Aberrant attribution of salience to in fact little informative events might explain the emergence of positive symptoms in schizophrenia and has been linked to belief uncertainty. Uncertainty is thought to be encoded by neuromodulators, including norepinephrine. However, norepinephrinergic encoding of uncertainty, measured as task-related pupil dilation, has rarely been explored in schizophrenia. Here, we addressed this question by comparing individuals with a disorder from the schizophrenia spectrum to a non-psychiatric control group on behavioral and pupillometric measures in a probabilistic prediction task, where different levels of uncertainty were introduced. Behaviorally, patients performed similar to controls, but their belief uncertainty was higher, particularly when instability of the task environment was high, suggesting an increased sensitivity to this instability. Furthermore, while pupil dilation scaled positively with uncertainty, this was less the case for patients, suggesting aberrant neuromodulatory regulation of neural gain, which may hinder the reduction of uncertainty in the long run. Together, the findings point to abnormal uncertainty processing and norepinephrinergic signaling in schizophrenia, potentially informing future development of both psychopharmacological therapies and psychotherapeutic approaches that deal with the processing of uncertain information.Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
About The Expert