The Long-Latency Reflex: A Biomarker for Functional Impairment Following Stroke

项目摘要/摘要 中风后行走经常受到损害，然而目前针对行走的康复策略并不能 在功能上产生有意义的改进。我们的长期研究目标是改善步行恢复 中风后。缺乏功能改善可能部分归因于 慢性中风患者存在感觉运动障碍。然而，这也可能是由于缺乏生物标记物。 这充分确定了哪些人可能对给定的治疗有反应。迫切需要非 侵入性生物标记物可以预测中风后的行走能力和康复潜力。这项研究 PLAN提出了一种功能生物标记物，利用肌肉拉伸和肌电(EMG)来量化 与行走和其他肢体功能有关的神经回路的健康。这个生物标记物的存在 长潜伏期反射(LLR)可能起源于跨皮质反射通路。经皮质反射是一种 多突触反射环是整合感觉运动信息的关键。评估……的潜力 LLR的存在作为生物标记物，拟议的研究将证明健康对照之间的差异 和慢性中风患者在探索感觉的健康和短期易变性的同时， 通路的整合部分和运动部分。具体目标是：1)描述大脑皮层 卒中后LLRS的贡献及其与下肢功能的关系2)评估LLRS的影响 拉伸速度和背景激活对LLR的影响；3)评价配对联想效应 对LLR的刺激。通过探索感觉、棘上整合和运动组件 通过皮质反射途径，我们的目标是更好地了解个体功能障碍的部位。 LLR减少或不存在。我们的总体假设是LLR功能障碍源于经皮质 反射途径，它是一个重要的生理生物标志物，识别它将减少影响 在中风后的行走评估中观察到的异质性。我们的前期工作和其他人的工作 提示部分但不是全部的慢性中风患者在跨皮质反射方面有损害。 路径。功能障碍的跨皮质反射可能导致功能评分下降和功能受限。 这些个体的行走能力。通过进行这些实验所获得的知识将有助于 了解中风后患者的运动生理学功能障碍。未来的工作将决定 LLRs对治疗结果的先验预测能力。对任务的拟议表征-- 依赖的LLRs将导致临床上可获得的中风后步行功能障碍的可变性生物标志物。 这个伙伴和指导团队非常适合实现这些目标，所获得的知识将 有助于改善中风后的步行康复。

Project Summary/Abstract Walking is often impaired after a stroke, yet current rehabilitation strategies targeted towards walking fail to produce meaningful improvements in function. Our long-term research goal is to improve walking recovery following stroke. Lack of functional improvement may be attributable in part to the vast heterogeneity of sensorimotor impairments present in chronic stroke. However, this could also be due to a lack of biomarkers that adequately identify which individuals may respond to a given treatment. There is a critical need for non- invasive biomarkers that can predict walking ability and potential for recovery following stroke. This research plan proposes a functional biomarker that utilizes muscle stretch and electromyography (EMG) to quantify the health of neural circuitry that relates to walking and other lower extremity function. This biomarker, presence of the long-latency reflex (LLR), likely arises from the transcortical reflex pathway. The transcortical reflex is a polysynaptic reflex loop that is critical for integration of sensorimotor information. To evaluate the potential for LLR presence as a biomarker, the proposed research will demonstrate differences between healthy controls and individuals with chronic stroke while probing the health and short-term mutability of the sensory, integratory, and motor portions of the pathway. The specific aims are to: 1) characterize the cortical contribution of LLRs post-stroke and its relationship to lower extremity function, 2) assess the influence of stretch velocity and background activation on LLRs, and 3) to evaluate the effect of paired associative stimulation on LLRs. Through probing the sensory, supraspinal integratory, and motor components of the transcortical reflex pathway, we aim to gain a greater understanding of the locus of dysfunction in individuals with diminished or absent LLRs. Our overall hypothesis is that LLR dysfunction is derived from the transcortical reflex pathway, and that it is an important physiologic biomarker, identification of which will reduce the impact of heterogeneity observed in walking assessments post-stroke. Our preliminary work and the work of others indicates that some, but not all, individuals with chronic stroke have impairment in the transcortical reflex pathway. A dysfunctional transcortical reflex likely contributes to decreased functional scores and limited walking capacity in these individuals. The knowledge gained by performing these experiments will contribute to understanding dysfunctional motor physiology in persons following stroke. Future work will determine the capacity of LLRs for a priori prediction of treatment outcomes. The proposed characterization of task- dependent LLRs will lead to a clinically accessible biomarker for mutability of walking dysfunction post-stroke. This fellow and mentorship team are well-suited to achieve these aims and the knowledge gained will contribute to improving walking rehabilitation following stroke.