Cerebral networks of locomotor learning and retention in older adults

衰老通常会导致步行功能大幅下降，尤其是对于需要承担更多任务的步行任务 诸如越障之类的复杂情况。部分原因是缺乏持续的复杂步行练习 （久坐的生活方式）加上与年龄相关的大脑结构和大脑网络完整性缺陷。 神经康复有助于恢复老年人失去的行走功能，但主要且持久 改进是难以捉摸的。神经康复的基石是运动学习，被定义为持久的 由于练习或经验而导致执行运动任务的能力发生变化。不幸的是，在大多数临床 在不同的环境中，提供足够密集的运动学习干预的时间和成本要求并不高 可行的。需要研究制定增强步行运动学习的策略 （“运动学习”）以提高神经康复的有效性。 本研究的目的是使用非侵入性脑刺激来增强运动学习并 研究负责行动不便的老年人的运动学习的大脑网络。 我们已经证明，额叶脑区域，特别是前额叶皮层，对于控制复杂的神经系统至关重要。 步行任务。我们的神经影像学和神经调节研究还表明，前额皮质结构和 网络连接对于获取和巩固新的运动技能非常重要。然而，存在重大差距 存在关于步行任务的学习。拟议的研究旨在解决这一差距。我们的试点数据 来自老年人的研究表明，在 学习复杂的障碍行走任务有助于多日保持任务表现。在 拟议的研究我们将在这项试点工作的基础上进行全面的试验，该试验还调查了 与大脑结构、功能活动和网络连接相关的机制。我们将解决 以下具体目标： 具体目标 1：确定前额叶 tDCS 在多大程度上增强任务练习对记忆的影响 复杂障碍行走任务的表现。 具体目标 2：确定绩效保持与个体差异相关的程度 基线和练习引起的大脑测量变化（工作记忆、灰质体积、任务- 基于前额叶活动和大脑网络分离）。 具体目标 3：研究 tDCS 在多大程度上改变静息状态网络隔离。 我们预计前额叶 tDCS 将增强运动学习的保留，并且我们的数据将提供 第一个证据表明特定大脑机制负责老年人的运动学习/保留 流动性不足。这一新知识将提供临床上可行的干预方法并揭示 未来干预措施的机械目标，以加强运动学习和康复。

Aging often leads to substantial declines in walking function, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to a lack of continued practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery of lost walking function in older adults, but major and persistent improvements are elusive. A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the ability to perform a motor task due to practice or experience. Unfortunately, in most clinical settings, the time and cost demands of delivering a sufficiently intensive motor learning intervention is not feasible. There is a need for research to develop strategies for enhancing motor learning of walking (“locomotor learning”) in order to improve the effectiveness of neurorehabilitation. The objective of this study is to use non-invasive brain stimulation to augment locomotor learning and to investigate brain networks that are responsible for locomotor learning in mobility-compromised older adults. We have shown that frontal brain regions, particularly prefrontal cortex, are crucial to control of complex walking tasks. Our neuroimaging and neuromodulation studies also show that prefrontal cortex structure and network connectivity are important for acquisition and consolidation of new motor skills. However, a major gap exists regarding learning of walking tasks. The proposed study is designed to address this gap. Our pilot data from older adults shows that prefrontal transcranial direct current stimulation (tDCS) administered during learning of a complex obstacle walking task contributes to multi-day retention of task performance. In the proposed study we will build upon this pilot work by conducting a full scale trial that also investigates mechanisms related to brain structure, functional activity, and network connectivity. We will address the following specific aims: Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task practice for retention of performance on a complex obstacle walking task. Specific Aim 2: Determine the extent to which retention of performance is associated with individual differences in baseline and practice-induced changes in brain measures (working memory, gray matter volume, task- based prefrontal activity, and brain network segregation). Specific Aim 3: Investigate the extent to which tDCS modifies resting state network segregation. We anticipate that prefrontal tDCS will augment retention of locomotor learning, and that our data will provide the first evidence of specific brain mechanisms responsible for locomotor learning/retention in older adults with mobility deficits. This new knowledge will provide a clinically feasible intervention approach as well as reveal mechanistic targets for future interventions to enhance locomotor learning and rehabilitation.