Emma Jane Rose - US grants

Project Summary/Abstract In recent years there have been notable advances in the biomedical sciences in identifying the biological pathways that confer risk for or resilience to high-risk behaviors, such as substance use disorders (SUDs). Of particular note are lines of neuroscientific enquiry that have helped to identify the neurobiological mediators and moderators of SUD risk (e.g., changes in brain structure, function, and connectivity that underlie SUD and related behaviors). The data obtained from these studies is potentially highly relevant for the prevention of SUD, however, the effective transfer and application of this knowledge from the neurosciences and related biomedical fields to prevention science, and back again, is sorely lacking. Advances in the integration of neuroscience and prevention (i.e., so-called ?neuro-prevention?) are needed and have the potential to inform the delineation of which types of intervention work for whom, why, and under what circumstances. Such progress may lead to the development of more effective and potentially better targeted preventive interventions for SUD. The work of the Program for Translational Research on Adversity and Neurodevelopment (P-TRAN) at the Pennsylvania State University is focused on this goal, aiming to promote a transdisciplinary, translational neuroscience approach to the prevention of adverse outcomes. The translational arm of the P- TRAN program focusses on the active transfer of knowledge regarding the neurodevelopmental trajectories that underlie risk for SUD to the development, implementation, and scaling of evidence-based prevention programs and related policies. To further advance this work and to promote a neuro-prevention approach to SUD, within P-TRAN and to a wider cadre of researchers whose work is or could be aligned with this framework, the P-TRAN network is proposing to hold annual or biennial symposia that will convene relevant experts in the biomedical and prevention sciences, as well as trainees in these domains. We are proposing to utilize the R13 mechanism to support two perspectives and empirical methods in an initial meetings that will integrate theoretical attempt to lay a foundation for : (1) educational and training opportunities in neuro-prevention for SUDs; (2) determining domains of neuroscientific enquiry that may delineate neurobiological moderators and mediators of preventive strategies for SUD; (3) considering novel prevention strategies that incorporate neurodevelopmental factors; (4) identifying barriers to the adoption of a neuro-prevention approach to SUDs; and (5) planning educational and collaborative opportunities that will elevate the field and prepare the next generation of SUD researchers with research interests in neuro-prevention.

Project Summary Food insecurity (FI) ? i.e., the ?lack of consistent access to enough food for an active and healthy life? - is a relatively common type of adversity in the United States and one which disproportionately impacts families in rural counties (e.g., ~17% of rural families experience FI, compared to ~10% of all US families). FI is associated with an increased risk for substance use (SU) in adults and adolescence and SU risk is also generally greater for adolescents in rural areas, compared to their urban and suburban peers. While a causal link between FI and SUD liability has not been established, prior work supports the postulation that the experience of FI might increase the risk for SU via an impact on the neural substrates of reward processing. For example, of the key components of FI (i.e., acute and repeated food deprivation and associated hunger, stress, and poor nutrition), stress and poor nutrition have been shown to influence SU-relevant neurodevelopmental trajectories, while food deprivation in children impacts neural processing for food rewards. Furthermore, in adult humans and animal models, food deprivation increases reward sensitivity and risky decision-making for primary and secondary rewards and increases drug-seeking and craving via functional alterations in reward network areas in the brain (i.e., mesocorticolimbic regions). To more fully understand how food deprivation in the context of FI might influence reward processes, this developmental study will examine whether states of acute food deprivation that are sufficient to cause subjective feelings of hunger enhance sensitivity for food and non-food rewards and increase risky decision-making (Aim 1). Moreover, we will consider how associations between food deprivation and the neural substrates of reward processing are impacted by FI (Aim 2) and whether FI mediates the associations between related factors (e.g., SES) and reward processes (Aim 3) To address these aims, children (8-10 years old) from food secure (N=30) and insecure (N=30) households in rural PA will undergo a counter-balanced, repeated measures fMRI paradigm, once while food deprived (i.e., fasted) and once after a meal sufficient to satiate them (i.e., fed). We will focus on children in order to minimize the impact of aspects of adolescence that might also influence these processes and confound our results (e.g., SU, puberty). During fMRI participants will complete 2 versions of a reward task in which they will make reward-related decisions (i.e., placing a bet of varying magnitude) for food (i.e., candy) and non-food (i.e., money) rewards Data analyses will model the impacts of food deprivation (fasted/fed; Aim 1) and food security status (secure/insecure; Aim 2) on reward neurobiology. Mediation analysis will consider the relative contributions of FI vs. SES (Aim 3) and exploratory analysis will consider potential moderators of FI-related effects (i.e., stress, nutrition, chronicity of FI; Aim 4). By considering whether food deprivation in the context of FI drives functional alterations in reward processes, this exploratory R21 study will constitute a critical first step in identifying pathways by which FI drives SU-liability.