The present 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 that includes the ventromedial prefrontal cortices (VMPC). This hypothesis is relevant to the comprehensive study of aging, and addresses, from a neurobiological perspective, the question of why so many older adults fall prey to fraud.
Pilot data have suggested that a sizeable number of healthy older adults (approximately 35-40%) perform disadvantageously on a laboratory task (the Iowa Gambling Task; IGT), which is sensitive to reasoning and decision-making defects in patients with acquired damage to the VMPC. These same older adults display defective psychophysiological responses in anticipation of risky decisions, as well as a tendency to fall prey to deceptive advertising. We propose to test the hypothesis that older adults with decision-making impairments will evidence focal physiological changes in VMPC that will not be apparent in other brain regions (i.e., dorsolateral prefrontal cortices (DLPFC) or medial temporal lobe (MTL)), through the use of complementary functional neuroimaging approaches involving activation BOLD fMRI and resting [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). Alternative hypothesized neural substrates for decision-making (i.e., DLPFC and MTL) will also be examined during fMRI and FDG-PET, to rule out other explanations for the decision-making deficit, such as early (presymptomatic) Alzheimer’s disease.
An age- and sex-stratified sample of 48 healthy older adults, aged 60-90 years, enrolled in the PI’s NIA K01 project, and who have been identified as “Impaired” (n = 24) or “Unimpaired” (n = 24) based on their IGT performance, will participate. The participants’ previously collected structural MRI data will be coregistered with fMRI and FDG-PET data. The fMRI design will be conducted in a 3T scanner, in which participants will complete three cognitive tasks, with manipulations of parametric difficulty embedded in each. Task #1, an n-back task, will be carried out with a block design, and will tax the DLPFC; task #2, a probabilistic reversal learning task, will be carried out with an event-related design, and will tax the VMPC; and Task #3, a face-name association task, will be carried out with a mixed block and event-related design, and will tax the anterior hippocampus of MTL.
Regarding fMRI, several approaches will be undertaken to minimize signal dropout in the VMPC region of interest. In a separate scanning session, the resting FDG-PET protocol will occur and be similar to a standard clinical FDG brain such that classic patterns of hypometabolism can be evaluated (frontal hypometabolism vs. bitemporoparietal hypometabolism). Finally, a blood sample will be drawn from all 48 participants, in conjunction with the FDG-PET session, to identify participants who possess the APOE-e4 allele.