PTSD and Trauma-related Symptoms
Conditions
Brief summary
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
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.
Interventions
Low intensity focused ultrasound neuromodulation of the ventral anterior cingulate cortex
DEVICESham modulation
Low intensity focused ultrasound with a Sorbothane membrane cover to prevent acoustic energy transmission
Sponsors
Laureate Institute for Brain Research, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LIFU target engagement | Study day 1 to day 7 (plus or minus 3 days) | Percent BOLD signal change in vACC and amygdala regions of interest |
| Behavioral changes | Day 0 to Day 7 (plus or minus 3 days) | Change in reaction time (ms) and error rate (percentage of correct answers) on emotional conflict task; difference between optimal and observed flight initiation distance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LIFU effects on physiology | Day 0 to day 14 (plus or minus 6 days) | 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 |
| LIFU effects on PTSD symptoms | Dy 0 to day 14 (plus or minus 6) | Change in PCL-5 score |
| fMRI-heart rate variability correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and heart rate variability (ms) as measured by Oura Ring |
| fMRI-resting heart rate correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and resting heart rate (beats per minute) as measured by Oura ring |
| fMRI-REM sleep correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and %REM sleep (minutes) as measured by Oura ring |
| fMRI-deep sleep correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and %deep sleep (minutes) as measured by Oura ring |
| fMRI-PTSD Symptom Correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and PCL-5 score. |
| fMRI-Emotion Regulation Correlation | Day 0 to day 14 (plus or minus 6) | Correlations between vACC/amygdala BOLD signal extracted beta-weights and Cognitive-Emotion Regulation Questionnaire Score. |
Countries
United States
Contacts
CONTACTAdrienne Taren, MD, PhD
Outcome results
None listed