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Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model

Author

Listed:
  • Bastijn J. G. Boom

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

  • Alfredo Elhazaz-Fernandez

    (Royal Netherlands Academy of Arts and Sciences)

  • Peter A. Rasmussen

    (Royal Netherlands Academy of Arts and Sciences)

  • Enny H. Beest

    (Royal Netherlands Academy of Arts and Sciences)

  • Aishwarya Parthasarathy

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

  • Damiaan Denys

    (University of Amsterdam)

  • Ingo Willuhn

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

Abstract

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.

Suggested Citation

  • Bastijn J. G. Boom & Alfredo Elhazaz-Fernandez & Peter A. Rasmussen & Enny H. Beest & Aishwarya Parthasarathy & Damiaan Denys & Ingo Willuhn, 2023. "Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41026-x
    DOI: 10.1038/s41467-023-41026-x
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    References listed on IDEAS

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    1. Eric Lowet & Krishnakanth Kondabolu & Samuel Zhou & Rebecca A. Mount & Yangyang Wang & Cara R. Ravasio & Xue Han, 2022. "Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Pino Alonso & Daniel Cuadras & Loes Gabriëls & Damiaan Denys & Wayne Goodman & Ben D Greenberg & Fiacro Jimenez-Ponce & Jens Kuhn & Doris Lenartz & Luc Mallet & Bart Nuttin & Eva Real & Cinto Segalas , 2015. "Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-16, July.
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