Ifat Levy - US grants

DESCRIPTION (provided by applicant): Our attitude towards risk shapes nearly every aspect of our behavior. It affects our willingness to take drugs of abuse, to make efficient financial investments, and to select amongst healthcare options. We know that these attitudes change over the lifespan and that these changes make us vulnerable in different ways as we age. Adolescents engage in risky behaviors that hugely increase their mortality rates. Elders typically show the opposite profile, avoiding risky behaviors to a fault. But what is it about our behavior that changes as we age? What specific behavioral propensities and neurobiological features of aging can account for the changing attitudes we take towards risks? In this application we propose to combine economic, psychological and neurobiological approaches to the study of risky behavior in an effort to paint a portrait of risk attitudes across the lifespan at the behavioral and neural levels. Behavioral economic analyses suggests that risk-taking behavior results from the three largely independent attitudes towards risks: (1) Technical risk-aversion, which reflects a trade- off between the probability of gains or losses and the magnitude of those gains and losses, (2) Ambiguity aversion, which reflects the subject's sensitivity to uncertainty, and (3) Loss aversion, which reflects a subject's differential sensitivity to losses and gains. We hypothesize that the reduction in risk-taking behavior across the lifespan that is widely observed is primarily due to an increase in ambiguity aversion, rather than to an increase in risk or loss attitudes. Further, we hypothesize that, if anything, humans should become less technically risk averse and loss averse as they age. At the neural level, we also know that there are clear structural patterns in brain development that may well underlie these behavioral changes observed across the lifespan. Of particular interest to our hypothesis is the observation that frontal regions mature late, actually thinning during development and actually continue to thin throughout the lifespan. Activational patterns fronto-cortical decision areas also change throughout the lifespan. These data suggest that both morphologic and functional properties of the frontal cortex may contribute to these changes in risk-related behavior over the lifespan, a hypothesis we propose to test with a mixture of behavioral and functional imaging techniques. PUBLIC HEALTH RELEVANCE: Our attitude towards risk shapes nearly every aspect of our behavior, including our willingness to take drugs of abuse, to make efficient financial investments, and to select amongst healthcare options. We know that these attitudes change over the lifespan and that these changes make us vulnerable in different ways as we age. We propose an analysis of the precise behavioral and neural basis of risk attitudes across the lifespan in an effort to better understand the neural basis of behaviors such as drug abuse, adolescent risk-taking, and healthcare decision-making.

DESCRIPTION (provided by applicant): Our attitude towards risk shapes nearly every aspect of our behavior. It affects our willingness to take drugs of abuse, to make efficient financial investments, and to select amongst healthcare options. We know that these attitudes change over the lifespan and that these changes make us vulnerable in different ways as we age. Adolescents engage in risky behaviors that hugely increase their mortality rates. Elders typically show the opposite profile, avoiding risky behaviors to a fault. But what is it about our behavior that changes as we age? What specific behavioral propensities and neurobiological features of aging can account for the changing attitudes we take towards risks? In this application we propose to combine economic, psychological and neurobiological approaches to the study of risky behavior in an effort to paint a portrait of risk attitudes across the lifespan at the behavioral and neural levels. Behavioral economic analyses suggests that risk-taking behavior results from the three largely independent attitudes towards risks: (1) Technical risk-aversion, which reflects a trade- off between the probability of gains or losses and the magnitude of those gains and losses, (2) Ambiguity aversion, which reflects the subject's sensitivity to uncertainty, and (3) Loss aversion, which reflects a subject's differential sensitivity to losses and gains. We hypothesize that the reduction in risk-taking behavior across the lifespan that is widely observed is primarily due to an increase in ambiguity aversion, rather than to an increase in risk or loss attitudes. Further, we hypothesize that, if anything, humans should become less technically risk averse and loss averse as they age. At the neural level, we also know that there are clear structural patterns in brain development that may well underlie these behavioral changes observed across the lifespan. Of particular interest to our hypothesis is the observation that frontal regions mature late, actually thinning during development and actually continue to thin throughout the lifespan. Activational patterns fronto-cortical decision areas also change throughout the lifespan. These data suggest that both morphologic and functional properties of the frontal cortex may contribute to these changes in risk-related behavior over the lifespan, a hypothesis we propose to test with a mixture of behavioral and functional imaging techniques. PUBLIC HEALTH RELEVANCE: Our attitude towards risk shapes nearly every aspect of our behavior, including our willingness to take drugs of abuse, to make efficient financial investments, and to select amongst healthcare options. We know that these attitudes change over the lifespan and that these changes make us vulnerable in different ways as we age. We propose an analysis of the precise behavioral and neural basis of risk attitudes across the lifespan in an effort to better understand the neural basis of behaviors such as drug abuse, adolescent risk-taking, and healthcare decision-making.

