Effect of levodopa on postural motor learning in Parkinson disease

Portland Va Medical Center, Portland OR

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION: Falls among those with Parkinson's disease (PD) lead to frailty, depression, reduced quality of life, and mortality. Balance rehabilitation is an effective means of improving postural responses, and may prevent falls. However, there may be ways to improve the benefits of these interventions. For example, dopamine is known to play an important role in motor learning, the basis of motor rehabilitation, as it is essential for neuroplasticity in the striatum and cortex. Those with PD have reduced dopamine in the striatum, and, not surprisingly, changes in motor learning. Dopamine replacement therapy (i.e. levodopa) is a common pharmacologic intervention for those with PD and may alter the degree to which PD patients learn and retain motor skills. Therefore, there may be an interaction between these two treatment strategies, such that levodopa may alter benefits from motor rehabilitation. However, the effects of levodopa on learning, particularly postural motor learning, are not well understood. Further, littl is known about the neural link between postural motor learning and levodopa. Cortical excitability is altered in people with PD, improved by levodopa, and has been associated with motor learning. Therefore, the altered cortical excitability in people with PD may be related to their relatively poor postural motor learning. The primary goal of this project is to investigate whether postural motor learning is altered by levodopa. Understanding how dopamine replacement therapy affects postural motor learning is critical for developing the most effective rehabilitation interventions. A secondary goal is to determine how neural adaptations (cortical excitability) are related to changes in motor learning. This information will provide a better understanding of the neural underpinnings of postural motor learning. In addition, it may inform follow-up studies aimed at improving postural motor learning during rehabilitation. There are currently tools which can safely alter cortical excitability in humans, including repetitive transcranial magnetic stimulation (TMS). Therefore, if cortical excitability is related to postural motor learning, it may be possible to improve learning through modulation of brain excitability. However, an important first step is to understand whether cortical excitability is associated to postural motor learning. The current investigation is an important first step towards this goal. I addition to these research goals, the proposed project will place the applicant on a path to realize his long-term career goals of becoming an independent clinical researcher within the VA system, and an expert in balance and postural control. Through this award, the applicant will gain a variety of new skills. First, he will learn how to assess and alter postural control through the use of postural perturbations. Second, he will gain knowledge of motor learning as it relates to rehabilitation and improved function. Third, he will obtain additional experience working with individuals with PD. Finally, the applicant will gain experience collecting, analyzing, and interpreting transcranial magnetic stimulation (TMS) data. These experiences will provide him with the skills and pilot data necessary to apply for a CDA-2 focusing on additional ways to improve postural gains through training, including repetitive TMS. This follow-up project may pair TMS with the applicant's experience with functional imaging, resulting in a powerful combination of tools to both adapt (via TMS) and monitor (via imaging) changes in brain function related to motor learning and rehabilitation. In sum, this project and other training opportunities through the Oregon Health & Science University and the Portland VA will provide the applicant with tools and skills necessary to become a productive and independent researcher.