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

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.