Transcutaneous vagal nerve stimulation improvement of sleep quality in veterans with PTSD with or without history of mild TBI

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Problem: Post traumatic stress disorder (PTSD) severely limits quality of life. Current PTSD treatments have limited and variable efficacy. New and more effective treatments are necessary. Patients with PTSD often have disrupted sleep. These patients are more likely to wake up multiple times a night, and have decreased slow wave sleep and increased REM sleep. Further, autonomic and behavioral components during sleep are consistent with a continued fight or flight state while asleep. This includes higher heart rate, lower parasympathetic tone, and greater likelihood of nightmares. PTSD is also associated with higher insomnia severity scores as well as regional neurotransmitter disruptions in systems critical for the regulation of affect. Poor sleep quality is associated with poor health outcomes that overlap with those that are experienced in PTSD. These include associations with the development of cardiovascular disease, diabetes and inflammatory diseases including arthritis. Effective treatment of sleep problems in this population could have substantial impact on these symptoms and improve quality of life. Heterogeneity in PTSD, including hyperarousal symptom expression and prior occurring mild traumatic brain injury (mTBI), may influence individual differences in treatment response. mTBI is a common occurring preceding injury to PTSD and damage to limbic white matter structures may influence presentation of PTSD. Current pharmacological approaches often have side effects like negative impacts on sleep architecture, addiction, and cognitive performance consequences. Further, Veterans often report that they use alcohol and other drugs in order to fall asleep and stop nightmares, compounding the issue. Vagal nerve stimulation (VNS) approaches have potential, especially in this population to improve sleep quality and to also improve hyperarousal symptoms of PTSD. Vagal nerve stimulation (VNS) induces activation of the parasympathetic nervous system and suppression of amygdala activity, addressing the core components of hyperarousal symptoms of PTSD. Conventional VNS requires neurosurgery. However, we will investigate a novel, non-invasive approach: transcutaneous vagal nerve stimulation (tVNS). tVNS has a high potential for success in this population. Preliminary work. Our pilot data demonstrate increased slow wave sleep, and decreased REM sleep and sleep latency after one hour of tVNS at “lights out.” The mechanism for this may be the result of decreasing hyperarousal symptoms during the first hour of sleep; all participants showed increased high frequency heart rate variability during tVNS compared with sham. We have also previously demonstrated tVNS improvement of hyperarousal signs of PTSD including upregulation of parasympathetic nervous system and attenuation of sympathetic nervous system activity during ‘startle’ in Veterans with PTSD with or without history of mTBI. Plan Our objective is to use tVNS in Veterans with PTSD with or without history of mTBI to evaluate its efficacy in changing sleep architecture (aim 1) and hyperarousal symptoms (aim 2). We will also assess the impact of pre-occurring mTBI and heterogeneity of PTSD symptoms on treatment response (aim 3) as well as safety and tolerability features. We will use a within-subject sham-controlled cross-over design to assess the impact of tVNS administered at “lights out” for one hour on several critical sleep variables including sleep onset, slow wave sleep, REM sleep, and autonomic nervous system behavior.