Patient-specific structural connectomic differences of deep brain stimulation targets in treatment-resistant obsessive-compulsive disorder patients

Deep brain stimulation (DBS) is an established therapy for treatment-resistant obsessive-compulsive disorder (trOCD), yet clinical outcomes vary. This partly due to differential cortico-striato-thalamo-cortical-networks (CSTC) engagement across stimulation anatomical-regions-targets. This study compared the structural and functional connectivity profiles of three anatomical-regions that have also served as target points for DBS in different centers for trOCD: the nucleus accumbens/anterior-limb of the internal-capsule (NAc/ALIC), medial-forebrain-bundle (MFB), and anteromedial subthalamic nucleus (amSTN). We retrospectively analysed structural and diffusion MRI data from 22 trOCD patients treated with NAc/ALIC DBS at the University Hospital Cologne. Whole-brain probabilistic-tractography using single-shell-three-tissue constrained-spherical-deconvolution was applied to reconstruct patient-specific structural connectivity matrices. For each hemisphere, tracts were generated for all three anatomic targets, and structural connectivity matrices were extracted using weighted-streamline count, fractional anisotropy (FA), and mean diffusivity (MD) across 13 cortico-subcortical regions implicated in OCD pathophysiology. Then we characterized each target’s connectivity to key OCD functional networks derived from meta-analytic data. NAc/ALIC demonstrated stronger structural fronto-limbic connectivity: medial-orbitofrontal cortex, anterior-cingulate, insula, and accumbens (p < 0.0001), associated with the affect (AN), salience (SN), default-mode (DMN), and reward-motivation (RMN) networks. MFB predominantly connected with reward-related regions: pallidum and rostral-middle-frontal cortex (p < 0.0001). amSTN is mainly connected to SN and the cognitive/motor control network (CMCN): precentral and paracentral gyri (p < 0.0001). These findings suggest target-specific network profiles and partially overlapping networks, supporting the probe-of-concept of patient-specific tractography for precision trOCD-DBS planning. While promising for symptom-specific targeting in trOCD, validation in multicentric-trials remains necessary.