Characterizing Lower Extremity Neurophysiological Responses to Sensory Augmentation after Stroke

项目摘要/摘要 中风后，行走能力可能会受到影响，这可能会导致生活质量下降，能力下降。 进行日常生活活动。中风后步行恢复由神经系统重组(例如， 神经可塑性)，然而，我们对这些与改善行走功能相关的过程的理解是 由于行走本身的神经生理学复杂性而受到限制。此外，目前评估中风的做法- 受影响的神经可塑性主要集中在运动系统上。最令人感兴趣的是感官和 启动、维持和协调所必需的马达系统(例如，感应马达集成-SMI) 走路的同时提供身体状态和动作的持续反馈。此外，中风后感觉受损 可导致下肢功能障碍、平衡问题和跌倒，突出了调查其影响的必要性 卒中对SMI的影响与步行功能和康复的关系。考虑到SMI在行走中的重要性， 这些感知运动网络可以抑制塑料的变化，这可能是改善行走的一个重要媒介。 因此，有必要建立相应的检测感觉运动可塑性的方法。为了解决这一知识差距， 在F99阶段(目标1)，我将描述中风后患者的下肢感觉运动可塑性。这就做 特别针对初级感觉皮质(S1)和初级运动皮质(M1)之间的联系 使用配对联想刺激(PAS)，一种新的检测感觉运动可塑性的方法。PAS基于 在重复刺激S1内突触前和突触后神经元中的联想可塑性的Hebbian原理 而M1导致突触效率的提高，证明是快速和持久的经颅磁化增加 刺激诱发的肌肉反应，或运动诱发电位(MEP)幅度。我们打算说明 SMI的个体差异，通过调整刺激之间的时间，并测量其花费的时间电 通过体感诱发电位刺激达到S1。认为PAS后MEP波幅的变化 以反映S1和M1之间的诱导联想可塑性，并被证明反映了上肢 功能有限，仅在下肢完成有限的工作。因此，我们假设个性化的PAS协议， 将促进MEP波幅的增加，而变化将与临床步行功能的测量相关。 在K00阶段(目标2)，我将通过多种方式继续进行中风后感觉和运动重组的高级培训。 了解步行和平衡恢复的模式技术。我会寻找博士后导师，这将使 我希望在博士前工作的基础上，获得先进的电生理学和神经成像技能。我也会 注重个别化评估和确定治疗反应的基本机制 在康复过程中的个人之间。F99/K00将帮助我通过以下方式促进独立 研究培训和职业发展，正在实现我成为一名独立研究员的长期目标 一个学术医疗中心。拟议的工作和职业方向旨在为腿部康复提供信息 通过提供功能和结构上的神经恢复相关的努力。

PROJECT SUMMARY/ABSTRACT After a stroke, walking ability can be compromised, which can lead to reduced quality of life and decreased ability to perform activities of daily living. Post-stroke walking recovery is mediated by nervous system reorganization (e.g., neuroplasticity), however our understanding of these processes related to improvements in walking function are limited due to the neurophysiological complexity of walking itself. Additionally, current practices of assessing stroke- impacted neuroplasticity are heavily focused on the motor system. Of keen interest is the integration of sensory and motor systems (e.g., sensorimotor integration-SMI), which are necessary for initiating, sustaining, and coordinating walking while providing continuous feedback on body state and actions. Additionally, impaired sensation post-stroke can lead to lower extremity dysfunction, balance problems, and falls, highlighting the need to investigate the effects of stroke on SMI in relation to walking function and recovery. Given the importance of SMI in walking, the capacity for these sensorimotor networks to exibit plastic changes may be a crucial mediator for improvements in walking funciton, thus necessitating relevant methods of assaying sensorimotor plasticity. To address this gap in knowledge, in the F99 Phase (Aim 1) I will characterize lower extremity sensorimotor plasticity in individuals post-stroke. I will specifically target the connections between the primary sensory cortex (S1) and and the primary motor cortex (M1) using paired associative stimulation (PAS), a novel method of assaying sensorimotor plasticity. PAS is based on the Hebbian principle of associative plasticity, in that repetitive stimulation of pre- and post-synaptic neurons within S1 and M1 leads to increased synaptic efficacy, evidenced by rapid and long-lasting increases in transcranial magnetic stimulation-induced muscle responses, or motor evoked potential (MEP) amplitude. We intend to account for individual differences in SMI by adjusting the timing between stimuli, and measuring the time it takes the electrical stimulation to reach S1, via somatosensory evoked potentials. Changes in MEP amplitude following PAS are thought to reflect the induced associative plasticity between S1 and M1, and are shown to be reflective of upper extremity function, with limited work done in the lower extremities. Therefore, we hypothesize that individualized PAS protocols, will facilitate increases in MEP amplitude, and changes will be associated with clinical measures of walking function. In the K00 Phase (Aim 2), I will pursue advanced training in post-stroke sensory and motor reorganization via multi- modal techniques to understand walking and balance recovery. I will seek out postdoctoral mentorship that will allow me to build on my predoctoral work by acquiring advanced electrophysiological and neuroimaging skills. I will also focus on individualized assessments and the identification of mechanisms underlying the response to treatment between individuals over the course of rehabilitation. The F99/K00 will help facilitate my path to independence through research training and career development, enroute to my long-term goal of becoming an independent researcher at an academic medical center. The proposed work and career direction aim to inform lower extremity rehabilitation efforts by providing functional and structural neural correlates of recovery.