Deep brain stimulation for obsessive-compulsive disorder: evolution of tractography-based targeting

OBJECTIVE: Deep brain stimulation (DBS) in the anterior limb of the internal capsule (ALIC) for obsessive-compulsive disorder (OCD) can result in large improvements in symptoms and quality of life. However, without a consistent stimulation target within the anatomically variable ALIC region, the therapy has required long and unpredictable trial-and-error periods of parameter optimization to achieve these clinically meaningful benefits. To facilitate scalability and clinical implementation of ALIC DBS for OCD, this study aimed to demonstrate the evolution of prospective DBS targeting using patient-specific tractography. METHODS: Initially, the authors targeted a white matter map of ALIC bundles and cortical regions previously implied in DBS for OCD. They then generated a map of the ALIC connection shared by 6 participants with OCD who responded to DBS. This common responder map implicated white matter connections to the ventromedial prefrontal/orbitofrontal cortex (vmPFC/OFC), ventrolateral prefrontal cortex (vlPFC), and midbrain. Next, we prospectively targeted a new series of 7 patients guided by this common map. Finally, we generated a tractography-based predictive model based on individual stimulation-response outcomes to estimate the relative importance of each targeted ALIC pathway. RESULTS: Targeting a sweet spot in the common responder ALIC map that optimally connected the patient-specific vmPFC/OFC, vlPFC, and midbrain led to a consistent and predictable reduction of OCD symptoms, with 8 of 10 patients attaining a clinically meaningful Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score reduction in symptom severity of at least 35%. Individualized tractography-based targeting improved the primary OCD symptoms independent of hypomania or other changes in mood or anxiety and required minimal parameter changes away from the empirical tractography-based target spot. The tractography-based stimulation model generated a connectivity profile of left and right ALIC pathways that selectively predicted Y-BOCS score reduction and could be used to optimize future targeting further. CONCLUSIONS: The authors' results show how patient-specific tractography can facilitate clinically effective precision targeting in ALIC DBS for OCD.