GeoSAE: Geometric Prior-Guided Layer-Wise Sparse Autoencoder Annotation of Brain MRI Foundation Models
On the map: Mechanistic interpretability → Interpreting biomedical and science models
Abstract (arXiv)
Brain MRI foundation models learn rich representations of anatomy, but interpreting what clinical information they encode remains an open problem. Standard sparse autoencoders (SAEs) suffer from severe feature collapse in deep transformer layers, and in Alzheimer's disease (AD) research, aging confounds nearly every clinical variable, making naive annotation unreliable. We propose GeoSAE, a geometry-guided SAE framework that uses the foundation model's learned manifold structure to prevent feature collapse and annotates each surviving feature via age-deconfounded partial correlations. Applied to ~14k T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging biomarkers and Lifestyle (AIBL) datasets, GeoSAE identifies a compact, fully interpretable feature set that predicts mild cognitive impairment (MCI)-to-AD conversion (AUC 0.746) using only 2% of the embedding dimensions, while comorbidity-annotated features achieve only chance-level performance. The identified features replicate across cohorts without retraining (r=0.97) and localize to neuroanatomically distinct regions consistent with Braak staging. This shows that geometry-guided SAEs can extract interpretable, biomarkers from frozen brain MRI foundation models.
Key facts. Cited by 1 paper in the map (data through 14 Oct 2026). Placed in Interpreting biomedical and science models, one of 13 directions in Mechanistic interpretability. Builds on 27 of its 42 references that are in the map. First posted on arXiv 3 May 2026.
Builds on
27 of 42 references.
Closest ancestors · 4
Same direction, newest first
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- 2024Learning biologically relevant features in a pathology foundation model using sparse autoencoders15 Jul
Other references · 23
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- 2016Understanding intermediate layers using linear classifier probescited by 1,353
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- 2024Scaling and evaluating sparse autoencoderscited by 553
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- 2024Jumping Ahead: Improving Reconstruction Fidelity with JumpReLU Sparse Autoencoderscited by 300
- 2013k-Sparse Autoencoderscited by 215
- 2022Disentangled Representation Learningcited by 112
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- 2025Building a General SimCLR Self-Supervised Foundation Model Across Neurological Diseases to Advance 3D Brain MRI Diagnosescited by 10
- 2025Learning Concept-Driven Logical Rules for Interpretable and Generalizable Medical Image Classificationcited by 4
- 2023Biomarker Investigation using Multiple Brain Measures from MRI through XAI in Alzheimer's Disease Classificationcited by 2
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