Impaired error-likelihood prediction in medial prefrontal cortex in schizophrenia.

The cognitive impairment in individuals with schizophrenia includes deficits of working memory in dorsolateral prefrontal cortex and deficits of performance monitoring in medial prefrontal cortex (MPFC). Recent work suggests a more general role for MPFC in predicting the outcome of actions and then evaluating those predictions. Here we investigate, in individuals with schizophrenia, two specific effects associated with this role: the error likelihood effect (occurring on trials with correct performance, but features that predict a high probability of errors), and the error unexpectedness effect (occurring on trials with an error, but features that predict errors are of low probability). In a rapid event-related fMRI design with a modified version of the change-signal task, a cue incidentally predicting error likelihood was encoded into working memory by participants in order to perform a secondary delayed match-to-sample task. There were four key findings: (1) individuals with schizophrenia exhibited poorer working memory performance and reduced error signals in MPFC; (2) even in control and schizophrenia subgroups matched on working memory performance, the schizophrenia subgroup showed a deficit in error-likelihood prediction in MPFC at the time of the predictive cue; (3) the schizophrenia subgroup also showed a deficit in evaluative error-unexpectedness activity when errors were committed; and (4) a mediation analysis indicated that error-likelihood predictions successfully explained error-unexpectedness evaluations in both controls and patients. Collectively, these findings suggest that individuals with schizophrenia have a disturbance in the evaluation of outcomes that is the result of a primary deficit in the prediction of error likelihood in MPFC.