Wavelet Scattering Transform for Interpretable Schizophrenia Biomarker Discovery and Classification from Resting-State EEG

Schizophrenia is a debilitating neuropsychiatric disorder characterized by profound cortical network dysregulation, for which objective, clinically translatable EEG based biomarkers remain underdeveloped. Existing automated classification pipelines rely predominantly on static power spectral density features inherently blind to amplitude modulation dynamics and cross-frequency coupling, phenomena central to schizophrenia pathophysiology, while adopting epoch level cross validation strategies that introduce temporal data leakage, artificially inflate reported performance.

This study introduces a mathematically principled diagnostic framework integrating the multi-order Wavelet Scattering Transform(WST), strict Leave One Subject Out (LOSO) cross-validation, and SHAP explainability for simultaneous EEG classification and biomarker discovery. Hierarchical WST coefficients capturing multi-scale amplitude modulation structure were extracted from resting state multichannel EEG.

Subject-level ANOVA with Benjamini Hochberg false discovery rate correction identified significant biomarkers, with Random Forest and SVM classifiers evaluated under strict LOSO cross validation and subject-level majority voting. Second-order scattering coefficients encoding cross frequency coupling dominated the discriminative biomarker set, with gamma-band features most prevalent, demonstrating that temporal amplitude modulation constitutes the primary electrophysiological signature of schizophrenia.

Electrode P3 was identified as the single most discriminative site. Under rigorous subject independent evaluation, the Random Forest achieved 90.48% accuracy (AUC = 0.9339; sensitivity = 95.56%).

The proposed WST framework establishes a rigorous, interpretable standard for EEG-driven psychiatric biomarker discovery that can also be applicable in the detection of schizophrenia subtypes in the future.