Browsing by Author "Meyers, Eric"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item Effects of Vagus Nerve Stimulation on Extinction of Conditioned Fear and Post-Traumatic Stress Disorder Symptoms in RatsNoble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.; Noble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.Item Enhancing Plasticity Using Vagus Nerve Stimulation Improves Recovery Following Neurological Injury(2017-05) Meyers, Eric; Hays, Seth; Rennaker, Robert LDamage to the central and peripheral nervous system cause physical disability, and impairment following injury is often permanent. Stroke is the leading cause of physical disability in the United States, affecting 800,000 people per year and that number is on the rise. Similarly, 20 million Americans suffer from peripheral nerve injury related disability making it alongside of stroke as one of the leading causes of disabilities in the United States. These lesions frequently affect movement control of the upper extremities, and loss of hand function is devastating for patients. There is currently an unmet clinical need for therapeutic interventions to restore function in patients suffering from these injuries. Previous work has demonstrated that vagus nerve stimulation (VNS) paired with rehabilitative training is effective in treating motor dysfunction following stroke, traumatic brain injury, and most recently spinal cord injury. In healthy subjects, VNS paired with motor training enhances plasticity in the paired motor networks. It is believed that VNS paired with rehabilitative training works through a similar plasticity-enhancing mechanism to reorganize damaged motor networks. This dissertation work demonstrates VNS paired with rehabilitative training enhances plasticity and recovery following stroke and peripheral nerve injury. In a stroke injury model we first describe the development of a novel method of assessing forelimb supination, a movement that is severely diminished following stroke. Next, we demonstrate that pairing VNS with supination training doubles the beneficial effects of rehabilitative training without VNS. We further demonstrate that the VNS-dependent benefits on the supination task transfer to an untrained task emphasizing volitional forelimb strength, and the benefits of VNS last for two months following the cessation of VNS. Transneuronal tracing from musculature of the rehabilitated forelimb demonstrates enhanced synaptic connectivity in the VNS-treated subjects. The second half of this dissertation focuses on peripheral nerve injuries affecting the upper extremities. We first describe a novel forelimb peripheral nerve injury model and demonstrate the effectiveness of the isometric pull task to quantitatively measure chronic motor deficits following injury. We next show that VNS paired with rehabilitative training following PNI improves forelimb motor and sensory function. Physiological and anatomical assessments indicate enhanced plasticity in motor networks specific to the rehabilitated movement that likely subserve improved recovery. Lastly, we demonstrate that cortical plasticity is critical for recovery following PNI by disrupting cortical cholinergic innervation thus blocking cortical plasticity. Subjects receiving NB lesions and VNS demonstrate markedly less recovery than VNS subjects and do not demonstrate motor map plasticity. The results of this dissertation first extend the findings of recent studies that demonstrate the effectiveness of VNS paired with rehabilitative training to treat motor dysfunction following stroke. We demonstrate the substantial clinical utility of VNS therapy and reveal an anatomical substrate of recovery following stroke. Furthermore, we show initial evidence for the effectiveness of plasticity-enhancing therapies to improve motor and sensory dysfunction following peripheral nerve injuries.Item Vagus Nerve Stimulation and Rehabilitation Improves Recovery of a Motor Task after Neurological Injury(2015-06-25) Choi, Rachel; Meyers, Eric; Ganzer, Patrick; Hays, Seth; Kilgard, Michael P.; Rennaker, Robert L.; 0000 0001 3852 473X (Kilgard, MP); 0000 0001 2879 2132 (Rennaker, RL)Ischemic stroke and spinal cord injury are neurological injuries that produce persisting motor deficits. Additionally, the majority of those suffering from impairments due to ischemic stroke or spinal cord injury rarely fully recover complete function with current treatment options. Here, we investigate the use of vagus nerve stimulation (VNS), which facilitates specific and long-lasting plasticity after injury. Sprague-Dawley rats affected by a spinal cord contusion at C5 and administered VNS paired with rehabilitation exhibited significant recovery of forelimb strength on an isometric pull task. We also propose similar recovery of supination function in Sprague-Dawley rats affected by endothelin-1‐induced focal motor cortex ischemic stroke. Thus, VNS paired with rehabilitation may be an effective therapeutic tool in the event of neurological injury such as ischemic stroke or spinal cord injury.