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.

This study includes experiments 2 & 3 to address Aim 3--threat-related 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). Simultaneous EEG/fMRI recordings and behavioral responses will be acquired before and after tACS/sham tACS/tRNS stimulation. 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. Experiments 2 & 3 include a visual search task and an olfactory detection task, respectively, and both experiments include threat and neutral stimuli.

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.

All IPD that underlie results in a publication.

Starting 6 months after publication.

All researchers.