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Main Authors: Siegel, Nys Tjade, Cole, James H., Habes, Mohamad, Haufe, Stefan, Ritter, Kerstin, Schulz, Marc-André
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2508.02560
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author Siegel, Nys Tjade
Cole, James H.
Habes, Mohamad
Haufe, Stefan
Ritter, Kerstin
Schulz, Marc-André
author_facet Siegel, Nys Tjade
Cole, James H.
Habes, Mohamad
Haufe, Stefan
Ritter, Kerstin
Schulz, Marc-André
contents Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.
format Preprint
id arxiv_https___arxiv_org_abs_2508_02560
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Explainable AI Methods for Neuroimaging: Systematic Failures of Common Tools, the Need for Domain-Specific Validation, and a Proposal for Safe Application
Siegel, Nys Tjade
Cole, James H.
Habes, Mohamad
Haufe, Stefan
Ritter, Kerstin
Schulz, Marc-André
Machine Learning
Computer Vision and Pattern Recognition
Image and Video Processing
Neurons and Cognition
Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.
title Explainable AI Methods for Neuroimaging: Systematic Failures of Common Tools, the Need for Domain-Specific Validation, and a Proposal for Safe Application
topic Machine Learning
Computer Vision and Pattern Recognition
Image and Video Processing
Neurons and Cognition
url https://arxiv.org/abs/2508.02560