Patient-specific subnetwork connectivity predicts deep brain stimulation response in obsessive-compulsive disorder

Deep brain stimulation (DBS) can be an effective treatment for severe obsessive-compulsive disorder (OCD), but response is variable, and objective, reliable predictors of who will respond positively are absent. In three individuals with OCD, we implanted intracranial electrodes across the cortico-striato-limbic network before DBS. Prefrontal gamma activity, most prominently in the orbitofrontal cortex (OFC), distinguished high-from low-symptom OCD states reproducibly across days. Acute stimulation of the ventral capsule/ventral striatum relieved OCD symptoms and, in one patient, significantly shifted this OFC gamma signal. Effective connectivity from therapeutic stimulation sites to these prefrontal regions defined three patient-specific OCD subnetworks; the baseline strength of the nucleus accumbens/ventral pallidum-OFC subnetwork predicted acute and long-term DBS response. Imaging-based modeling of current propagation in stimulation-activated ventral capsule to the OFC tracked acute response, suggesting that this prediction could be approximated from imaging alone. These findings outline a predictive, subnetwork-level framework for personalized DBS in OCD.

Prefrontal gamma encodes OCD symptom state and persists across recording daysAcute VC/VS stimulation relieves symptoms and can shift the prefrontal gamma signalBaseline subnetwork connectivity predicts acute and long-term DBS responseModeled ALIC-to-OFC tract activation approximates this prediction from imaging.

Scangos and colleagues mapped three patients with obsessive-compulsive disorder with intracranial electrodes before deep brain stimulation. Prefrontal gamma activity tracked symptom state, and baseline connectivity from stimulation sites to these prefrontal regions predicted acute and long-term stimulation response. Modeled activation of ALIC-to-OFC tracts was associated with response, offering a route to this prediction from imaging alone.