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Biol Psychiatry. 2019 May 1;85(9):726-734. doi: 10.1016/j.biopsych.2019.01.017. Epub 2019 Jan 30.

A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects.

Author information

1
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.
2
Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
3
Highly Specialised Service for OCD and BDD (England), SW London and St George's NHS Trust, London, United Kingdom.
4
Highly Specialised Service for OCD and BDD (England), Hertfordshire Partnership University NHS Foundation Trust, Welwyn Garden City, United Kingdom; Centre for Clinical & Health Research Services, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.
5
Division of Neuroscience, School of Medicine, University of Dundee, Dundee, United Kingdom; Advanced Interventions Service, NHS Tayside, Ninewells Hospital and Medical School, Dundee, United Kingdom.
6
Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom.
7
Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
8
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. Electronic address: e.joyce@ucl.ac.uk.

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.

KEYWORDS:

Anteromedial subthalamic nucleus; DBS; Deep brain stimulation; OCD; Obsessive-compulsive disorder; Ventral internal capsule

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