• Himanshu Tyagi, Annemieke M Apergis-Schoute, Harith Akram, Tom Foltynie, Patricia Limousin, Lynne M Drummond, Naomi A Fineberg, Keith Matthews, Marjan Jahanshahi, Trevor W Robbins, Barbara J Sahakian, Ludvic Zrinzo, Marwan Hariz, and Eileen M Joyce.
• Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; The National Hospital for Neurology and Neurosurgery, London, United Kingdom.
• Biol. Psychiatry. 2019 May 1; 85 (9): 726-734.

BackgroundDeep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.MethodsSix patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.ResultsDBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.ConclusionsBoth the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

21 keywords...

hide…