This study effects the effects of transcutaneous cervical vagal nerve stimulation (tcVNS) or a sham control on brain, physiology, and PTSD symptoms in Veterans with posttraumatic stress disorder (PTSD). Veterans undergo brain imaging and physiological measures in conjunction with traumatic scripts before and after three months of twice daily treatment with tcVNS or sham stimulation at home.

Description: This study assesses brain function measured with High Resolution Positron Emission Tomography (HR-PET) during exposure to stressful traumatic scripts paired with tcVNS or sham stimulation, with secondary measures of blood inflammatory biomarkers, and sympathetic function. Participants then undergo three months of twice daily home treatment with repeat measures.

Drug/Device Handling: [O-15] radiolabeled water has a half-life of 110 seconds and is made on site at the Emory Center for Systems Imaging (CSI). Dr. Bremner holds the Investigational New Drug (IND) approval for use of radiolabeled water at Emory University. The investigators have performed hundreds of studies in human subjects at Emory and there have been no adverse events or untoward effects to date.

tcVNS with the GammaCore device is approved by the Emory IRB for a recently completed study in PTSD and others in progress for Opioid Use Disorder and was shown to be well tolerated and there have been no adverse events or untoward effects with the device. The FDA granted Breakthrough Device Designation for PTSD for the gammaCore tcVNS device based on the investigators' studies. Devices are blinded by ElectroCore and the devices and information are kept by the Data Manager under double lock and key. Device records are kept by the Data Manager and stored on Redcap or secured research drives. Devices are given to the study team along with a device schedule under direct supervision from the investigator.

Inclusion Criteria:

• Veterans between the ages of 18 and 75 will be included with a diagnosis of PTSD based on DSM-5 criteria

Exclusion Criteria:

Subjects will be excluded with:

• a history of mild traumatic brain injury (mTBI) based on VA Criteria
• moderate or greater TBI
• positive pregnancy test
• meningitis or other neurological disorder
• alcohol or substance abuse use disorder based on DSM-5 criteria within the past 12 months
• current or lifetime history of schizophrenia, schizoaffective disorder, bipolar I disorder, anorexia nervosa or bulimia, based on DSM-5
• active suicidal ideation with a plan
• a history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness that would preclude participation based on clinical judgment of the PI
• active opiate or benzodiazepine treatment
• history of structural abnormality on brain MRI or CT if one has been performed in the past

De identified data will be made available three months after study completion

Three months after study completion

Three months after study completion for twelve months

Sham stimulation comparison