Biomechanical and neural mechanisms of post-stroke gait training

中风在皮质和脊髓回路中诱导一连串的神经生理学变化，导致 生物力学步态损伤(瘫痪推进力降低、足下垂)和步态功能障碍(速度减慢)。 虽然提高步态速度是中风步态康复的主要目标，但以步行速度为主要目标 不考虑生物力学和神经机制的步态康复结果不能满足新兴的 精准医学的标准，这是康复研究的未来。因此，在这里，我们将确认一个 神经生物学(自上而下)和生物力学(自下而上)的新理论框架 2步态疗法如何提高中风后步行速度的机制。快速跑步机步行(快速)，一种良好的 研究和临床使用的干预措施，提高步态速度。然而，快速带来的速度提升 人们中风后可能会以肢体间不对称、能量效率低下和适应不良为代价 神经可塑性。最近的研究表明，结合快速电刺激和功能性电刺激 (FastFES)不仅可以提高步态速度，还可以降低笔划步态的能量消耗(EC)。 因为减少EC对于保持更快的步速和促进社区活动至关重要， 影响卒中后EC的生物力学因素值得更深入的研究。以所获得的知识为基础 根据之前的FastFES工作和我们的初步数据，Aim 1将测试我们的假设，与FastFES相反， FastFES促进瘫痪腿更多地用于向前推进，从而改善肢体之间的相互作用 生物力学的不对称性，我们假设会降低EC。步态康复本质上是再训练 中枢神经系统。我们对步态背后的神经可塑性机制缺乏了解 干预措施仍然是改善步态康复结果的障碍。目标2将确定，对于 第一次，如果和如何FastFES和快速调制神经回路的兴奋性影响卒中和 牵涉到运动控制。中风导致受损运动皮质(M1)兴奋性降低和 皮质脊髓束(CST)输出和脊髓反射兴奋性升高。我们实验室的新发现表明 与Fast不同，FastFES增强了受损的CST和M1的兴奋性，恢复了更正常的CST输出。FastFES 而Fast对脊柱兴奋性的影响也不同。像大多数步态治疗一样，Fast and FastFES必须 应对治疗反应的高度个体间差异(参与者的子集是 响应者“)。目标3将解决基线测量或神经生理学的短期变化 生物标记物(CST和脊柱兴奋性)可以预测长期训练效果。我们机制的结果-- 重点临床研究将阐明FAST和FastFES如何、为什么以及对谁产生临床益处。 这项工作的总体影响将是未来尖端步态疗法的发展，这些疗法是单独-- 根据神经生物学、生物力学和临床特征量身定做，以改善步态质量和 步态功能，与NICHD通过“最佳”康复改善健康的使命很好地一致。

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.