l-DOPA changes ventral striatum recruitment during motor sequence learning in Parkinson's disease

We previously reported a differential effect of dopaminergic medication across the time course of motor sequence learning in early stage Parkinson's (PD) patients [1]. There was a medication-associated impairment specific to the early phase of learning. In the current study, we investigated the BOLD responses associated with this deleterious medication effect on motor sequence learning. We hypothesized that levodopa (l-DOPA) would negatively affect the recruitment of the ventral striatal circuitry during the early phase of learning. Seventeen early stage PD patients ON and OFF l-DOPA and 21 healthy control participants performed an explicit motor sequence learning task inside the MRI scanner. We observed sequence learning-specific activation during the early phase in the ventral putamen for controls and PD OFF but not for PD ON l-DOPA. A comparison of activation between PD OFF and PD ON showed that activation within the ventral putamen was decreased in PD ON compared to PD OFF. The extent of the l-DOPA associated activation decrease in the ventral putamen showed a small, positive correlation with the degree of sequence learning performance decrease in the early phase of learning (r=0.45-0.54 across measures, p<0.05, one-tailed). These findings provide evidence for the negative effects of l-DOPA in PD patients on the ventral putamen circuitry involved in early motor sequence learning, and provide support for a role of this structure in the sequence learning process.