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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/8931011
• 关键词: Acute; Address; Aerobic Exercise; Affect; Alleles; Attenuated; Behavioral; Biological Markers; Brain; Brain-Derived Neurotrophic Factor; Code; Cognitive; Development; Exercise; Genes; Genetic Polymorphism; Goals; Health; Human; Individual; Intervention; Knowledge; Learning; Literature; Mediating; Motor; Movement; Neuronal Plasticity; Persons; Process; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Serum; Single Nucleotide Polymorphism; Stroke; Survivors; United States; Up-Regulation; Upper Extremity; Walking; Work; brain behavior; chronic stroke; design; disability; genetic information; improved; innovation; learned behavior; meetings; motor learning; novel; post stroke; programs; stroke recovery; stroke rehabilitation

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提高中风后功能流动性的恢复，以减少势后残疾。中风后，个人必须学习或重新学习因对大脑损害而受到破坏的运动。神经可塑性是大脑学习行为和神经可塑性的机制，并可能在中风后进行学习。然而，文献几乎没有提供有关重新学习运动过程或促进或阻碍这种学习后的机制的信息。尤其是，尽管恢复步行的过程通常是中风幸存者的主要目标，但对恢复行走的过程鲜为人知。缺乏对导致学习减慢的因素或可以促进学习的因素的理解，阻碍了我们设计最佳康复干预措施的能力。我们建议，在理解脑衍生的神经营养因子（BDNF）在神经可塑性和运动学习中的作用方面的最新发展可能会大写以解决这一差距。长期以来，BDNF一直是皮质可塑性和运动学习的中介因素，使其成为中风后运动学习的基础的脑行为关系的逻辑目标。神经系统完整 在BDNF基因代码（VAL66MET）中具有共同单核苷酸多态性的人类，影响活动依赖性BDNF分泌，表现出运动学习的不足，并且中风的人和多态性的人从中风中恢复较差。该提案的目标1将决定BDNF Val66met多态性对中风后学习新的步行任务的影响，因此，将确定一种潜在的生物标志物，可用于触觉后康复。相比之下，由高强度有氧运动的单一回合促进了活性依赖性成熟形式的释放，从而增强了神经学完整的人类认知和运动学习。该提案的目标2将确定一次，简短的练习对中风后学习新颖的步行任务的影响。由于假设高强度锻炼以通过BDNF介导的机制改善运动学习，因此运动的任何效果都可能会在多态性的受试者中减弱。因此，我们将研究BDNF Val66met多态性对此目标的结果的影响。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，这些信息可用于开发创新的康复干预措施，从而促进神经可塑性，从而改善中风后的恢复。