eprintid: 10070548 rev_number: 26 eprint_status: archive userid: 608 dir: disk0/10/07/05/48 datestamp: 2019-03-20 15:29:14 lastmod: 2021-09-20 00:12:41 status_changed: 2019-03-20 15:29:14 type: article metadata_visibility: show creators_name: Tyagi, H creators_name: Apergis-Schoute, AM creators_name: Akram, H creators_name: Foltynie, T creators_name: Limousin, P creators_name: Drummond, LM creators_name: Fineberg, NA creators_name: Matthews, K creators_name: Jahanshahi, M creators_name: Robbins, TW creators_name: Sahakian, BJ creators_name: Zrinzo, L creators_name: Hariz, M creators_name: Joyce, EM title: A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects ispublished: inpress subjects: UCH divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F84 divisions: F85 keywords: Anteromedial subthalamic nucleus, DBS, Deep brain stimulation, OCD, Obsessive-compulsive disorder, Ventral internal capsule note: Copyright © 2019 Society of Biological Psychiatry. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: BACKGROUND: Deep 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. METHODS: Six 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. RESULTS: DBS 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. CONCLUSIONS: Both 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. date: 2019-01-30 date_type: published official_url: http://doi.org/10.1016/j.biopsych.2019.01.017 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1638815 doi: 10.1016/j.biopsych.2019.01.017 pii: S0006-3223(19)30063-0 lyricists_name: Akram, Harith lyricists_name: Foltynie, Thomas lyricists_name: Hariz, Marwan lyricists_name: Jahanshahi, Marjan lyricists_name: Joyce, Eileen lyricists_name: Limousin, Patricia lyricists_name: Tyagi, Himanshu lyricists_name: Zrinzo, Ludvic lyricists_id: HAKRA15 lyricists_id: TFOLT83 lyricists_id: MIHAR20 lyricists_id: MJAHA29 lyricists_id: EMJOY57 lyricists_id: PDLIM44 lyricists_id: TYAGI07 lyricists_id: LUZRI77 actors_name: Cuccu, Clara actors_id: CCCUC40 actors_role: owner full_text_status: public publication: Biological Psychiatry event_location: United States issn: 1873-2402 citation: Tyagi, H; Apergis-Schoute, AM; Akram, H; Foltynie, T; Limousin, P; Drummond, LM; Fineberg, NA; ... Joyce, EM; + view all <#> Tyagi, H; Apergis-Schoute, AM; Akram, H; Foltynie, T; Limousin, P; Drummond, LM; Fineberg, NA; Matthews, K; Jahanshahi, M; Robbins, TW; Sahakian, BJ; Zrinzo, L; Hariz, M; Joyce, EM; - view fewer <#> (2019) A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects. Biological Psychiatry 10.1016/j.biopsych.2019.01.017 <https://doi.org/10.1016/j.biopsych.2019.01.017>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10070548/1/Tyagi_1-s2.0-S0006322319300630-main.pdf