Conditional Flow Matching for Single-Neuron Electrophysiology: Capturing Multimodal Responses Across Stimuli

Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications -- omitting channels or reducing morphological detail -- introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

EEG foundation models can learn generalizable representations from large-scale EEG corpora to enable single-backbone transfer across diverse clinical and brain-computer interface tasks. Existing models typically discretize the continuous multi-channel EEG waveform into patches or codebook tokens and train a transformer with masked self-supervision. Recognizing that this discretization fragments continuous brain rhythms and obscures fine-grained temporal dynamics, we present B[FM]$^2$(Brain Foundation Model via Flow Matching), whose inductive bias aligns with the data by pretraining directly on the raw signal using continuous-time flow matching without patches, tokenization, or masking. However, multi-channel EEG signals pose an architectural challenge for flow matching: time is densely sampled and highly autocorrelated (thousands of timepoints), while the electrode axis is short (tens of channels) at distinct scalp positions. To address this time-electrode asymmetry, we introduce SplitUNet, a velocity network that factorizes each block into separate 1D temporal and 1D electrode convolutions and downsamples only along time, preserving electrode topology throughout the hierarchy. B[FM]$^2$ sets a new state of the art on 7 of 9 standard downstream EEG classification tasks, using a pretraining budget of only 36,895 segments ($\approx$ 307h), 1-2 orders of magnitude ($\approx$ 30x) less than required by existing EEG foundation models. Further, it generates synthetic EEGs that two board-certified neurologists cannot distinguish from brain data (Cohen's $κ=$ -0.096). https://jd730.github.io/projects/BFM2

High-fidelity EEG generation is critical for alleviating data scarcity and addressing privacy constraints in large-scale neural modeling. Despite recent progress, most existing approaches formulate EEG generation via discrete denoising objectives, which inadequately reflect the inherently continuous temporal dynamics and spectral structure of neural activity. As a result, these methods often struggle to preserve long-range temporal dependencies and exhibit mismatches in the spectral and temporal structure of the generated signals. In this work, we argue that effective EEG generation requires models that operate directly on the continuous evolution of neural signals. We introduce Just EEG Transformer (JET), a generative framework based on conditional flow matching that models EEG as raw sequences evolving along continuous trajectories. By learning a smooth vector field that transports noise to the EEG data distribution, JET captures temporal continuity and transient dynamics without relying on discretized denoising schemes or domain-specific representations. To ensure that the learned dynamics remain consistent with key properties of EEG signals, we introduce principled constraints that preserve spectral structure, temporal stationarity, and signal-level statistics. Across three large-scale benchmarks, JET consistently achieves state-of-the-art performance, reducing TS-FID by over 40% compared to strong baselines. Extensive analyses show that JET captures key structural properties of neural dynamics, providing a scalable and principled approach to EEG generation. Project page: https://y-research-sbu.github.io/JET/ .