Post-ingestive signals conveying information about the nutritive properties of food are critical for regulating ingestive behavior. Here, using an auction task concomitant to fMRI scanning, we demonstrate that participants are willing to pay more for fat + carbohydrate compared with equally familiar, liked, and caloric fat or carbohydrate foods and that this potentiated reward is associated with response in areas critical for reward valuation, including the dorsal striatum and mediodorsal thalamus. We also show that individuals are better able to estimate the energy density of fat compared with carbohydrate and fat + carbohydrate foods, an effect associated with functional connectivity between visual (fusiform gyrus) and valuation (ventromedial prefrontal cortex) areas. These results provide the first demonstration that foods high in fat and carbohydrate are, calorie for calorie, valued more than foods containing only fat or carbohydrate and that this effect is associated with greater recruitment of central reward circuits.

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Highlights d Food intake induces orosensory and post-ingestive dopamine release in humans d Both recruit distinct pathways: orosensory integrative and higher cognitive centers d Dopamine release in ''wanting''-associated regions mirrors subjective desire to eat d Post-ingestive dopamine release in the putamen is inversely correlated to ''wanting''

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To date, the spatiotemporal release of specific neurotransmitters at physiological levels in the human brain cannot be detected. Here, we present a method that relates minute-by-minute fluctuations of the positron emission tomography (PET) radioligand [11C]raclopride directly to subsecond dopamine release events. We show theoretically that synaptic dopamine release induces low frequency temporal variations of extrasynaptic extracellular dopamine levels, at time scales of one minute, that can evoke detectable temporal variations in the [11C]raclopride signal. Hence, dopaminergic activity can be monitored via temporal fluctuations in the [11C]raclopride PET signal. We validate this theory using fast-scan cyclic voltammetry and [11C]raclopride PET in mice during chemogenetic activation of dopaminergic neurons. We then apply the method to data from human subjects given a palatable milkshake and discover immediate and—for the first time—delayed food-induced dopamine release. This method enables time-dependent regional monitoring of stimulus-evoked dopamine release at physiological levels.

Olfactory perception determines food selection behavior depending on energy homeostasis and nutritional status. The mechanisms, however, by which metabolic signals in turn regulate olfactory perception remain largely unclear. Given the evidence for direct insulin action on olfactory neurons, we tested olfactory performance (olfactory threshold, olfactory discrimination) in 36 subjects of normal- and overweight after administration of three different insulin doses (40 I.U., 100 I.U., 160 I.U.) or corresponding placebo volume in a within-subject design. Poor peripheral insulin sensitivity as quantified by HOMA-IR in baseline condition and increases in systemic insulin levels reactive to intranasal administration predicted poor olfactory performance. In contrast, intranasal insulin enhanced odor perception with a dose-dependent improvement of olfactory threshold. These findings indicate a new diametric impact of insulin on olfactory perception depending on peripheral or central availability.

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