WORKING MEMORY IN PARKINSONS DISEASE AND AGING
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Memory impairment is a common problem in Parkinson's disease (PD). The overall aim of this proposal is to apply cognitive neuropsychological theories and functional neuroimaging techniques to the study of a specific component of working memory function in Parkinson's disease (PD) patients. We anticipate that these complementary methods will nurture cross- fertilization of cognitive and neural models of working memory, yielding important insights for this elusive cognitive domain. Moreover, these insights will lead to new ways of diagnosing and treating the memory dysfunction in PD patients. The FIRST AIM is to determine the nature of the working memory deficits in PD. We hypothesize an impairment in a specific component of working memory called the "central executive system" (CES), a system that is critical for allocating limited attentional resources and regulating verbal and spatial passive slave memory buffers. We will test the functioning of the CES in PD patients and age-matched controls using dual- task paradigms which have been designed to directly test this system. An alternative hypothesis, that PD patients have weakened working memory representations rather than a defective CES, will also be tested using the fan-effect paradigm. Individual patient analyses will be used to contrast performance on dual-task paradigms, the fan-effect paradigm and clinical measures of executive functioning. We expect that these more narrowly- defined paradigms will identify the specific nature of the working memory deficits found in PD. The SECOND AIM is to define the neural basis of working memory. Nonhuman primate studies suggest that the dorsolateral prefrontal cortex is critical for working memory. Physiological studies have not examined the CES of working memory in either nonhuman primates or humans. Cognitive activation studies during dual-task paradigms using functional MRI will be performed in normal human subjects to define the neural network subserving the CES of working memory. We hypothesize that the dorsolateral prefrontal cortex will activate during dual-task paradigms. Using fMRI, we will also examine the ability of PD patients with CES deficits to recruit dorsolateral prefrontal cortex during dual-task performance. We hypothesize that these patients will fail to activate the dorsolateral prefrontal cortex when performing these CES tasks, suggesting that this region is functionally defective in this Parkinson's disease.
