Gregory Russell Samanez Larkin, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): As the proportion of older adults continues to grow at an unprecedented rate, aging adults may be required to make increasingly more independent health-related and financial decisions. Thus, it is increasingly imperative to better understand the impact of age-related changes in both cognitive and affective processing on decision-making. Both behavioral and neural evidence suggests that younger and older adults differ in the processing of monetary incentives (e.g., older adults show attenuated anticipation of monetary losses), which could have specific consequences for financial decisions (e.g., older adults may be generally less sensitive to the warning signs of potential negative outcomes). Although these affective preferences may be healthy and adaptive for regulating emotional experience and optimizing well-being, they may have harmful effects on financial learning and decision making. The main objective of the proposed research is to examine age differences in incentive learning and incentive-based decision-making using both behavioral measures of performance and functional magnetic resonance imaging. The specific aims of this proposal are to (1) investigate the influence of reinforcement valence on incentive processing across the life span, (2) examine whether older adults show the same valence asymmetry in more [unreadable] cognitively demanding reversal learning, and (3) examine whether older adults differ from younger adults both in rational risky decision-making and risk preference in a more applied investment decision paradigm. Findings from this line of basic research may have implications for scientists' understanding of how processes underlying decision-making change with age, and might eventually also facilitate identification of markers for suboptimal decisions in older adults. The long-term goal of this line of research is to improve the financial and emotional health of older adults by improving decision-making at the individual level. [unreadable] [unreadable] [unreadable]

Anterior; Anxiety; Aversive Stimulus; Avoidance Learning; CRISP; Central Lobe; Chronic; Computer Retrieval of Information on Scientific Projects Database; Functional Magnetic Resonance Imaging; Funding; Grant; Individual Differences; Institution; Insula; Insula of Reil; Investigators; Island of Reil; Learning; MRI, Functional; Magnetic Resonance Imaging, Functional; Measures; NIH; National Institutes of Health; National Institutes of Health (U.S.); Outcome; Participant; Patient Self-Report; Research; Research Personnel; Research Resources; Researchers; Resources; Self-Report; Source; United States National Institutes of Health; experience; fMRI

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. As human life expectancy continues to rise, financial decisions of aging investors may have an increasing impact on the global economy. In this study, we examined age differences in financial decisions across the adult life span by combining functional neuroimaging with a dynamic financial investment task. To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. When making decisions, individuals must often compensate for cognitive limitations, particularly in the face of advanced age. Recent findings suggest that age-related variability in striatal activity may increase financial risk-taking mistakes in older adults. In two studies, we sought to further characterize neural contributions to optimal financial risk taking and to determine whether decision aids could improve financial risk taking. To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)

DESCRIPTION (provided by applicant): Increases in human life expectancy over the twentieth century will continue to expand the proportion of older adults in the global population, magnifying the relative economic impact of their health-related and financial decisions. Thus, it is increasingly imperative to better characterize and understand age-related changes in reward processing and decision making across the adult life span. New in vivo brain imaging techniques using magnetic resonance imaging (MRI) and positron emission tomography (PET) now allow more precise measurement of the human reward system. Highly detailed visualization of structures across the brain is now possible using ultra high field strength 7-Tesla MRI scanners. The use of high-resolution protocols (i.e., slice prescriptions that selectively measure a subsection of the brain) at high field strength has the potential to both structurally and functionally dissociate individual nuclei in the reward system. Measurement of dopamine receptor availability in both striatal and extrastriatal (e.g., midbrain, frontal cortical) regions is now possible using the radioligand [18F]fallypride in PET imaging. These imaging techniques facilitate previously unavailable in-depth measurement across the brain. The main objective of this fellowship grant is to train the applicant in the use of novel methods for imaging the human reward system across the adult life span. Training will also include broadening the applicant's base of knowledge through directed reading, honing teaching and mentoring skills, and building laboratory and grant management skills to ensure productivity and success throughout the applicant's career. The specific aims are to train the applicant to (1) use high-resolution, ultra high field strength, (7-Tesla) MRI to examine structural and functional age-related changes in individual subregions of the midbrain across adulthood, (2) combine [18F]fallypride PET and functional MRI to characterize associations between dopamine receptor availability and aspects of reward processing and behavioral control in healthy adults, and (3) integrate structural (MRI) and functional (PET, fMRI) measures of neural integrity to investigate age-related changes in decision making from young adulthood to middle age. The goal of all aims is to precisely characterize the neural changes underlying age-related changes in cognition, specifically related to decision making and behavioral control. The fellowship will support the next stage of training on the applicant's path to becoming an independent psychological scientist in the cognitive neuroscience of aging. After completion of training, the applicant's goal is to combine these new methods to not only more precisely quantify age-related change in the human reward system but also to investigate the implications of these changes throughout the adult life span. The long-term goal of the applicant's career is to conduct basic scientific research that contributes directly to interventions aimed at easing the cognitive strain and improving emotional and economic health in the daily lives of aging adults. PUBLIC HEALTH RELEVANCE: This research training plan aims to use cutting edge neuroimaging technology to expand understanding of processes underlying decision making and behavioral control over the adult life span. This work has the potential to facilitate identification of markers for suboptimal decisions in older adults in order to inform the design of appropriate interventions. The long-term goal of this line of research is to improve the financial and emotional health of older adults by improving decision making at the individual level.

