Effect of levodopa on postural motor learning in Parkinson disease

说明： 帕金森氏症(PD)患者跌倒会导致虚弱、抑郁、生活质量下降和死亡率。平衡康复是改善体位反应的有效手段，可以预防跌倒。然而，可能有一些方法可以提高这些干预的好处。例如，众所周知，多巴胺在运动学习中发挥着重要作用，这是运动康复的基础，因为它对纹状体和皮质的神经可塑性至关重要。帕金森病患者纹状体中的多巴胺减少，运动学习的改变也就不足为奇了。多巴胺替代疗法(即左旋多巴)是帕金森病患者常见的药物干预措施，可能会改变帕金森病患者学习和保留运动技能的程度。因此，这两种治疗策略之间可能存在交互作用，因此左旋多巴可能会改变运动康复的益处。然而，左旋多巴对学习的影响，特别是姿势运动学习，还没有被很好地理解。此外，人们对姿势运动学习和左旋多巴之间的神经联系知之甚少。帕金森病患者的皮质兴奋性发生改变，左旋多巴改善，并与运动学习有关。因此，帕金森病患者皮质兴奋性的改变可能与他们相对较差的姿势运动学习有关。这个项目的主要目标是调查左旋多巴是否改变了姿势运动学习。了解多巴胺替代疗法如何影响姿势运动学习，对于开发最有效的康复干预措施至关重要。第二个目标是确定神经适应(皮质兴奋性)如何与运动学习的变化相关。这些信息将提供对姿势运动学习的神经基础的更好的理解。此外，它还可以为旨在改善康复期间姿势运动学习的后续研究提供信息。目前有一些工具可以安全地改变人类的皮质兴奋性，包括重复的经颅磁刺激(TMS)。因此，如果皮质兴奋性与体位有关 运动学习，有可能通过调节大脑兴奋性来改善学习。然而，重要的第一步是了解大脑皮层兴奋性是否与姿势运动学习有关。目前的调查是朝着这一目标迈出的重要的第一步。除了这些研究目标外，拟议的项目将使申请者走上实现其长期职业目标的道路，即成为退伍军人管理局系统内的独立临床研究人员，以及平衡和姿势控制方面的专家。通过这个奖项，申请者将获得各种新技能。首先，他将学习如何通过以下方式评估和改变姿势控制 姿势扰动的使用。其次，他将获得运动学习的知识，因为它与康复和改善功能有关。第三，他将获得更多与帕金森病患者合作的经验。最后，申请者将获得收集、分析和解释经颅磁刺激(TMS)数据的经验。这些经验将为他提供申请CDA-2所需的技能和试点数据，重点放在通过培训改善姿势获得的其他方法上，包括重复的TMS。这个后续项目可能会将TMS与申请者的功能成像经验配对，从而产生一个强大的工具组合，以适应(通过TMS)和监测(通过成像)与运动学习和康复相关的大脑功能的变化。总之，这个项目以及通过俄勒冈健康与科学大学和波特兰退伍军人管理局提供的其他培训机会将为申请者提供必要的工具和技能，使其成为一名多产的独立研究人员。

DESCRIPTION: Falls among those with Parkinson's disease (PD) lead to frailty, depression, reduced quality of life, and mortality. Balance rehabilitation is an effective means of improving postural responses, and may prevent falls. However, there may be ways to improve the benefits of these interventions. For example, dopamine is known to play an important role in motor learning, the basis of motor rehabilitation, as it is essential for neuroplasticity in the striatum and cortex. Those with PD have reduced dopamine in the striatum, and, not surprisingly, changes in motor learning. Dopamine replacement therapy (i.e. levodopa) is a common pharmacologic intervention for those with PD and may alter the degree to which PD patients learn and retain motor skills. Therefore, there may be an interaction between these two treatment strategies, such that levodopa may alter benefits from motor rehabilitation. However, the effects of levodopa on learning, particularly postural motor learning, are not well understood. Further, littl is known about the neural link between postural motor learning and levodopa. Cortical excitability is altered in people with PD, improved by levodopa, and has been associated with motor learning. Therefore, the altered cortical excitability in people with PD may be related to their relatively poor postural motor learning. The primary goal of this project is to investigate whether postural motor learning is altered by levodopa. Understanding how dopamine replacement therapy affects postural motor learning is critical for developing the most effective rehabilitation interventions. A secondary goal is to determine how neural adaptations (cortical excitability) are related to changes in motor learning. This information will provide a better understanding of the neural underpinnings of postural motor learning. In addition, it may inform follow-up studies aimed at improving postural motor learning during rehabilitation. There are currently tools which can safely alter cortical excitability in humans, including repetitive transcranial magnetic stimulation (TMS). Therefore, if cortical excitability is related to postural motor learning, it may be possible to improve learning through modulation of brain excitability. However, an important first step is to understand whether cortical excitability is associated to postural motor learning. The current investigation is an important first step towards this goal. I addition to these research goals, the proposed project will place the applicant on a path to realize his long-term career goals of becoming an independent clinical researcher within the VA system, and an expert in balance and postural control. Through this award, the applicant will gain a variety of new skills. First, he will learn how to assess and alter postural control through the use of postural perturbations. Second, he will gain knowledge of motor learning as it relates to rehabilitation and improved function. Third, he will obtain additional experience working with individuals with PD. Finally, the applicant will gain experience collecting, analyzing, and interpreting transcranial magnetic stimulation (TMS) data. These experiences will provide him with the skills and pilot data necessary to apply for a CDA-2 focusing on additional ways to improve postural gains through training, including repetitive TMS. This follow-up project may pair TMS with the applicant's experience with functional imaging, resulting in a powerful combination of tools to both adapt (via TMS) and monitor (via imaging) changes in brain function related to motor learning and rehabilitation. In sum, this project and other training opportunities through the Oregon Health & Science University and the Portland VA will provide the applicant with tools and skills necessary to become a productive and independent researcher.