0148 Non-Invasive Deep Brain Neuromodulation to Enhance REM Sleep for Trauma Adaptation

Abstract Introduction Service members (SMs) experience disproportionately high rates of post-traumatic stress disorder (PTSD), often arising after emotional trauma or delayed neuropsychiatric effects of mild traumatic brain injury (mTBI). Chronic disruption of Rapid Eye Movement (REM) sleep is a hallmark of both conditions, reducing the brain’s ability to downregulate negative emotional memories. REM disturbances are closely tied to hyperarousal, abnormal noradrenergic tone, and persistent consolidation of traumatic memories. There is a critical need for non-pharmacologic tools that can restore healthy REM sleep in this population. Methods This study evaluates a novel, wearable low-intensity focused ultrasound (LIFU) device designed to modulate deep brain structures non-invasively. We target two REM-regulatory nuclei, the basolateral amygdala (BLA) and centromedian thalamus (CMT), given their roles in REM initiation, maintenance, emotional salience, and hyperarousal control. Participants completed three overnight polysomnography sessions in a randomized crossover design (sham, BLA-targeted, CMT-targeted). LIFU was delivered in closed-loop fashion during sleep using custom detection algorithms. Urine samples were collected before bed and upon waking. A multimodal framework quantifies neuromodulatory effects across: Sleep: architecture, REM percentage and stability, slow-wave density, spindle counts. Neurophysiology: REM-related theta power and aperiodic EEG markers of excitation-inhibition balance. Autonomic function: heart rate and heart rate variability. Molecular biomarkers: urinary noradrenaline and dopamine as indices of noradrenergic state. Results LIFU stimulation of the BLA/CMT is expected to: • Increase REM percentage, duration, and stability, and enhance slow-wave density. • Boost REM-related theta activity and steepen the aperiodic EEG slope. • Shift autonomic physiology toward parasympathetic dominance (higher HRV). • Reduce urinary noradrenaline, reflecting decreased hyperarousal and improved emotional memory regulation. These convergent changes are expected to yield a more restorative REM profile. Data collection and analysis are ongoing, with completion anticipated by February 2026. Conclusion By precisely targeting deep REM-regulatory circuits, wearable LIFU may provide a deployable, non-pharmacologic intervention to mitigate PTSD- and mTBI-related sleep pathology in SMs, improving readiness and long-term brain health. Support (if any) This project was supported by DARPA REM REST Program. The views expressed are those of the authors and do not reflect official policy of USUHS or the Department of War. No financial conflicts of interest are declared.