Towards the Development of a Deep Learning Framework Using Adaptive and Non-Adaptive Time-Frequency Features for EEG-Based Depression Therapy Prediction

<b>Background/Objectives:</b> Predicting individual response to depression therapy prior to treatment initiation remains a critical clinical challenge, as the response rate to both selective serotonin reuptake inhibitors (SSRIs) and repetitive transcranial magnetic stimulation (rTMS) is approximately 50%, leaving treatment selection largely trial-based. This study presents a computer-aided decision (CAD) framework that predicts depression therapy outcomes from pre-treatment electroencephalogram (EEG) signals using advanced time-frequency representations and pretrained convolutional neural networks (CNNs). <b>Methods:</b> EEG signals from 30 SSRI patients and 46 rTMS patients are transformed into time-frequency images using Continuous Wavelet Transform (CWT), Variational Mode Decomposition (VMD), and their pixel-level fusion. Four pretrained CNN architectures, including ResNet-18, MobileNet-V3, EfficientNet-B0, and TinyViT-Hybrid, are fine-tuned and evaluated under both image-independent and subject-independent 6-fold cross-validation (CV). <b>Results:</b> Results reveal a clear therapy-specific pattern: CWT-based representations yield superior discrimination for SSRI outcome prediction, with ResNet-18 achieving 99.43% image-level accuracy, while VMD-based representations are statistically superior for rTMS outcome prediction, with ResNet-18 reaching 98.77%. Pixel-level fusion of CWT and VMD does not consistently improve performance over the best individual representation in either therapy context. Pairwise Wilcoxon signed-rank tests confirm a two-tier architectural hierarchy in which ResNet-18 and TinyViT-Hybrid significantly outperform MobileNet-V3 and EfficientNet-B0 across all conditions, while remaining statistically indistinguishable from each other. At the subject level, the framework achieves 82.50% and 83.53% accuracy for SSRI and rTMS, respectively, under strict subject-independent evaluation. Per-channel analysis reveals occipital dominance for SSRI under CWT and frontotemporal dominance for rTMS under VMD, consistent with known neurophysiological mechanisms. <b>Conclusions:</b> These findings demonstrate that the choice of time-frequency representation is therapy-specific and at least as important as architectural complexity, and that competitive performance can be achieved without recurrent or attention layers by combining well-designed spectral images with a simple pretrained residual network.