Abstract: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 \textit{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, \textit{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. Code and parameters of Brain-DiT are available at \href{https://github.com/REDMAO4869/Brain-DiT}{Link}.
Abstract:Foundation models are emerging as a powerful paradigm for fMRI analysis, but current approaches face a dual bottleneck of data- and training-efficiency. Atlas-based methods aggregate voxel signals into fixed regions of interest, reducing data dimensionality but discarding fine-grained spatial details, and requiring extremely large cohorts to train effectively as general-purpose foundation models. Atlas-free methods, on the other hand, operate directly on voxel-level information - preserving spatial fidelity but are prohibitively memory- and compute-intensive, making large-scale pre-training infeasible. We introduce SLIM-Brain (Sample-efficient, Low-memory fMRI Foundation Model for Human Brain), a new atlas-free foundation model that simultaneously improves both data- and training-efficiency. SLIM-Brain adopts a two-stage adaptive design: (i) a lightweight temporal extractor captures global context across full sequences and ranks data windows by saliency, and (ii) a 4D hierarchical encoder (Hiera-JEPA) learns fine-grained voxel-level representations only from the top-$k$ selected windows, while deleting about 70% masked patches. Extensive experiments across seven public benchmarks show that SLIM-Brain establishes new state-of-the-art performance on diverse tasks, while requiring only 4 thousand pre-training sessions and approximately 30% of GPU memory comparing to traditional voxel-level methods.




Abstract:Predicting the response of a cancer cell line to a therapeutic drug is pivotal for personalized medicine. Despite numerous deep learning methods that have been developed for drug response prediction, integrating diverse information about biological entities and predicting the directional response remain major challenges. Here, we propose a novel interpretable predictive model, DRExplainer, which leverages a directed graph convolutional network to enhance the prediction in a directed bipartite network framework. DRExplainer constructs a directed bipartite network integrating multi-omics profiles of cell lines, the chemical structure of drugs and known drug response to achieve directed prediction. Then, DRExplainer identifies the most relevant subgraph to each prediction in this directed bipartite network by learning a mask, facilitating critical medical decision-making. Additionally, we introduce a quantifiable method for model interpretability that leverages a ground truth benchmark dataset curated from biological features. In computational experiments, DRExplainer outperforms state-of-the-art predictive methods and another graph-based explanation method under the same experimental setting. Finally, the case studies further validate the interpretability and the effectiveness of DRExplainer in predictive novel drug response. Our code is available at: https://github.com/vshy-dream/DRExplainer.