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

19 Citations (Scopus)
108 Downloads (Pure)

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

Keywords

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

Fingerprint Dive into the research topics of 'A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects'. Together they form a unique fingerprint.

  • Profiles

    No photo of Keith Matthews

    Matthews, Keith

    Person: Academic

    Cite this

    Tyagi, H., Apergis-Schoute, A. M., Akram, H., Foltynie, T., Limousin, P., Drummond, L. M., Fineberg, N. A., Matthews, K., Jahanshahi, M., Robbins, T. W., Sahakian, B. J., Zrinzo, L., Hariz, M., & Joyce, E. M. (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, 85(9), 726-734. https://doi.org/10.1016/j.biopsych.2019.01.017