Metabolism and the Mind: Investigating the Link Between Glucose Control and Reinforcement Learning in Humans.

Background: Signals from the body profoundly influence cognition. This process is known as interoception, and has been extensively studied in the cardiac, respiratory, and gastric domains; in contrast, metabolic influences remain poorly understood. Here, we focus on the link between glucose control and cognition, motivated by the observation that there is substantial, unexplained comorbidity between type 2 diabetes and depression. In rodents, insulin modulates dopamine signaling in the ventral striatum. We therefore hypothesized that, in humans, differences in glucose control would be associated with altered reward learning. Methods: To test this hypothesis, we recruited 48 participants from the general population, who each completed a glucose tolerance test, a monetary reward learning task known to relate to dopamine function, and mental health questionnaires. We fitted an established reinforcement learning model to the task data to obtain computational parameters characterizing participants' learning, and then examined the associations between these parameters and their glucose control. Results: We discovered that poorer glucose control was associated with greater reliance on recent rewards during learning, which was in turn associated with higher levels of depression symptoms. There was also more modest evidence for the association between glucose control and depression symptoms. Conclusions: Together, our results identify a specific neurocognitive process, reward learning, by which metabolic information may influence cognition, and which may explain the link between metabolic diseases such as type 2 diabetes and depression.