Mild Traumatic Brain Injury (mTBI) is an important concern of the Veterans Administration that affects many veterans who served in combat in Afghanistan and Iraq and is frequently associated with Posttraumatic stress disorder (PTSD). When these conditions occur together they are associated with considerable morbidity, increased healthcare costs and loss of economic productivity. Current treatments for mTBI and PTSD have limitations, and in many veterans these become lifelong disorders. Electrical treatments represent a new horizon in the approach to disorders related to neurotrauma. One type of treatment is Vagal Nerve Stimulation (VNS), which shows promise for neurotrauma in that it promotes neuroplasticity, enhances new learning, and blocks stress physiology both through effects on brain regions involved in modulation of stress as well reduction of peripheral sympathetic and inflammatory and enhancement of parasympathetic function. This is mediated through afferent and efferent branches of the vagus nerve that project to both the brain and peripheral inflammatory and autonomic systems. Earlier generations of VNS were limited by the need for complicated surgical and anesthetic procedures, high cost, and lack of reimbursement by insurance for procedures or routine healthcare follow-up. This prevented wide-spread implementation of these treatments. New non-invasive Vagal Nerve Stimulation (nVNS) devices are more economical and do not require surgical implantation. Our preliminary data shows that nVNS (but not sham stimulation) blocks effects of stress on peripheral vasoconstriction and increased sympathetic tone as measured with direct cardiovascular measures (pre-ejection period, or PEP), reduces inflammatory markers (interleukin-6, or IL-6), enhances anterior cingulate function, blocks insula response to stress, promotes memory and reduces PTSD symptoms. This project will explore the effects of nVNS or sham treatment on brain, cardiovascular / sympathetic and immune response to stress in combat veterans with mTBI and PTSD. Subjects will undergo exposure to stress in conjunction with High Resolution Positron Emission Tomography (HR-PET) and radiolabeled water measurement of brain blood flow, and peripheral cardiovascular /sympathetic function and immune biomarkers in blood. We hypothesize that nVNS but not sham stimulation will result in an increase in anterior cingulate and reduced insula function with stress tasks and hippocampal function with memory tasks, and block cardiovascular / sympathetic and immune response to stress in patients with mTBI and PTSD. Furthermore we hypothesize that daily nVNS (but not sham) for three months will lead to an enhancement in memory function, reduction in PTSD symptoms, and modulate brain and autonomic responses to stress. This project will provide information about mechanisms of nVNS on the neurobiology and physiology of mTBI with comorbid PTSD and ways in which it may ameliorate symptoms and enhance cognition. This may be a promising future approach for rehabilitation of veterans with neurotrauma.

Public Health Relevance

Mild Traumatic Brain Injury (mTBI) is an important priority for the Veterans Administration which affects many veterans of the conflicts in Iraq and Afghanistan, and when it co-occurs with posttraumatic stress disorder (PTSD) is associated with increased symptoms of post-concussion syndrome and suicidality, as well as worse health and cognitive outcomes. Currently there is no single effective treatment or rehabilitation for co-morbid mTBI and PTSD that addresses all the symptoms and the potential risk of progression of neurotrauma in these veterans. This project will look at a novel and newly available treatment for mTBI and PTSD called non-invasive Vagal Nerve Stimulation (nVNS) and how it affects brain and physiological responses to memory tasks and stress in veterans with mTBI and PTSD.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Brain Health & Injury (RRD1)
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Veterans Health Administration
United States
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