Prefrontal cortex connectivity profiles distinguish rapid from slow responders to deep brain stimulation in obsessive-compulsive disorder

Introduction Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) can benefit patients with treatment-refractory obsessive-compulsive disorder (OCD). However, time to respond post-operatively ranges from weeks to over a year. We examined neuroanatomical determinants of this variability. Methods We studied 16 treatment-refractory OCD patients who responded to VC/VS DBS, classifying them as rapid (less than or equal to 3 months) or slow (greater than 3 months) responders. We compared contact locations along anterior-posterior, dorsal-ventral, and medial-lateral axes. In 11 patients with diffusion-weighted magnetic resonance imaging (dMRI), we utilized volumes of tissue activated (VTAs) for both initial and most recent effective DBS settings to filter tractograms of the anterior limb of the internal capsule to 11 predefined prefrontal cortical regions. We analyzed streamline counts as a proxy for connectivity strength with mixed-effects models. Results Rapid (n=8) and slow (n=8) responders exhibited a clear bimodal distribution of time-to-response, supported by a Bayesian Information Criterion difference of 9.14. Rapid responders right-hemisphere contacts were positioned more superiorly, and there was a trend toward their left-hemisphere contacts being positioned more posteriorly. Connectivity fingerprints and mixed-effects modeling showed greater dorsolateral prefrontal cortex engagement in rapid responders than in slow responders, whereas slow responders showed enhanced central orbitofrontal cortex connectivity over time. Discussion Variability in VC/VS contact placement corresponds to distinct prefrontal cortical connectivity patterns and response timelines. Patient-specific targeting and connectivity-informed programming may accelerate response to treatment.