Mechanisms of Low-Intensity Focused Ultrasound Neuromodulation for Post-Traumatic Stress Disorder in Frontline Healthcare Workers

Laureate Institute For Brain Research, Tulsa OK

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Abstract

One in three emergency medical personnel have Post-Traumatic Stress Disorder (PTSD), the highest rates among civilian workers, which contributes significantly to the annual $232 billion burden of PTSD in the United States. A potential neural mechanism underlying PTSD is the persistent disruption of top-down regulatory control that the ventral anterior cingulate (vACC) exerts on limbic structures—particularly the amygdala—contributing to heightened threat responses and increased PTSD symptom vulnerability. Despite mounting evidence that occupational trauma leads to PTSD symptomatology in frontline healthcare workers, a critical gap exists in the study of this maladaptive fronto-limbic circuitry shift within this population, and whether modulating this circuitry can impact behavioral and neural pathways, with the long-term goal of developing safe, scalable, and effective interventions. The ability to directly target this neural circuitry has been limited by prior neuromodulation approaches that were unable to target deeper structures. To address this urgent need, the proposed study will first examine the baseline relationships between vACC-amygdala circuitry, PTSD symptomatology, and physiological dysregulation in frontline healthcare workers, and then determine the degree to which a single session of personalized (structural magnetic resonance imaging [MRI]-localized) low-intensity focused ultrasound (LIFU) of the vACC changes: (1) the proposed mechanism of action (MRI resting and task-based ACC-limbic connectivity); and (2) behavioral outcome measures (threat sensitivity, affect regulation) in emergency medical personnel with elevated PTSD symptoms. We hypothesize that vACC LIFU modulation will disrupt the hyperactive large-sale, cortico-subcortical circuit involving vACC and amygdala that perpetuates PTSD symptomatology. We will also monitor sleep, activity, and heart rate variability to identify physiological patterns that may predict symptom trajectory and offer further insights into potential intervention targets for this population. The proposed study represents a novel integration of neuromodulation, neuroimaging, and biometrics aimed at reducing the burden of trauma for frontline healthcare workers.