Behavioral and neurophysiologic processes of locomotor learning after stroke

中风后运动学习的行为和神经生理过程

基本信息

批准号：
8931011
负责人：
DARCY S. REISMAN
金额：
$ 19.42万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-22 至 2018-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Stroke is the leading cause of disability in the United States. The long-term objective of our research is to advance the recovery of functional mobility following stroke to reduce post-stroke disability. After stroke, individuals must learn or relearn movements that have been disrupted due to damage to the brain. Neuroplasticity is the mechanism by which the brain learns behavior and neuroplasticity and learning can occur after stroke. Yet, the literature provides little information about the process of relearning movements or the mechanisms that facilitate or impede this learning after stroke. In particular, very little s known about the process of relearning to walk following stroke, even though recovery of walking is often the primary goal of stroke survivors. A lack of understanding of the factors that contribute to slowed learning, or that can facilitate improved learning, hamper our ability to design optimal rehabilitation interventions. We propose that recent developments in our understanding of the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity and motor learning may be capitalized on to address this gap. BDNF has long been known to be a mediating factor in cortical plasticity and motor learning, making it a logical target for the stud of the brain-behavior relationships that underlie post-stroke motor learning. Neurologically intact humans with a common single-nucleotide polymorphism in the BDNF gene code (Val66Met) that affects activity-dependent BDNF secretion, show deficits in motor learning and persons with stroke and the polymorphism show poorer initial recovery from stroke. Aim 1 of this proposal will determine the impact of the BDNF Val66Met polymorphism on learning a novel walking task after stroke and as such, will identify a potential biomarker that could be used to individualize post-stroke rehabilitation. In contrast, increases in the release of the activity-dependent mature form of BDNF, facilitated by a single bout of high intensity aerobic exercise enhances cognitive and motor learning in neurologically intact humans. Aim 2 of this proposal will determine the effect of a single, short bout of intense exercise on learning a novel walking task after stroke. Because the high intensity exercise bout is hypothesized to improve motor learning through a BDNF mediated mechanism, it is possible that any effect of the exercise will be attenuated in subjects with the polymorphism. We will therefore examine the effect of the BDNF Val66Met polymorphism on the results in this Aim. The knowledge gained from the studies in this proposal will provide exciting new information that can be used in the development of innovative rehabilitation interventions that promote neuroplasticity to improve recovery after stroke.

描述（由申请人提供）：中风是美国残疾的主要原因。我们研究的长期目标是促进中风后功能活动的恢复，以减少中风后残疾。中风后，个人必须学习或重新学习因大脑损伤而中断的运动。神经可塑性是大脑学习行为的机制，神经可塑性和学习可以在中风后发生。然而，文献几乎没有提供有关中风后重新学习动作的过程或促进或阻碍这种学习的机制的信息。特别是，尽管恢复行走通常是中风幸存者的首要目标，但人们对中风后重新学习行走的过程知之甚少。对导致学习减慢或有助于提高学习的因素缺乏了解，会妨碍我们设计最佳康复干预措施的能力。我们建议，我们对脑源性神经营养因子（BDNF）在神经可塑性和运动学习中的作用的理解的最新进展可以用来弥补这一差距。长期以来，BDNF 一直被认为是皮质可塑性和运动学习的中介因素，这使其成为研究中风后运动学习背后的大脑行为关系的逻辑目标。神经系统完好 BDNF 基因代码 (Val66Met) 中存在影响活动依赖性 BDNF 分泌的常见单核苷酸多态性的人类表现出运动学习缺陷，而中风患者中，该多态性显示出中风的初始恢复较差。该提案的目标 1 将确定 BDNF Val66Met 多态性对中风后学习新步行任务的影响，因此将确定可用于个体化中风后康复的潜在生物标志物。相比之下，单次高强度有氧运动会促进活动依赖性成熟形式的 BDNF 释放的增加，从而增强神经系统完好的人类的认知和运动学习。该提案的目标 2 将确定单次短暂的剧烈运动对中风后学习新步行任务的效果。因为假设高强度运动可以通过 BDNF 介导的机制改善运动学习，所以运动的任何效果在具有多态性的受试者中可能会减弱。因此，我们将检查 BDNF Val66Met 多态性对该目标结果的影响。从本提案中的研究中获得的知识将提供令人兴奋的新信息，可用于开发创新的康复干预措施，促进神经可塑性，以改善中风后的恢复。