A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder

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Abstract

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham ( p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points ( χ ² (11) = 39.8, p = 3.8 × 10 ⁻⁵), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points ( p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

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The Human Connectome Project consortium led by Washington University, University of Minnesota, and Oxford University is undertaking a systematic effort to map macroscopic human brain circuits and their relationship to behavior in a large population of healthy adults. This overview article focuses on progress made during the first half of the 5-year project in refining the methods for data acquisition and analysis. Preliminary analyses based on a finalized set of acquisition and preprocessing protocols demonstrate the exceptionally high quality of the data from each modality. The first quarterly release of imaging and behavioral data via the ConnectomeDB database demonstrates the commitment to making HCP datasets freely accessible. Altogether, the progress to date provides grounds for optimism that the HCP datasets and associated methods and software will become increasingly valuable resources for characterizing human brain connectivity and function, their relationship to behavior, and their heritability and genetic underpinnings. Copyright © 2013 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Philip E. Mosley:

ORCID: http://orcid.org/0000-0003-1721-3419

philip.mosley@qimrberghofer.edu.au

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 29 March 2021

Publication date PMC-release: 29 March 2021

Publication date Collection: 2021

Volume: 11

Electronic Location Identifier: 190

Affiliations

[1 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, ; Herston, QLD Australia

[2 ]Neurosciences Queensland, St Andrew’s War Memorial Hospital, Spring Hill, QLD Australia

[3 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Queensland Brain Institute, , University of Queensland, ; St Lucia, QLD Australia

[4 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Faculty of Medicine, , University of Queensland, ; Herston, QLD Australia

[5 ]GRID grid.417021.1, ISNI 0000 0004 0627 7561, Brizbrain and Spine, the Wesley Hospital, ; Auchenflower, QLD Australia

[6 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, , University of New South Wales, ; Sydney, NSW Australia

[7 ]GRID grid.415193.b, Neuropsychiatric Institute, The Prince of Wales Hospital, ; Randwick, NSW Australia

[8 ]The OCD Clinic, Bulimba, QLD Australia

[9 ]GRID grid.1022.1, ISNI 0000 0004 0437 5432, School of Applied Psychology, , Griffith University, ; Gold Coast, QLD Australia

[10 ]GRID grid.263817.9, Joint Center for Neuroscience and Neural Engineering, and Department of Biology, , Southern University of Science and Technology, ; Shenzhen, Guangdong Province P. R. China

Author information

Philip E. Mosley http://orcid.org/0000-0003-1721-3419

François Windels http://orcid.org/0000-0001-5341-2197

Perminder Sachdev http://orcid.org/0000-0002-9595-3220

Pankaj Sah http://orcid.org/0000-0001-5063-1589

Article

Publisher ID: 1307

DOI: 10.1038/s41398-021-01307-9

PMC ID: 8007749

PubMed ID: 33782383

SO-VID: 83a86ea3-8c5e-4edd-9bb6-71cd32b72b83

License:

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