Characterizing Lower Extremity Neurophysiological Responses to Sensory Augmentation after Stroke

中风后下肢对感觉增强的神经生理反应特征

• 批准号: 10829133
• 负责人: Jasmine Jamilah Cash
• 金额: $ 4.41万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10829133
• 关键词: Academic Medical Centers; Activities of Daily Living; Address; Award; Behavior; Biological Assay; Biological Markers; Brain Stem; Central Nervous System; Clinical; Communication; Complex; Corticospinal Tracts; Diffusion; Effectiveness; Electric Stimulation; Electroencephalography; Electrophysiology (science); Equilibrium; Exhibits; Feedback; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hypesthesia; Image; Impairment; Individual; Individual Differences; Investigation; Knowledge; Learning; Lower Extremity; Measures; Mediating; Mediator; Mentors; Mentorship; Methods; Motor; Motor Cortex; Motor Evoked Potentials; Motor output; Muscle; Nervous System; Neuronal Plasticity; Outcome; Performance; Phase; Postdoctoral Fellow; Process; Prognosis; Protocols documentation; Quality of life; Recovery; Rehabilitation therapy; Research; Research Personnel; Research Training; Role; Route; Sensory; Shapes; Signal Transduction; Somatosensory Cortex; Somatosensory Evoked Potentials; Spinal Cord; Stimulus; Stroke; Structure; Synapses; System; Techniques; Time; Training; Transcranial magnetic stimulation; Translations; Upper Extremity; Walking; Work; balance recovery; career; career development; conventional therapy; equilibration disorder; experience; fall risk; falls; functional independence; high risk; improved; independent ambulation; interest; method development; multimodality; neural; neural correlate; neuroimaging; neurophysiology; neuroregulation; novel; post stroke; postsynaptic neurons; pre-doctoral; presynaptic neurons; response; sensory cortex; sensory input; sensory integration; skills; spasticity; stroke recovery; stroke survivor; treatment response

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.

项目概要/摘要 中风后，行走能力可能会受到影响，从而导致生活质量下降和活动能力下降 进行日常生活活动。中风后步行恢复是由神经系统重组介导的（例如， 神经可塑性），但是我们对这些与步行功能改善相关的过程的理解是 由于步行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。人们非常感兴趣的是感觉和感觉的整合 运动系统（例如，感觉运动整合-SMI），这是启动、维持和协调所必需的 行走的同时提供有关身体状态和动作的持续反馈。此外，中风后感觉受损 可能导致下肢功能障碍、平衡问题和跌倒，强调需要研究其影响 中风对 SMI 的影响与步行功能和恢复有关。鉴于 SMI 在步行中的重要性， 这些表现出可塑性变化的感觉运动网络可能是改善步行的关键中介因素 功能，因此需要相关的方法来测定感觉运动可塑性。为了解决这一知识差距， 在 F99 阶段（目标 1），我将描述中风后个体下肢感觉运动可塑性的特征。我会 专门针对初级感觉皮层 (S1) 和初级运动皮层 (M1) 之间的连接 使用配对联想刺激（PAS），这是一种测定感觉运动可塑性的新方法。 PAS 是基于 联想可塑性的赫布原理，即 S1 内突触前和突触后神经元的重复刺激 M1 导致突触功效增强，经颅磁力快速而持久的增强就证明了这一点 刺激引起的肌肉反应，或运动诱发电位 (MEP) 幅度。我们打算考虑 通过调整刺激之间的时间并测量电刺激所需的时间来研究 SMI 的个体差异 通过体感诱发电位刺激达到 S1。 PAS 后 MEP 振幅的变化被认为 反映 S1 和 M1 之间诱导的关联可塑性，并且被证明可以反映上肢 功能，下肢所做的工作有限。因此，我们假设个性化的 PAS 协议， 将促进 MEP 幅度的增加，并且变化将与步行功能的临床测量相关。 在 K00 阶段（目标 2），我将通过多种方式进行中风后感觉和运动重组的高级训练。 了解行走和平衡恢复的模态技术。我将寻求博士后指导，以便 我通过获得先进的电生理学和神经影像学技能来巩固我的博士前工作。我也会 注重个体化评估和确定治疗反应的潜在机制 康复过程中个体之间的关系。 F99/K00 将帮助我走向独立之路 研究培训和职业发展，实现我成为独立研究员的长期目标 学术医疗中心。拟议的工作和职业方向旨在为下肢康复提供信息 通过提供恢复的功能和结构神经相关性来努力。