PROJECT SUMMARY/ABSTRACT The goal of this Pathway to Independence Award is to expand the base of knowledge, methodological expertise, and theoretical development skills of the candidate as he transitions from a post-doctoral trainee to an independent scientist focused on the decision neuroscience of aging. A wealth of behavioral research on the psychology of aging reveals change over the life span in both cognition and motivation. Many prominent theories of cognitive aging are centered on changes in neuromodulation, focusing specifically on the neurotransmitter dopamine (DA). However, DA is not only implicated in variability in cognitive function, but also plays an important role in motivation. Yet, the relation between age-related changes in DA functioning and motivational factors has received little study. The goal of the initial K99 mentored phase is to begin to examine interactions between motivation and cognition across adulthood, increase the candidate's base of knowledge of the dopamine system, gain experience with computational modeling, and expand the candidate's expertise with multiple imaging measures. To achieve these goals, the candidate will conduct a collaborative multimodal imaging project focused on clarifying the link between DA functioning and self regulation (R21-DA033611). The project will include behavioral and fMRI measures of inhibitory control as well as PET measures of receptor availability across the brain in a group of healthy adults. All participants will complete two behavioral tasks that capture distinct aspects of motivated cognitive control and engage distinct, albeit overlapping neural networks. The candidate will begin to extend this line of work as well as his previous work on age differences in decision making into a cross-sectional study of age differences in motivated cognition and decision making in this K99 phase. The proposed R00 project will examine relationships between motivated cognitive control and decision making across adulthood (ages 20-80). In addition to a PET scan, subjects will complete behavioral tasks while undergoing fMRI that assess reward processing and inhibitory control. Participants will also complete a full battery of cognitive and motivational individual difference measures, incentive-compatible behavioral economics tasks, as well as a subset of the Health and Retirement Study (HRS) survey. This project will also serve as a foundational study for the development of a longitudinal multi-modal imaging protocol. Together, the mentored and independent phases of this project will provide a framework toward developing a more integrative and comprehensive theory of human aging that incorporates neuroscientific theories of the role of DA function for cognition and motivation with psychological theories of aging. A long-term goal of the candidate's career is to develop a computationally-informed and neurobiologically-specific theory of motivated cognition across adult development and aging. Support through this mechanism will greatly increase the likelihood of the candidate's obtaining an R01 to support a longitudinal multimodal imaging study at an earlier career stage than otherwise possible.

PROJECT SUMMARY / ABSTRACT In an age of unprecedented longevity, health and well-being in old age reflect decisions and behavioral practices that span decades. Seemingly minor decisions and actions people take in everyday life have cumulative, long-term consequences that affect stress, opportunities for engagement, and health in old age. Financial security is strongly related to physical and mental health, and the majority of Americans are not financially secure. Even among those who have sufficient resources to save and invest, many lack the skills and motivation required to engage in wise planning and habits that support health and well-being at advanced ages. Independent of the potential causal relationships among financial health, physical health and psychological well-being, long-term financial and health-related planning share many common features. Social science is beginning to address these issues but the vast amount of existing research relies on individuals' performance on hypothetical tasks in laboratory settings or responses on surveys. Private industries often have very large and rich data resources that reflect behavior in everyday life. A lack of connection between well-controlled laboratory studies and actual behavior creates a major barrier to progress in understanding behavior and developing scalable interventions to improve financial, mental, and physical health. The financial services and healthcare industries are key stakeholders in finding effective solutions but at present collaborations between social scientists and private sector companies are limited to occasional consulting and proprietary research. Collaborations are typically difficult to establish, limited by complex privacy concerns, logistical issues and mutual distrust about how the findings might be used. Yet, partnerships between researchers and private sector companies represent extraordinary opportunities to answer important questions about decisions and actions that predict long-term health outcomes. The goal of this project is to bring a unique interdisciplinary perspective to the understanding of optimal and suboptimal decision making across adulthood. By training early-stage researchers to effectively establish research partnerships with industry, we can facilitate the development of research projects that promise to improve health and financial well-being for aging individuals and society.

