Type 2 Diabetes (T2D) is a significant public health burden in the United States, affecting more than 20 million people over the age of 20. Diabetes has pathogenic effects on numerous organ systems, causing complications related to kidney function, vision, and the cardiovascular system. One precursor to T2D is insulin resistance. One organ that is particularly sensitive to insulin is the brain, where insulin is actively transported across the blood brain barrier. To date, however, few human studies have investigated how brain structure and function are altered in individuals with insulin resistance. The brain controls numerous physiological systems in the body, and one such system is the autonomic nervous system. Individuals with insulin resistance and T2D have alterations in their autonomic nervous system activity that can increase their risk for death due to cardiovascular disease. The goal of the present proposal is to investigate how activity in one particular brain region, the ventral striatum, covaries with fasting insulin levels and autonomic function. This research fits well within the strategic aims of the National Institute of Diabetes and Digestive and Kidney Diseases, especially within the Integrative Biology of Obesity Program, which supports "basic and clinical research investigating the neural and endocrine mechanisms contributing to obesity and the pathophysiological consequences of obesity, particularly type 2 diabetes." This application will enable the Applicant to receive formal training in the physiology and pathology of the endocrine system that underlies T2D, as well as extend his training in functional neuroimaging to include advanced techniques to understand the interactions between brain regions and how they covary with physiological conditions. Combined with the measurement of autonomic activity, this research will further our understanding of the mechanisms by which insulin resistance alters autonomic activity and increases risk for pathogenic outcomes. PUBLIC HEALTH RELEVANCE: Insulin resistance is a precursor to Type 2 Diabetes, a public health epidemic in the United States afflicting more than 20 million people. Type 2 Diabetes increases risk for cardiovascular disease, possibly through alterations in the autonomic nervous system. The proposed study will examine how resting brain activity covaries with insulin resistance and autonomic activity to help understand the pathways by which insulin and autonomic function are related.