A Neurosensory Account of Anxiety and Stress (Study 1)

Intrinsic and Novelty-related Sensory Cortical (SC) Disinhibition and Sensory-Prefrontal-cortex-Amygdala (SPA) Pathology in Posttraumatic Stress Disorder (PTSD) (Aims 1 & 2; Expts. 1a &1b)

This study will take a basic neuroscience approach to investigate pathological mechanisms underlying PTSD. Additionally, the study aims to identify how Transcranial Alternating Current Stimulation (tACS) brain stimulation can modulate and correct neural networks and related emotions of anxious arousal and hypervigilance, with the goal of assessing tACS brain stimulation technology as a novel intervention for symptoms of anxiety.

Study Overview

• Status: Recruiting
• Conditions: Posttraumatic Stress Disorder (PTSD); Intrinsic and Novelty-related Sensory Cortical (SC) Disinhibition
• Intervention / Treatment: Device: Sham for Transcranial Alternating Current Stimulation (tACS); Device: Transcranial Random Noise stimulation (tRNS); Device: Alternating Current Stimulation (tACS)

Detailed Description

This study includes experiments 1a & 1b to address Aims 1 and -- Intrinsic and Novelty-related Sensory Cortical (SC) Disinhibition and Sensory-Prefrontal-cortex-Amygdala (SPA) pathology in PTSD. The goal of this study is to develop and test a novel pathophysiology of PTSD by integrating sensory cortical (SC) and amygdala-prefrontal cortex (PFC) dysfunctions into a tripartite Sensory-Prefrontal-Cortex-Amygdala (SPA) model.

The investigators will recruit 80 healthy subjects and 80 patients with PTSD in a randomized, double-blind, controlled design, where they be randomly assigned to 1) Transcranial Alternating Current Stimulation (tACS) at individual alpha peak frequency (active condition); 2) sham control tACS; or 3) active control, which will be transcranial random noise stimulation (tRNS) (random frequency 1-200 Hz). During tACS/sham tACS/tRNS stimulation, stimulation electrodes will be placed inside the holders of an EEG cap attached to the head of the participant. Simultaneous EEG- fMRI recordings during the resting state (in experiment 1a) and during a novelty task (in experiment 1b) will be acquired before and after tACS/tRNS stimulation.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wen Li, PhD; Phone Number: (713) 486-2700; Email: Wen.Li.1@uth.tmc.edu
• Study Contact Backup: Name: Jada Malveaux, MA; Phone Number: (713) 486-2700; Email: Jada.Malveaux@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Wen Li, PhD; Phone Number: (713) 486-2700; Email: Wen.Li.1@uth.tmc.edu
      • Contact: Jada Malveaux, PhD; Phone Number: (713) 486-2700; Email: Jada.Malveaux@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial Alternating Current Stimulation (tACS)	Device: Alternating Current Stimulation (tACS); A weak electrical current will be passed through the scalp over targeted cortical regions via a transcranial electrical stimulation system (Soterix Medical, Inc), for a span of 10 to 40 minutes at a time. Participants will receive a 2 milliamp (mA) sinusoidal current oscillating at individual participants' baseline peak alpha frequencies (PAF; 7-13 Hz), which will be determined by a 3-min resting state EEG recording during the setup. Current intensities will be modified to address individual participants' subjective reports of discomfort, with a maximum intensity of 2 mA. Stimulation electrodes will be placed within an EEG cap fitted over the participant's head.
Sham Comparator: Sham for Transcranial Alternating Current Stimulation (tACS)	Device: Sham for Transcranial Alternating Current Stimulation (tACS); Stimulation electrodes will be placed on the scalp, but no current will be passed. Stimulation electrodes will be placed within an EEG cap fitted over the participant's head.
Active Comparator: Active Control - Transcranial Random Noise stimulation (tRNS)	Device: Transcranial Random Noise stimulation (tRNS); A weak electrical currents will be passed through the scalp over targeted cortical regions via a transcranial electrical stimulation system (Soterix Medical, Inc), for a span of 10 to 40 minutes at a time. Participants will receive a 2 mA sinusoidal current oscillating at random frequency (1-200 Hz). Current intensities will be modified to address individual participants' subjective reports of discomfort, with a maximum intensity of 2 mA. Stimulation electrodes will be placed within an EEG cap fitted over the participant's head.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in neural oscillatory activity as assessed by electroencephalogram (EEG) alpha power change	baseline (pre-stimulation); immediately post-stimulation (about 10 to 40 minutes after start of stimulation)
Change in cortical activity as assessed by functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) signal change	baseline (pre-stimulation); immediately post-stimulation (about 10 to 40 minutes after start of stimulation)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in salience detection and vigilance behavior as assessed by skin conductance measured in microsiemens (μS)	baseline (pre-stimulation); immediately post-stimulation (about 10 to 40 minutes after start of stimulation)
Change in salience detection and vigilance behavior as assessed by percent accuracy on an oddball detection task	baseline (pre-stimulation); immediately post-stimulation (about 10 to 40 minutes after start of stimulation)
Change in salience detection and vigilance behavior as assessed by reaction time in milliseconds (ms) on an oddball detection task	baseline (pre-stimulation); immediately post-stimulation (about 10 to 40 minutes after start of stimulation)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Wen Li, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

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; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: HSC-MS-23-1106 (study 1); R01MH132209 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication.
• IPD Sharing Time Frame: Starting 6 months after publication.
• IPD Sharing Access Criteria: All researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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