This revised Mentored Research Scientist Development (K01) application is a request for funding to support the training and research necessary for Natalie Denburg, Ph.D. to become an independent investigator in aging, cognition, and structural imaging. The applicant is seeking additional training and education in neuroimaging, in particular, and the University of Iowa is a superb place to carry out such training. Dr. Denburg's long-term research objective is to have an independent program of research aimed at the study of aging cognition from the perspectives of both psychological processes and neural substrates. The study aims at investigating the hypothesis that some seemingly normal older persons (i.e., without overt neurological or psychiatric disease) have deficits in reasoning and decision-making, due to dysfunction in a neural system which includes the ventromedial prefrontal cortices (VMPC). This hypothesis addresses the question of why so many older adults fall prey to fraud, and is relevant to the comprehensive study of aging. Pilot data from the laboratory where the PI has been trained have suggested that a sizeable number of normal older adults are impaired on a laboratory task (the Gambling Task; GT) sensitive to reasoning and decision-making defects in patients with acquired damage to the VMPC. To test this hypothesis, 120 adults aged 26-85, all free of neurological and psychiatric disease, will be studied. Three specific objectives will be pursued aimed at behavioral, psychophysiological, and neuroanatomical levels: (1) A significant proportion of older adults will be impaired on the GT. Evaluation of the participants' medical histories (e.g., evidence of cardiovascular disease), neuropsychological profiles (e.g., executive dysfunction), and real-world decisionmaking abilities (e.g., miscomprehension of deceptive advertising claims), will allow for an examination of the extent to which these factors can account for, or correlate with, the GT defect. Older adults with decisionmaking defects on the GT will manifest (2) defective psychophysiological responses, particularly in anticipation of dsky decisions, and (3) disproportionate structural changes in VMPC. Alternative hypothesized neural substrates for decision-making (e.g., medial temporal lobe) will also be examined. The findings may inform intervention, in addition to influencing legal and social policy regarding advertising.
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