201 Tractography Analysis of Deep Brain Stimulation for Obsessive-Compulsive Disorder

Abstract

INTRODUCTION: Deep brain stimulation of the anterior limb of the internal capsule (ALIC-DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Animal tracing studies and human tractography suggest that the putative ALIC target for OCD impacts brain circuits for reward, affect and inhibitory control, including projections to orbitofrontal (OFC) and ventromedial (vmPFC) cortex, ventrolateral cortex (vlPFC), dorsal anterior cingulate cortex (dACC), dorsal medial cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC). The recent development of directional segmented DBS leads may allow for selective stimulation of these ALIC-projections. METHODS: We generated structural connectivity maps of therapeutic stimulation using probabilistic tractography in OCD patients treated with ALIC-DBS. Response was defined as = 35% improvement in YBOCS after routine clinical parameter optimization. We also generated the volume of tissue activation (VTA) based on the stimulation parameters at the last follow-up. We estimated probability of connections between the VTA and each projection to the prefrontal regions (vmPFC/OFC, vlPFC, dlPFC, dmPFC, and dACC) in responders and non-responders. To further explore how connectivity would explain clinical improvement, we correlated connectivity values from stimulation sites to cortical regions to the percentage of change in YBOCS using Spearman correlation. Finally, we developed directional tractography activation models and explored personalized circuit-specific targeting and stimulation for patients with directional DBS-leads. RESULTS: All patients with ALIC DBS displayed stimulation of OFC/vmPFC and dmPFC connections. However, non-responders had incomplete stimulation of vlPFC, dACC and dlPFC compared to responders. Correlation analysis revealed that fibers from the dorsolateral ALIC to vlPFC were positively associated with improvement in Y-BOCS scores, while connections from ventral ALIC to vmPFC were negatively associated. We were able to successfully construct a stimulation tractography model of directional segmented lead configurations along the medial-lateral axis, which we used for personalized DBS targeting and programming in our most recent patients. Early observations suggest that this directional precision-strategy allows for fast improvement in patient-specific symptom domains for reward, affect and inhibitory control. CONCLUSION: Our findings suggest that the therapeutic benefit of ALIC DBS for OCD is associated with stimulation of a subset of specific ALIC WM pathways, which can be selectively targeted using directional DBS-systems.