Unveiling the decision making process in Alzheimer's disease diagnosis: a case-based counterfactual methodology for explainable deep learning

Valoor, Adarsh and Gangadharan, G.R. (2025) Unveiling the decision making process in Alzheimer's disease diagnosis: a case-based counterfactual methodology for explainable deep learning. Journal of Neuroscience Methods, 413, [110318]. (doi:10.1016/j.jneumeth.2024.110318).

Abstract

Background: the field of Alzheimer's disease (AD) diagnosis is undergoing significant transformation due to the application of deep learning (DL) models. While DL surpasses traditional machine learning in disease prediction from structural magnetic resonance imaging (sMRI), the lack of explainability limits clinical adoption. Counterfactual inference offers a way to integrate causal explanations into these models, enhancing their robustness and transparency. 

New method: this study develops a novel methodology combining U-Net and generative adversarial network (GAN) models to create comprehensive counterfactual diagnostic maps for AD. The proposed methodology uses case-based counterfactual reasoning for robust decision classification for counterfactual maps to understand how changes in specific features affect the model's predictions. Comparison with existing methods: The proposed methodology is compared with state-of-the-art visual explanation techniques across the ADNI dataset. The proposed methodology is also benchmarked against other gradient-based and generative models for its ability to generate comprehensive counterfactual maps. 

Results: the results demonstrate that the proposed methodology significantly outperforms existing methods in accuracy, sensitivity, and specificity while providing detailed counterfactual maps that visualize how slight changes in brain morphology could lead to different diagnostic outcomes. The proposed methodology achieves an accuracy of 95 % and an AUC of 0.97, illustrating its superiority in capturing subtle yet crucial anatomical features. 

Conclusions: by generating intuitive visual explanations, the proposed methodology improves the interpretability and robustness of AD diagnostic models, making them more reliable and accountable. The use of counterfactual inference enhances clinicians' understanding of disease progression and the impact of different interventions, fostering precision medicine in AD care.

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Contributors

Author: Adarsh Valoor

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