# Abstracts of Funded Grants in response to the National Institute on Aging Neuroeconomics of Aging RFA

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  **Principal        **BENNETT, DAVID A**           
  Investigator:**                                   

  **Title:**         **Degraded Rationality:        
                     Subclinical Neuropathology and 
                     Neuroeconomic Behavior in      
                     Older Adults**                 

  **Institution:**   RUSH UNIVERSITY MEDICAL CENTER 
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**DESCRIPTION** (provided by applicant): The burgeoning field of
neuroeconomics, representing the interface between economics,
psychology, and neuroscience, offers the opportunity to understand the
neural mechanisms underlying a wide variety of human social behaviors.
The proposed study, submitted in response to RFA-AG-06-011
Neuroeconomics of Aging (R21), will incorporate economic behaviors,
including temporal discounting, risk tolerance, trust, and financial
literacy into an ongoing longitudinal epidemiologic clinical-pathologic
study of aging, the Rush Memory and Aging Project. We will test the
hypothesis that Alzheimer\'s disease pathology accounts for individual
differences in economic behaviors in older persons without dementia.
Preliminary data is provided demonstrating that the majority of older
persons without dementia accumulate Alzheimer\'s disease pathology
(neurofibrillary tangles and amyloid) in neural systems that sub serve
economic behaviors. These include regions that support analytic decision
making including the dorsolateral prefrontal cortex, posterior parietal
cortex, and anterior cingulate cortex, and regions that support
affective decision making including nucleus accumbens, orbital frontal
cortex, amygdala, anterior caudate nucleus, and anterior insular cortex.
We introduce the term degraded rationality to refer to the consequences
of pathological changes in the brain on both economic behaviors. The
results have important implications for economic modeling of the
economic decisions of older persons. The proposed study offers the
possibility of identifying the pathologic basis individual differences
in economic behaviors in older persons without clinical dementia. As the
U.S. population ages, a greater understanding of economic decision
making in old age as it applies to savings behavior, inter-generational
transfers, retirement planning, advanced directives, and insurance
decisions are needed. The results of the proposed study could lay the
foundation for a series of studies that address these and other aspects
of economic decision making in older persons without dementia.

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  **Principal        **BRAVER, TODD**                
  Investigator:**                                    

  **Title:**         **NEUROECONOMICS OF AGE RELATED 
                     CHANGES IN COGNITIVE CONTROL**  

  **Institution:**   WASHINGTON UNIVERSITY           
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**DESCRIPTION** (provided by applicant): This proposal explores the
neural and psychological mechanisms that underlie economic
decision-making behavior in older adults. Economic decisions are a
critical component of everyday life, and may have special relevance for
older adults (e.g., saving vs. spending decisions, retirement planning,
health care choices, and medication compliance). Basic research in the
cognitive neuroscience of aging has suggested that older adults show
declines in the ability to control thoughts and actions based on
internal goals, and that this may stem from age-related changes in the
function of the lateral prefrontal cortex and mid-brain dopamine system.
Yet currently, almost nothing is known about whether and how these
cognitive and neural changes associated with advancing age impact
economic-related behaviors. The current proposal provides a highly novel
perspective on this issue, by leveraging and integrating theoretical
developments in three areas: a) the cognitive neuroscience of aging; c)
neural mechanisms of cognitive control; and c) behavioral economics
research. Through the use of novel experimental paradigms and
state-of-the-art neuroimaging methods, the proposed studies will
systematically examine core components of economic decision-making that
may be particularly impacted by age-related changes in cognitive
control, including risk-taking and uncertainty, inter- temporal choice,
exploration, affective framing effects, and individual difference
influences. The findings of these studies promise to provide critical
new data regarding economic choice behavior in older adults, and the
relationship of such behavior to age-related changes in the neural
substrates of cognitive control. This project has high relevance for
public health by providing critical information regarding how older
adults make economic decisions (e.g., saving vs. spending money) in
terms of age-related changes in brain function. An improved
understanding of the brain basis of age-related changes in economic
decision-making will be critical for determining why and how older
adults might be impaired in some decision-related behaviors but not
others, and in developing appropriate corrective interventions to
address such impairments.

