Appetitive and aversive cue reactivities differentiate neural subtypes of alcohol drinkers

Craving reflects the subjective urge to use drugs and can be triggered by both positive and negative emotional states. No studies have systematically investigated the relative roles of these mechanisms in the pathophysiology of substance misuse. Here, we performed meta-analyses of drug cue-elicited reactivity and win and loss processing in the monetary incentive delay task to identify distinct neural correlates of appetitive and aversive responses to drug cues. We then characterized the appetitive and aversive cue responses in seventy-six alcohol drinkers performing a cue craving task during fMRI. Imaging data were processed according to published routines. The appetitive circuit involved medial cortical regions and the ventral striatum, and the aversive circuit involved the insula, caudate and mid-cingulate cortex. We observed a significant correlation of cue-elicited activity (β estimates) of the appetitive and aversive circuit. However, individuals varied in appetitive and aversive cue responses. From the regression of appetitive (y) vs. aversive (x) β, we identified participants in the top 1/3 each of those with positive and negative residuals as “approach” (n = 15) and “avoidance” (n = 11) and the others as the “mixed” (n = 50) subtype. In clinical characteristics, the avoidance subtype showed higher sensitivity to punishment and, in contrast, the approach subtype showed higher levels of sensation seeking and alcohol expectancy for social and physical pressure. The findings highlighted distinct neural underpinnings of appetitive and aversive components of cue-elicited reactivity and provided evidence for potential subtypes of alcohol drinkers.