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dc.contributor.authorTyagi, H-
dc.contributor.authorApergis-Schoute, AM-
dc.contributor.authorAkram, H-
dc.contributor.authorFoltynie, T-
dc.contributor.authorLimousin, P-
dc.contributor.authorDrummond, LM-
dc.contributor.authorFineberg, NA-
dc.contributor.authorMatthews, K-
dc.contributor.authorJahanshahi, M-
dc.contributor.authorRobbins, TW-
dc.contributor.authorSahakian, BJ-
dc.contributor.authorZrinzo, L-
dc.contributor.authorHariz, M-
dc.contributor.authorJoyce, EM-
dc.identifier.citationBiological Psychiatry, 2019, 8(9), pp. 726-734en
dc.description.abstractBACKGROUND: 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.en
dc.description.sponsorshipThis work was supported by Medical Research Council Grant No. MR/J012009/1, National Institute for Health Research University College London Hospitals Biomedical Research Centre (to EMJ), the Monument Trust and the Parkinson’s Appeal UK (to MH, LZ, TF, PL), the Brain Research Trust (to HA), Wellcome Trust Award Grant No. WT 104631/Z/14/Z (to TWR), and the National Institute for Health Research Cambridge Biomedical Research Centre mental health theme (to TWR, BJS, AMA-S).en
dc.publisherElsevier for Society of Biological Psychiatryen
dc.rightsCopyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectAnteromedial subthalamic nucleusen
dc.subjectDeep brain stimulationen
dc.subjectObsessive-compulsive disorderen
dc.subjectVentral internal capsuleen
dc.titleA Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects.en
dc.typeJournal Articleen
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Neuroscience, Psychology and Behaviouren
Appears in Collections:Published Articles, Dept. of Neuroscience, Psychology and Behaviour

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