Deep Learning CNN and Recurrence Analysis for Alpha Gamma EEG Biomarkers in Fragile X Syndrome

Repetitive transcranial magnetic stimulation (rTMS) is a non invasive therapy for Major Depressive Disorder (MDD). In this study, we generate images using two time frequency methods to represent EEG signals: Fourier-Bessel Series Expansion with Euclidean Distance (FBSE-ED) and Discrete Wavelet Transform (DWT). We propose an efficient deep learning classifier to predict the outcome of rTMS depression therapy. In this study, we use a private rTMS databases to train a lightweight custom Convolutional Neural Network (CNN) using 10-fold cross validation strategy in order to avoid any bias in our results. The results show that the FBSE-ED representation achieves the highest classification accuracy of 93.60%, outperforming traditional time-frequency technique (DWT). In addition, the proposed architecture with FBSE-ED image representation technique outperforms more complex EEG-Specific deep learning models (EEGNet, DeepConvNet, SleepEEGNet) by 3.62-10.72% and pretrained models (Xception, DenseNet201, and MobileNetV2) by 23.03-27.35%. For more experiments, we utilize another private rTMS database as test database to show the robustness of the proposed model. Our results suggest that integrating advanced signal decomposition with deep learning can facilitate early prediction of rTMS treatment response and support more targeted clinical decision-making. The proposed framework is interpretable, computationally efficient, and well-suited for deployment in real-world local psychiatric clinics.

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.

Deep learning for EEG-based seizure detection faces critical challenges: severe annotation scarcity and extreme class imbalance, where ictal events comprise less than 10% of clinical recordings. We present DiffEEG, a 9.6M-parameter self-supervised foundation model that addresses both limitations through denoising diffusion pre-training and reinforcement learning (RL)-based fine-tuning. Pre-trained on 1.3M unlabeled segments from the Temple University Hospital Seizure Corpus (TUHSZ), DiffEEG learns generic neural representations via a 1D U-Net with multi-head self-attention. For downstream adaptation, a reinforced decision layer employs policy gradient optimization to directly maximize F1-score, prioritizing sensitivity to rare seizure events over overall accuracy. Under strict patient-wise evaluation (279 patients, Leave-One-Fold-Out), DiffEEG achieves 61% accuracy and 59% F1 for 4-class seizure subtyping, and 81% accuracy with 85% weighted F1 for binary detection, maintaining clinically viable seizure recall (59%) despite extreme imbalance (6.7% prevalence). Segment-level evaluation establishes an upper bound of 97.6% accuracy, confirming strong architectural capacity. DiffEEG demonstrates that diffusion-based pre-training combined with metric-aware reinforcement learning enables clinically deployable seizure monitoring with minimal labeled data requirements.