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.