Explainable Deep Learning for MRI-Negative Temporal Lobe Epilepsy: Classification and Brain Region Analysis

Background/Objectives: Deep learning has achieved remarkable success in medical image analysis; however, limited model interpretability remains a major barrier to its clinical translation. MRI-negative temporal lobe epilepsy (TLE) is characterized by the absence of readily identifiable structural abnormalities on conventional MRI. Methods: We propose a hierarchical, multiscale 3D residual network (H-MSResNet) combined with layer-wise relevance propagation (LRP). The study included structural T1-weighted MRIs from 101 patients with MRI-negative TLE and 101 healthy controls. Model classification performance was evaluated using a fivefold cross-validation approach. Subsequently, group-level LRP analysis was integrated with a standard brain atlas to quantify the anatomical regions contributing to the model’s decisions. Results: H-MSResNet achieved an average classification accuracy of 76.27% and a best single-fold accuracy of 82.50%, with higher accuracy, specificity, and F1 score but lower sensitivity and AUC than the two comparison models. Group-level, LRP-based analysis combined with a standard brain atlas revealed that the model’s decision-making primarily focused on structures related to the temporal lobe and limbic system, including regions such as the hippocampus, parahippocampal gyrus, and amygdala. Population-level attribution also showed interhemispheric differences across several regions. Conclusions: Structural MRIs of MRI-negative TLE contain latent discriminative information that can be recognized by deep learning models. The H-MSResNet and LRP framework provides viable, explainable methodological support for the computer-aided diagnosis and brain region analysis of MRI-negative epilepsy.