# Responsive Neurostimulation for Post-Traumatic Stress Disorder

> **NIH NIH UH3** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $919,503

## Abstract

Project Summary/Abstract
Post-traumatic stress disorder (PTSD) refractory to treatment is marked by failure of fear extinction and its
biological substrate, amygdala reactivity to trauma reminders13,14. Decades of research have clarified the
neuronal mechanisms coordinating fear extinction and consolidation15. Fear cells and extinction cells in the
basolateral amygdala (BLA) alter their firing rate based on the nature of the stimulus and the influence from the
medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC)16,17. Together, the BLA, mPFC, and the
vHPC form an anxiety-processing network15,2 where the BLA links stimulus to emotion, the vHPC provides
memory context, and the mPFC coordinates extinction or consolidation. Local field potential (LFP) recordings
from the BLA have revealed specific signals that correspond to an enhanced fear state. We have previously
shown that neuromodulation of the BLA can promote extinction in a rodent model18 and in a treatment-
refractory PTSD patient19. This action is likely carried by disrupting fear signals within the BLA; however,
continuous neurostimulation may also disrupt normal function of the amygdala. The present application
proposes to investigate the use of Responsive Neurostimulation (RNS, Neuropace) in six (6) veterans
suffering from severe treatment-resistant PTSD. This dual-activity device will allow us to chronically record
LFPs from the BLA under specific conditions such as fear conditioning, exposure to trauma reminders, and
emotional memory encoding and retrieval. In addition, the neural activity will be captured during real-life
symptoms of flashback and nightmares. These recordings will provide us with the specific electrophysiological
biomarkers of hypervigilance and re-experiencing. The device will then be programmed to detect and treat
these biomarkers with a pre-determined electrical pulse. The patients will be followed prospectively using
psychological scales but also with functional neuroimaging and electroencephalograms. These modalities will
be used to determine the extent of circuit engagement as a result of the therapy. By approaching PTSD from a
fear processing mechanism perspective, our project will serve as a proof of concept for other circuit-
based therapies in psychiatry. This proposal is a multi-departmental effort involving 11 investigators
across 7 departments and requires a close collaboration between clinical and basic scientists. As a
result, the findings underlying our chronic recordings will bridge the basic science results from fear conditioning
research to clinical neural processes in PTSD patients.

## Key facts

- **NIH application ID:** 10241410
- **Project number:** 5UH3NS107673-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jean-Philippe Langevin
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $919,503
- **Award type:** 5
- **Project period:** 2019-09-30 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241410

## Citation

> US National Institutes of Health, RePORTER application 10241410, Responsive Neurostimulation for Post-Traumatic Stress Disorder (5UH3NS107673-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10241410. Licensed CC0.

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