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| **Principal    | **GABRIELI, JOHN**              |                   |
| I              |                                 |                   |
| nvestigator:** |                                 |                   |
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| **Title:**     | **Neuroimaging the impact of    |                   |
|                | aging on**                      |                   |
|                |                                 |                   |
|                | **economic decisions**          |                   |
+----------------+---------------------------------+-------------------+
| **             | MASSACHUSETTS INSTITUTE OF      |                   |
| Institution:** | TECHNOLOGY                      |                   |
+----------------+---------------------------------+-------------------+

**DESCRIPTION** (provided by applicant): This proposal aims to examine
how healthy aging influences the psychological and neural bases of
economic choice. Older individuals face important and often complex
decisions about retirement, income distribution, insurance, and other
financial and health-related matters. These decisions invariably have
consequences that extend into the future, and usually involve some risk.
There is clear evidence that healthy aging alters many of the
psychological capacities and neural systems that are likely to be
engaged by such economic decisions. This proposal develops an integrated
approach to age-related changes in the neural mechanisms involved in
both temporal and probabilistic discounting, providing an in-depth and
integrated approach to this important domain. Temporal discounting
refers to the observation that individuals experience diminishing value
from anticipated money or goods as they become more remote in time.
Experiment 1 proposes methodological improvements over prior studies of
temporal discounting that should allow unambiguous fMRI measurement of
neural responses to immediate and delayed alternatives, which may invoke
different - and possibly competing - neural circuits. Because aging is
known to impact functional activation within the frontal-striatal system
and associated control behaviors, this proposal hypothesizes that aging
will affect the functional connectivity of these networks such that
age-related differences in discounting behavior will be correlated with
differential activity in the reward and control networks. Decisions
involving risk require discounting of uncertain consequences relative to
certain ones. Experiment 2 proposes to measure probabilistic discounting
using similar procedures employed for time discounting, and to image the
same participants. By examining both temporal and probabilistic
discounting in the same individuals, we will be able to establish
whether they involve distinct neural systems, and whether age affects
temporal and probabilistic discounting in the same way. The relationship
of individual differences among older adults to choices in economic
domains is unknown. Neuropsychological and behavioral measures of
executive control will be collected for each participant so that the
status of control processes can be related to discounting behavior and
brain function in Experiments 1 and 2. In addition, trait measures of
individual differences in time preferences, impulsivity, and
risk-seeking will be collected in order to determine whether such traits
are correlated with functional activation in executive control or reward
processing circuits. In addition, the relationship of age differences in
discounting to socio-economic and socio-emotional/personality dimensions
will be assessed in order to distinguish the effects of age-associated
neuro-cognitive changes from environmental and personality effects.
Older individuals face important and often complex decisions about
retirement, income distribution, insurance, and other financial matters,
and there is clear evidence that healthy aging alters many of the
psychological capacities and neural systems that are likely to be
engaged by such economic decisions. By examining behavioral and neural
indices of two types of economic discounting (temporal and
probabilistic), this proposal aims to establish whether they involve
distinct neural systems, and whether age affects temporal and
probabilistic discounting in the same way. In addition, this proposal
examines how variability among older adults in executive control
function, socio-economic status, and socio-emotional and personality
dimensions affect discounting behavior and its neural correlates.

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  **Principal        **HUETTEL, SCOTT A**                
  Investigator:**                                        

