Olfactory connectivity mediates sleep-dependent food choices in humans

Sleep deprivation has marked effects on food intake, shifting food choices toward energy-dense options. Here we test the hypothesis that neural processing in central olfactory circuits, in tandem with the endocannabinoid system (ECS), plays a key role in mediating this relationship. We combined a partial sleep-deprivation protocol, pattern-based olfactory neuroimaging, and ad libitum food intake to test how central olfactory mechanisms alter food intake after sleep deprivation. We found that sleep restriction increased levels of the ECS compound 2-oleoylglycerol (2-OG), enhanced encoding of food odors in piriform cortex, and shifted food choices toward energy-dense food items. Importantly, the relationship between changes in 2-OG and food choices was formally mediated by odor-evoked connectivity between the piriform cortex and insula, a region involved in integrating feeding-related signals. These findings describe a potential neurobiological pathway by which state-dependent changes in the ECS may modulate chemosensory processing to regulate food choices.