Modulating brain networks to reduce gait variability in older adults at risk of falling

项目摘要 我的职业目标是通过以下方式来改善老年人的步态康复和降低福尔斯风险 进行创新研究，重点是神经控制和步态和流动性的增强。我是 特别感兴趣的是开发个性化，多模式和以患者为中心的干预措施， 两者都是独立的，并与目前的循证老年病康复方案相结合。 虽然步行是一项重复性的任务，但一个人在步行过程中的运动时空模式因步幅而异 大步前进这种步态变异性，如果足够高，是预测老年人的福尔斯和认知能力下降。 尽管如此，引起步态变异的神经机制还没有完全理解。因此，我们缺乏 有效的干预措施，以尽量减少老年人的步态变异。然而，我们的团队已经证明， 老年人，那些步态变异性升高的人表现出更差的能力，以持续的表现， 随着时间的认知任务（即，持续关注）。我的研究还将步态变异性与功能性 这两个大规模的大脑网络之间的连接被认为是持续注意力不足的， 背侧注意力网络（DAN）和默认网络（DN）-在多个老年人队列中。基于 基于这些发现，我们设计了一种新型的多通道经颅直流电刺激（tDCS） 干预以同时促进DAN的兴奋性和抑制DN的兴奋性。我们 初步数据表明，与假手术相比，单次暴露于该tDCS可降低步态变异性 在刺激后进行测试。我的首要假设是，这种形式的tDCS可以调节 DAN和DN之间的功能连接，从而减少老年人的步态变异性。在这个项目中， 我们将通过检查单次tDCS对静息状态的急性后效应来检验这一假设 功能连接（目标1），以及确定多疗程tDCS干预对步态的影响 变异性和相关结果（目标2）。我们将招募30名没有重大疾病的老年人， 高于典型步态变异性。参与者将首先完成基线评估和两次fMRI访视。 然后将相同的受试者随机分配至tDCS干预组（10次，每日一次，20分钟）或 a ShamàtDCS干预组（第一周5次，每日一次，20分钟假手术，随后5次，每日一次， 在第2周每天进行20分钟的tDCS治疗）。步态变异性的主要结局将每天使用 在整个研究期间使用经过验证的智能手机应用程序。我们希望证明tDCS可以调节 功能连接和减少老年人的步态变异。该项目的成果预计将 通知设计一个更大的，更明确的tDCS试验，旨在优化大脑连接，因为它涉及 老年人的步态变化。这项研究，结合先进的神经影像学的具体培训， 神经调节，衰老中的认知神经科学，以及在脆弱的老年人中进行临床研究 成人，将大大促进我的努力过渡到一个独立的临床科学家。

PROJECT SUMMARY My career goal is to lead efforts to improve gait rehabilitation and mitigate falls risk in older adults by conducting innovative research focused on the neural control and enhancement of gait and mobility. I am particularly interested in developing individualized, multi-modal, and patient-centered interventions that can both stand alone and be combined with current evidenced-based geriatrics rehabilitation programming. Though walking is a repetitive task, one’s temporospatial patterns of movement during walking vary from stride to stride. This gait variability, if sufficiently high, is predictive of both falls and cognitive decline in older adults. Still, the neural mechanisms that give rise to gait variability are not completely understood. We thus lack effective interventions to minimize gait variability in older adults. However, our team has demonstrated that in older adults, those with elevated gait variability exhibit worse ability to sustain performance on a continuous cognitive task over time (i.e., sustained attention). My work has also linked gait variability to the functional connectivity between the two large-scale brain networks believed to underserve sustained attention—namely, the dorsal attention network (DAN) and the default network (DN)—in multiple cohorts of older adults. Based upon these discoveries, we designed a novel multi-channel transcranial direct current stimulation (tDCS) intervention to simultaneously facilitate the excitability of the DAN and inhibit the excitability of the DN. Our preliminary data suggests that a single exposure to this tDCS, as compared to sham, reduces gait variability when tested just following stimulation. My overarching hypothesis is that this form of tDCS can modulate the functional connectivity between the DAN and DN and thus reduce gait variability in older adults. In this project, we will test this hypothesis by examining the acute after-effects of a single session of tDCS on resting-state functional connectivity (Aim 1), as well as determining the effects of a multi-session tDCS intervention on gait variability and related outcomes (Aim 2). We will recruit 30 older adults free of major disease that exhibit higher-than-typical gait variability. Participants will first complete a baseline assessment and two fMRI visits. The same participants will then be randomized to a tDCS intervention arm (ten, once-daily, 20-min sessions) or a ShamàtDCS intervention arm (five, once-daily, 20-min sessions of sham in week one followed by five, once- daily, 20-min sessions of tDCS in week 2). The primary outcome of gait variability will be assessed daily using a validated smartphone app for the entire study period. We expect to demonstrate that tDCS can modulate functional connectivity and reduce gait variability in older adults. The results from this project are expected to inform the design of a larger, more definitive trial of tDCS designed to optimize brain connectivity as it relates to gait variability in older adults. This research, combined with specific training in advanced neuroimaging and neuromodulation, cognitive neuroscience in aging, and the conduct a clinical research in vulnerable older adults, will greatly facilitate my efforts to transition into an independence clinician scientist.