David V. Smith, Ph.D. - US grants

? DESCRIPTION (provided by applicant): Navigating our complex social world depends critically on our ability to compare various opportunities and adapt our behavior based on the rewards received from the outcomes of our decisions, other individuals, and larger social groups. Although rewards can promote adaptive decisions-and enhance individual and societal welfare-deficits in the ability to process rewards can impact our physical and mental health, increasing vulnerability to a number of significant public health issues such as addiction, obesity, and psychopathology. Yet, understanding the mechanistic link between reward and different public health issues presents a significant conceptual challenge, as rewards arise in social and nonsocial contexts and are composed of multiple properties that may have different influences on behavior. In particular, affective reward properties signal whether an outcome was positive or negative while informative reward properties signal how to adapt behavior to maximize future rewards. The principal research goal of this project is to study how interactions between multiple brain regions-particularly the striatum and prefrontal cortex-support affective and informative reward properties in social and nonsocial contexts. This research goal complements several training goals that help the applicant acquire new skills (e.g., physiological recordings of arousal and multivariate pattern analysis, MVPA), broaden knowledge base through directed readings and coursework, and prepare for a future career as an independent investigator and instructor. These training goals will contribute to the applicant's long-term success while providing essential new skills needed for the proposed research. The proposed studies utilize functional magnetic resonance imaging (fMRI) combined with physiological measures of arousal and MVPA to investigate two specific aims. Our first aim investigates the neuroanatomical pathways for reward to test the hypotheses that a) affective and informative reward properties are decoded by distinct subregions of the striatum; and b) these subregions show distinct functional connectivity profiles with prefrontal cortex. This demonstration would have translational potential, elucidating a mechanism for developing treatments that target deficits in distinct reward properties. Our second aim investigates how social context modulates reward properties, specifically testing the hypothesis that autonomic and neural responses to affective (but not informative) reward properties can be manipulated by social context. Collectively, these findings would further our understanding of the neural and behavioral mechanisms that shape complex social behavior, potentially providing clinicians with new insight into disorders marked by deficits in social reward processing, particularly autism, anorexia nervosa, and schizophrenia.

Project Summary Our behavior is inextricably linked to a wide range of rewards, from economic incentives (e.g., monetary compensation) to social incentives (e.g., praise from a peer). Receipt of reward promotes learning, evokes pleasure, and increases brain activity within the striatum?a key structure within the reward circuit. Although striatal responses to reward are correlated with learning and positive emotions, it remains unclear how the experience of reward in humans is causally linked to the striatum. Indeed, the striatum is buried deep inside the brain, making it inaccessible to approaches that assess causality via noninvasive brain stimulation. The goal of this project is to determine whether reward-related responses within the striatum can be influenced via stimulation applied to cortical connections. We will use a novel form of noninvasive neuromodulation, that we coined short-term transcranial alternating current stimulation (st-tACS) to prefrontal cortex while participants engage in reward tasks that reliably evoke activation within the striatum. We will address two specific aims. In our first aim, we will investigate whether st-tACS alters striatal responses to reward and pleasure associated with a simple guessing game. In our second aim, we will investigate whether st-tACS alters striatal responses to reward and learning. We hypothesize that st-tACS applied to prefrontal cortex will increase striatal responses to reward, an effect that will be tied to increased pleasure (Aim 1) and increased learning (Aim 2). These findings would therefore establish causal links between the human striatum and reward. Moreover, remote modulation of the human striatum could expand the purview of noninvasive brain stimulation approaches, potentially establishing a foundation for new therapeutic directions for psychopathologies characterized by aberrant responses to reward.

Project Summary Older adults are often victims of financial exploitation, which results in annual losses of at least $3 billion. Threat of exploitation may be greater in those at risk for Alzheimer's Disease and Related Dementias (ADRD). While most cases of financial exploitation are perpetrated by strangers, perpetration by individuals within the victim's social network (e.g., friends and family) is common. Although these observations highlight the social nature of financial exploitation, we know very little about how neural systems in older adults and those at risk for ADRD integrate information from the social domain to inform financial decision making. Tasks involving social information processing evoke activation in the temporal-parietal junction (TPJ) and dorsomedial prefrontal cortex; whereas tasks involving financial decision making and reward processing evoke activation in the striatum and ventromedial prefrontal cortex. It remains unclear whether responses within these neural systems?and connectivity between them and other regions?differ as a function of age and risk for financial exploitation. We recently demonstrated age differences in TPJ response during social decision-making in the context of financial exchange (e.g., trust and fairness). We have also shown that the influence of social context (e.g., presence of a peer) on striatal responses to reward is attenuated in older adults relative to younger adults. Building on these exciting preliminary data, the goal of the current proposal is to characterize neural responses during social decision making and reward processing across adulthood and quantify how these responses relate to risk for financial exploitation. We will recruit a large sample of adults (ages 21 to 80+ years) to participate in a neuroimaging experiment investigating social reward processing and the interplay between social context and financial decision making. We will also administer neuropsychological and health assessments, as well as questionnaires assessing socioemotional functioning and risk for financial exploitation. Our project will address four aims. We will examine how neural responses to social and nonsocial reward and decisions based on trust and fairness differ across the lifespan (Aim 1). Although neural responses evoked by our tasks may be associated with risk for financial exploitation, it is imperative to determine how such responses interact with sociodemographic factors, cognitive decline, socioemotional functioning, and health (Aim 2). Notably, our quantification of health status will leverage two understudied risk factors for ADRD?vascular health and white matter hyperintensities?and relate these factors to financial exploitation. Finally, we will re-test a subset of participants with mild cognitive impairment (MCI) two years after their baseline visit and assess changes in social reward processing and risk for financial exploitation (Aim 3). Overall, our project will generate new insights into the interplay between social and financial decision making across the lifespan and individuals at risk for ADRD and start the road to translation by characterizing risk factors for financial exploitation among vulnerable groups.