Posttraumatic stress disorder (PTSD) is an important concern of the Veterans Administration, associated with considerable morbidity, increased mental healthcare costs and loss of economic productivity. A recent State of the Science conference convened by the Department of Defense on Discovering Drug Targets for PTSD concluded that a decade of research costing millions of dollars had yielded few new effective drug treatments for PTSD. In addition to limitations in efficacy, pharmacological treatments can be limited by side effects or poor compliance, while psychotherapeutic interventions may not be tolerated due to re-activation of traumatic memories. Electrical treatments represent a new horizon in the treatment of PTSD and psychiatric disorders in general. Earlier generations of electrical treatments were limited by the need for complicated surgical and anesthetic procedures, high cost, and lack of reimbursement by insurance for procedures or routine psychiatric follow-up. This prevented wide-spread implementation of these treatments in psychiatry. New non-invasive transcutaneous cervical (neck) Vagal Nerve Stimulation (tcVNS) devices that are economical and do not require surgical implantation overcome these limitations of electrical treatments, as well as avoiding side effects or other limitations to medication treatments for PTSD. VNS results in both enhancement of anterior cingulate and reduction in insula responses to traumatic stress scripts as well as peripheral cardiovascular / sympathetic and immune function, all of which indicate that they could act on neurobiological and physiological systems that maintain symptoms of PTSD. Our preliminary data shows that tcVNS (but not sham stimulation) when applied in conjunction with exposure to scripts of specific traumatic memories blocks the effects of stress on increased peripheral vasoconstriction and sympathetic tone as measured with direct cardiovascular measures (pre-ejection period, or PEP) and reduces inflammatory markers (Interleukin-6) and insula response while enhancing anterior cingulate function in PTSD. This project will explore the effects of tcVNS or sham treatment on brain, cardiovascular / sympathetic and immune response to stress in veterans with PTSD. Veterans will undergo exposure to traumatic script stress in conjunction with High Resolution Positron Emission Tomography (HRPET) measurement of brain function and peripheral cardiovascular /sympathetic function and immune biomarkers in blood. Veterans will then undergo three months of twice daily treatment with tcVNS or sham stimulation followed by a repeat of these measures. We hypothesize that tcVNS but not sham stimulation will result in a reduction in brain / cardiovascular / sympathetic and immune response to stress in veterans with PTSD, as well as symptoms of PTSD with long term treatment. This project will provide information about mechanisms of tcVNS on the neurobiology and physiology of PTSD and ways in which it may a...