Rösser N, Heuschmann P, Wersching H, Breitenstein C, Knecht S, Flöel A. Levodopa improves procedural motor learning in chronic stroke patients. Objective To test the hypothesis that administration of dopamine precursor levodopa improves procedural motor learning (defined as the ability to acquire novel movement patterns gradually through practice) in patients with residual motor deficits in the chronic phase after stroke (≥1y after stroke). Design A double-blind, placebo-controlled, randomized crossover design. Setting Neurology department in a German university. Participants Eighteen patients with chronic motor dysfunction because of stroke (13 men, 5 women; age range, 53–78y; mean time poststroke ± SD, 3.3±2.1y). Intervention Patients received 3 doses of levodopa (100mg of levodopa plus 25mg of carbidopa) or placebo before 1 session of procedural motor learning. Main Outcome Measures Procedural motor learning performed by using the paretic hand assessed by using a modified version of the serial reaction time task with a probabilistic sequence. The primary outcome measure was the difference in reaction times between random and sequential elements. Results Levodopa significantly improved our primary outcome measure, procedural motor learning, compared with placebo (P<.05). Reaction times to random elements, analysis of error rates, psychophysical assessments, and performance in a simple motor task were comparable between conditions, indicating that better learning under levodopa was not caused by differences in response styles, arousal, mood, or motor reaction times but that levodopa modulated learning. Conclusions Our results show that levodopa may improve procedural motor learning in patients with chronic stroke, in line with our hypothesis. These findings suggest that this interventional strategy in combination with customary rehabilitative treatments could significantly improve the outcome of neurorehabilitation in the chronic stage after stroke. (Clinicaltrials.gov identifier NCT00126087.)