Thursday, April 10, 2025
4/10/2025
Sub-second catecholamine dynamics underlying food reward in humans - SUMMARY The prevalence of obesity in the United States (US) has been consistently rising. For individuals with obesity the lifetime risk of developing type 2 diabetes (T2D) is 3-7 times greater than for those without. Despite substantial advances in obesity treatment, obesity and T2D remain global public health challenges. Recent estimates suggest dietary factors contribute to >300,000 deaths per year in the US, making decisions about what foods to eat a leading and modifiable driver of disease burden. While changes in brain systems involved in energy balance and homeostatic regulation are thought to contribute to obesity, importantly, changes in neural systems associated with attention, reward learning, and affective regulation also occur. These changes may allow reward systems to override satiety signals and promote eating. Consequently, a detailed understanding of the underlying neurochemistry of attention, reward, and valence is key to understanding the neurobiology of eating behavior and obesity. A wealth of literature, largely generated in model organisms, supports the general hypothesis that alterations in brain catecholamine signaling (i.e., dopamine and norepinephrine release) are key drivers of food intake and reward-based decision making. The importance of studies in rodents on mechanisms of food reward, learning, motivation, and by extension the neurobiology of obesity cannot be overstated. However, much of this literature has not been translated to humans. This represents a fundamental gap in our understanding of the essential human health behavior of food choice and food reward. The long-term goal of this research is to provide a framework to translate and extend mechanistic studies of food reward in rodents to humans. To that end, here we will leverage innovations from our group in two domains: 1. the capacity to detect sub-second changes in dopamine (DA) and norepinephrine (NE) and distinguish them from each other, 2. the ability to perform these measurements on electrodes routinely implanted in clinical settings, in this case for phase II Epilepsy Monitoring. Bringing together a team that combines expertise in human neuroscience of ingestion, neuromodulation, and computational modeling, we will test the central hypothesis that DA and NE dynamics will differentially encode aspects of food and non-food reward dependent on body mass index (BMI). In Aim 1, we will measure catecholamine dynamics from the amygdala during a food-based learning task. In Aim 2, we will measure catecholamine dynamics from the amygdala during a task using emotion, food, and neutral words. Completion of this proposal will begin to bridge the translational gap between studies in rodents and humans. It will also provide a needed foundation for more in-depth testing of the relationship between brain mechanisms of food reward and peripheral markers of metabolic health and disease.
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