunction.
• Deep brain stimulation (DBS) and connectomics offer insights into human brain pathways.
• Understanding specific circuit contributions to diverse symptoms is crucial for effective treatment.

Purpose of the Study:

• To identify neural circuits underlying obsessive-compulsive symptoms in OCD and TS patients.
• To investigate the relationship between stimulation sites, clinical outcomes, and symptom profiles.
• To delineate a circuit taxonomy for compulsivity and guide personalized neuromodulation.

Main Methods:

• Analysis of clinical outcomes and stimulation sites from 77 OCD and 39 TS patients (244 electrodes, 15 cohorts, 8 targets).
• Utilized high-resolution connectomics in conjunction with DBS.
• Employed cross-validation schemes and patient subset analyses for reproducibility.

Main Results:

• Engagement of the defined 'OCD response tract' predicted global symptom improvement in both OCD and TS.
• Specific symptom clusters (obsessions, compulsions, anxiety, depression) mapped to distinct, overlapping subcircuits in the anterior limb of the internal capsule.
• Global functional recovery was associated with combined engagement of multiple symptom-specific tracts.

Conclusions:

• Invasive neuromodulation can delineate a multi-symptom circuit taxonomy of compulsivity.
• Findings highlight a fine-scale, reproducible architecture of circuit dysfunction in OCD.
• This circuit taxonomy may inform personalized neuromodulation strategies for treatment-refractory patients.