LIFU Mechanisms for PTSD in Healthcare Workers

Mechanisms of Low Intensity Focused Ultrasound of the Ventral Anterior Cingulate Cortex for Post-Traumatic Stress Disorder in Frontline Healthcare Workers

The goal of this clinical trial is to evaluate whether low-intensity focused ultrasound (LIFU) of the ventral anterior cingulate cortex (vACC) can normalize dysfunctional brain activation patterns and behaviors in frontline healthcare workers with post-traumatic stress disorder. The main questions it aims to answer are:

• Does LIFU of the vACC effect activity and connectivity of the vACC and amygdala?
• Does LIFU of the vACC reduce post-traumatic stress symptoms? Researchers will compare LIFU to sham modulation to see if LIFU modulates activity of vACC-amygdala circuitry and affects threat sensitivity and emotion regulation.

Participants will:

• Complete two fMRI sessions (before and after LIFU)
• Receive a single session of LIFU or sham modulation of the vACC
• Wear a wearable device that tracks sleep and heart rate metrics

The study employs a double-blind, randomized, sham-controlled design to evaluate whether low-intensity focused ultrasound (LIFU) targeting the ventral anterior cingulate cortex (vACC) can normalize fronto-limbic circuitry and reduce post-traumatic stress symptomatology in frontline healthcare workers. Sixty-six frontline healthcare professionals aged 18-65 (PCL-5 ≥ 33 or at least partial PTSD on the MINI) will complete baseline assessments that include structural MRI, resting-state fMRI, and two task-based scans. Concurrently, participants initiate continuous Oura Ring wearable monitoring and daily ecological momentary assessment (EMA) surveys. Subjects will return for active or sham LIFU neuromodulation of the vACC. Before and after LIFU, identical MRI and questionnaire batteries quantify acute neural and behavioral change.

Inclusion Criteria:

1. Adults in a frontline healthcare position (e.g. emergency medical services)
2. Ages 18-65 years
3. PTSD Checklist for DSM-5 (PCL-5) score ≥ 33 and < 65, OR at least partial PTSD as measured by the MINI
4. English proficiency as evaluated by language ability during screening

Exclusion Criteria:

1. Neurological disorders
2. DSM-5 diagnosis of psychotic disorders, eating disorder, obsessive-compulsive disorder, moderate to severe alcohol or substance use disorder within the past year, bipolar disorder, or major depressive disorder with psychosis
3. Suicidal intent or plan (as measured by Suicide-Risk-Assessment-C-SSRS "Yes" answers to items 3, 4 or 5 of Suicidal Ideation-Past 1 month section, or any "Yes" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months.
4. History of severe traumatic brain injury (as indicated by score ≥ 3 on the Tulsa Head Injury Screen) or of skull fractures
5. Contraindications to MRI as determined by the MR Environment Screening
6. Pregnancy, determined by urine pregnancy test administered prior to every MRI scanning procedure
7. Evidence of inability to comply with study procedures based on experimenter judgement.
8. Change in the dose or prescription of a medication within the 6 weeks before enrolling in the study that could affect brain functioning, e.g., anxiolytics, antipsychotics, antidepressants, benzodiazepines, or mood stabilizers.
9. Non-correctable vision or hearing problems
10. Unstable medical diagnoses
11. Any structural abnormalities in the LIFU target region on screening brain MRI.