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

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. Rao, Michael S. Fanselow, Michelle G. Craske, Scott E. Krahl, James W. Y. Chen, Merit Vick, Nicholas R. Hasulak, Jonathan C. Kao, Ralph J. Koek, Nanthia Suthana () and Jean-Philippe Langevin ()
Additional contact information
Jay L. Gill: University of California
Julia A. Schneiders: University of California
Matthias Stangl: University of California
Zahra M. Aghajan: University of California
Mauricio Vallejo: University of California
Sonja Hiller: University of California
Uros Topalovic: 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
Michelle G. Craske: University of California
Scott E. Krahl: Research and Development Service; Department of Veterans Affairs Greater Los Angeles Healthcare System
James W. Y. Chen: Neurology Service; Department of Veterans Affairs Greater Los Angeles Healthcare System
Merit Vick: NeuroPace Inc.
Nicholas R. Hasulak: University of California
Jonathan C. Kao: University of California
Ralph J. Koek: University of California
Nanthia Suthana: University of California
Jean-Philippe Langevin: University of California

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38712-1

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