Reward Feedback Alterations in Unmedicated Schizophrenia Patients: Relevance for Delusions

Background: Increased attribution of incentive salience to neutral or aversive stimuli might be associated with dysfunction of neuronal processing of positive and negative reinforcement and contribute to the formation of delusions in schizophrenia. Methods: Fifteen unmedicated patients with schizophrenia (8 drug-naive and 7 drug-free for at least 3 months) and 15 age- and gender-matched healthy control participants underwent functional magnetic resonance imaging to investigate neural responses to feedback of (successful vs. unsuccessful) monetary gain or avoidance of loss. Functional connectivity was assessed between the medial prefrontal cortex (MPFC) and ventral striatum (VS), brain areas known to be activated by feedback of reward and loss. Results: Responses to negative outcome in reward trials (omission of expected reward) were exaggerated in the MPFC of patients with schizophrenia. In contrast, schizophrenia patients showed reduced neural responses to successful versus unsuccessful avoidance of loss in the VS. Increased severity of delusions in schizophrenia patients was associated with a decrease in MPFC activation elicited by successful versus unsuccessful avoidance of loss. Functional connectivity between the MPFC and the VS was reduced in patients with schizophrenia compared with healthy control subjects. Conclusions: These findings demonstrate a differential impairment of-and reduced connectivity between-VS and MPFC during processing of reward and loss-avoidance in drug-free patients with schizophrenia. Moreover, our results provide a link between the formation of delusions and the neural processing of aversive outcomes.