Brain Networks of Turning Performance with Aging and Stroke

这个CDA-1提案的目的是启动我在移动功能领域的独立研究生涯 和神经损伤退伍军人的康复。具体地说，我感兴趣的是神经控制， 老年人和中风患者行走时的转身功能经常受损。利用我的 之前的培训和经验，评估和分析转弯性能，我建议扩大我的 通过增加临床试验、神经影像学和神经调节方面的培训来提高技能。我召集了一个 这些特定领域的专家团队在马尔科姆兰德尔退伍军人医疗中心担任教职 和佛罗里达大学。该CDA-1提案得到了大卫克拉克博士（主要） 导师）正在进行的Merit Review研究，旨在确定前额经颅直流电的影响 刺激（tDCS）在增强复杂的运动学习的老年人与移动障碍。最近 克拉克及其同事的研究表明，前额叶皮层网络在控制大脑活动中起着关键作用。 复杂的行走任务和新的运动技能的获得和巩固（如 神经成像和神经调节研究）。这些发现为母体Merit提供了科学依据 回顾研究并支持创新使用tDCS作为辅助手段，以加强复杂步行训练 任务克拉克博士的新的复杂运动学习协议训练研究参与者练习复杂的步行 诸如在障碍物上行走、在柔性（软）地形上行走以及转弯等任务。在评估各种 功能步态测量，母Merit Review研究不包括转身作为结局测量。 本CDA-1中提出的转向评估将是本研究的新补充。值得注意的是，转弯是一个复杂的 运动需要神经控制、运动规划、动态平衡和协调。的那一刻起 我们醒来，当我们入睡时，我们几乎一半的步伐包含某种程度的转弯，这可能导致 如果表现不佳，会造成严重的伤害。例如，在转弯时摔倒导致臀部受伤的可能性是其他人的八倍。 骨折与笔直向前走时摔倒相比。此外，老年人360度旋转持续时间延长 与跌倒风险增加、丧失独立性和步行速度降低密切相关。但我们的 对转向功能下降的具体特征和机制的理解仍然很差 了解，并且恢复转向功能的潜力是不确定的。拟议的综合发展区-1将研究 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，本提案的目的是阐明tDCS和复杂运动学习是否可以 提高转弯性能，并进一步确定转弯性能增益与 认知功能、神经解剖结构和功能的基线测量（用磁共振成像测量） 磁共振成像（MRI）和[神经生理功能（经颅磁刺激测量; TMS）]。具体目标1将检验360 °和360 °转弯相关性能增益和保持率的假设， 与假tDCS组相比，活性tDCS组的180次旋转将更大。为了验证这一点，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 无线惯性传感器具体目标2将测试的假设，更大的转弯改善360度 和180次旋转测试将与更大的基线工作记忆（2a），更大的基线灰质 体积（2b）和更大的基线功能网络连接（2c）。[具体目标3将检验假设 具有更大基线皮层抑制（通过TMS测量）的参与者将表现出更大的360度范围， 180度转弯性能提升。]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，这将提供初步数据，为未来的CDA-2赠款提交，提出了一个 更大规模的临床试验，为行动不便的退伍军人进行康复治疗。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，并提高退伍军人的生活质量。

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.