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?

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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.