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.

Aberrations in how people form expectations about rewards and how they respond to receiving rewards are thought to underlie major depressive disorder (MDD). However, the underlying mechanism linking the appetitive reward system, specifically anticipation and outcome, is still not fully understood. To examine the neural correlates of monetary anticipation and outcome in currently depressed subjects with MDD, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies using the monetary incentive delay task. During reward anticipation, the depressed patients exhibited an increased response in the bilateral middle cingulate cortex (MCC) extending to the anterior cingulate cortex, the medial prefrontal cortex, the left inferior frontal gyrus (IFG), and the postcentral gyrus, but a reduced response in the mesolimbic circuit, including the left striatum, insula, amygdala, right cerebellum, striatum, and IFG, compared to controls. During the outcome stage, MDD showed higher activity in the left inferior temporal gyrus, and lower activity in the mesocortical pathway, including the bilateral MCC, left caudate nucleus, precentral gyrus, thalamus, cerebellum, right striatum, insula, IFG, middle frontal gyrus, and temporal pole. Our findings suggest that cMDD may be characterised by state-dependent hyper-responsivity in cortical regions during the anticipation phase, and hypo-responsivity of the mesocortico-limbic circuit across the two phases of the reward response. Our study showed dissociable neural circuit responses to monetary stimuli during reward anticipation and outcome, which help to understand the dysfunction in different aspects of reward processing, particularly motivational v. hedonic deficits in depression.

The capacity to anticipate and detect rewarding outcomes is fundamental for the development of adaptive decision‐making and goal‐oriented behavior. Delineating the neural correlates of different stages of reward processing is imperative for understanding the neurobiological mechanism underlying alcohol use disorder (AUD). To examine the neural correlates of monetary anticipation and outcome in AUD patients, we performed two separate voxel‐wise meta‐analyses of functional neuroimaging studies, including 12 studies investigating reward anticipation and 7 studies investigating reward outcome using the monetary incentive delay task. During the anticipation stage, AUD patients displayed decreased activation in response to monetary cues in mesocortical‐limbic circuits and sensory areas, including the ventral striatum (VS), insula, hippocampus, inferior occipital gyrus, supramarginal gyrus, lingual gyrus and fusiform gyrus. During the outcome stage, AUD patients exhibited reduced activation in the dorsal striatum, VS and insula, and increased activation in the orbital frontal cortex and medial temporal area. Our findings suggest that different activation patterns are associated with nondrug rewards during different reward processing stages, potentially reflecting a changed sensitivity to monetary reward in AUD.

Background Aberrant striatal responses to reward anticipation have been observed in schizophrenia. However, it is unclear whether these dysfunctions predate the onset of psychosis, and whether reward anticipation is impaired in individuals at clinical high risk for schizophrenia (CHR). Methods To examine the neural correlates of monetary anticipation in the prodromal phase of schizophrenia, we performed a whole-brain meta-analysis of thirteen functional neuroimaging studies that compared reward anticipation signals between CHR individuals and healthy controls (HC). Three databases (PubMed, Web of Science, and ScienceDirect) were systematically searched from 1 January 2000 to 1 May 2022. Results Thirteen whole-brain functional magnetic resonance imaging (fMRI) studies including 318 CHR subjects and 426 HC were identified through comprehensive literature searches. Relative to HC, CHR subjects showed increased brain responses in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), and decreased activation in the mesolimbic circuit, including the putamen, parahippocampal gyrus, insula, cerebellum, and supramarginal gyrus, during reward anticipation. Conclusions Our findings in the CHR group confirmed the existence of abnormal motivational-related activation during reward anticipation, thus demonstrating the pathophysiological characteristics of the risk populations. These results have the potential to lead to the early identification and more accurate prediction of subsequent psychosis, as well as a deeper understanding of the neurobiology of high-risk state of psychotic disorder.