Abstract
BACKGROUND: Deep learning has demonstrated significant potential in advancing computer-aided diagnosis for neuropsychiatric disorders, such as migraine, enabling patient-specific diagnosis at an individual level. However, despite the superior accuracy of deep learning models, the interpretability of image classification models remains limited. Their black-box nature continues to pose a major obstacle in clinical applications, hindering biomarker discovery and personalized treatment. OBJECTIVE: This study aims to investigate explainable artificial intelligence (XAI) techniques combined with multiple functional magnetic resonance imaging (fMRI) indicators to (1) compare their efficacy in migraine classification, (2) identify optimal model-indicator pairings, and (3) evaluate XAI's potential in clinical diagnostics by localizing discriminative brain regions. METHODS: We analyzed resting-state fMRI data from 64 participants, including 21 (33%) patients with migraine without aura, 15 (23%) patients with migraine with aura, and 28 (44%) healthy controls. Three fMRI metrics-amplitude of low-frequency fluctuation, regional homogeneity, and regional functional connectivity strength (RFCS)-were extracted and classified using GoogleNet, ResNet18, and Vision Transformer. For comprehensive model comparison, conventional machine learning methods, including support vector machine and random forest, were also used as benchmarks. Model performance was evaluated through accuracy and area under the curve metrics, while activation heat maps were generated via gradient-weighted class activation mapping for convolutional neural networks and self-attention mechanisms for Vision Transformer. RESULTS: The GoogleNet model combined with RFCS indicators achieved the best classification performance, with an accuracy of >98.44% and an area under the receiver operating characteristic curve of 0.99 for the test set. In addition, among the 3 indicators, the RFCS indicator improved accuracy by approximately 8% compared with the amplitude of low-frequency fluctuation. Brain activation heat maps generated by XAI technology revealed that the precuneus and cuneus were the most discriminative brain regions, with slight activation also observed in the frontal gyrus. CONCLUSIONS: The use of XAI technology combined with brain region features provides visual explanations for the progression of migraine in patients. Understanding the decision-making process of the network has significant potential for clinical diagnosis of migraines, offering promising applications in enhancing diagnostic accuracy and aiding in the development of new diagnostic techniques.