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A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder

Author

Listed:
  • Jay L. Gill

    (University of California
    University of California)

  • Julia A. Schneiders

    (University of California
    Research and Development Service; Department of Veterans Affairs Greater Los Angeles Healthcare System)

  • Matthias Stangl

    (University of California)

  • Zahra M. Aghajan

    (University of California
    University of California)

  • Mauricio Vallejo

    (University of California)

  • Sonja Hiller

    (University of California)

  • Uros Topalovic

    (University of California
    University of California)

  • Cory S. Inman

    (University of Utah)

  • Diane Villaroman

    (University of California)

  • Ausaf Bari

    (University of California)

  • Avishek Adhikari

    (University of California)

  • Vikram R. Rao

    (University of California)

  • Michael S. Fanselow

    (University of California
    University of California)

  • Michelle G. Craske

    (University of California
    University of California)

  • Scott E. Krahl

    (Research and Development Service; Department of Veterans Affairs Greater Los Angeles Healthcare System
    University of California)

  • James W. Y. Chen

    (Neurology Service; Department of Veterans Affairs Greater Los Angeles Healthcare System
    University of California)

  • Merit Vick

    (NeuroPace Inc.)

  • Nicholas R. Hasulak

    (University of California
    Phoenix Research Consulting LLC)

  • Jonathan C. Kao

    (University of California)

  • Ralph J. Koek

    (University of California
    Psychiatry and Mental Health Service; Department of Veterans Affairs Greater Los Angeles Healthcare System)

  • Nanthia Suthana

    (University of California
    University of California
    University of California
    University of California)

  • Jean-Philippe Langevin

    (University of California
    Neurosurgery Service; Department of Veterans Affairs Greater Los Angeles Healthcare System)

Abstract

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5–9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Suggested Citation

  • Jay L. Gill & Julia A. Schneiders & Matthias Stangl & Zahra M. Aghajan & Mauricio Vallejo & Sonja Hiller & Uros Topalovic & Cory S. Inman & Diane Villaroman & Ausaf Bari & Avishek Adhikari & Vikram R., 2023. "A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38712-1
    DOI: 10.1038/s41467-023-38712-1
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    References listed on IDEAS

    as
    1. Matthias Stangl & Uros Topalovic & Cory S. Inman & Sonja Hiller & Diane Villaroman & Zahra M. Aghajan & Leonardo Christov-Moore & Nicholas R. Hasulak & Vikram R. Rao & Casey H. Halpern & Dawn Eliashiv, 2021. "Boundary-anchored neural mechanisms of location-encoding for self and others," Nature, Nature, vol. 589(7842), pages 420-425, January.
    2. Jie Zheng & Kristopher L. Anderson & Stephanie L. Leal & Avgusta Shestyuk & Gultekin Gulsen & Lilit Mnatsakanyan & Sumeet Vadera & Frank P. K. Hsu & Michael A. Yassa & Robert T. Knight & Jack J. Lin, 2017. "Amygdala-hippocampal dynamics during salient information processing," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
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