Altered striatal-opercular intrinsic connectivity reflects decreased aversion to losses in alcohol use disorder

The persistence of addictive behaviours despite their adverse consequences highlights decreased punishment sensitivity as a facet of decision-making impairments in Alcohol Use Disorder (AUD). This attitude departs from the typical loss aversion (LA) pattern, i.e. the stronger sensitivity to negative than positive outcomes, previously associated with striatal and limbic-somatosensory responsiveness in healthy individuals. Consistent evidence highlights decreased LA as a marker of disease severity in AUD, but its neural bases remain largely unexplored. AUD-specific modulations of frontolateral activity by LA were previously related to the higher executive demands of anticipating losses than gains, but the relationship between LA and executive/working-memory performance in AUD is debated. Building on previous evidence of overlapping neural bases of LA during decision-making and at rest, we investigated a possible neural signature of altered LA in AUDs, and its connections with executive skills, in terms of complementary facets of resting-state functioning. In patients, smaller LA than controls, unrelated to executive performance, reflected reduced connectivity within striatal and medial temporal networks, and altered connectivity from these regions to the insular-opercular cortex. AUD-specific loss-related modulations of intrinsic connectivity thus involved structures previously associated both with drug-seeking and with coding the trade-off between appetitive and aversive motivational drives. These findings fit the hypothesis that altered striatal coding of choice-related incentive value, and interoceptive responsiveness to prospective outcomes, enhance neural sensitivity to drug-related stimuli in addictions. LA and its neural bases might prove useful markers of AUD severity and effectiveness of rehabilitation strategies targeting the salience of negative choice outcomes.