Effect of levodopa on postural motor learning in Parkinson disease

左旋多巴对帕金森病姿势运动学习的影响

• 批准号: 9046400
• 负责人: Daniel Soren Peterson
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9046400
• 关键词: Adult; Affect; Award; Balance training; Brain; Cessation of life; Clinical; Corpus striatum structure; Data; Dopamine; Elderly; Equilibrium; Expert Systems; Fall prevention; Functional Imaging; Functional disorder; Future; Goals; Health; Health Sciences; Hour; Human; Image; Individual; Injury; Intervention; Investigation; Knowledge; Lead; Learning; Levodopa; Life; Link; Measures; Mental Depression; Monitor; Motor Cortex; Motor Skills; Movement; Musculoskeletal Equilibrium; Neuronal Plasticity; Neurotransmitters; Oregon; Parkinson Disease; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Play; Postural response; Process; Psychological Transfer; Quality of life; Rehabilitation therapy; Replacement Therapy; Research; Research Personnel; Role; Sum; Surface; Testing; Training; Transcranial magnetic stimulation; Translations; Universities; Veterans; Withdrawal; Work; base; career; common treatment; equilibration disorder; experience; fall risk; falls; follow-up; frailty; improved; improved functioning; mortality; motor learning; motor rehabilitation; neuroadaptation; neuromechanism; neurophysiology; novel; relating to nervous system; repetitive transcranial magnetic stimulation; skills; tool; training opportunity; treatment strategy; young adult

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.

产品说明： 帕金森病（PD）患者的福尔斯会导致虚弱、抑郁、生活质量下降和死亡。平衡康复是改善姿势反应的有效手段，并可预防福尔斯。然而，可能有办法提高这些干预措施的效益。例如，已知多巴胺在运动学习（运动康复的基础）中发挥重要作用，因为它对纹状体和皮质中的神经可塑性至关重要。那些患有帕金森病的人纹状体中的多巴胺减少，并且，毫不奇怪，运动学习的变化。多巴胺替代疗法（即左旋多巴）是PD患者的常见药物干预，可能会改变PD患者学习和保持运动技能的程度。因此，这两种治疗策略之间可能存在相互作用，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，还没有很好的理解。此外，很少有人知道姿势运动学习和左旋多巴之间的神经联系。皮质兴奋性在PD患者中改变，左旋多巴改善，并与运动学习有关。因此，帕金森病患者大脑皮层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会改变姿势运动学习。了解多巴胺替代疗法如何影响姿势运动学习对于制定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（皮层兴奋性）如何与运动学习的变化相关。这些信息将提供一个更好的了解姿势运动学习的神经基础。此外，它可以为后续研究提供信息，旨在改善康复期间的姿势运动学习。目前有一些工具可以安全地改变人类大脑皮层的兴奋性，包括重复经颅磁刺激（TMS）。因此，如果皮质兴奋性与姿势有关， 在运动学习中，通过调节大脑兴奋性来改善学习是可能的。然而，重要的第一步是了解皮质兴奋性是否与姿势运动学习相关。目前的调查是实现这一目标的重要的第一步。 除了这些研究目标外，拟议的项目将使申请人走上实现其长期职业目标的道路，即成为VA系统内的独立临床研究人员，以及平衡和姿势控制专家。通过这个奖项，申请人将获得各种新技能。首先，他将学习如何评估和改变姿势控制， 使用姿势扰动。其次，他将获得运动学习的知识，因为它涉及到康复和改善功能。第三，他将获得与PD患者合作的额外经验。最后，申请人将获得收集，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，重点是通过训练（包括重复TMS）改善姿势增益的其他方法。这个后续项目可以将TMS与申请人的功能成像经验配对，从而形成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变化。总之，这个项目和其他培训机会，通过俄勒冈州健康与科学大学和波特兰VA将提供必要的工具和技能，成为一个富有成效的和独立的研究人员的申请人。