Dopamine overdose and motor sequence learning

17 The capacity to learn new motor sequences is fundamental to adaptive motor behavior. 18 The early phase of motor sequence learning relies on the ventral and anterior striatal 19 circuitry whereas the late phase relies on the dorsal and posterior striatal circuitry 20 (Lehericy et al., 2005). Early Parkinson’s disease (PD) is mainly characterized by 21 dopaminergic denervation of the dorsal and posterior striatum while sparing anterior and 22 ventral regions. Dopaminergic medication improves dorsal and posterior striatum 23 function by compensating for the loss of dopamine. However, previous work has shown 24 that dopaminergic medication interferes with the ventral and anterior striatum function, 25 by overdosing this relatively intact structure in early state PD (Cools, 2006). Here we 26 test whether these effects are also observed over the time course of motor sequence 27 learning. Fourteen PD patients ON and OFF dopaminergic medications and eleven 28 healthy age matched control participants performed an explicit motor sequence learning 29 task. When sequence learning was compared across different learning phases in 30 patients ON and OFF medication, a significant impairment associated with medication 31 was observed in the early relative to later phases of learning. The rate of learning in the 32 early phase measured trial by trial in patients ON was significantly slower than controls 33 and when patients were OFF. No significant impairment was found in the later learning 34 phases. These results demonstrate that dopaminergic medications may selectively 35 impair early phase motor sequence learning. These results extend and generalize the 36 dopamine overdose effects previously reported for (antero)ventral striatum-mediated 37 cognitive tasks to motor sequence learning. 38