The Influence of Obesity and Insulin Sensitivity on Reward Processing and Decision Making - PROJECT SUMMARY This proposal is for a K01 Mentored Research Scientist Development Award for Mary Elizabeth Baugh, PhD, RD. Dr. Baugh’s long-term goal is to become an independent investigator studying the synergistic role of metabolic and neural signals on energy balance and eating behaviors and translating these insights into novel, individualized treatments for obesity and metabolic disease. Substantial evidence in both animal models and human neuroimaging studies highlights altered brain morphology, functional connectivity, and reward responses in obesity; however, it is much less clear whether these brain alterations map on to behavioral patterns of learning and decision-making. There is a growing appreciation for the impact of post-ingestive metabolic signals on brain regions involved in food reward and eating behaviors, and recent evidence suggests altered brain insulin activity disrupts regulatory mechanisms governing eating behaviors in reward and decision-making brain regions. Given that obesity and insulin resistance commonly co-occur, and that most central insulin is derived from peripherally circulating insulin, the central hypothesis of this proposal is that reward learning and decision-making are attenuated in obesity and that reduced insulin sensitivity influences this alteration. Data from Dr. Baugh’s pilot study support this hypothesis, suggesting that lower glycemic control is associated with reductions in behavioral reward learning. The aims of the proposed research are to assesses the influence of excess adiposity and insulin sensitivity on 1) post-ingestive reward learning using a flavor-nutrient learning paradigm, which is based on Pavlovian classical conditioning, and 2) decision-making for food and non-food rewards using probabilistic selection tasks paired with computational modeling of learning parameters. Dr. Baugh has an exceptional training background in clinical physiology and metabolism but requires protected time to gain expertise in theoretical concepts of appetitive and cognitive neuroscience and develop the necessary practical skills to launch her independent research program as a tenure-track faculty member. The mentorship team, training objectives, and research aims outlined in this proposal will provide an exceptional foundation for Dr. Baugh, and the Fralin Biomedical Research Institute at VTC is an ideal environment for such training. Her co-primary mentors, Drs. Alexandra DiFeliceantonio and Pearl Chiu have complementary expertise the neurobiology of eating behaviors and computational modeling of reward and decision-making, respectively. Dr. Baugh’s training plan will focus on 1) expanding her theoretical knowledge of neural and behavioral underpinnings of food reward and eating behaviors, 2) expanding her theoretical knowledge of computational neuroscience, 3) enhancing her skills in scientific rigor, reproducibility, and statistical analysis in clinical trials, and 4) enhancing her technical skills in functional magnetic resonance imaging (fMRI) study design, data acquisition, data procession, and data analysis. Overall, the trajectory of this work and Dr. Baugh’s career goals have the potential to guide more biologically informed, individualized strategies for treatment of obesity and metabolic disorders.
