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

项目总结 我的职业目标是通过以下方式领导改善步态康复和降低老年人跌倒风险的努力 进行创新研究，重点是神经控制以及步态和机动性的增强。我是 对开发个性化、多模式和以患者为中心的干预措施特别感兴趣，这些干预措施可以 两者都是独立的，并与当前以证据为基础的老年病康复规划相结合。 虽然步行是一项重复的任务，但一个人在步行过程中的时空运动模式随着步幅的不同而不同 大踏步前进。这种步态的可变性，如果足够高，可以预测老年人的跌倒和认知能力下降。 尽管如此，导致步态变化的神经机制还没有完全弄清楚。因此，我们缺乏 有效的干预措施，将老年人的步态变异性降至最低。然而，我们的团队已经在 老年人，那些步态变异性增加的人表现出更差的持续运动能力 随着时间推移的认知任务(即持续的注意力)。我的工作还将步态可变性与功能性 这两个大规模大脑网络之间的连接被认为不利于持续的注意力--即， 背部注意网络(DAN)和默认网络(DN)--在多个老年人队列中。基座 基于这些发现，我们设计了一种新颖的多通道经颅直流电刺激(Tdcs)。 干预可同时促进DAN的兴奋性，抑制糖尿病肾病的兴奋性。我们的 初步数据表明，与假手术相比，单次暴露于这种tdcs可降低步态变异性。 在刺激后进行测试时。我的主要假设是，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可变性。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遗症来检验这一假说。 功能连通性(目标1)，以及确定多时段tdcs干预对步态的影响 可变性和相关结果(目标2)。我们将招募30名没有重大疾病的老年人 比典型的步态变异性更高。参与者将首先完成基线评估和两次功能磁共振检查。 然后，相同的参与者将被随机分配到tDCS干预组(每天10次，每次20分钟)或 ShamàtDCS干预臂(第一周每天五次，20分钟的Sham治疗，然后是五次，一次- 第二周，每天20分钟的tdcs课程)。步态可变性的主要结果将每天使用 在整个研究期间都经过验证的智能手机应用程序。我们希望证明tdcs可以调节 老年人的功能连通性和减少步态变异性。这个项目的结果预计将 告知设计更大规模、更明确的tdcs试验，旨在优化相关的大脑连接。 老年人的步态可变性。这项研究，结合高级神经成像和 神经调节、认知神经科学在衰老中的作用，以及对脆弱老年人的临床研究 成年人，将极大地促进我努力过渡到一名独立的临床医生科学家。

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.