Cortical salience network activation precedes the development of delusion severity

Background: Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown. Method: To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale. Results: Both tasks activated the CSN in comparison with rest. Activation of CSN (‘illness evaluation v. control task’ contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation. Conclusions: Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.