  **Title:**         **Neural Compensation and Economic  
                     Decision Making in Aging**          

  **Institution:**   DUKE UNIVERSITY                     
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**DESCRIPTION** (provided by applicant): Changes in decision making are
ubiquitous throughout aging. As examples, the decisions of older adults
are more economically conservative and more likely to be compromised by
irrelevant information. Historically, these deficits have been explained
using concepts derived from behavioral research within cognitive
psychology. In this application, we contend that a different,
neuroeconomic approach is necessary, one that augments constructs
derived from behavioral phenomena with those derived from
neuroscientific research. Our approach rests on three hypotheses. First,
we hypothesize that many decision-making differences between middle-aged
and peri-retirement adults are the result of deficits in information
integration: specifically a lack of access to source information, a
difficulty in inhibiting irrelevant information, and an increased
reliance on emotional information. Second, we contend that age-related
deficits are manifest not only in their effects on behavior, but also in
their effects on specific patterns of brain function, as younger and
older adults employ different sets of cognitive competencies to solve
decision problems. Third, we hypothesize that both laboratory and
real-world decision behavior will be better predicted by a combination
of behavioral and brain- based constructs than by either source of
information alone. To test these predictions, we propose an integrated
program of behavioral and functional neuroimaging research. Middle aged
(40-50y) and peri-retirement (60-70y) adults will be initially screened
on a variety of standard cognitive tasks. Two fMRI experiments will use
an economically valid advertising paradigm, in which subjects will view
a series of products accompanied by valenced facts with source
attribution. One experiment will manipulate source credibility, while
the other will manipulate information load. Unlike standard
neuroeconomic paradigms (e.g., decisions between gambles), subjects will
report their judgments about the items at a later time period (e.g.,
mimicking the advertising-purchasing delay). We will create regression
models that include both cognitive measures of behavior and neuroscience
measures of brain function, such as the degree of frontal compensation.
Our critical, albeit exploratory prediction, is that both product
attitudes and real world financial behavior (e.g., the risk level of the
subjects' portfolios) will be best explained by using both behavioral
and neuroscience constructs. The decision making of older adults is
subject to many biases, from a difficulty in accurately integrating
information to the increased reliance on emotional information, and
these biases lead to problems in investment, health-care choice, and
other economic arenas. The proposed experiments will elucidate the
changes in the elderly brain that underlie decision-making biases.
Better understanding of this brain-behavior relation could lead to
interventions or clinical advances that remediate problems with decision
making in the elderly, resulting in benefits to public health.

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  **Principal        **KNUTSON, BRIAN D**               
  Investigator:**                                       

  **Title:**         **Anticipation of Reward and Risk  
                     Across the Lifespan**              

  **Institution:**   STANFORD UNIVERSITY                
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**DESCRIPTION** (provided by applicant): Increased life expectancies
create a need for greater financial decision making on the part of
individuals. Yet little research has examined how financial decision
making changes over the course of the lifespan. We propose to
investigate behavioral and neural responses during anticipation of
financial reward and risk in young, middle-aged, and old samples. We
will also examine the influence of incidental affective cues and
cognitive load on financial risk taking in these groups. The proposed
studies are guided by a neuroeconomic model of how anticipatory affect
can influence financial risk taking. Findings promise to elucidate not
only how the brain anticipates reward and risk, but also how this may
change with age. Since people are living longer than ever before, they
must increasingly make important decisions about their financial future
\-- yet little research has examined financial risk- taking, or how this
behavior changes with age. We propose to use cutting edge brain imaging
technology to examine predictors of financial risk taking in young,
middle-aged, and older adults. The findings promise to illuminate how
individuals make both optimal and suboptimal financial decisions over
the course of the lifespan.

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| **Principal     | **MATHER, MARA**             |                    |
| Investigator:** |                              |                    |
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| **Title:**      | **The Effects of Stress on   |                    |
|                 | Reward Learning**            |                    |
|                 |                              |                    |
|                 | **Among Younger and Older    |                    |
|                 | Adults**                     |                    |
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| *               | UNIVERSITY OF SOUTHERN       |                    |
| *Institution:** | CALIFORNIA                   |                    |
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**DESCRIPTION** (provided by applicant): Stress affects brain systems
involved in risk and reward processing and influences learning and
retention of emotionally arousing information. Yet, despite the fact
that important decisions and stress often go hand in hand, little is
known about the influence of stress on decision processes. This proposal
outlines studies to investigate the effect of acute stress on learning
and performance in investment tasks for younger and older adults. Stress
is likely to have a significant impact on both younger and older adults'
decision processes, but the effects may differ for the two groups.
Previous research indicates that as people age, they are increasingly
likely to prioritize emotion regulation and that this leads to age
differences in attention and memory, with older adults showing a
positivity (or anti-negativity) effect. Because of this increased focus
on affect regulation, older adults are more likely than younger adults
to be disproportionately influenced by reward outcomes (rather than loss
outcomes) in their decisions. Stress should to amplify (Experiment 1) or
diminish (Experiment 2) these age differences, depending on the timing
of the stress. In addition, both age and stress should influence
decision makers' ability to abandon a no-longer successful strategy and
learn a new one (Experiment 3). Understanding the ways in which stress
can influence decision processes differently for older and younger
adults should promote development of ways to avoid decision biases and
errors. Important decisions, such as those regarding personal finances
and health care, often involve substantial stress, especially among
older adults. The studies in this proposal will provide important
information about how stress affects learning and decisions and how
those effects may vary with age.