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) affects a significant proportion of the population, with general population estimates ranging from 6.4% to 6.8%. To-date there is no biological markers to identify individuals at risk for PTSD, and available treatments are only partially successful. Understanding the behavioral and neural mechanisms that underlie the development and maintenance of PTSD is important in order to inform and refine behavioral and pharmacotherapeutic interventions designed to improve patients' quality of life and, ideally, to prevent the disorder in the first place. One aspect of mst traumas that is widely ignored in the context of PTSD is the high levels of uncertainty surrounding highly adverse circumstances. In the battlefield, for example, soldiers are aware of the various dangers to themselves and others, but are seldom able to estimate the likelihood for the realization of those dangers. An adverse outcome combined with the distress of uncertainty is likely to be associated with more deleterious outcomes (e.g., greater severity of PTSD symptoms) than the same outcome in the absence of such distress. The individual's ability to cope with uncertainty may therefore determine their reaction to extreme harmful events, as well as their ability to psychologically adapt to such events. At the same time, the association of uncertainty with harmful outcomes may subsequently augment the individual's aversion for uncertainty. Behavioral economics analysis suggests that behavior under uncertainty is affected by the individual's weighting of two separate factors: (1) risk attitude, which reflects a trade-of between the probabilities of gains or losses, and the magnitude of those gains and losses~ and (2) ambiguity attitude, which reflects an individual's sensitivity to missing information about these probabilities. Neuroeconomics studies show that risk and ambiguity attitudes are reflected in the neural activation in regions of the medial prefrontal cortex (MPFC), the striatum and the amygdala, all areas that have been implicated in valuation processes in general. Intriguingly, these very same areas show structural and functional abnormalities in PTSD. In this proposal, we aim to characterize behavior under uncertainty and its neural correlates in trauma survivors with and without PTSD and healthy controls with no trauma experience. We hypothesize that individuals with PTSD will be more averse to ambiguity, and that trauma controls will be less averse to ambiguity compared to non-trauma-exposed controls. We further hypothesize that in individuals with PTSD activity in valuation areas, which normally reflects attitudes towards risk and ambiguity will cease to do so under conditions of ambiguous losses. We plan to test these hypotheses using a combination of functional MRI and experimental economics behavioral methods.

? DESCRIPTION (provided by applicant): Some of the most important decisions that older adults make are about medical care. These decisions can be very complicated, as they often involve a number of different options, each with its own burden of treatment and possible outcomes. Medical-treatment choices typically involve high levels of uncertainty regarding the possible outcomes of each available treatment. While we know a great deal about decision- making under uncertainty in young adults, research on age-related changes in choice behavior is scarce, and mostly focuses on simple financial decision-making. Financial decision-making is also the focus of most of the research which examined the neural mechanisms of decision-making processes, even in young adults. We know that regions in the prefrontal and parietal cortices, as well as basal ganglia circuits, take part in these processes, and we also know that these same brain areas experience structural thinning, reduction in dopaminergic receptors and changes in activation patterns in aging. We do not know, however, whether choice behavior in the monetary domain can predict choices in other types of significant personal decisions that older adults face, such as medical decisions. We also do not know whether age-related changes in uncertainty attitudes and their underlying neural patterns follow similar trajectories i the monetary and the medical domains. In this application we propose to combine economic, psychological and neurobiological approaches to the study of decision-making under uncertainty in the medical and monetary domains in young and older adults, in an effort to characterize these decision processes at the behavioral and neurobiological levels. Our approach is built on behavioral economics analysis, which suggests that decisions under uncertainty are affected not just by the individual's assessment of outcomes and their probabilities (risk attitude), but also by the individual's sensitivity to missing information about these probabilities (ambiguity attitude). Combining experimental economics techniques with functional and structural MRI we will be able to characterize individual attitudes towards risk and ambiguity in each decision domain, and to look for the neural correlates of these individual attitudes. In a group analysis we will compare these behavioral and neuronal characteristics between young and older adults. The proposed studies are likely to lead to significant insights into the behavioral and neurobiological processes that underlie decision-making in elders, and thus are likely to contribute to improving the quality of life of a large proportion of the population.

