(Verbatim from applicant?s abstract) This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) entitled """"""""Imaging Procedural + Working Memory in Parkinson?s Disease."""""""" While the main features of Parkinson?s disease (PD) refer to motor symptoms, cognitive function is also affected, particularly in the realms of working memory and procedural learning. Working memory refers to the maintenance of information """"""""on-line"""""""" and procedural learning refers to experience-induced changes in performance. Performance on procedural learning tasks may improve after an intervening period of sleep, a process called procedural consolidation. Dopamine plays a crucial modulatory role on both working memory and procedural learning networks, and this may be the basis for cognitive dysfunction in PD. The goal of this project is to investigate the role of dopamine in working memory and procedural learning in PD patients using a combination of sensitive behavioral tasks and functional MRI (fMRI). PD patients in a dopaminergic deficient state and a dopaminergic repleted state will be compared to control subjects to ascertain the role of dopamine in working memory and procedural learning. fMRI studies of working memory and procedural learning will demonstrate the effects of dopamine on the neural systems subserving these tasks. Subjects will then be tested behaviorally at three time points over 24 hours to determine the effect of consolidation on task performance. By comparing the changes in performance at the three time points, the role of sleep in consolidation can be isolated. It is hypothesized that the combination of dopaminergic repletion and consolidation can improve cognitive performance on tasks. A second fMRI will then be acquired after 24 hours to determine the changes in the neural systems that correspond to the behavioral changes of procedural consolidation. The results will have implications not only for the basis of cognitive symptoms in Parkinson?s disease, but also for the fundamental mechanisms of procedural learning and consolidation. The training program supplements the candidate?s background in clinical investigation and behavioral neurology with additional training in functional imaging and cognitive neuroscience. The program capitalizes on the rich resources in the Boston area. It provides specific training in fMRI, advanced statistics, and research ethics. The integrated training and research program will allow the candidate to develop the tools to become an independent investigator of the cognitive deficits in Parkinson?s disease.
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