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%的中风病例导致上肢功能下降，这对日常生活有严重的负面影响。运动恢复通常通过专业辅助的运动康复训练，以及通过各种机器人、虚拟现实和脑刺激技术的实验来实现。许多康复技术试图在中风后恢复病理性不足的神经活动以恢复功能，因为中风引起脑组织损伤，随后在周围未受损组织中皮层运动表征的重组。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促进运动康复。VNS包括在迷走神经的左颈束周围包裹一个袖带电极，在过去的十年中，随着几个有希望的动物模型的发现表明能够以目标依赖的方式诱导神经可塑性，这种方法再次出现。在动物模型中，VNS脉冲的时间配对与运动康复配对可以恢复脑卒中后病理性不足的神经活动。这种VNS和恢复性行为干预的复杂配对被称为“靶向可塑性”，是一种很有前途的神经精神干预治疗方法，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）的无创替代方法已成为传统植入VNS的一种有前途的替代方法。然而，taVNS的目标是迷走神经的耳部分支，迷走神经支配人耳并激活传入和传出迷走神经网络，从而可以无创、简单、快速地转换颈部植入的VNS结果。本研究旨在开发无创、闭环taVNS作为脑卒中后神经可塑性增强剂和加速上肢运动恢复

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.