Improving clinical interpretability of linear neuroimaging models through feature whitening

Foundation models provide powerful representations for brain MRI analysis, but their predictions remain difficult to interpret in anatomically meaningful terms. Clinical assessment of brain MRI is commonly organized around anatomically defined structures and regional abnormalities, whereas conventional explanation methods typically produce voxel- or patch-level importance maps that do not explicitly quantify the contributions of individual brain regions. To address this mismatch, we propose RegionFM, an interpretable framework that integrates anatomical segmentation with brain MRI foundation-model embeddings. RegionFM first divides each MRI scan into anatomical regions and constructs a separate MRI volume for each region. A frozen foundation model then encodes each region into an embedding, and a region-additive logistic model combines these embeddings such that every anatomical region contributes an explicit scalar term to the final prediction. This formulation supports both subject-level and cohort-level analyses of regional contributions. We evaluate RegionFM on cognitive-impairment classification using embeddings from multiple pretrained brain MRI foundation models. The results show that RegionFM maintains performance comparable to less interpretable fine-tuning approaches while providing anatomically grounded explanations. Randomized embedding ablations yield near-chance performance, indicating that the predictions rely on meaningful structure captured by the foundation-model embeddings rather than simple feature statistics. Overall, RegionFM better aligns model explanations with anatomy-based clinical reasoning while maintaining competitive predictive performance.

Deep neural networks learn representations where individual features often lack interpretable meaning; a single neuron may activate for scattered, unrelated inputs. We introduce coherence, a geometric property inspired by neural coding in the brain, where neurons like grid cells and head direction cells respond to contiguous regions of state space. A non-negative matrix is coherent if each row (sample) attends to geometrically clustered columns (features) and vice versa, and in addition every sample is well described by some feature and every feature is needed by some sample. We prove that coherent matrices induce a bounded interleaving between the Vietoris-Rips filtrations of samples and features, guaranteeing that both spaces share compatible topological structure. This geometric constraint facilitates interpretability. For example, if data lies on a circle, coherent features must tile that circle into contiguous arcs. We introduce Coh, a differentiable objective function based on Fréchet variance that enforces coherence during training. Unlike sparsity, which bounds how many samples a feature activates on, coherence bounds which samples, requiring geometric connectivity rather than only rarity. This yields not just interpretable features but an interpretable feature space. We validate Coh in an auto-encoder using synthetic and rotated MNIST datasets and in a token embedding of BERT using language data.

Gradient-based saliency methods are widely used to interpret deep neural networks, yet they often produce noisy and unstable explanations that poorly align with semantically meaningful input features. We argue that a fundamental cause of this behavior lies in the geometry of learned representations: correlated feature dimensions diffuse attribution gradients across redundant directions, resulting in blurred and unreliable saliency maps. To address this issue, we identify feature correlation as a structural limitation of gradient-based interpretability and propose SaliencyDecor, a training framework that enforces feature decorrelation to improve attribution fidelity without modifying saliency methods or model architectures by reshaping the feature space toward orthogonality, our approach promotes more concentrated gradient flow and improves the fidelity of saliency-based explanations. SaliencyDecor jointly optimizes classification, prediction consistency under feature masking, and a decorrelation regularizer, requiring no architectural changes or inference-time overhead. Extensive experiments across multiple benchmarks and architectures demonstrate that our method produces substantially sharper and more object-focused saliency maps while simultaneously improving predictive performance, achieving accuracy gains across the datasets. These results establish our method as a principled mechanism for enhancing both interpretability and accuracy, challenging the conventional trade-off between explanation quality and model performance.