StimFlow: Synthesizing Brain Activity from Images via Stimulus-conditioned Flow Matching

Current fMRI encoding models frame prediction as deterministic regression, yet identical stimuli evoke a distribution of neural responses (arising from physiological noise, hemodynamic variability, and cognitive fluctuations) that a single point estimate cannot capture. This work introduces MultiFlow, a generative fMRI encoding framework based on Conditional Flow Matching (CFM) and a formulation termed Stimulus-Informed Source Flow Matching (SISFM). SISFM generalises CFM by conditioning the source distribution on the stimulus: a learnable temporal convolution shapes the source mean with an HRF-length receptive field, while a variance head shrinks its scale, shortening the expected transport path. SISFM is instantiated with a Diffusion Transformer (DiT-X) decoder parameterising the velocity field, with sub-layer Attention Residuals, heterogeneous fusion of ten frozen vision, audio, language, and audiovisual backbones, and per-subject Yeo-network heads. On the Algonauts 2025 dataset, a single MultiFlow checkpoint recovers most of the benefit of large deterministic ensembles: it trails the 1000-model TRIBE ensemble in-distribution by 0.003 PCC (0.3163 vs. 0.3195), and the strongest in- and out-of-distribution ensembles (VIBE-20, MedARC-50) by 0.010 and 0.009 PCC, using a single trained model rather than an ensemble of 20-1000. The same checkpoint also provides stimulus-conditioned uncertainty estimates and sample-based diversity.

Task-based fMRI provides a direct readout of task-evoked neural dynamics, but it is expensive and difficult to acquire at scale, motivating rest-to-task synthesis from widely available resting-state fMRI (rsfMRI). We propose FM-fMRI, an event-conditioned flow-matching model that learns a continuous-time conditional vector field to generate task ROI time series from a subject's rsfMRI and the task event information. The formulation enables fast ODE-based sampling and flexible conditioning over heterogeneous event schedules. Rather than optimizing for pointwise reconstruction, we evaluated generated signals using complementary criteria that probe temporal and spectral structure, subject and group-level connectome consistency, and distributional alignment. On the public Human Connectome Project and internal BioPoint autism cohort, FM-fMRI achieves the strongest spectral and connectivity agreement and improved distribution-level matching over conditional diffusion, generative adversarial networks (GANs), and variational autoencoders (VAEs) baselines. Furthermore, we augment the BioPoint cohort by synthesizing task-fMRI ROI time series with our method, improving downstream autism classification and demonstrating practical utility in data-limited clinical settings. The code will be available on GitHub.

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.