Does dopaminergic neuromodulation enhance procedural motor learning an activities of daily living in healthy elderly subjects and in patients with chronic motor deficits after stroke? Which mechanisms underlie the enhancement?

适应性行为需要程序性运动学习，即运动技能的习得。程序性学习在中风后慢性运动障碍的康复中尤为重要。内源性多巴胺能系统是运动功能和学习的有效调节剂。我自己的工作可以证明，基本运动记忆的形成，是获得更复杂运动技能的第一步，可以通过左旋多巴在健康受试者和中风患者中预先用药来增强。本建议的目的是：(a)将这些令人兴奋的发现扩展到程序性运动学习和日常生活活动；(b)阐明潜在的机制。研究左旋多巴对老年健康受试者和脑卒中患者程序性运动学习和日常生活活动的影响。这种影响的潜在机制将通过探索左旋多巴增强学习的NMDA受体依赖性来描述。如果我能证明左旋多巴对运动学习的影响，我计划使用功能性磁共振成像来评估学习和多巴胺能神经调节相互作用导致的各自神经网络激活和连通性的变化。

Adaptive behavior requires procedural motor learning, i.e. the acquisition of motor skills. Procedural learning is particularly critical in the rehabilitation of chronic motor deficits after stroke. A potent modulator of motor function and learning is found in the endogenous dopaminergic system. My own work could demonstrate that formation of an elementary motor memory, which constitutes the first step in acquiring more complex motor skills, can be enhanced by pre-medication with levodopa in both healthy subjects and in stroke patients. The aim of the present proposal is to: (a) expand these exciting findings to procedural motor learning and activities of daily living; and to (b) illuminate the underlying mechanisms. The effect of levodopa on procedural motor learning and activities of daily living will be studied in healthy elderly subjects and stroke patients. The underlying mechanisms of this effect will be delineated by exploring NMDA receptor-dependency of levodopa-enhanced learning. If I can demonstrate the levodopa effect on motor learning, I plan to use functional magnetic resonance imaging to assess changes in activation and connectivity in the respective neural networks resulting from the interaction of learning and dopaminergic neuromodulation.