Neurosensory account of anxiety and stress — experiment 2

Threat-related Sensory Cortical (SC) Disinhibition and SPA Pathology in Posttraumatic Stress Disorder (PTSD) (Aim 3; Expts. 2&3)

This trial tests whether a mild, noninvasive brain stimulation (tACS) tuned to each person's alpha rhythm can change brain activity and reduce anxious arousal and hypervigilance in adults with PTSD compared with sham and random-noise stimulation.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: The University of Texas Health Science Center, Houston (Academic / other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07079839 on ClinicalTrials.gov

What this trial studies

The investigators will recruit 80 adults with PTSD and 80 healthy controls and randomly assign participants, double-blind, to active tACS at individual alpha peak frequency, sham tACS, or active control transcranial random noise stimulation (tRNS). Participants complete simultaneous EEG/fMRI and behavioral testing before and after stimulation while performing a visual search task and an olfactory detection task that include threat and neutral stimuli. Stimulation electrodes are placed in holders on an EEG cap to permit concurrent recording, and the protocol tests a proposed Sensory-Prefrontal-Cortex-Amygdala (SPA) model of threat-related sensory cortical disinhibition and PTSD pathophysiology. The design aims to link neural changes with behavioral markers of anxious arousal and hypervigilance and to compare tACS effects to sham and active control stimulation.

Who should consider this trial

Good fit: Ideal candidates are right-handed adults aged 18–50 with a PTSD diagnosis, normal or corrected vision and normal smell, who meet tACS safety screening and have stable psychotropic medications for at least two months if medicated.

Not a fit: Patients with major medical or neurological illnesses, a history of seizures or serious head injury, or who fall outside the age or sensory/handedness criteria are unlikely to be eligible and therefore would not benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could point to a noninvasive way to normalize sensory–prefrontal–amygdala network activity and reduce hypervigilance and anxious arousal in people with PTSD.

How similar studies have performed: Related noninvasive brain stimulation approaches such as rTMS and tDCS have shown preliminary promise for anxiety and PTSD symptoms, but tACS is less well tested and evidence is currently limited and exploratory.

Eligibility criteria

Inclusion Criteria:

* Right-handed
* With normal or corrected-to-normal vision and normal olfaction
* Between the ages of 18 and 50 years
* Meeting the tACS screening criteria (see List I below; e.g., lack of a serious head injury or loss of consciousness)
* Patients: Diagnosis of PTSD
* Patients: If taking psychotropic medications, medication stability in the past 2 months
* If having mild substance use disorder (for patients) or occasional substance use, abstention from use 48 hours before the experiment.

Exclusion Criteria:

* A history of diagnosis for a major medical illness (e.g., cancer, metabolic syndrome, cardiovascular disease, inflammatory disorders) or a neurological disorder (e.g., seizure, stroke, Parkinson's disease).
* Patients: Concurrent Axis I diagnosis (depression, anxiety, and mild substance use disorder are allowed given their high comorbidity with PTSD).
* Healthy controls: A history of diagnosis for a Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 Axis I disorder or current use of psychoactive medications.
* Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior that poses an immediate danger to self or others.
* History of head trauma with unconsciousness (\> 5 minutes)
* Report that they regularly drink 3 or more alcoholic beverages a day.
* Report that they are unable to abstain from substance use (including alcohol, nicotine, cannabis, amphetamines, narcotics, solvents, cocaine, hallucinogens, tranquilizers, barbiturates, etc.) or sleep medication for 48 hours before being scanned.
* Are on calcium channel blockers (e.g., verapamil, nifedipine) or alpha-blockers (e.g., prazosin, terazosin) and are unable to stop these medications for a 48-hour period prior to scanning (to exclude the impact of these medications on the interpretation of fMRI/EEG).
* Failed Urine Drug Screening Test: A rapid urine screening test that utilizes monoclonal antibodies to detect elevated levels of specific drugs (including alcohol, amphetamines, benzodiazepines, barbiturates, cocaine, marijuana, opiates, etc.) in urine (iCup)
* Pregnancy based on urine test. The safety of magnetic resonance (MR) systems has not been established for fetuses
* Having electrically, magnetically, or mechanically activated implants (e.g., cardiac pacemakers), because the electromagnetic fields produced by the MR system may interfere with the operation of these devices.

Where this trial is running

Houston, Texas

• The University of Texas Health Science Center at Houston — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Wen Li, PhD — The University of Texas Health Science Center, Houston
• Study coordinator: Wen Li, PhD

Conditions Threat-related Sensory Cortical Disinhibition; Posttraumatic Stress Disorder