Feedback Learning and L-Dopa in Parkinson's Disease

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DESCRIPTION (provided by applicant): Many previous studies have shown that patients with Parkinson's disease (PD) suffer from a variety of cognitive deficits. Although early studies of these deficits focused primarily on executive or working memory tasks sensitive to frontal lobe impairment, more recent studies have demonstrated that patients with PD are also impaired on procedural learning tasks acquired incrementally through error-correcting feedback. However, procedural learning in PD patients is strongly influenced by L-Dopa, a dopamine precursor that alleviates motor symptoms by increasing global levels of dopamine. Preliminary data from our lab and others indicate that L-dopa may contribute to some learning deficits in early-stage PD, such that patient performance actually improves when patients are tested off their normal medication. This contrasts markedly with other data showing that L-dopa remediates PD performance on "frontal" tasks. The current proposal focuses on the specific aim of understanding how L-Dopa medication interacts with feedback processing during associative learning by Parkinson's patients. In particular, we will test two specific hypotheses relevant to this aim: Specific Hypothesis #1: Parkinson's patients are more impaired at associative learning through feedback training when on L-Dopa medication than when off-medication. Specific Hypothesis #2: Parkinson's patients, both on and off medication, can learn these same associative tasks normally when trained in an observational rather than feedback format; this is consistent with our prior functional imaging studies in healthy normal subjects which indicate that observational training activates more medial temporal lobe structures, rather than striatal regions, as compared to feedback training. The standard current practice for treating PD is with dopaminergic precursors and agonists, where the efficacy of these drugs is evaluated by assessing relief of motor symptoms. However, a better understanding of how PD and dopaminergic drugs affect cognition may allow treatment to take cognitive symptoms into account when assessing drug efficacy. Thus, the proposed work can provide a framework for future development of treatment programs that address both motor and cognitive functioning. In addition, our proposed studies will lead to behavioral markers that could be useful for assessing individual patients' cognitive symptoms. This will allow doctors to identify optimal dosing and medication combinations for each individual patient that lead to enhanced motor and cognitive functioning.