PROJECT SUMMARY / ABSTRACT The overall goal of this grant is to continue supporting the multidisciplinary Scientific Research Network on Decision Neuroscience and Aging. The integrative emerging area that this grant will support combines the strengths of several fields including psychology, neuroscience, and economics to facilitate rapid scientific progress and directly contribute to the development of effective interventions and policies to improve health and well being across the life span. Over five years this network grant will support scientific meetings, intensive training workshops for researchers at all stages, collaboration and mentorship initiatives, and pilot grant competitions for researchers new to the field. These activities will directly support the growth, development, and sustainability of the decision neuroscience of aging. This grant will support growth of the network through dissemination activities. Scientific meetings will increase awareness of the latest findings with the goal of drawing new researchers into the area and encouraging new collaborations. A small grant competition will encourage scientists to join the area and will stimulate new research through small scale pilots. This network grant will support development of the area through methods workshops and an outside mentorship program. Short, intensive workshops will focus on training researchers at all stages in the collection and analysis of various emerging behavioral (e.g., health-related, social, economic) and biological (e.g., neurochemical, genetic, hormonal) measures. The development of these skills is currently difficult to achieve in traditional single discipline training programs, but will be essential for taking advantage of the growing number of large multivariate and multi-level integrative datasets generated by this area in the future. In general the network will focus on investing in the sustainability of this field by ensuring that graduate students, post-doctoral fellows, and junior and senior faculty are invited to participate in all activities. Workshops, meetings, small pilot grants, and collaboration initiatives will facilitate the transition from a small group of individuals managing network activities to a strong field of researchers leading future work in this area. After completion of activities, this emerging area will be in better position for network members to pursue funding to support the network in the future using more traditional mechanisms.

PROJECT SUMMARY / ABSTRACT Many financial and social decisions made throughout life can powerfully influence health outcomes in old age. To address these issues, two multidisciplinary areas of life-span research have emerged in recent years: neuroeconomics and social neuroscience. Despite the promise of these areas, unfortunately it remains rare for individual institutions to provide truly multidisciplinary training opportunities in either neuroeconomics or social neuroscience. The proposed activities will address this by offering workshops and summer schools to a broad audience of junior scientists all over the country. The goal of neuroeconomics is to better understand human decision making. Neuroeconomics uses an economic approach to understanding decision behavior that can potentially be generalized not only for the maximization of financial well being but also mental and physical health. Social neuroscience integrates multiple areas of psychology and neuroscience to better understand human social behavior. The social neuroscience approach identifies ways to optimize social, emotional, and physical health and well being. The primary goal of the proposed training activities is to provide the attendees with a broad base of knowledge and skills from the many subfields within neuroeconomics and social neuroscience. Another goal of the proposed events is to begin to bring together the neuroeconomics and social neuroscience communities for an even more integrative approach. Social neuroscience and neuroeconomics have largely grown up as separate fields, with separate conferences and very little cross-talk between communities despite a great deal of overlap in research interests (e.g., neural mechanisms of affective and social decision making, learning and valuation). To better understand the predictors of and strategies for optimizing health and well being in old age, scientific life-span research will need to continue to further integrate approaches, evidence, and theories from multiple disciplines given the multi-dimensional contributions to long-term health and well being. We expect that the novel training activities proposed here will increase the number of future scientists effectively working at the intersection of multiple fields which will promote creativity, facilitate communication across areas, introduce novel applications of methods and approaches to other areas, and promote more creative science.

