Medial prefrontal cortex guides goal-directed decision-making about hunger and thirst

Decision-making guided by self-evaluation of bodily need states (interoception) is thought to be important for cognitive control over eating or drinking 1 . However, interoception of body states is notoriously unreliable 2–4 because hunger and thirst have similar motivational characteristics 5 . Consequently, individuals may inaccurately assess their need state and consume food when dehydrated, leading some healthcare professionals to advise overweight patients to drink water before eating 6–8 . Neuroimaging in humans 9–11 and recordings in rodents 12–15 indicate medial prefrontal frontal cortex (mPFC) involvement in need state-dependent decisions about hunger and thirst, but mPFC surgical lesions 16,17 and electrical activity perturbations have little influence on eating or drinking 18,19 . To investigate need-state dependent decision-making as well as the function of mPFC in hunger and thirst, we developed an instrumental foraging task for mice that mimics key elements of human decisions. When homeostatic need state was variable, mice did not show intrinsic knowledge of hunger or thirst state but, instead, rapidly identified their need after consumption of small portions of food and water (outcome evaluation). We observed a food-seeking bias, even in thirsty mice, that required outcome evaluation for mice to correctly seek water. mPFC was required for need state-dependent decisions about hunger and thirst, specifically under variable need state conditions. Food-seeking or water-seeking choices were controlled by multiple decision-making processes, and mPFC was involved in goal-directed decisions about the identity of need states. Thus, we have discovered a role for mPFC in decision-making about hunger and thirst, which is relevant for human behaviors that contribute to obesity.