Biomechanical and neural mechanisms of post-stroke gait training

中风后步态训练的生物力学和神经机制

• 批准号: 10219315
• 负责人: Trisha Kesar
• 金额: $ 61.05万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-02 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10219315
• 关键词: Address; Ankle; Bilateral; Biological Markers; Biomechanics; Brain; Characteristics; Clinical; Communities; Corticospinal Tracts; Data; Development; Enhancing Lesion; Financial compensation; Foot-drop; Functional disorder; Future; Gait; Gait speed; Goals; Health; Impairment; Individual; Intervention; Kinetics; Knowledge; Leg; Lesion; Limb structure; Locomotion; Measures; Mission; Motor Cortex; Movement; Muscle; National Institute of Child Health and Human Development; Neuraxis; Neurobiology; Neuronal Plasticity; Output; Paresis; Participant; Patients; Pattern; Physical therapy; Physiological; Play; Practice Guidelines; Primary Lesion; Randomized; Recovery; Rehabilitation Outcome; Rehabilitation therapy; Role; Speed; Spinal; Stroke; Testing; Time; Training; Walking; Work; base; clinical investigation; clinically relevant; cost; demographics; effective therapy; follow-up; functional electrical stimulation; gait rehabilitation; improved; inter-individual variation; kinematics; leg paresis; locomotor control; motor learning; neural circuit; neuromechanism; neuropathology; neurophysiology; novel; post stroke; precision medicine; rehabilitation research; relating to nervous system; response; spinal reflex; stroke survivor; treadmill; treatment response; walking intervention; walking speed

Stroke induces a cascade of neurophysiologic changes in cortical and spinal circuits that result in biomechanical gait impairments (reduced paretic propulsion, footdrop) and gait dysfunction (reduced speed). While increasing gait speed is a major goal of stroke gait rehabilitation, targeting walking speed as a primary gait rehabilitation outcome without regard to biomechanical and neural mechanisms fails to meet the emerging standards of precision medicine, which is the future of rehabilitation research. Thus, here, we will confirm a novel theoretical framework regarding neurobiological (top-­down) and biomechanics (bottom-­up) mechanisms of how 2 gait treatments improve walking speed post-­stroke. Fast treadmill walking (Fast), a well-­ studied and clinically-­used intervention, improves gait speed. However, Fast-­induced speed improvements in people post-­stroke may occur at the cost of inter-­limb asymmetry, energy inefficiency, and maladaptive neuroplasticity. Recent work has demonstrated that combining Fast with functional electrical stimulation (FastFES) not only leads to improvements in gait speed but also reduces energy cost (EC) of stroke gait. Because reduced EC is crucial for sustaining faster gait speeds and promoting community activity, biomechanical factors influencing EC post-­stroke merit more in-­depth study. Building upon knowledge gained from previous FastFES work and our preliminary data, Aim 1 will test our hypothesis that in contrast to Fast, FastFES promotes greater use of the paretic leg for forward propulsion, thereby improving inter-­limb biomechanical asymmetry, which we hypothesize reduces EC. Gait rehabilitation essentially involves retraining the central nervous system. Our lack of understanding of neuroplasticity mechanisms underlying gait interventions continues to be a barrier to improving gait rehabilitation outcomes. Aim 2 will determine, for the first time, if and how FastFES and Fast modulate excitability of neural circuits impacted by stroke and implicated in locomotor control. Stroke leads to decrease in lesioned motor cortex (M1) excitability and corticospinal tract (CST) output, and elevated spinal reflex excitability. New findings from our lab suggest that unlike Fast, FastFES enhances lesioned CST and M1 excitability, restoring more normal CST output. FastFES and Fast also differ in their effects on spinal excitability. Like most gait treatments, Fast and FastFES must contend with high inter-­individual variability in treatment responses (a subset of participants are “non-­ responders”). Aim 3 will address whether baseline measures or short-­term changes in neurophysiological biomarkers (CST and spinal excitability) can predict long-­term training-­effects. Results from our mechanism-­ focused clinical investigation will elucidate how, why, and for whom Fast and FastFES induce clinical benefits. The overall impact of this work will be future development of cutting-­edge gait treatments that are individually-­ tailored based on neurobiological, biomechanical, and clinical characteristics to improve both gait quality and gait function, well-­aligned with the NICHD mission of improving health through ‘optimal’ rehabilitation.

中风引起了一系列的皮质和脊柱回路的神经生理变化，导致导致 生物力学步态障碍（减少了毛线推进，脚轮）和步态功能障碍（降低速度）。 虽然步态速度提高是中风步态康复的主要目标 步态康复结果而无需考虑生物力学和神经机制，无法满足新兴 精确医学的标准，这是康复研究的未来。在这里，我们将确认 有关神经生物学（自上而下）和生物力学（自下而上）的新理论框架 两种战斗治疗方法如何改善行走速度的机制。快速跑步机行走（快速），一个很好的 研究且临床中使用的干预措施可提高步态速度。但是，快速诱导的速度提高了 中风后的人可能是以限制间不对称性，能量效率低下和适应不良的代价发生的 神经可塑性。最近的工作表明，将快速与功能电刺激结合在一起 （Fastfes）不仅可以提高步态速度，而且还会降低中风步态的能量成本（EC）。 因为减少的EC对于维持更快的速度和促进社区活动至关重要，所以 生物力学因素会影响势力后值得更多深入研究。在获得知识的基础上 从以前的Fastfes工作和我们的初步数据中，AIM 1将测试我们的假设，与快速相比， Fastfes促进了更多的侧腿用于正向推进的使用，从而改善了LIMB 生物力学不对称性，我们假设这降低了EC。步态康复本质上涉及重新训练 中枢神经系统。我们对步态的神经塑性机制缺乏了解 干预措施仍然是改善步态康复结果的障碍。 AIM 2将确定 第一次，是否以及如何快速和快速调节受到中风和影响的神经回路的刺激性 在运动控制中实现。中风会导致病变的运动皮层（M1）令人兴奋，并且 皮质脊髓区（CST）输出和脊柱反射兴奋性升高。我们实验室的新发现表明 与快速相比，FastFes增强了病变的CST和M1兴奋性，从而恢复了更为正常的CST输出。 fastfes 快速对它们对脊柱令人兴奋的影响也有所不同。像大多数聚会治疗一样，快速和快速夫人必须 与治疗反应的高个体间差异抗衡（参与者的一部分是“非 - AIM 3将解决基线测量或神经生理学的短期变化 生物标志物（CST和脊柱兴奋）可以预测长期训练效应。我们机制的结果 集中的临床研究将阐明如何，为什么以及为谁快速和快速夫人引起临床益处。 这项工作的总体影响将是未来的发展，尖端的满足疗法是个性的 根据神经生物学，生物力学和临床特征量身定制 步态功能与通过“最佳”康复改善健康的NICHD使命非常合并。