EEG microstate biomarkers for schizophrenia: a novel approach using deep neural networks

Schizophrenia remains a challenging neuropsychiatric disorder with complex diagnostic processes. Current clinical approaches often rely on subjective assessments, highlighting the critical need for objective, quantitative diagnostic methods. This study aimed to develop a robust classification approach for schizophrenia using EEG microstate analysis and advanced machine learning techniques. We analyzed EEG signals from 14 healthy individuals and 14 patients with schizophrenia during a 15-min resting-state session across 19 EEG channels. A data augmentation strategy expanded the dataset to 56 subjects in each group. The signals were preprocessed and segmented into five frequency bands (delta, theta, alpha, beta, gamma) and five microstates (A, B, C, D, E) using k-means clustering. Five key features were extracted from each microstate: duration, occurrence, standard deviation, coverage, and frequency. A Deep Neural Network (DNN) model, along with other machine learning classifiers, was developed to classify the data. A comprehensive fivefold cross-validation approach evaluated model performance across various EEG channels, frequency bands, and feature combinations. Significant alterations in microstate transition probabilities were observed, particularly in higher frequency bands. The gamma band showed the most pronounced differences, with a notable disruption in D → A transitions (absolute difference = 0.100). The Random Forest classifier achieved the highest accuracy of 99.94% ± 0.12%, utilizing theta band features from the F8 frontal channel. The deep neural network model demonstrated robust performance with 98.31% ± 0.68% accuracy, primarily in the occipital region. Feature size 2 consistently provided optimal classification across most models. Our study introduces a novel, high-precision EEG microstate analysis approach for schizophrenia diagnosis, offering an objective diagnostic tool with potential applications in neuropsychiatric disorders. The findings reveal critical insights into neural dynamics associated with schizophrenia, demonstrating the potential for transforming clinical diagnostic practices through advanced machine learning and neurophysiological feature extraction.