DESCRIPTION (provided by applicant): Vital financial decisions are made during pre-retirement age that can influence financial well-being for the rest of an individual's life. Howeve, very little psychological and neurobiological research has examined financial decision making in this pre-retirement late middle age range. An overarching goal of this grant is to begin to construct a more comprehensive model of the specific psychological and neural mechanisms that support financial decisions in young adulthood and late middle age. All aims seek to understand adult age differences in cost-benefit decisions and the specific role of dopaminergic neuro-modulation in supporting these preferences in young and late middle-age adults. We particularly focus on decisions with effort costs, but we will also examine the influence of dopamine (DA) on risky choice. A single multimodal neuroimaging study will examine age and individual differences in basic cognitive and motivational variables, decision making behavior, neural reward circuits using fMRI, multiple aspects of the DA system collected across three radio- ligand PET imaging sessions, and behavioral sensitivity to the drug amphetamine. Using radioligand PET imaging of D2-like receptors and release with [18F]fallypride and DA transporters (DAT) with [18F]FECNT, the project will provide the first examination of the specific role of multiple aspects of DA function in supporting the core motivational processes underlying cost-benefit decision making in healthy young and middle-aged adults. We expect to observe differential age effects in both functional neural activity assessed with fMRI and DA function assessed with PET. Across imaging methods, we expect to observe some level of preservation of function in the ventral striatum and midbrain in late middle age. However, we expect to observe larger age differences in lateral cortical D2 receptors, striatal and ventromedial prefrontal DA release, and DAT expression. We expect these neurobiological age differences, especially in medial prefrontal and striatal networks, to be associated with decision making, such that individual differences in the function of these systems are associated with individual differences in the tolerance of effort costs. We will also include an amphetamine challenge to examine the influence of DA release on decision preferences. This will be the first study of human age differences in DA release, and the first study of DA drug effects on decision making across adulthood. The parallel use of the DAT ligand [18F]FECNT will allow us to uniquely assess the relative and possibly synergistic impact of presynaptic and postsynaptic DA variables, and to further provide a unique assessment of the relations between DAT expression and amphetamine-induced DA release and the behavioral effect of amphetamine. Beyond contributions to the study of human aging, the work will clarify the neural substrates of cost-benefit decision making across adulthood. This multimodal, adult developmental approach has the potential to more precisely characterize the neurobiological systems involved in motivation and decision making, and has the potential to identify focused targets for future interventions.

Effects of aging on episodic memory-dependent decision making Most studies of human decision making use tasks in which information relevant to the decision is either completely available or never available. Yet, in many real-life scenarios decision making requires retrieving in- formation from specific past events, or episodic memory. Clarifying the role of episodic memory in decision making is critical for understanding decision making deficits in healthy older adults, who show significant epi- sodic memory decline. Our overarching goal is to clarify how episodic memory impairments in older age con- tribute to decision making. In particular, we focus on the neural mechanisms of age differences in decision making using functional MRI measures of brain activity and connectivity and diffusion tensor imaging measures of white-matter integrity. We investigate two decision-making tasks, the multi-attribute choice task and the time discounting task, and have 3 specific aims. Our first aim is to investigate age differences in mul- ti-attribute decision making as function of episodic memory demands and decision making demands. In Study 1, we manipulate episodic memory demands by varying whether or not the decision amount requires retrieving previously learned information, and decision making demands by instructing participants to using a simple or a more elaborate decision strategy. Study 1 focuses on remembering the past but episodic memory is also nec- essary for for thinking about the future. Our second aim is to examine age differences in the time discounting task as a function of episodic future thinking, which is known to be impaired in older adults Study 2 investi- gates the effects of episodic tags on monetary intertemporal decision making. Finally, our third aim is to spec- ify how individual differences in brain integrity modulate age differences in episodic memory-dependent deci- sion making. Individual differences in episodic memory in older age have been linked to an executive factor as- sociated with the frontal lobes, and a memory factor associated with the medial temporal lobes. We examine how these two factors account for individual differences in white-matter integrity among older adults and how these individual differences modulate the results of Studies 1 and 2. In sum, the proposed studies investigate the neural mechanisms of age differences in episodic memory-dependent decisions, which are common in eve- ryday life. The research will link two previously disconnected areas of research, the cognitive neuroscience of aging and neuroeconomics of aging. The studies will contribute to a more comprehensive scientific under- standing of brain aging that is more easily translatable to critical behavior in everyday life. The work has the potential to identify mechanisms to improve episodic memory-dependent choice across all stages of adulthood, which will contribute to improving health and well-being in old age.