# Skull-stripping induces shortcut learning in MRI-based Alzheimer's disease classification

arXiv: https://arxiv.org/abs/2501.15831 · HTML: https://mlsanity.com/paper/2501.15831/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 48 references that are in the map.
- First posted on arXiv 27 Jan 2025.

## Builds on (most cited first, 11 of 11)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Deep Inside Convolutional Networks: Visualising Image Classification Models and Saliency Maps](https://mlsanity.com/paper/1312.6034/) (2013)
- [Shortcut Learning in Deep Neural Networks](https://mlsanity.com/paper/2004.07780/) (2020)
- [Striving for Simplicity: The All Convolutional Net](https://mlsanity.com/paper/1412.6806/) (2014)
- [Unmasking Clever Hans Predictors and Assessing What Machines Really Learn](https://mlsanity.com/paper/1902.10178/) (2019)
- [Methods for Interpreting and Understanding Deep Neural Networks](https://mlsanity.com/paper/1706.07979/) (2017)
- [Accounting for Variance in Machine Learning Benchmarks](https://mlsanity.com/paper/2103.03098/) (2021)
- [Convolutional Neural Networks for Classification of Alzheimer's Disease: Overview and Reproducible Evaluation](https://mlsanity.com/paper/1904.07773/) (2019)
- [Uncovering convolutional neural network decisions for diagnosing multiple sclerosis on conventional MRI using layer-wise relevance propagation](https://mlsanity.com/paper/1904.08771/) (2019)
- [Efficacy of MRI data harmonization in the age of machine learning. A multicenter study across 36 datasets](https://mlsanity.com/paper/2211.04125/) (2022)
- [Explainable concept mappings of MRI: Revealing the mechanisms underlying deep learning-based brain disease classification](https://mlsanity.com/paper/2404.10433/) (2024)

## Abstract (arXiv)

Objectives: High classification accuracy of Alzheimer's disease (AD) from structural MRI has been achieved using deep neural networks, yet the specific image features contributing to these decisions remain unclear. In this study, the contributions of T1-weighted (T1w) gray-white matter texture, volumetric information, and preprocessing -- particularly skull-stripping -- were systematically assessed. Methods: A dataset of 990 matched T1w MRIs from AD patients and cognitively normal controls from the ADNI database were used. Preprocessing was varied through skull-stripping and intensity binarization to isolate texture and shape contributions. A 3D convolutional neural network was trained on each configuration, and classification performance was compared using exact McNemar tests with discrete Bonferroni-Holm correction. Feature relevance was analyzed using Layer-wise Relevance Propagation, image similarity metrics, and spectral clustering of relevance maps. Results: Despite substantial differences in image content, classification accuracy, sensitivity, and specificity remained stable across preprocessing conditions. Models trained on binarized images preserved performance, indicating minimal reliance on gray-white matter texture. Instead, volumetric features -- particularly brain contours introduced through skull-stripping -- were consistently used by the models. Conclusions: This behavior reflects a shortcut learning phenomenon, where preprocessing artifacts act as potentially unintended cues. The resulting Clever Hans effect emphasizes the critical importance of interpretability tools to reveal hidden biases and to ensure robust and trustworthy deep learning in medical imaging.