Neural correlates of prediction error in patients with schizophrenia: evidence from an fMRI meta-analysis

Abnormal processes of learning from prediction errors, i.e. the discrepancies between expectations and outcomes, are thought to underlie motivational impairments in schizophrenia. Although dopaminergic abnormalities in the mesocorticolimbic reward circuit have been found in patients with schizophrenia, the pathway through which prediction error signals are processed in schizophrenia has yet to be elucidated. To determine the neural correlates of prediction error processing in schizophrenia, we conducted a meta-analysis of whole-brain neuroimaging studies that investigated prediction error signal processing in schizophrenia patients and healthy controls. A total of 14 studies (324 schizophrenia patients and 348 healthy controls) using the reinforcement learning paradigm were included. Our meta-analysis showed that, relative to healthy controls, schizophrenia patients showed increased activity in the precentral gyrus and middle frontal gyrus and reduced activity in the mesolimbic circuit, including the striatum, thalamus, amygdala, hippocampus, anterior cingulate cortex, insula, superior temporal gyrus, and cerebellum, when processing prediction errors. We also found hyperactivity in frontal areas and hypoactivity in mesolimbic areas when encoding prediction error signals in schizophrenia patients, potentially indicating abnormal dopamine signaling of reward prediction error and suggesting failure to represent the value of alternative responses during prediction error learning and decision making.