Insular cortex predictions regulate glucose homeostasis

Brain-body interactions are essential for physical and emotional homeostasis. The brain uses information from the external world to predict upcoming bodily changes. This process involves interoceptive predictions, which are thought to play a central role in brain-body interactions. Yet there is little direct experimental evidence causally linking interoceptive predictions to regulation of bodily physiology. Here we address this by focusing on insular cortex and glucose homeostasis. We find that just before the onset of a meal, insular cortex exhibits a transient burst of activity, reflecting a prediction of the future metabolic state. This transient predictive burst of activity is essential for anticipatory insulin release, subsequent post-meal insulin release, post-meal glucose and lipid homeostasis, and post-meal metabolism signaling in the liver. Our results highlight that insular cortex predictive computations are essential for anticipatory physiological control and for subsequently maintaining metabolic homeostasis.Competing Interest StatementThe authors have declared no competing interest.European Research Council, 101039145Israel Science Foundation, 3015/22NIH Common Fund, https://ror.org/001d55x84, DP2DA060436Max Planck SocietyCenter for New Scientists of the Weizmann Institute of Science