Our findings are consistent with the putative disruptions to components of reward circuitry in addiction. The mPFC was central to our findings, with altered function in response to reward, altered coordination with the nucleus accumbens, and functional associations with pathophysiologic characteristics of alcohol dependence. This region has several key functions in the processing of reward, including both responding directly to reward as a target of midbrain dopamine neurons and serving as a regulatory region for striatal response to reward [8]. The dorsal mPFC is also thought to work in coordination with the DLPFC to regulate affective response [35]. Thus, our findings of less mPFC response to monetary reward in adults with alcohol dependence—and in those alcohol-dependent adults with a family history of the disorder—suggest that low responding in this region could reflect ineffective modulation of basic reward responding in a way that facilitates addictive behavior. This change in modulation could be a stable vulnerability in those with high familial loading for alcohol-related problems. Our findings of altered mPFC functional connectivity with the nucleus accumbens in alcohol dependent adults, as well
