Brain Networks of Turning Performance with Aging and Stroke

这项CDA-1提案的目的是开启我在移动功能领域的独立研究生涯 以及有神经损伤的退伍军人的康复。具体地说，我感兴趣的是神经控制 走路时转身，这对老年人和中风患者来说往往是有害的。利用我的 之前的培训和在评估和分析车削性能方面的经验，我建议扩大我的 通过增加临床试验、神经成像和神经调节方面的培训来提高技能。我已经组织了一次辅导 在马尔科姆·兰德尔退伍军人医学中心担任教职的这些特定领域的专家团队 以及佛罗里达大学。这项CDA-1提案得到了David Clark博士基础设施的支持(主要 Mentor)正在进行的旨在确定额前经颅直流电影响的优点回顾研究 刺激(TDC)在增强行动能力障碍老年人复杂运动学习中的作用。近期 Clark和他的同事的研究表明，前额叶皮质网络在控制中起着关键作用 复杂的行走任务以及新的运动技能的获得和巩固(如 神经成像和神经调节研究)。这些发现为父母功勋的形成提供了科学依据 回顾研究并支持创新地使用tdcs作为佐剂来加强复杂步行的训练 任务。克拉克博士的新复杂运动学习方案训练研究参与者练习复杂行走 诸如跨越障碍物、跨越顺从(软)地形和转弯等任务。在评估各种 功能性步态测量，家长功绩回顾研究不包括转身作为结果测量。 在这份CDA-1中提出的转向评估将是这项研究的一个新补充。值得注意的是，转向是一件复杂的事情。 运动需要神经控制、运动规划、动态平衡和协调。从那一刻起 我们醒来，当我们入睡时，我们几乎一半的脚步都会有一定程度的转弯，这可能会导致 如果表现不佳，会造成严重受伤。例如，转身时摔倒导致臀部骨折的可能性是普通人的8倍。 与直线行走时摔倒相比，骨折更容易发生。此外，老年人的360˚旋转持续时间延长 与跌倒风险增加、丧失独立性和行走速度减慢密切相关。然而，我们的 对旋转功能下降的具体特征和机制的了解仍然很差 明白，而且恢复转动功能的潜力是不确定的。拟议的CDA-1将进行研究 TDCS与复杂的步行干预相结合是否可以特别提高转弯性能。 因此，这项建议的目的是阐明tdcs和复杂运动学习是否可以 提高车削性能，并进一步确定车削性能收益与 认知功能、神经解剖结构和功能的基线测量(用磁力测量 磁共振成像；MRI)和[神经生理功能(用经颅磁刺激测量； TMS)]。特定目标1将测试这一假设，即将360˚和 与假TDCS组相比，活动TDCS组的180˚匝数将更大。为了测试这一点，我们将测量 在四个不同的时间点(基线、干预后1天、1周和1个月)使用 无线惯性传感器。《特定目标2》将测试这样一种假设，即360˚上更大的转向改进 180˚转身测试将与-更多的基线工作记忆(2a)，更多的基线灰质 容量(2b)和更高的基准功能网络连接(2c)。[具体目标3将检验这一假设 基线皮层抑制程度较高的参与者(经TM测量)将表现出更大的360˚和 180˚车削性能提升。]这项试点研究将招募40名行动不便的老年人和10名 参与者中风后，这将为未来的CDA-2拨款提交提供初步数据，建议 行动不便退伍军人转身康复的更大规模临床试验。的长期目标 本研究旨在改善退伍军人的转弯性能，降低跌倒风险，提高生活质量。

The objective of this CDA-1 proposal is to launch my independent research career in the area of mobility function and rehabilitation in Veterans with neurological impairments. Specifically, I am interested in the neural control of turning while walking, which is often impaired for older adults and people who have had a stroke. Leveraging my prior training and experience in assessing and analyzing turning performance, I am proposing to expand my skillset by adding training in clinical trials, neuroimaging, and neuromodulation. I have assembled a mentoring team of experts in these particular fields who hold faculty appointments at Malcom Randall VA Medical Center and the University of Florida. This CDA-1 proposal is supported by the infrastructure of Dr. David Clark’s (primary mentor) ongoing Merit Review study that aims to determine the effects of prefrontal transcranial direct current stimulation (tDCS) in augmenting complex locomotor learning in older adults with mobility impairment. Recent research from Clark and colleagues indicates that the prefrontal cortical networks play a critical role in the control of complex walking tasks and the acquisition and consolidation of new motor skills (as suggested by neuroimaging and neuromodulation studies). These findings provide the scientific basis for the parent Merit Review study and supports the innovative use of tDCS as an adjuvant to enhance training for complex walking tasks. Dr. Clark’s novel complex locomotor learning protocol trains study participants to practice complex walking tasks such as walking over obstacles, over compliant (soft) terrain, and turning. While assessing a variety of functional gait measures, the parent Merit Review study does NOT include turning as an outcome measure. Turning assessments proposed in this CDA-1 will be a novel addition to the study. Notably, turning is a complex movement requiring neural control, movement planning, dynamic balance, and coordination. From the moment we wake up, to when we fall asleep, nearly half of our steps incorporate some degree of a turn, which can result in serious injury if performed poorly. For instance, a fall while turning is eight times more likely to result in a hip fracture compared to a fall while walking straight ahead. Additionally, prolonged 360˚ turn duration in older adults is strongly associated with increased fall risk, loss of independence, and reduced walking speed. However, our understanding of the specific characteristics and mechanisms of declines in turning function remain poorly understood, and the potential for restoration of turning function is uncertain. The proposed CDA-1 will study whether tDCS combined with a complex walking intervention can specifically enhance turning performance. Therefore, the objective of this proposal is to elucidate whether tDCS and complex locomotor learning can enhance turning performance and furthermore, identify associations between gains in turning performance and baseline measures of cognitive function, neuroanatomical structure and function (measured with magnetic resonance imaging; MRI), and [neurophysiological function (measured with transcranial magnetic stimulation; TMS)]. Specific Aim 1 will test the hypothesis that turn related performance gains and retention for the 360˚ and 180˚ turns will be greater for the active tDCS group vs. the sham tDCS group. To test this, we will measure turning performance at four distinct timepoints (baseline, 1-day, 1-week, and 1-month post intervention) using wireless inertial sensors. Specific Aim 2 will test the hypothesis that larger turning improvements on the 360˚ and 180˚ turn tests will be associated with – greater baseline working memory (2a), greater baseline gray matter volume (2b), and greater baseline functional network connectivity (2c). [Specific Aim 3 will test the hypothesis that participants with greater baseline cortical inhibition (measured by TMS) will demonstrate larger 360˚ and 180˚ turning performance gains.] This pilot study will enroll 40 mobility compromised older adults and 10 participants post-stroke which will provide preliminary data for a future CDA-2 grant submission, proposing a larger scale clinical trial of turning rehabilitation for mobility compromised Veterans. The long-term objectives of this research are to improve turning performance, mitigate fall risk, and improve the quality of life for Veterans.