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

描述(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都可以归因于行走困难。有证据表明，锻炼可能是传统疗法的重要补充，特别是在运动功能方面。特别是，舞蹈和跑步机训练被单独证明可以改善步行能力和生活质量。目前还不清楚舞蹈或跑步机训练是否有类似的效果，或者其中一种是否优于另一种。此外，我们对这些运动干预带来益处的机制的了解极其有限。这项研究旨在通过直接比较舞蹈、跑步机训练和伸展运动(对照组)来解决这些知识差距。主要感兴趣的领域是对步态的影响，其次是疾病严重性、平衡性和生活质量。我们不仅将确定干预措施对运动能力的影响，还将调查干预措施对休息和想象步行任务中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、跑步机训练或伸展/柔韧控制组。参与者将在3个不同的时间点接受为期6个月的评估。我们假设舞蹈和跑步机训练都会导致前向行走的改善，但与跑步机训练相比，跳舞会导致后退行走的更大改善。此外，我们假设探戈和跑步机干预将对大脑功能和连接性产生不同的影响。我们希望舞蹈能增强运动前区域和辅助运动区域的活性和连通性。我们期望跑步机训练能增强初级躯体感觉皮质和小脑的活性和连通性。我们预计对照组的大脑活动或连接性不会发生变化。相关性帕金森病影响100-150万美国人，导致严重残疾，生活质量下降，每年医疗费用支出超过340亿美元。行走困难是导致残疾的主要原因，而行走速度是死亡率的有力预测因素。运动疗法有望改善步行和生活质量。特别是，舞蹈和跑步机训练被报道可以改善步行，但还没有对这些方法进行头对头的比较，这些干预措施的神经生理学效应仍然未知。这项研究将直接比较舞蹈、跑步机训练和拉伸(对照组)的效果，并将利用神经成像技术来探索这些干预措施对大脑功能和连接性的神经生理学影响。所获得的结果将有助于我们更好地了解运动是否以及如何影响帕金森病的功能，以及哪些脑区参与其中。所获得的知识有可能改变我们治疗帕金森病步态困难的方法，因为它有助于开发新的或改进的运动干预措施和/或确定新的脑深部刺激手术靶点。 公共卫生相关性：帕金森病(PD)影响100-150万美国人，导致严重残疾、生活质量下降，每年的医疗费用支出超过340亿美元。行走问题是导致帕金森病患者残疾的主要原因，开发治疗步态障碍的方法对于降低死亡率、提高生活质量和降低护理成本至关重要。运动是一种很有前途的辅助疗法，可以在步行和其他方面的功能方面提供重要的好处，但关于哪种形式的运动是最好的，缺乏知识。此外，我们对运动的潜在神经生理学机制及其对运动控制的影响的了解非常有限。这项研究将直接比较探戈舞和跑步机训练这两种运动项目，并与参加伸展运动的对照组进行比较，以确定它们对帕金森氏症患者步态和功能的影响。我们将利用脑成像技术来研究参与这些锻炼计划是如何改变大脑功能的。所获得的信息将为开发最佳运动干预措施提供信息，也许还有其他治疗方法，专门针对帕金森病患者的行走问题而设计。

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. PUBLIC HEALTH RELEVANCE: Parkinson disease (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. Problems with walking are a major contributor to disability in PD and the development of treatments to address gait dysfunction is critical to reduce mortality, improve quality of life and reduce costs for care. Exercise is a promising adjunct therapy that may provide important benefits with respect to walking and other aspects of function, but knowledge is lacking regarding which form of exercise is best. Additionally, we have a very limited understanding of the underlying neurophysiologic mechanisms of exercise and its effects on locomotor control. This study will directly compare the two exercise programs, tango dancing and treadmill training, to each other and to a control group that participates in a stretching program to determine their effects on gait and function in people with PD. We will utilize brain imaging techniques to examine how participation in these exercise programs modifies brain function. The information gained will inform the development of optimal exercise interventions, and perhaps other treatment approaches, designed to specifically target walking problems in PD.