Behavioral and neurophysiologic processes of locomotor learning after stroke

描述(申请人提供)：在美国，中风是导致残疾的主要原因。我们研究的长期目标是促进卒中后功能活动的恢复，以减少卒中后的残疾。中风后，人们必须学习或重新学习由于大脑损伤而中断的动作。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，文献很少提供关于中风后重新学习运动的过程或促进或阻碍这种学习的机制的信息。特别是，S对中风后重新学习行走的过程知之甚少，尽管恢复行走往往是中风幸存者的首要目标。缺乏对导致学习减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。我们认为，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能会被用来弥补这一差距。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，使其成为研究中风后运动学习所依据的大脑-行为关系的合理靶子。神经学上完好 具有常见的BDNF基因密码(Val66Met)单核苷酸多态影响活动依赖型BDNF分泌的人，表现出运动学习障碍和中风患者，该多态表现出较差的中风初期康复。这项建议的目的1将确定BDNF Val66Met基因多态对中风后学习新的步行任务的影响，并因此将确定一个潜在的生物标记物，可用于中风后康复的个体化。相比之下，在一次高强度有氧运动的推动下，依赖活动的成熟形式脑源性神经营养因子的释放增加，增强了神经学完好的人类的认知和运动学习。这项建议的目标2将确定一次短时间的高强度运动对中风后学习新的步行任务的影响。由于高强度运动的假设是通过脑源性神经营养因子介导的机制来改善运动学习，因此运动的任何效果在具有这种多态的受试者中都有可能减弱。因此，我们将研究BDNF Val66Met多态对这一目标结果的影响。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，以改善中风后的康复。

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.