The differential neural substrates for reward choice under gain-loss contexts and risk in alcohol use disorder: Evidence from a voxel-based meta-analysis

Making a risky decision is a complex process that involves the evaluation of both the values of the options and the associated risk level; this process is distinct from reward processing in gain versus loss contexts. Although disrupted reward processing in mesolimbic dopamine circuitry is suggested to underlie pathological incentive processing in patients with alcohol use disorder (AUD), the differential neural processes subserving these motivational tendencies for risk situations or gain/loss choices in decision-making have not been identified.To examine the common or distinct neural mechanisms in the evaluation of risk versus outcomes for AUD, we conducted two separate coordinate-based meta-analyses of functional neuroimaging studies by using Seed-Based d Mapping software to evaluate 13 studies investigating gain and loss processing and 10 studies investigating risky decision-making.During gain and loss processing, relative to healthy controls, AUD patients showed reduced activation in the mesocortical-limbic circuit, including the orbital prefrontal cortex (OFC), dorsal striatum, insula, hippocampus, cerebellum, cuneus cortex and superior temporal gyrus, but hyperactivation in the inferior temporal gyrus and paracentral lobule (extending to the middle cingulate cortex (MCC) and precuneus). During decision-making under risk, AUD patients exhibited hypoactivity of the prefrontal and cingulate cortices, including the posterior cingulate cortex (extending to the MCC), middle frontal gyrus, medial prefrontal cortex, dorsolateral prefrontal cortex, OFC and anterior cingulate cortex.Our results extend existing neurological evidence by showing that a reduced response in the mesocortical-limbic circuit is found in gain versus loss processing, with decreased responsivity in cortical regions in risk decision-making. Our results implicate dissociable neural circuit responses for gain-loss processing and risk decision-making, which contribute to a better understanding of the pathophysiological mechanism underlying nondrug incentive and risk processing in individuals with AUD.