A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder

Clinical and Imaging Evidence for Dissociable Effects

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, Eileen M. Joyce (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)726-734
Number of pages9
JournalBiological Psychiatry
Volume85
Issue number9
Early online date30 Jan 2019
DOIs
Publication statusPublished - 1 May 2019

Fingerprint

Anterior Thalamic Nuclei
Subthalamic Nucleus
Deep Brain Stimulation
Obsessive-Compulsive Disorder
Capsules
Corpus Striatum
Cognitive Therapy
Prefrontal Cortex
Neuropsychological Tests
Gyrus Cinguli
Inpatients
Electrodes
Therapeutics

Keywords

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

Cite this

Tyagi, Himanshu ; Apergis-Schoute, Annemieke M. ; Akram, Harith ; Foltynie, Tom ; Limousin, Patricia ; Drummond, Lynne M. ; Fineberg, Naomi A. ; Matthews, Keith ; Jahanshahi, Marjan ; Robbins, Trevor W. ; Sahakian, Barbara J. ; Zrinzo, Ludvic ; Hariz, Marwan ; Joyce, Eileen M. / A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder : Clinical and Imaging Evidence for Dissociable Effects. In: Biological Psychiatry. 2019 ; Vol. 85, No. 9. pp. 726-734.
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title = "A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects",
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, Obsessive-compulsive disorder, OCD, Ventral internal capsule",
author = "Himanshu Tyagi and Apergis-Schoute, {Annemieke M.} and Harith Akram and Tom Foltynie and Patricia Limousin and Drummond, {Lynne M.} and Fineberg, {Naomi A.} and Keith Matthews and Marjan Jahanshahi and Robbins, {Trevor W.} and Sahakian, {Barbara J.} and Ludvic Zrinzo and Marwan Hariz and Joyce, {Eileen M.}",
note = "This 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).",
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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 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, vol. 85, no. 9, pp. 726-734. https://doi.org/10.1016/j.biopsych.2019.01.017

A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder : Clinical and Imaging Evidence for Dissociable Effects. / Tyagi, Himanshu; Apergis-Schoute, Annemieke M.; Akram, Harith; Foltynie, Tom; Limousin, Patricia; Drummond, Lynne M.; Fineberg, Naomi A.; Matthews, Keith; Jahanshahi, Marjan; Robbins, Trevor W.; Sahakian, Barbara J.; Zrinzo, Ludvic; Hariz, Marwan; Joyce, Eileen M. (Lead / Corresponding author).

In: Biological Psychiatry, Vol. 85, No. 9, 01.05.2019, p. 726-734.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder

T2 - Clinical and Imaging Evidence for Dissociable Effects

AU - Tyagi, Himanshu

AU - Apergis-Schoute, Annemieke M.

AU - Akram, Harith

AU - Foltynie, Tom

AU - Limousin, Patricia

AU - Drummond, Lynne M.

AU - Fineberg, Naomi A.

AU - Matthews, Keith

AU - Jahanshahi, Marjan

AU - Robbins, Trevor W.

AU - Sahakian, Barbara J.

AU - Zrinzo, Ludvic

AU - Hariz, Marwan

AU - Joyce, Eileen M.

N1 - This 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).

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Anteromedial subthalamic nucleus

KW - DBS

KW - Deep brain stimulation

KW - Obsessive-compulsive disorder

KW - OCD

KW - Ventral internal capsule

U2 - 10.1016/j.biopsych.2019.01.017

DO - 10.1016/j.biopsych.2019.01.017

M3 - Article

VL - 85

SP - 726

EP - 734

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 9

ER -