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| **Principal     | **MAYR, ULRICH E**           |                    |
| Investigator:** |                              |                    |
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| **Title:**      | **Aging and Altruism:        |                    |
|                 | Towards a Neuroeconomic**    |                    |
|                 |                              |                    |
|                 | **Model of Age-Related       |                    |
|                 | Changes in Giving**          |                    |
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| *               | UNIVERSITY OF OREGON         |                    |
| *Institution:** |                              |                    |
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**DESCRIPTION** (provided by applicant): In democracies, individual
decisions about voluntary giving and voting determine the type and
amount of public goods. Understanding the neural processes that
determine these public-good decisions is important for distinguishing
between economic theories, which in turn can inform public policy.
Recent neuroeconomic work has provided initial evidence that charitable
giving may be driven by both \"pure altruism\" from experiencing
increases to the public good regardless of their cause (Harbaugh, Mayr,
& Burghart, under review), and \"warm glow\" from the agency effect of
having chosen to give (Moll et la., 2006). This work has also shown that
both activity in neural reward centers and in prefrontal regions
independently predicts rates of giving to a charity. However, these
results come from experiments with predominantly young adults. In
practice, the level and type of public goods are determined by the
decisions of older adults, who give more and vote more often than the
young do. At the same time, there are known neuro-cognitive changes that
occur with age that might affect economic decisions. Therefore, our
first specific aim is to generalize and extend the existing results on
the neural basis of public-good decisions across a large sample of young
(age 25-35, n=50) and older adults (age 65- 75, n=50). The experimental
protocol will include (a) a condition in which the subjects' payoff and
the funding for a public good change in a mandatory, tax-like manner,
(b) a voluntary-giving condition where people can accept transfers or
not, and (c) a voting condition where majority rule among a group of
participants determines if taxes will be levied on all and transferred
to the charity. By considering both taxation and contributions from
older segments of the society, this design covers the most critical
sources of funding for public good. Our second specific aim is to test
hypotheses about how neural and psychological changes across the life
span translate into age-related changes in public-good decisions. For
example, we predict that age-related decline in the ability to represent
long-term goals in prefrontal cortex reduces the tendency to voluntarily
provide or vote for public goods. However, age-related increases in
warm- glow should exert an opposing positive effect on
charitable-giving, but not on voting for taxation since, which provides
less opportunity for warm glow. In our preliminary work, we also found
that the mere opportunity of free choice triggered reward-center
responses, but also \"neural costs\" in terms of substantial prefrontal
activity. Given that prefrontal activity should be particularly
demanding for old adults, we predict a reduction of the free-choice
benefit in old adults, a result with potentially important consequences
for comparing welfare benefits of taxation and giving across age groups.
In preliminary work on young adults using economic experiments and fMRI
scanning we have shown that it is possible to use neural activation in
reward centers as a measure of the marginal rate of substitution between
payoffs to oneself and to a charity, and that this measure predicts
voluntary giving decisions. We propose to apply similar methods to a
population of older subjects, and to both charitable giving and voting
experiments. The objective is to see if economic models can explain
these behaviors in the age groups that are most likely to give and to
vote, and to see how age related changes in the brain are related to the
observed changes in voting and charitable giving that occur with age.

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| **Principal     | **PHILLIPS, PAUL E. M.**     |                    |
| Investigator:** |                              |                    |
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| **Title:**      | **Dopaminergic modulation of |                    |
|                 | cost/benefit**               |                    |
|                 |                              |                    |
|                 | **decision making during     |                    |
|                 | aging**                      |                    |
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| *               | UNIVERSITY OF WASHINGTON     |                    |
| *Institution:** |                              |                    |
+-----------------+------------------------------+--------------------+

