The proposed project aims to use functional magnetic resonance imaging (fMRI) to examine the relationship between memory deficits in Parkinson's disease (PD) and underlying changes in frontostriatal functioning. Increasing our understanding of how the frontostriatal system is functionally disrupted in PD is crucial for increasing our knowledge about the cognitive and neurological deficits associated with PD, and also for generating targeted neuropharmacological and behavioral strategies for alleviating the debilitating effects of the disease. Frontostriatal pathways are known to be affected in PD. These pathways are critical components of neural circuits supporting working memory and explicit and implicit long-term memory, all of which are impaired in PD. In this proposal, fMRI provides direct measurements of physiological dysfunction within particular frontostriatal pathways during performance of different memory tasks. In a series of 4 experiments, fMRI is used to assess the functional integrity of frontostriatal circuitry in PD patients and control subjects during 1. Explicit and implicit sequence learning; 2. Spatial and non-spatial working memory; 3. Performance of a long-term retrieval task, and 4. Performance of verbal and picture encoding tasks. This battery of short and long-term, and implicit and explicit memory tasks is used to define differences in the functional dynamics of frontostriatal circuits in PD. Our central hypothesis is that the memory deficits found in PD reflect altered processing within frontostriatal circuits. A secondary hypothesis is that additional memory systems, including the medial temporal-prefrontal network, are relatively spared by the disease. The fMRI data combined with the memory performance findings with PD patients is expected to provide information about PD that directly links dysfunction of particular frontostriatal pathways with specific impairments on working memory and explicit and implicit long-term memory tasks. The proposed studies are significant, as the findings will contribute to our understanding of the functional neuroanatomy underlying different types of memory disturbances in PD. By further characterizing and defining brain areas underlying memory disturbances in PD, the studies will add to our knowledge of how PD disrupts cognitive function during.
