High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study

Abstract

High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (Sucrose_High)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SR_enjoy) and sedative (SR_sed) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SR_enjoy on the prime's ascending limb correlated positively with [Sucrose_High > Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.