From Gene to Brain and Behavior: Dopaminergic Effects on Motor Sequence Learning in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder affecting the dopamine neurotransmitter system which is crucial for motor control and cognitive function. Dopaminergic medications alleviate Parkisonian motor symptoms however evidence shows that they also interfere with normal functioning in other domains. The current dissertation aimed to determine the effect of dopaminergic medication on motor sequence learning which underlies daily motor adaptability. In order to gain a thorough understanding of the nature of medication effects on sequence learning behavior, I performed four separate studies using behavioral, pharmacological, functional brain imaging and genetics approaches. The first study determined the behavioral effects of medication over the time course of motor sequence learning. I report a selective medication-associated learning impairment in the early acquisition phase of sequence learning. The second study addressed the neural underpinnings of L-DOPA medication effects during motor sequence learning. The results showed an L-DOPA associated decrease in ventral putamen activation which correlated with the degree of L-DOPA associated motor sequence learning impairment at the early phase. The last two studies aimed to identify how factors contributing to the endogenous level of dopamine transmission interact with L-DOPA associated sequence learning changes. In the third study, the level of nigrostriatal dopaminergic denervation (assessed with C-DTBZ PET) was used as an