Expectation modulates the hedonic experiences of and midbrain responses to sweet flavour

Non-nutritive sweeteners are sugar substitutes that may promote weight management by reducing an individual’s calorie intake. It is, however, unclear whether (i) sugar and non-nutritive sweetener elicit distinct orosensory responses in the human brain, and (ii) whether the neural responses to these flavours are modulated by expectancy. Addressing these questions has direct relevance to our understanding of food choice behaviour and how it may be modified in dietary interventions. We screened N=99 healthy adults of either sex to select a sample (N=27, M[SD] age = 24.25[2.94] years) who reported similar perceptual experiences of sugar and sweetener, thus removing a potential confound of sensory differences, for fMRI scanning. While scanning, they received sugar- and artificially-sweetened beverages in two conditioning paradigms, which manipulated participants' expectation of flavour delivery: first in a probabilistic and second in a deterministic way. Participants' ability to accurately distinguish sugar from non-nutritive sweetener depended largely on their expectations, which also significantly affected the perceived pleasantness of each flavour. Expectation altered brain responses to flavour delivery during the deterministic task only, where the (mistaken) expectation of sugar significantly increased midbrain responses to sweetener compared to when sweetener was expected. Trial-wise confidence and pleasantness ratings differentially scaled with brain responses to sugar and sweetener delivery. These results highlight the importance of expectancy in both the behavioural and neural encoding of sweet flavour, particularly when sensory information is unreliable. The expectation of sugar appears to increase the subjective value of noncaloric sweetener, which may result from flavour-nutrient conditioning that preferentially reinforcers sugar. Significance statement Artificial sweeteners have become common alternatives to sugar-sweetened beverages. The perceived reward from sweet flavour depends not only on the sweetener but also on our expectations of its resulting pleasantness. However, it remains unknown if shared brain circuits encode sugar and non-nutritive sweetener—and our expectations surrounding them. Here, we examined brain responses to sugar- and artificially-sweetened beverages in healthy humans who could not reliably discriminate them, and we manipulated their expectation of flavour delivery. Expectation altered participants' accuracy and perceived pleasantness of each flavour, where the expectation of sugar increased midbrain responses and perceived pleasantness of artificial sweetener. The rewarding effects of sugar appeared to exceed those of sweetener, which may reflect flavour-nutrient conditioning that shapes food choice behaviour.