Biomarkers for Prediction of Schizophrenia: Insights From Resting-State EEG Microstates

Schizophrenia is a devastating disease with a prevalence of 1% in populations around the world. Current diagnostic techniques of schizophrenia and high-risk population are based on subjective psychiatric interviews. Early diagnosis and intervention can mitigate progression and improve treatment outcomes. However, the lack of biomarkers that support objective examinations has been a long-term bottleneck in clinical diagnosis and assessment of schizophrenia and its high-risk state. In the present study, resting-state 128-channel electroencephalogram (EEG) data were acquired from 65 participants, including clinically-stable individuals with first-episode schizophrenia (FESZ), individuals at ultra-high-risk (UHR) and high-risk (HR), and healthy controls (HC). Microstate analysis was used to assess the dynamics of functional networks in these participants. Three features were extracted for each class of microstate (A, B, C, D, E, F): duration, occurrence and time coverage. Furthermore, clinical examinations and cognitive tests were performed. Behavioral results showed poorer performances in the participants as the disease progressed. Moreover, microstate features computed from resting-state EEG microstates (especially microstate class D) were capable of distinguishing the four groups of individuals. Combined biomarkers including clinical examinations, cognitive tests and EEG microstate parameters were identified as a potential effective diagnostic tool, achieving the highest classification performance using the random forest model compared with the support vector machine (SVM) and long short term memory (LSTM) networks, with an average classification of 92%, mean sensitivity of 91.8%, and specificity of 90.8% among the four groups, which were much higher than that only using behavioral features. The results demonstrate that microstate-based indicators together with behavioral results may act as biomarkers for early diagnosis and prediction of at-risk individuals of schizophrenia. Furthermore, our findings illustrate the potential use of resting-state EEG in clinical screening, classification and quantitative evaluation of patients with neurodevelopmental disorders.