Abstract
Background: Delusions are the fixed false beliefs that characterize serious mental illnesses like schizophrenia. Prediction errors are surprise signals that guide learning. They have been observed during causal learning in the right dorsolateral prefrontal cortex (rDLPFC). They are registered inappropriately in people with delusions, driving learning towards irrelevant events. This learning correlates with delusion severity. We do not know, however, whether the rDLPFC is receiving the error signal, bottom-up, from other nodes, or, alternatively, whether rDLPFC prediction errors are communicated top-down from rDLPFC. It is also possible that the direction of processing differs between patients with delusions compared with otherwise healthy individuals who espouse delusion-like beliefs but are not delusional per se. Methods: Here, we attempt to distinguish these possibilities using cognitive computational neuroimaging, functional, and effective connectivity analyses of task-based fMRI data in people with schizophrenia (SZ, n=29), people with extreme esoteric beliefs (EEB, n=25), and controls with neither (CTR, n=24), focusing on prediction error processing. Results: During Kamin Blocking of causal learning people who endorse delusions evince aberrant prediction error signals in right dorsolateral prefrontal cortex and anterior insula which correlate with delusion severity. Psychophysiological interaction analysis reveals errant coupling between these regions in people with delusions. Effective connectivity analysis locates the dysfunction in schizophrenia to bottom-up prediction error drive from insula to DLPFC. Conclusion: These data provide quantitative computational metrics for distinguishing delusions from other less problematic beliefs and establish that, in schizophrenia, aberrant prediction errors during causal learning arise from errant bottom-up drive from the insula to the rDLPFC. This may then serve as a marker for clinically relevant odd belief and a target for treatment.