Positive alcohol expectancy and resting-state functional connectivity of the insula in problem drinking

Positive alcohol expectancy (AE), a significant predictor of excessive alcohol consumption, is associated with heightened drinking motivation and reduced control. As the insula interacts with the limbic and prefrontal structures to integrate stimulus saliency, interoception, and cognitive control, the region may play a unique role in modulating AE. Here, we examined resting-state functional connectivity of the right and left insula in relation to AE in 180 adult drinkers. Whole-brain multiple regressions and path analysis were performed to delineate the inter-relationship between AE, insular connectivity, and drinking severity. We found that heightened AE was associated with diminished right insular connectivity with regions involved in negative emotion processing and self-control, including the amygdala, putamen, and ventromedial prefrontal cortex. In contrast, there was a positive relationship between AE and right insular connectivity with regions implicated in motivated responses to alcohol stimuli, including the superior parietal lobule, postcentral and superior frontal gyri. Path analysis showed that the two sets of right insular connectivity exhibited opposing associations with AE and that their net strength (i.e., "control minus motivation") was negatively correlated with AE and drinking severity. Analyses of the left insula seed, in contrast, did not yield regional connectivity in significant correlation with AE. These findings highlight the roles of right insula connectivity in motivational and regulatory processes that may differentially modulate drinking behavior. Recruitment of the motivational circuit and/or disengagement of the affective control circuit would be associated with heightened AE and heavier alcohol consumption.