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; Jean-Philippe Langevin

doi:10.1038/s41467-023-38712-1

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

Nat Commun. 2023 May 24;14(1):2997. doi: 10.1038/s41467-023-38712-1.

Authors

Jay L Gill^#^{1

2}, Julia A Schneiders^#^{1

3}, Matthias Stangl¹, Zahra M Aghajan^{1

4}, Mauricio Vallejo¹, Sonja Hiller¹, Uros Topalovic^{1

5}, Cory S Inman⁶, Diane Villaroman¹, Ausaf Bari⁴, Avishek Adhikari⁷, Vikram R Rao⁸, Michael S Fanselow^{1

7}, Michelle G Craske^{1

7}, Scott E Krahl^{3

4}, James W Y Chen^{9

10}, Merit Vick¹¹, Nicholas R Hasulak^{1

12}, Jonathan C Kao⁵, Ralph J Koek^{1

13}, Nanthia Suthana^{14

15

16

17}, Jean-Philippe Langevin^{18

19}

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
² Medical Scientist Training Program, University of California, Los Angeles, CA, USA.
³ Research and Development Service; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁴ Department of Neurosurgery, University of California, Los Angeles, CA, USA.
⁵ Department of Electrical and Computer Engineering, University of California, Los Angeles, CA, USA.
⁶ Department of Psychology, University of Utah, Salt Lake City, UT, USA.
⁷ Department of Psychology, University of California, Los Angeles, CA, USA.
⁸ Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
⁹ Neurology Service; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
¹⁰ Department of Neurology, University of California, Los Angeles, CA, USA.
¹¹ NeuroPace Inc., Mountain View, CA, USA.
¹² Phoenix Research Consulting LLC, Gilbert, AZ, USA.
¹³ Psychiatry and Mental Health Service; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
¹⁴ Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA. nsuthana@mednet.ucla.edu.
¹⁵ Department of Neurosurgery, University of California, Los Angeles, CA, USA. nsuthana@mednet.ucla.edu.
¹⁶ Department of Psychology, University of California, Los Angeles, CA, USA. nsuthana@mednet.ucla.edu.
¹⁷ Department of Bioengineering, University of California, Los Angeles, CA, USA. nsuthana@mednet.ucla.edu.
¹⁸ Department of Neurosurgery, University of California, Los Angeles, CA, USA. jlangevin@mednet.ucla.edu.
¹⁹ Neurosurgery Service; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. jlangevin@mednet.ucla.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Affect
Amygdala
Animals
Emotions
Gastropoda*
Humans
Male
Pilot Projects
Stress Disorders, Post-Traumatic* / therapy

Associated data

ClinicalTrials.gov/NCT04152993

Abstract

Publication types

MeSH terms

Associated data

Grants and funding