Neural Mechanisms of Age-Related Decision-Making: Direct Evidence from Physiology

Natalie Denburg, Ph.D.

University of Iowa College of Medicine

Funded in June, 2007: $100000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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Is there a Brain Basis for the Tendency by Some Older People to Fall Prey to Fraud?

This study will use fMRI and PET imaging to determine whether age-related physiological changes in a part of the prefrontal cortex are associated with deficits in reasoning and decision-making that make some older people unusually vulnerable to falling prey to fraud.

The researchers hypothesize that some older persons with no apparent neurological or psychiatric disease have a dysfunction in a neural system located in a part of the frontal lobes (“ventromedial prefrontal cortex,” VMPC) that impairs their logical thinking and increases their susceptibility to fraud.  These adults display flawed responses to deceptive advertising and to anticipating risky decisions.  The investigators will compare 24 adults (aged 60-90 years) who demonstrated impaired decision-making on the laboratory-based “Iowa Gambling Task” to 24 same-aged adults with unimpaired performance. Researchers will use BOLD-MRI and PET imaging to assess the VMPC brain area as participants undertake “reversal learning” tasks. They also will image two brain areas involved in dementia as participants undertake working memory and face-name tasks, to rule out the possibility that pre-symptomatic dementia accounts for any findings in the impaired group.

Significance:  If a physiological brain basis for faulty decision-making in adults susceptible to fraud is substantiated, the research opens new avenues for therapeutic research.  Moreover, the study would establish imaging as an important tool for identifying adults with the problem, so that family members and others could protect them.     

ABSTRACT

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Neural Mechanisms of Age-Related Decision-Making: Direct Evidence from Physiology

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. 

INVESTIGATOR BIOGRAPHIES

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Natalie Denburg, Ph.D.

Dr. Natalie Denburg is an Assistant Professor of Neurology and Neuroscience at the University of Iowa Carver College of Medicine.  She received her Ph.D. in Clinical Psychology, with an emphasis in neuropsychology and geropsychology, from Michigan State University in 1997.  Following an internship at the University of California, San Diego, Dr. Denburg completed her post-doctoral fellowship in neuropsychology at the University of Iowa.  She joined the Iowa faculty in 2005.  Research interests include decision-making abilities in older adults, human frontal lobe dysfunction, public policy, the impact of cancer and chemotherapy on cognition in older adults, and the recovery of cognitive function following stroke.  Dr. Denburg’s research is supported by the NIH, the Scottish Rite Masonic Foundation, and the American Cancer Society.