Optimization of closed-loop taVNS for motor rehabilitation

美国每年有近80万人中风，运动障碍是最常见的长期功能性残疾。85%的中风病例会导致上肢功能下降，这对日常生活产生严重的负面影响。运动恢复最常见的是通过专业辅助运动康复训练，并通过各种机器人，虚拟现实和大脑刺激技术进行实验。这些康复技术中的许多试图恢复中风后病理学上不充分的神经活动以恢复功能，因为中风诱导对脑组织的损伤以及周围未损伤组织中的皮质运动表征的随后重组。迷走神经刺激（VNS）可以通过增加神经可塑性和加速神经活动和功能的恢复来增强运动康复。迷走神经刺激涉及将袖带电极缠绕在迷走神经的左颈束周围，并且在过去十年中，在几个有希望的动物模型研究结果表明能够以靶点依赖性方式诱导神经可塑性之后，迷走神经刺激再次出现。在动物模型中，与运动康复配对的VNS爆发的时间配对可以恢复中风后病理上不足的神经活动。VNS和恢复性行为干预的这种复杂配对被称为“靶向可塑性”，是治疗神经精神干预的一种有前途的方法，在卒中后康复中具有潜在的变革潜力。最近，一种被称为经皮耳迷走神经刺激（taVNS）的非侵入性替代方案已成为传统植入VNS的有前途的替代方案。然而，taVNS靶向迷走神经的耳分支，其支配人耳并激活传入和传出迷走神经网络，从而允许无创、简单和快速地翻译颈部植入的VNS发现。该提案旨在开发非侵入性闭环taVNS作为神经可塑性增强剂，并加速卒中后上肢运动恢复 康复活动.

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.