Deep learning models for neuroimaging have largely been developed for individual tasks, limiting knowledge transfer across applications. Here we introduce GenFAR, a modular deep learning framework that learns general, clinically informed features from brain MRIs. We trained this modular architecture on 49,246 individuals across 11 cohorts, using 17 diverse classification and regression tasks spanning cognition, clinical, diagnosis, demographics, and biomarkers. This yields aggregated, focused feature sets that capture rich, clinically- and biologically-relevant brain representations. We developed a sequential learning approach where tasks progressively build on previously learned representations. Through an analysis of 5,000 task sequences, we identified an optimal sequence length of six tasks and introduced a Donor Score metric to quantify each task's contribution to downstream performance. This analysis revealed five consistently strong donor tasks (Age, AD/MCI, MMSE, Hypertension, Hyperlipidemia) that formed the base of our sequential model. We demonstrated the utility of our learned representation, in various tasks beyond those included in the training set, to serve as the foundation for specialized secondary predictors. We further showed that using the learned feature representation can substantially increase the sample efficiency of secondary deep learning training tasks and models, as well as improve their accuracy.
Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO
Current fMRI foundation models primarily rely on a limited range of brain states and mismatched pretraining tasks, restricting their ability to learn generalized representations across diverse brain states. We present Brain-DiT, a universal multi-state fMRI foundation model pretrained on 349,898 sessions from 24 datasets spanning resting, task, naturalistic, disease, and sleep states. Unlike prior fMRI foundation models that rely on masked reconstruction in the raw-signal space or a latent space, Brain-DiT adopts metadata-conditioned diffusion pretraining with a Diffusion Transformer (DiT), enabling the model to learn multi-scale representations that capture both fine-grained functional structure and global semantics. Across extensive evaluations and ablations on 7 downstream tasks, we find consistent evidence that diffusion-based generative pretraining is a stronger proxy than reconstruction or alignment, with metadata-conditioned pretraining further improving downstream performance by disentangling intrinsic neural dynamics from population-level variability. We also observe that downstream tasks exhibit distinct preferences for representational scale: ADNI classification benefits more from global semantic representations, whereas age/sex prediction comparatively relies more on fine-grained local structure.
Diffusion MRI probes brain microstructure with particular sensitivity to early cerebrovascular and neurodegenerative changes. Neurite Orientation Dispersion and Density Imaging (NODDI) decomposes the diffusion signal into three biophysically interpretable maps: neurite density index (NDI), orientation dispersion index (ODI), and free water fraction (FWF), capturing neurite packing, fiber coherence, and extracellular fluid. These 3D maps offer a rich substrate for transferable microstructural representations, yet integrating them is challenging: standard representation learning struggles to disentangle the unique information in each map from their shared and synergistic interactions. We present BrainFIBRE, the first foundation model for brain microstructure, pretrained on NODDI-derived maps from 55,592 UK Biobank participants. We propose Self-supervised Partial Information Decomposition (SPID), which extends PID-guided multimodal learning to the self-supervised regime for the first time. A novel Counterfactual Candidate Construction (CCC) paradigm perturbs inter-modality alignment through modality dropping and swapping, providing the contrastive signal for a Mixture-of-Experts architecture to disentangle unique, synergistic, and redundant information without any downstream label. On both Caucasian and Asian cohorts, BrainFIBRE achieves state-of-the-art performance across diverse tasks predicting age, sex, cerebrovascular and neurodegenerative markers, and cognition, while yielding neurobiologically interpretable representations that reveal task- and cohort-specific interaction patterns. BrainFIBRE establishes a versatile foundation for neuroimaging analysis at the microstructural level.