Paired Associative Stimulation to Facilitate Plantarflexor Power Following Stroke

项目概要/摘要 拟议的SPiRE建立在初步工作的基础上，在初步工作中，我们观察到 皮质脊髓束服务于跖屈肌和行走功能，特别是踝跖屈肌力量， 慢性中风后轻偏瘫患者。我们已经观察到以下之间的强大关联：i）PF 皮质脊髓功效，和ii）皮质脊髓驱动和PF功率的调节，特别是在治疗后个体中。 中风重要的是，临床和人口统计学因素包括：年龄，卒中慢性化和病变部位， 解释，也不修改，这些协会。结合起来，这些发现导致我们的中心前提， 皮质脊髓束为跖屈肌服务的功效的改善将能够增加踝PF功率 并有助于改善中风后个体的行走功能。在这里，我们建议调查使用 配对联合刺激（PAS），以提高皮质脊髓的功效，并通过靶向足底屈肌 神经可塑性我们将探讨三种方法来PAS，以确定其功效，以提高：i）神经 反应，ii）生物力学效应（A2），以及iii）神经和生物力学效应的保留。 目标.拟议的SPiRE侧重于优化PAS在以下方面的功效所需的方法学变量： a）皮质脊髓对跖屈肌的功效，和B）具有后- 中风行走功能障碍通过实现我们的目标，SPiRE产生的数据将有助于 制定更有针对性和相关性的假设，以在未来的研究中进行测试， 竞争优势评审。然而，在进行更大规模的研究之前，我们首先要确定 以及PAS的影响程度。除了探讨与考绩制度有关的方法问题外， 将使我们能够确定未来项目的适当范围，包括样本 大小和剂量。我们的目标与SPiRE（RX-20 - 009）的计划指导方针一致， 特别是涉及高级调查员的案件。具体而言：（一）这项工作以前没有得到资助;（二） 本提案中要解决的问题代表了一个新的研究领域和一个新的合作， PI，以及iii）我们寻求开发我们的方法，确定可行性，并生成初步/探索性数据 为了确定效应量和计算未来大规模人类研究的统计功效， 科目我们将比较PAS靶向踝关节跖屈时的效果：休息时， 次极量活动和行走时。

Project Summary/Abstract The proposed SPiRE builds on preliminary work in which we have observed a relationship between efficacy of the corticospinal tract serving the plantarflexors and walking function, specifically ankle plantarflexor power, in individuals with chronic post-stroke hemiparesis. We have observed robust associations between: i) PF corticospinal efficacy, and ii) modulation of corticospinal drive, and PF power, particularly in individuals post- stroke. Importantly, clinical and demographic factors including: age, stroke chronicity, and lesion location, neither explain, nor modify, these associations. In combination, these findings lead to our central premise, that improved efficacy of the corticospinal tract serving the plantarflexors will enable augmentation of ankle PF power and contribute to improved walking function in individuals post-stroke. Here we propose to investigate use of paired associative stimulation (PAS) to enhance corticospinal efficacy and to the plantarflexors through targeted neuroplasticity. We will explore three approaches to PAS to determine its efficacy for enhancing: i) neural responses, ii) biomechanical effects (A2), and iii) retention of neural and biomechanical effects. Objectives. The proposed SPiRE focused on methodological variables required to optimize efficacy of PAS on: a) corticospinal efficacy to the plantarflexors, and b) walking function (quantified as A2) in Veterans with post- stroke walking dysfunction. By achieving our aims, data generated from this SPiRE will contribute to development of more focused and relevant hypotheses to be tested in future studies supported through competitive Merit Review. However, before motivating a larger study, we first seek to determine the salience and magnitude of effects of PAS. In addition to exploring methodological issues related to PAS, data generated from the proposed SPiRE will enable us to determine the appropriate scope of a future project including sample size and dosing. Our objectives are consistent with the programmatic guidelines of the SPiRE (RX-20-009), particularly as they relate to senior investigators. Specifically: i) this work has not previously been funded; ii) the question to be addressed in this proposal represents a new area of research, and a new collaboration, for the PI, and iii) we seek to develop our methodology, determine feasibility, and generate preliminary/exploratory data for sake of determining effect sizes and computing statistical power for future large scale studies in human subjects. We will compare effects of PAS targeting ankle plantarflexion when delivered: at rest, during submaximal activity, and during walking.