Sleep Deprivation Selectively Upregulates an Amygdala–Hypothalamic Circuit Involved in Food Reward

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation or restriction, neuroimaging studies revealed upregulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum, and insula. To address this ongoing debate between hormonal versus hedonic factors underlying sleep-loss-associated weight gain, we rigorously tested the association between sleep deprivation and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from 32 lean, healthy, human male participants, they underwent fMRI while performing a neuroeconomic, value-based decision-making task with snack food and trinket rewards following a full night of habitual sleep and a night of sleep deprivation in a repeated-measures crossover design. We found that des-acyl ghrelin concentrations were increased after sleep deprivation compared with habitual sleep. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after sleep deprivation. Furthermore, fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala–hypothalamic coupling after a single night of sleep deprivation. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl, or total ghrelin concentrations. Our results suggest that increased food valuation after sleep loss might be due to hedonic rather than hormonal mechanisms. SIGNIFICANCE STATEMENT Epidemiological studies suggest an association between overweight and reduced nocturnal sleep, but the relative contributions of hedonic and hormonal factors to overeating after sleep loss are a matter of ongoing controversy. Here, we tested the association between sleep deprivation and food cue processing in a repeated-measures crossover design using fMRI. We found that willingness to pay increased for food items only after sleep deprivation. fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. However, there was no evidence for hormonal modulations of behavioral or fMRI findings. Our results suggest that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.