BrainWorld: A Structural-Prior-Conditioned Generative Model for Whole-Brain 4D fMRI Dynamics

Flow matching and diffusion models enable conditional generation across domains ranging from images to proteins, with recent extensions to out-of-distribution contexts. Yet generative models of neural time series have largely remained restricted to categorical conditioning, precluding compositional and zero-shot generalization. In this work, we propose a per-timestep conditioned diffusion transformer for generating realistic fMRI brain dynamics during unseen cognitive tasks by injecting both compositional language and optional spatial priors in-context. Such zero-shot generation could enable counterfactual neuroscience by supporting in-silico design and evaluation of novel cognitive experiments before empirical validation. Leveraging this model, we evaluate across hundreds of held-out task conditions and characterize predictive performance in relation to the training manifold. From language alone, the model recovers region-specific recruitment across tasks and held-out spatial activation patterns. Spatial priors, when available, complement the text pathway by anchoring generation in regions of task space where language alone degrades, while retaining the compositional structure needed for counterfactual task specification. To our knowledge this is the first generative model of whole-cortex fMRI dynamics for unseen cognitive tasks, advancing counterfactual neuroscience and data-driven experimental design.

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.

Generative models have achieved success in producing apparently coherent 2D videos, but remain challenging in the physical world due to lack of 4D spatiotemporal scale. Typically, existing 4D generative models directly embed macro scale constraints to enhance overall spatiotemporal consistency. However, these methods only ensure global appearance coherence and fail to reveal the local dynamics of the physical world. Our insight is that global appearance structure and local dynamic topology empower 4D spatiotemporal cognition, thereby enabling 4D generation with spatiotemporal regularities. In this work, we propose ST-Gen4D, a 4D generation framework with 4D spatiotemporal cognition-based world model. Our model is guided by four key designs: 1) Spatiotemporal representation. We encode various modalities into multiple representations as a feature basis. 2) Spatiotemporal cognition. We sculpture these representations into global appearance graph and local dynamic graph, and fuse them via semantic-bridged spatiotemporal fusion to obtain a 4D cognition graph. 3) Spatiotemporal reasoning. We utilize a world model to derive future state based on the 4D cognition. 4) Spatiotemporal generation. We leverage the derived cognition as condition to guide latent diffusion for 4D Gaussian generation. By deeply integrating 4D intrinsic cognition with generative priors, our model guarantees the structural rationality and topological consistency of 4D generation. Moreover, we propose ST-4D datasets by aggregating public 4D datasets and self-built subset. Extensive experiments demonstrate the superiority of our ST-Gen4D across 3D and 4D generation tasks.