Background: Schizophrenia (SCZ) is associated with abnormal neural activities and brain connectivity. Electroencephalography (EEG) microstate is a voltage topographical representation of temporary brain network activations. Most research on EEG microstates in SCZ has focused on differences between patients and healthy controls (HC). However, changes in EEG microstates among SCZ patients across various stages of physiological and cognitive development have not been thoroughly assessed. Consequently, we stratified patients with SCZ into four age-specific cohorts (20-29 years (brain maturation), 30-39 years (stabilization), 40-49 years (early aging), and 50-59 years (advanced aging)) to evaluate EEG microstate alterations. Additionally, we assessed changes in EEG microstates in first-episode psychosis (FEP) before and after an 8-week treatment period.

Methods: We acquired 19-channel resting-state EEG from 140 chronic SCZ patients, aged 20 to 59 years, as well as from 19 FEP and 20 healthy controls. FEP patients underwent an 8-week inpatient follow-up. After pre-processing, EEG data from different groups were subjected to microstate analysis, and the K-Means clustering algorithm was applied to classify the data into 4 microstates. Subsequently, templates of these microstates were used to fit EEG signals from each patient, and the collected microstate parameters were analyzed.

Results: Patients with SCZ aged 20 to 29 years demonstrated an increased time coverage of microstate class D compared to other age cohorts. In individuals aged 30-39 years, the parameters of microstate class B-specifically time coverage and occurrence-exhibited significant reductions relative to those in the 40-49 and 50-59 years age groups. Compared to healthy controls, microstates class A parameters were significantly reduced in SCZ patients, while microstates class C parameters were prolonged; after 8 weeks of treatment, microstates class A parameters increased and microstates class C parameters decreased.

Conclusions: Alterations in microstate dynamics were observed among SCZ patients across developmental stages, suggesting potential changes in brain activity patterns. Changes in microstates A and C may serve as potential biomarkers for evaluating treatment efficacy, establishing a foundation for personalized therapeutic approaches.

Keywords: EEG microstates; aging; medication; resting state networks; schizophrenia.

© 2025 The Author(s). Published by IMR Press.