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.

Tractography-based targeting of the ventral intermediate nucleus

J Neurosurg 133:1002–1009, 2020

Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients.

METHODS T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced (“translated”) by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy.

RESULTS T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the “final” indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant.

CONCLUSIONS T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy

Neurosurgery 84:160–168, 2019

Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning.

OBJECTIVE: To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM).

METHODS: VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group.We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusionweighted imaging changes were also studied in fiber tracts of interest.

RESULTS: The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3mo(tremor score: 18.3±6.9 vs 8.1±4.4, P=.001).Nomotorweakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex.

CONCLUSION: This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

Electrophysiological validation of STN-SNr boundary depicted by susceptibility-weighted MRI

Electrophysiological validation of STN-SNr boundary depicted by susceptibility-weighted MRI

Acta Neurochir (2015) 157:2129–2134

Direct targeting of subthalamic nucleus (STN) without secondary electrophysiological verification during deep brain stimulation (DBS) is replacing atlas-based indirect targeting techniques. Recent groups have reported increased contrast and better delineation of STN and substantia nigra (SNr) in susceptibility-weighted imaging protocols (SWI). We aim to validate the STN-SNr boundary seen in MRISWI by correlating with intraoperative microelectrode recordings (MER) as a part of developing a multi-contrast DBSMRI planning protocol.

Methods Prospective service evaluation involving electrophysiological verification by correlation of MER trajectory and STN-SNr boundary seen in SWI in seven consecutive patients undergoing DBS surgery were analyzed. The angle of inclination of the STN-SNr boundary and DBS trajectory in the coronal plane were calculated. Considering 4-mm dispersion of a coronal 3 MER array, we predicted, measured, and correlated the depths at which each electrode engaged the boundary.

Results All central microelectrodes identified the STN-SNr boundary within 1 mm of the predicted depth with 100 % accuracy. Ninety percent of the lateral MER identified the STN-SNr boundary as predicted from SWI and angle of the encounter of the MER front.

Conclusions The study demonstrates that STN morphology can be depicted using SWI MRI and coincides reliably with the electrophysiological MER boundary. Thus, this imaging modality can be used to refine STN direct targeting protocols in DBS surgery for PD.

An Optimized 3-T Magnetic Resonance Imaging Sequence for Targeting the Subthalamic Nucleus

High-Resolution 3-Dimensional T2*-Weighted Angiography (HR 3-D SWAN)- An Optimized 3-T Magnetic Resonance Imaging Sequence for Targeting the Subthalamic Nucleus

Neurosurgery 74:615–627, 2014

Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for Parkinson’s disease.

OBJECTIVE: To characterize an optimized magnetic resonance imaging (MRI) sequence (high-resolution 3-dimensional T2*-weighted angiography [HR 3-D SWAN]) for direct STN targeting.

METHODS: Sequence distortions were measured using the Leksell stereotactic phantom. Eight consecutive candidates for STN-DBS underwent HR 3-D SWAN MRI for direct identification of the 16 STN. Two senior neurosurgeons independently determined the boundaries of STN on a semiquantitative scale (ranging from 1 [identification very easy] to 4 [identification very difficult]) and the anatomic target within the nucleus. The anatomic data were compared with electrophysiological recordings (48 microrecordings). We examined the anatomic location of the active contacts on MRI.

RESULTS: The mean distortion error over the phantom was 0.16 mm. For the 16 STNs, identification of the upper, internal, anterior, and external edges was considered to be easy (scores of 1 or 2). The distinction between the substantia nigra and the STN was rated 1 or 2 for all but 6 nuclei. In the mediolateral axis, electrophysiological recordings covered perfectly anatomic data. In the craniocaudal axis, the mean differences between the electrophysiological data and the anatomic data were 0.8 mm and 0.19 mm for the “entry” and “exit” of the STN, respectively. All active contacts were located within the STN on MRI.

CONCLUSION: HR 3-D SWAN allows easy visualization of the STN. Adapted to stereotactic requirement, the sequence simplifies direct targeting in STN-DBS surgery.

Bilateral subthalamic deep brain stimulation using single track microelectrode recording

Acta Neurochir (2011) 153:1087–1095 DOI 10.1007/s00701-011-0953-1

Microelectrode recording (MER) is widely used during deep brain stimulation (DBS) procedures because MER can identify structural borders and eloquent structures, localize somatotopic arrangements, and provide an outline of the three-dimensional shapes of target nuclei. However, MER may cause intracranial hemorrhage. We performed single track MER during DBS procedures, analyzed the accuracy of electrode positioning with MRI, and compared the amount of air and the potential risk of intracranial hemorrhage.

Method A total of 46 electrodes were placed in 23 patients who suffered from advanced Parkinson’s disease and who underwent bilateral subthalamic nucleus DBS using single track MER. Each patient’s Unified Parkinson’s Disease Rating Scale (UPDRS) score and levo-dopa equivalent dosage (LED) were estimated pre- and postoperatively. The accuracy of electrode positioning and fontal air thickness was measured by a pre- or postoperative magnetic resonance imaging (MRI) merging technique.

Findings The mean electrode positioning error was 0.92 mm (0.3–2.94 mm). The mean frontal air thickness on postoperative MRI was 3.85 mm (0–10.3 mm), which did not affect the electrode accuracy statistically (p=0.730). A total of nine electrodes required repositioning after single-track MER because they affected microstimulation or because an abnormally short STN length was observed during MER. In this series, one patient suffered from an intracranial hemorrhage after surgery that appeared to be due to venous infarction rather than related to MER.

Conclusions Although MER can facilitate accurate positioning of electrodes, multi-track MER may increase the risk of intracranial hemorrhage. The accuracy of electrode positioning appears to be acceptable under single track MER during STN DBS with careful electrophysiological and neurological monitoring. The risk of intracranial hemorrhage appears to be minimal, especially in elderly patients with atrophic brains.