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

J Neurosurg 144:293–304, 2026

This clinical study describes the development and prospective application of patient-specific tractography to refine anterior limb of the internal capsule (ALIC) deep brain stimulation (DBS) targeting for treatment-refractory obsessive-compulsive disorder (OCD). The authors generated a common responder connectivity map highlighting ALIC pathways to vmPFC/OFC, vlPFC, thalamus, STN, and midbrain, then used that map to guide implantation in a new cohort, achieving consistent and rapid Y-BOCS improvements.

The team also built a tractography-based stimulation model linking activation of specific unilateral ALIC pathways to symptom reduction, demonstrating selective prediction of obsessive–compulsive symptom improvement (but not mood or anxiety). Results suggest that tractography-guided “sweet spot” targeting at the ventral ALIC near the GPe can reduce trial-and-error programming and support precision ALIC DBS implementation.

Patient-specific tractography targeting: Using individualized diffusion MRI tractography to guide deep brain stimulation (DBS) lead placement in the anterior limb of the internal capsule (ALIC) for obsessive-compulsive disorder (OCD) enables more precise and consistent targeting of therapeutic white matter pathways.

Common responder map: A map of white matter connections shared by DBS responders was generated, highlighting key pathways to the ventromedial/orbitofrontal cortex (vmPFC/OFC), ventrolateral prefrontal cortex (vlPFC), and midbrain; targeting this “sweet spot” led to improved and predictable clinical outcomes.

Improved clinical efficacy: Tractography-based ALIC DBS resulted in an 80% response rate (≥35% Y-BOCS reduction) among prospective patients, with faster and more consistent OCD symptom improvement compared to prior methods.

Reduced trial-and-error programming: Targeting based on the common responder map minimized the need for multiple adjustments in stimulation parameters, streamlining clinical implementation.

Symptom specificity: Stimulation of the tractography-defined target selectively improved OCD symptoms (obsessions and compulsions) with less impact on mood or anxiety and minimal side effects such as hypomania.

Tractography-based predictive model: A quantitative model using patient-specific pathway activation predicted OCD symptom improvement (Y-BOCS reduction), with strongest predictive value for connections to vlPFC, vmPFC/OFC, thalamus, and midbrain, but not for depression or anxiety scores.

Updated common responder map validation: High-resolution 7T MRI data from additional responders confirmed the importance of connections to vlPFC, vmPFC/OFC, thalamus, and midbrain in therapeutic response.

Potential for clinical scalability: This precision targeting approach, if validated in larger cohorts, could enhance the predictability, effectiveness, and broader adoption of DBS for treatment-resistant OCD.

An International Radiosurgery Research Foundation Multicenter Retrospective Study of Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder

Neurosurgery, Volume 85, Issue 6, December 2019, Pages 808–816

Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC).
OBJECTIVE: To evaluate clinical outcomes of severe medically refractory OCD treated with GVC.
METHODS: This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed “responders” to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo).
RESULTS: The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered “responders,” and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P < .0005). Ten patients (25%) experienced post-GVC mood disturbance and neurological complications in 3 patients (7.5%). One patient developed radiation necrosis with edema that improved with steroids.
CONCLUSION: GVC serves as a reasonable treatment strategy for severe medical refractory OCD. Patients treated with 2 isocenters were more likely to have substantial improvement in OCD.