Distinct neurofunctional alterations during motivational and hedonic processing of natural and monetary rewards in depression – a neuroimaging meta-analysis

Reward processing alterations have been suggested as a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate reward processing deficits in depression. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary (extrinsic) and natural (intrinsic) rewards in depression have not been systematically examined. Here, we capitalized on a series of pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during anticipation of monetary rewards, receipt of monetary rewards, and receipt of natural rewards, and, (3) characterize the differences on the behavioral, network and molecular level. The coordinate-based meta-analysis included a total of 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex (ACC) and striatal reactivity towards rewards in depression. Subsequent quantitative comparison analysis indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen. These regions exhibited distinguishable profiles on the behavioral, network and receptor level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, particularly with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.