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

Study Overview

• Status: Recruiting
• Conditions: PTSD and Trauma-related Symptoms
• Intervention / Treatment: Device: Low intensity focused ultrasound; Device: Sham modulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adrienne Taren, MD, PhD; Phone Number: 918-340-4116; Email: ataren@laureateinstitute.org

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Recruiting
      • Laureate Institute for Brain Research
      • Contact: Adrienne Taren, MD, PhD; Phone Number: 918-340-4116; Email: ataren@laureateinstitute.org
      • Contact: Courtney Kilpatrick; Email: ckilpatrick@laureateinstitute.org
      • Principal Investigator: Adrienne Taren, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low intensity focused ultrasound (LIFU); LIFU of the ventral anterior cingulate cortex	Device: Low intensity focused ultrasound; Low intensity focused ultrasound neuromodulation of the ventral anterior cingulate cortex; Other Names: LIFU
Sham Comparator: Sham; Sham neuromodulation (Sorbothane membrane over ultrasound probe)	Device: Sham modulation; Low intensity focused ultrasound with a Sorbothane membrane cover to prevent acoustic energy transmission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LIFU target engagement	Percent BOLD signal change in vACC and amygdala regions of interest	Study day 1 to day 7 (plus or minus 3 days)
Behavioral changes	Change in reaction time (ms) and error rate (percentage of correct answers) on emotional conflict task; difference between optimal and observed flight initiation distance.	Day 0 to Day 7 (plus or minus 3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LIFU effects on PTSD symptoms	Change in PCL-5 score	Dy 0 to day 14 (plus or minus 6)
fMRI-PTSD Symptom Correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and PCL-5 score.	Day 0 to day 14 (plus or minus 6)
fMRI-Emotion Regulation Correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and Cognitive-Emotion Regulation Questionnaire Score.	Day 0 to day 14 (plus or minus 6)
LIFU effects on physiology	Change in heart rate variability (ms), change in resting heart rate (beats per minute), change in %REM sleep (minutes), change in %deep sleep (minutes) as measured by Oura Ring	Day 0 to day 14 (plus or minus 6 days)
fMRI-heart rate variability correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and heart rate variability (ms) as measured by Oura Ring	Day 0 to day 14 (plus or minus 6)
fMRI-resting heart rate correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and resting heart rate (beats per minute) as measured by Oura ring	Day 0 to day 14 (plus or minus 6)
fMRI-REM sleep correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and %REM sleep (minutes) as measured by Oura ring	Day 0 to day 14 (plus or minus 6)
fMRI-deep sleep correlation	Correlations between vACC/amygdala BOLD signal extracted beta-weights and %deep sleep (minutes) as measured by Oura ring	Day 0 to day 14 (plus or minus 6)

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: August 22, 2025
• First Submitted That Met QC Criteria: September 2, 2025
• First Posted (Actual): September 9, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 20252812

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No