PROJECT SUMMARY The overall goal of this project is to study three direct circuit based interventions for intractable OCD to (1) advance our understanding of the neurocircuitry of the disorder and to (2) leverage that understanding in order to develop individualized approaches to treatment that will improve safety and efficacy. Our first aim is to examine the effects of MRI guided laser thermal ventral capsulotomy in twenty patients with intractable OCD using diffusion imaging to identify cortifugal axons affected by the lesions in individuals that are related to treatment response. We will also study the effects of lesions on individual resting state and task based (PAAT) functional connectivity and their relationship to treatment outcome measures. We will utilize novel acquisition and analytic algorithms for individuals designed by Cores B and C as well as interact with Projects 1, 3 and 4 to identify false negatives and positives in the diffusion scans and to compare imaging results in patients undergoing intensive non-surgical treatments to those with lesions. The second aim is to conduct a pilot feasibility study, using a double blind crossover design, of a dual DBS implant in the vALIC and anterior cingulate bundle. The Medtronic Percept system will allow stimulation and recording of LFPs, in four patients with intractable OCD. We will stimulate and record in the vALIC and anterior cingulate, using pre-implant diffusion imaging and electric field modeling to identify which tracts are being activated. We will study the effects of stimulation at different contacts on the PAAT, and compare this to results obtained with electrophysiological recordings in the primate. Leveraging methodology developed by our collaborators (U Goodman, Dougherty) we will identify potential biomarkers of OCD provocation and treatment response. We will interact with Project 1 and 2 to compare anatomic and electrophysiological results across humans and primates as well as Cores B and C for imaging acquisition and analysis. Our third aim is to leverage ongoing studies of low intensity focused ultrasound in twenty-four patients with intractable OCD (Dougherty, Goodman PIs) and obtain pre post diffusion and task based (PAAT) functional imaging in those patients. We will compare these results to those found in lesions and DBS in the vALIC target and draw on CORE B and C as well as Project 1 and 2 to compare imaging results with nonsurgical OC subjects.