Effects of levodopa on motor sequence learning in Parkinson's disease

Background: Dopaminergic therapy with levodopa improves motor function in PD patients, but the effects of levodopa on cognition in PD remain uncertain. Objective: To use (H2O)-O-15 and PET to assess the effect of levodopa infusion on motor sequence learning in PD. Methods: Seven right-handed PD patients were scanned "on" and "off" levodopa while performing a sequence learning task. The changes in learning performance and regional brain activation that occurred during this intervention were assessed. Results: During PET imaging, levodopa infusion reduced learning performance as measured by subject report ( p < 0.05). This behavioral change was accompanied by enhanced activation during treatment in the right premotor cortex and a decline in the ipsilateral occipital association area ( p < 0.01). Levodopa-induced changes in learning-related activation responses in the occipital association cortex correlated with changes in learning indexes ( p < 0.01). Conclusions: Levodopa treatment appears to have subtle detrimental effects on cognitive function in nondemented PD patients. These effects may be mediated through an impairment in brain activation in occipital association cortex.