Posterior fronto-medial atrophy reflects decreased loss aversion, but not executive impairment, in alcohol use disorder.

Decreased punishment sensitivity in alcohol use disorder (AUD) might reflect a reduction in the typical human tendency to overweigh negative choice outcomes compared with equivalent positive ones, that is, 'loss aversion.' While this hypothesis is supported by previous reports of reduced loss aversion in AUD, it is still unknown whether such decreased sensitivity to prospective losses represents a specific facet of altered decision-making or a secondary effect of executive/working-memory impairments. We addressed this issue by assessing whether lower loss aversion in 22 AUD patients compared with 19 healthy controls is explained by their differential executive or working-memory performance and by investigating its neural basis in terms of grey matter density and cortical thickness via voxel- and surface-based morphometry, respectively. A significant decrease of loss aversion in patients, unrelated to their impaired executive/working-memory performance, reflected the reduction of posterior fronto-medial grey matter density and right frontopolar cortical thickness. Rather than their executive deficits, patients' reduced loss aversion reflects the structural damage of the posterior fronto-medial cortex previously associated with solving conflicts at the response level, where earlier functional magnetic resonance imaging (fMRI) studies have shown a 'neural loss aversion' pattern of steeper deactivation for losses than activation for gains, and of the frontopolar cortex in charge of managing competing goals. These findings highlight possible directions for addressing AUD patients' high relapse rate, for example, cognitive-behavioural rehabilitative interventions enhancing the awareness of the adverse outcomes of addiction or neurostimulation protocols targeting the regions processing their salience.