Mechanisms of motor learning and brain plasticity post stroke

Reisman, Darcy S.Stroke is the leading cause of long term disability in the United States. The ability to recover motor skill function post-stroke relies largely upon the adaptive capacity of the brain following neurologic insult. The mechanisms which enable neural plasticity post-stroke are similar to those which promote neural reorganization in the healthy brain during learning. As such, parameters of neuro-rehabilitation which optimize motor learning and enhance neural plasticity are of great interest to clinicians and researchers in the field of stroke rehabilitation. The overall goal of this dissertation was to identify key molecular and behavioral requisites of motor learning post-stroke. The split belt treadmill was utilized to investigate within session learning and retention of a novel locomotor pattern in neurologically intact individuals as well as those post stroke. To identify behavioral requisites of post-stroke learning, we examined characteristics of task practice, specifically variable and constant practice that would promote locomotor learning in those with chronic stroke. Although frequently utilized to promote motor relearning in individual's post-stroke, our results revealed that variable practice confers little benefit over constant practice in learning of a novel locomotor pattern in individuals post-stroke. The current study is the first to assess the effects of practice characteristics on learning of a complex lower-extremity task in subjects post-stroke. To identify mechanisms of neural plasticity that may moderate motor learning we examined the impact of a single nucleotide polymorphism on the BDNF gene (Val66Met) in learning of a novel locomotor task in subjects with chronic stroke. The results demonstrate that chronic stroke survivors, regardless of presence or absence of the polymorphism are able to adapt their walking pattern over a period of trial and error practice. The process of locomotor adaptation, however is slowed in those with the Val66Met polymorphism. To examine behavioral parameters of rehabilitation that may promote neuroplastic processes through a BDNF related mechanism, we examined the role of high intensity exercise on locomotor learning in neurologically intact subjects. Specifically, the role of high intensity exercise in upregulation of peripheral BDNF levels as well as the role of high intensity exercise in mediation of motor skill performance and retention of a novel locomotor task was explored. In addition the impact of a single nucleotide polymorphism on the BDNF gene (Val66Met) was examined in neurologically intact adults to assess the relationship between exercise and motor learning. The results of this study demonstrate that although high intensity exercise prior to a motor learning task resulted in increased peripheral BDNF this exercise does not provide additional benefit to learning of a novel locomotor pattern in neurologically intact adults. The current results also demonstrate that presence of a single nucleotide polymorphism on the BDNF gene (Val66Met) does not influence the magnitude of upregulation of serum BDNF with high intensity exercise, nor does it interfere with learning of a novel locomotor pattern.Ph.D.University of Delaware, Biomechanics and Movement Science Progra