**DESCRIPTION** (provided by applicant): How we weigh up the costs and
benefits of a potential outcome to guide choice is paramount to our
everyday functioning. In making these economic decisions one must
consider costs such as physical effort, the delay before the outcome is
presented, the certainty of the outcome and possible aversive
consequences, as well as social and financial costs. Dopamine plays an
important role in dealing with these costs: antagonism of dopamine is
sufficient to lower the physical effort rats will make, or the amount of
time they will wait to obtain greater rewards. Dopamine is also
implicated in risk-taking. Subsecond activity in dopamine neurons
encodes the outcome value within a range of available rewards, and these
rapid signals can promote decisions to engage in behaviors to obtain
rewards. This fast transmission may provide a threshold signal for the
costs an animal should endure to obtain a reward. Since they encode the
expected reward amplitude, this should drive animals to tolerate a
higher cost for better (expected) outcomes. However, during normal
aging, there are several changes in dopaminergic systems, including a
reduction in the expression of striatal dopamine receptors and in the
biological capacity for striatal dopamine release. This raises a number
of questions: 1) Is the diminished capacity for dopamine release
reflected in the amount of dopamine released during economic decision
making? 2) Do these age-related effects contribute to a change in
economic decision making? To address these questions, adult
(6-month-old) and aged (24-month-old) rats will be studied while they
perform decision making to \"purchase\" food options by lever pressing.
First potential behavioral differences in economic decision making
between age groups will be probed. Quantitative differences in the cost
the rats will forgo to obtain a larger reward offered concurrently with
a smaller but cheaper reward will be tested. In one set of experiments,
the currency of the imposed cost will be physical effort, where animals
will be required to make a higher number of lever presses to receive the
larger reward. In another set of experiments, risk-taking behavior will
be tested by allowing rats to choose between smaller rewards and larger,
but uncertain, rewards. Next, dopamine release will be measured in the
ventral striatum (nucleus accumbens) of adult or aged rats during
economic decision making. Dopamine will be monitored with subsecond
resolution using fast-scan cyclic voltammetry. Using a single-choice
paradigm, the way in which dopamine encodes reward value when reward is
available for effort or probabilistic costs will be tested. Finally, the
capacity of dopamine to modulate economic decision making in adult and
aged rats will be tested by electrically stimulating dopamine neurons at
the time within the task that an endogenous dopamine signal is normally
generated. This evoked dopamine release will boost the endogenous signal
and thus test the capacity of dopamine to overcome effortful or
probabilistic costs. Collectively these experiments will provide unique
insight into age-related changes in economic choice, dopamine
transmission during decision making and their interaction. Cognitive,
emotional and physical capabilities change during aging, in part by
age-related changes in brain motivational systems. How these changes
impact economic choices is unknown. The proposed work will use
behavioral and neurochemical methods to study age-related changes in
economic decision making in rats.

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| **Principal     | **SANFEY, ALAN**             |                    |
| Investigator:** |                              |                    |
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| **Title:**      | **Aging and social           |                    |
|                 | decision-making: a**         |                    |
|                 |                              |                    |
|                 | **Neuroeconomic approach**   |                    |
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| *               | UNIVERSITY OF ARIZONA        |                    |
| *Institution:** |                              |                    |
+-----------------+------------------------------+--------------------+

**DESCRIPTION** (provided by applicant): This project proposes a series
of experiments that will contribute to the burgeoning field of the
neuroeconomics of aging, which attempts understand the component
processes of decision-making across the lifespan by examining both
behavior and the underlying neural substrates. The proposed studies seek
to begin specifying the mechanisms of decisions, in particular the
deliberative and affective components that make up the decision-making
process. Affective influences on decision-making have been largely
ignored for many years, but recent interest in how our emotional states
can affect the type of decisions we make offer an exciting opportunity
to broaden our knowledge of this most important process. Further,
examining the degree to which affective and deliberative processing
differentially influence decision-making across the lifespan can provide
important clues for the assessment of these basic cognitive functions.
Specifically, the proposed experiments will use functional magnetic
resonance imaging (fMRI) to measure brain function of people engaged in
economic decision-making. This proposal builds on previous work by the
author examining the processes underlying human decision-making in a
consequential social interaction with another person. These studies have
found reliable, independent patterns of neural activity corresponding to
affective and deliberative biases, and shown that subsequent decisions
appear to be based on these different motives. In the present proposal,
hypotheses generated in this previous study will be systematically
tested. Experiments using fMRI and variants of Ultimatum and Trust Games
will explore in greater depth the degree to which affective and
deliberative processes influence decisions in both young and older
populations. The field of neuroeconomics is growing rapidly as
researchers from many different and disparate areas seek to understand
the neural basis of human decision-making behavior. It allows the study
of individuals in meaningful social interactions allied to sophisticated
methodological and technological approaches enabling investigation at
various levels, from behavioral responses to the neural activity that
underlie them. This approach offers a valuable method by which to assess
how decision-making operates across the lifespan, and this research can
have immediate impact in terms of better understanding real-life
decisions faced by elderly populations in a variety of important
domains.