Neural substrates of reward anticipation and outcome in schizophrenia: a meta-analysis of fMRI findings in the monetary incentive delay task

Dysfunction of the mesocorticolimbic dopaminergic reward system is a core feature of schizophrenia (SZ), yet its precise contributions to different stages of reward processing and their relevance to disease symptomology are not fully understood. We performed a coordinate-based meta-analysis, using the monetary incentive delay task, to identify which brain regions are implicated in different reward phases in functional magnetic resonance imaging in SZ. A total of 17 studies (368 SZ and 428 controls) were included in the reward anticipation, and 10 studies (229 SZ and 281 controls) were included in the reward outcome. Our meta-analysis revealed that during anticipation, patients showed hypoactivation in the striatum, anterior cingulate cortex, median cingulate cortex (MCC), amygdala, precentral gyrus, and superior temporal gyrus compared with controls. Striatum hypoactivation was negatively associated with negative symptoms and positively associated with the proportion of second-generation antipsychotic users (percentage of SGA users). During outcome, patients displayed hyperactivation in the striatum, insula, amygdala, hippocampus, parahippocampal gyrus, cerebellum, postcentral gyrus, and MCC, and hypoactivation in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC). Hypoactivity of mPFC during outcome was negatively associated with positive symptoms. Moderator analysis showed that the percentage of SGA users was a significant moderator of the association between symptom severity and brain activity in both the anticipation and outcome stages. Our findings identified the neural substrates for different reward phases in SZ and may help explain the neuropathological mechanisms underlying reward processing deficits in the disorder.