EXERCISE AND PARKINSON'S: COMPARING INTERVENTIONS AND EXPLORING NEURAL MECHANISMS

描述（由申请人提供）：帕金森病（PD）的特征是严重残疾和生活质量下降，这两者在很大程度上可归因于行走困难。有证据表明，运动可能是传统治疗的重要辅助手段，特别是在运动功能方面。特别是，舞蹈和跑步机训练分别被证明可以改善步行表现和生活质量。目前还不清楚舞蹈和跑步机训练是否有相似的效果，或者孰优孰弱。此外，我们对这些运动干预带来益处的机制的理解非常有限。本研究旨在通过直接比较舞蹈、跑步机训练和拉伸（对照组）来解决这些知识差距。主要研究领域是对步态的影响，其次是疾病严重程度、平衡和生活质量。我们不仅将确定干预对运动表现的影响，还将研究干预对休息和想象行走任务时大脑连通性和大脑功能的影响。参与者将被随机分配到舞蹈、跑步机训练或拉伸/柔韧性对照组。参与者将在6个月的时间里，在3个不同的时间点接受评估。我们假设舞蹈和跑步机训练都能提高向前行走的能力，但与跑步机训练相比，舞蹈对向后行走的改善更大。此外，我们假设探戈和跑步机干预会对大脑功能和连通性产生不同的影响。我们期望舞蹈能增强前运动区和辅助运动区的活动性和连通性。我们期望跑步机训练能增强初级体感皮层和小脑的活动和连通性。我们不期望控制组的大脑活动或连通性发生变化。相关性帕金森病影响了100 - 150万美国人，导致大量残疾，生活质量下降，每年花费超过340亿美元的医疗费用。行走困难是导致残疾的一个主要因素，而行走速度是死亡率的一个强有力的预测指标。运动疗法有望改善步行和生活质量。特别是，据报道，舞蹈和跑步机训练可以改善步行，但这些方法的正面比较尚未进行，这些干预措施的神经生理影响仍然未知。本研究将直接比较舞蹈、跑步机训练和拉伸（对照组）的效果，并利用神经成像技术探索这些干预对脑功能和连通性的神经生理学影响。获得的结果将帮助我们更好地了解运动是否以及如何影响PD的功能以及涉及哪些大脑区域。所获得的知识有可能改变我们治疗PD患者步态困难的方法，因为它有助于开发新的或改进的运动干预措施和/或确定深部脑刺激的新手术靶点。

DESCRIPTION (provided by applicant): Parkinson disease (PD) is characterized by substantial disability and reduced quality of life, both of which can be attributed in large part t difficulties with walking. Evidence suggests that exercise may be an important adjunct to traditional treatments, particularly with respect to locomotor function. In particular, dance and treadmill training have been individually shown to improve walking performance and quality of life. At present it is not clear whether dance or treadmill training have similar effects or if oneis superior to the other. Moreover, our understanding of the mechanisms by which these exercise interventions convey benefits is extremely limited. This study aims to address these knowledge gaps by directly comparing dance, treadmill training and stretching (control group). The primary area of interest is the effects on gait, with secondary measures of disease severity, balance, and quality of life. We will determine not only the effects of the interventions on locomotor performance, but will also investigate the effects of the interventions on brain connectivity and brain function at rest and during imagined walking tasks. Participants will be randomly assigned to dance, treadmill training, or a stretching/flexibility control group. Participants will be assesed over a period of 6 months at 3 different time points. We hypothesize that both dance and treadmill training will lead to improvements in forward walking, but that dance will result in greater improvements in backward walking compared to treadmill training. Furthermore, we hypothesize that the tango and treadmill interventions will have different effects of brain functio and connectivity. We expect dance to enhance the activity and connectivity of the premotor and supplementary motor areas. We expect treadmill training to enhance activity and connectivity of the primary somatosensory cortex and the cerebellum. We do not expect changes in brain activity or connectivity in the control group. Relevance PD affects 1-1.5 million Americans, leading to substantial disability, reduced quality of life, and an annual expenditure of more than $34 billion in health care costs. Difficulties with walking are a major contributor to disability ad walking speed is a strong predictor of mortality. Exercise therapies hold promise for improving walking as well as quality of life. In particular, dance and treadmill training have been reported o improve walking, but head to head comparisons of these methods have not been made and the neurophysiologic effects of these interventions remain unknown. This study will directly compare the effects of dance, treadmill training and stretching (control group) and will utilize neuroimaging techniques to explore the neurophysiologic effects of these interventions on brain function and connectivity. The results obtained will help us to better understand whether and how exercise influences function in PD and which brain regions are involved. The knowledge gained has the potential to alter our approach to the treatment of gait difficulties in PD, as it my assist in the development of new or improved exercise interventions and/or identification of new surgical targets for deep brain stimulation.