Brain-DiT: A Universal Multi-state fMRI Foundation Model with Metadata-Conditioned Pretraining

fMRI foundation models increasingly aggregate heterogeneous data across brain states, cohorts, and acquisition settings, yet pretraining domains are commonly treated as a flat mixture and downstream tasks are adapted independently. We study whether measured learning relations can organize both stages without modifying the backbone. During pretraining, a lightweight Brain-DiT proxy estimates difficulty and directed facilitation across ten fMRI domains, yielding a priority-guided cumulative domain curriculum combined with high-to-low-noise timestep scheduling and joint consolidation. During adaptation, controlled first- and higher-order transfer across fifteen tasks constructs a directed taskonomy, from which budgeted integer programming (BIP) selects directly supervised source tasks and target-specific routes. The joint priority-domain and high-to-low-timestep curriculum reduces v-NMSE, PSD-NMSE, and FC-MSE by 6.5%, 16.3%, and 10.5%, respectively, relative to uniform sampling over both dimensions, and shows strong downstream performance across six in- and out-of-domain tasks. The taskonomy reveals asymmetric, target-dependent transfer, while exploratory sealed-test evaluation shows larger descriptive gains for BIP policies when higher-order route spaces are available than for matched random controls. Together, these findings support organizing fMRI pretraining and adaptation by measured learning relations rather than treating domains and tasks as independent flat sets.

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

Foundation models pretrained using self-supervised learning have transformed computer vision by learning transferable representations from large-scale unlabeled data. However, existing foundation models for neuroimaging remain limited by task-specific training, slice-based learning strategies, or relatively small pretraining datasets, restricting their generalizability across diverse brain MRI applications. In this work, we present BrainNext, a general-purpose self-supervised foundation model for volumetric brain MRI analysis. BrainNext combines masked autoencoder (MAE) pretraining with a native three-dimensional Bi-Directional xLSTM-UNet architecture to learn rich anatomical representations from 60,551 unlabeled brain MRI examinations spanning multiple MRI modalities. The pretrained model is subsequently adapted to downstream tasks through lightweight task-specific fine-tuning. We evaluate BrainNext on the Foundation Models for Medical Imaging (FOMO) 2025 Method Track, encompassing classification, segmentation, and brain-age estimation, where it achieved second place overall and ranked first in the meningioma segmentation task on the official FOMO 2025 challenge leaderboard, demonstrating strong transferability across heterogeneous neuroimaging tasks. These results highlight the potential of large-scale self-supervised pretraining to learn robust and transferable volumetric representations, establishing BrainNext as a scalable foundation model for diverse brain MRI applications.