Validation-Aware Retrospective EEG Treatment-Response Modelling Using Chaotic Pattern of Prime Numbers Features: Segment-Level Separability and Subject-Wise Generalisation.

This study presents a validation-aware EEG framework based on Chaotic Pattern of Prime Numbers (CPPN) features for depression treatment-response modelling across one SSRI cohort and two rTMS cohorts. CPPN features were evaluated through a seven-protocol validation hierarchy spanning random segment splitting, segment-level cross-validation, nested segment-level cross-validation, leave-N-subjects-out, fixed-feature leave-one-subject-out (LOSO), nested leave-N-subjects-out, and nested LOSO, with normalisation, NCA ranking, feature-count selection where applicable, and model fitting confined to the appropriate training partitions. In the representative K-nearest neighbour (KNN) comparison, segment-level 10-fold CV achieved accuracies of 98.79% for Mumtaz SSRI, 99.32% for small Atieh rTMS, and 99.42% for big Atieh rTMS, demonstrating strong discriminative structure in the CPPN feature space. In the available segment-level KNN comparison, CPPN features with fold-internal NCA-selected feature sets exceeded conventional statistical EEG features by 29.53, 16.33, and 11.45 percentage points across the three cohorts. Subject-wise validation produced lower and more cohort-dependent estimates, with the best fixed-feature LOSO accuracy of 80.00% and the best nested LOSO accuracy of 73.33% in the small Atieh rTMS cohort. These results show that CPPN provides a compact, inspectable and computationally accessible EEG feature representation, while the validation hierarchy gives a transparent account of how performance changes from segment-level separability to held-out-subject evaluation. The main contribution is methodological: this study combines an original CPPN feature representation with explicit validation-depth analysis, leakage-aware feature selection, and interpretable channel/bin inspection. It therefore provides a rigorous basis for future externally validated EEG treatment-response studies without claiming prospective clinical deployment from the present retrospective cohorts.