Behavioral and neurophysiologic processes of locomotor learning 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卒中后功能活动的恢复，以减少卒中后残疾。中风后，个人必须学习或重新学习由于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，文献提供的信息很少再学习运动的过程或机制，促进或阻碍这种学习中风后。特别是，很少有人知道中风后重新学习行走的过程，即使恢复行走通常是中风幸存者的主要目标。缺乏对导致学习缓慢或有助于改善学习的因素的了解，阻碍了我们设计最佳康复干预措施的能力。我们建议，最近的发展，我们的理解脑源性神经营养因子（BDNF）在神经可塑性和运动学习的作用，可以利用来解决这个差距。BDNF长期以来被认为是皮质可塑性和运动学习的中介因子，使其成为研究脑-行为关系的逻辑目标，脑-行为关系是中风后运动学习的基础。神经功能完好 在影响活动依赖性BDNF分泌的BDNF基因密码（Val66Met）中具有共同单核苷酸多态性的人显示运动学习缺陷，而中风患者和该多态性显示中风的初始恢复较差。该提案的目的1将确定BDNF Val66Met多态性对中风后学习新的行走任务的影响，因此，将确定可用于个性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促进的活动依赖性BDNF成熟形式的释放增加，增强了神经系统完整的人类的认知和运动学习。本建议的目标2将确定中风后单次短时间剧烈运动对学习新的步行任务的影响。因为高强度运动回合被假设为通过BDNF介导的机制来改善运动学习，所以运动的任何效果都可能在具有多态性的受试者中减弱。因此，我们将研究BDNF Val66Met多态性对本目的结果的影响。从这项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。

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.