The aging population in the United States is rapidly rising. Older adults face complicated financial and healthcare decisions, which carry substantial consequences for themselves and for their families. It is therefore of high concern that older adults make more financial mistakes compared to their younger counterparts, and that they are increasingly subjected to exploitation by the people around them. A crucial aspect of most of these decisions is that they are made under conditions of high uncertainty. Shifts in behavior under uncertainty may therefore underlie some of the changes in decision making in aging. The cognitive and motivational bases for these shifts, however, are largely unknown. Understanding these bases is important, because it may guide the development of individually-tailored decision aids. This project aims to characterize age-related changes in uncertainty attitudes in the financial and medical domains, and to determine whether these depend on age-related changes in learning from feedback and in sensitivity to rewards and punishments.

Our world is highly uncertain and rapidly changing. Individuals vary substantially in their attitudes towards uncertainty: some seek it, while others avoid it at all costs. An important factor that affects individual uncertainty attitudes is age, yet age-related changes are not uniform, but rather they are context-dependent. This suggests that uncertainty attitudes result from interactions between several context-dependent processes. The studies conducted in this project test the general hypothesis that individual differences in decision traits are linked to differences in basic cognitive and motivational processes, and that age-related changes in these basic processes account for age-related changes in decision traits. Specifically, the studies will test the contribution of three basic processes to uncertainty attitudes: the ability to reduce uncertainty by learning from feedback, sensitivity to rewards, and sensitivity to punishments. The researchers will test this hypothesis in a group of cognitively healthy individuals between the ages of 18 and 90, using two behavioral tasks and one functional MRI task. The behavioral tasks will evaluate: (1) individual attitudes towards uncertainty in multiple domains (money gains, money losses and medical treatments), and (2) individual ability to flexibly learn from feedback. Functional neuroimaging will be used to measure neural responses to anticipated rewards and punishments. Resting-state fMRI will also be measured, to evaluate age-related changes in functional connectivity between brain areas that are involved in valuation, learning and choice. All collected data will be deposited in an open platform for neuroimaging data for public use by other investigators. The proposed work will lead to a detailed understanding of the role of learning, as well as reward and punishment processing, in individual uncertainty attitudes, and age-related changes in these attitudes. This understanding will provide constraints for future research on the neural basis of decision making, as well as policy making and decision aids for older adults. It will also serve as the basis for longitudinal and patient studies.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PROJECT SUMMARY The outcomes of our actions are seldom certain. Individuals vary substantially in their attitudes towards uncertainty: some seek it, while others avoid it at all costs. These individual differences are important, because they largely shape who we are, and because they are linked to variability in a host of maladaptive behaviors and mental disorders. The underlying causes for these individual differences, however, are poorly understood. To unravel the neural mechanisms of individual differences in behavior under uncertainty we must obtain a detailed understanding of that behavior. We do know that uncertainty attitudes are context dependent. For example, attitudes towards uncertain gains are not strongly correlated with attitudes towards uncertain losses. This suggests that uncertainty attitudes result from interactions between several cognitive and motivational processes. The proposed studies will test the contribution of three basic processes to uncertainty attitudes: the individual's ability to reduce uncertainty by learning from feedback, her sensitivity to rewards, and her sensitivity to punishments. We hypothesize that posterior parietal mechanisms play an important role in shaping individual uncertainty attitudes based on these cognitive and motivational processes. We plan to test these hypotheses in a group of 200 men and women from the general population, using three behavioral tasks in conjunction with structural and functional MRI. To ensure that our behavioral measures are independent of each other, we will estimate risk and ambiguity attitudes, in reward and punishment domains, in the absence of learning, and examine both learning and anticipation of rewards and punishments in the absence of decision making. The expected outcomes of the proposed work are twofold. At the behavioral level, we expect to obtain a detailed understanding of the role of learning, as well as reward and punishment processing, in individual uncertainty attitudes. At the neural level, we expect to identify structural features and functional mechanisms that underlie these individual differences, thus providing computational constraints on these processes. We expect these findings to guide the future development of individually-tailored decision aids and behavioral interventions for individuals with maladaptive decision processes.