Effect of dopaminergic medications on the time course of explicit motor sequence learning in Parkinson's disease

J Neurophysiol. 2010 Feb;103(2):942-9. doi: 10.1152/jn.00197.2009. Epub 2009 Dec 16.


The capacity to learn new motor sequences is fundamental to adaptive motor behavior. The early phase of motor sequence learning relies on the ventral and anterior striatal circuitry, whereas the late phase relies on the dorsal and posterior striatal circuitry. Early Parkinson's disease (PD) is mainly characterized by dopaminergic denervation of the dorsal and posterior striatum while sparing anterior and ventral regions. Dopaminergic medication improves dorsal and posterior striatum function by compensating for the loss of dopamine. However, previous work has shown that dopaminergic medication interferes with the ventral and anterior striatum function by overdosing this relatively intact structure in early-state PD. Here we test whether these effects are also observed over the time course of motor sequence learning. Fourteen PD patients ON and OFF dopaminergic medications and 11 healthy age-matched control participants performed an explicit motor sequence learning task. When sequence learning was compared across different learning phases in patients ON and OFF medication, a significant impairment associated with medication was observed in the early relative to later phases of learning. The rate of learning in the early phase measured trial by trial in patients ON medication was significantly slower than that in controls and when patients were OFF medication. No significant impairment was found in the later learning phases. These results demonstrate that dopaminergic medications may selectively impair early-phase motor sequence learning. These results extend and generalize the dopamine overdose effects previously reported for (antero)ventral striatum-mediated cognitive tasks to motor sequence learning.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / administration & dosage
  • Dopamine Agents / administration & dosage*
  • Female
  • Humans
  • Learning / drug effects*
  • Male
  • Middle Aged
  • Motor Skills / drug effects*
  • Movement Disorders / drug therapy*
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology*
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology*
  • Task Performance and Analysis


  • Antiparkinson Agents
  • Dopamine Agents