Optimization of closed-loop taVNS for motor rehabilitation

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Nearly 800,000 people in the United States have a stroke annually, with motor impairments being the most common long-term functional disability. 85% of stroke cases result in reductions in upper limb function, and this has a severe negative impact on daily living. Motor recovery is achieved most commonly through professionally assisted motor rehabilitation training, and experimentally through various robotic, virtual reality, and brain stimulation techniques. Many of these rehabilitation techniques attempt to restore pathologically insufficient neural activity post-stroke to regain function, as the stroke induces damage to brain tissue and subsequent reorganization of cortical motor representations in surrounding undamaged tissue. Vagus nerve stimulation (VNS) can enhance motor rehabilitation by increasing neuroplasticity and accelerating the restoration of neural activity and function when paired in a temporally synchronized manner. VNS involves wrapping a cuff electrode around the left cervical bundle of the vagus nerve and has seen a reemergence in the past decade following several promising animal model findings demonstrating the ability to induce neuroplasticity in a target-dependent manner. In animal models, the temporal pairing of VNS bursts paired with motor rehabilitation can restore pathologically insufficient neural activity post-stroke. This intricate pairing of VNS and restorative behavioral intervention is known as “targeted plasticity” and is a promising approach to treatment of neuropsychiatric interventions, with potentially transformative potential in post stroke rehabilitation. Recently, a noninvasive alternative known as transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising alternative to conventionally implanted VNS. taVNS, however, targets the auricular branch of the vagus nerve, which innervates the human ear and activates the afferent and efferent vagal networks, allowing for a noninvasive, simple, and rapid translation of cervically implanted VNS findings. This proposal aims to develop noninvasive, closed- loop taVNS as an enhancer of neuroplasticity and accelerate upper limb motor restoration in post-stroke rehabilitation.