Brownian Motion with a Pulse: A Biostatistician's Guide to Diffusions, Bridges, Functional PCA, and First-Passage Models
Authors: Eliuvish Han Cui
Organizations: Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, USA
Abstract
Brownian motion is a compact mathematical language for continuous-time uncertainty in biostatistics. This tutorial develops the process from construction and path properties to tools that recur in applied biomedical work: the Markov and strong Markov properties, the Karhunen-Loeve expansion, functional principal component analysis (Functional PCA), reflection principles, local time, stochastic differential equations (SDEs), Brownian bridges, and empirical-process limits. The applications emphasize longitudinal biomarkers, degradation modelling, first-passage endpoints, dynamic frailty, group-sequential monitoring, calibration diagnostics, recurrent-event processes, electronic health records, and wearable streams. A short cross-domain section uses literary and historical archives to make Brownian-bridge thinking concrete without shifting the paper away from biostatistics, and includes a reproducible chapter-level experiment on Frankenstein. The Black-Merton-Scholes model is included as a solved SDE template, not as a finance application in its own right. The aim is to connect rigorous probability with modelling decisions faced by biostatisticians when biological processes evolve between noisy observation times.
We establish Lp-universal approximation theorems for general path-dependent and non-anticipative functionals on suitable rough path spaces, showing that linear functionals acting on signatures of time-extended rough paths are dense with respect to the Lp-distance. To that end, we derive global universal approximation theorems for weighted rough path spaces. We demonstrate that these Lp-universal approximation theorems apply to Gaussian processes, in particular, to fractional Brownian motion. As a consequence, linear functionals on the signature of the time-extended Brownian motion can approximate any p-integrable stochastic process adapted to the Brownian filtration, including solutions to stochastic differential equations.
Over the past few years, diffusion-based Schrödinger bridge models have been proposed to approximate optimal transport dynamics between two prescribed boundary distributions, with successful applications to generative modeling. More precisely, these methods aim to estimate a path measure whose initial and terminal marginals match the two boundary distributions, while minimizing the Kullback-Leibler divergence with respect to a reference Markov process. In this work, we consider the generalized Schrödinger bridge problem, in which the reference process is a twisted Brownian motion, that is, a Feynman-Kac transform of a Brownian motion induced by a time-dependent differentiable potential. Building on the Iterative Markovian Fitting (IMF) paradigm, and in particular on its special case Diffusion Schrödinger Bridge Matching (DSBM), which corresponds to the zero potential case, we introduce Twisted Schrödinger Bridge Matching (TSBM), a diffusion-based method designed to handle both continuous- and discrete-time potentials. Unlike previous approaches, TSBM provides a rigorous extension of the IMF scheme to the generalized Schrödinger bridge problem. This derivation leads to a new bridge-matching loss that depends explicitly on the gradient of the potential and recovers the DSBM objective when the potential vanishes, yielding improved performance. We further introduce trajectory-based variance-reduction techniques that substantially stabilize optimization and may be useful beyond the present setting. Finally, we empirically demonstrate the benefits of TSBM for trajectory inference across increasingly high-dimensional settings, including crowd navigation and single-cell data. Code available at https://github.com/maxencenoble/twisted-sb-matching.
Hydrodynamic models of stochastic particle systems represented by coarse-grained stochastic partial differential equations (SPDE), such as the regularized Dean-Kawasaki (DK) equation, do not accurately capture the short-time system dynamics that is dominated by non-Markovian effects, and low particle density regimes where the distributions are highly non-Gaussian. We develop a generative flow matching method that directly models the probability distribution of fluxes from particle simulations that explicitly incorporates non-Markovian and non-Gaussian effects. As a demonstration, we use this method to simulate the Kramers first passage time problem for a system of non-interacting Brownian particles. We show the model accurately captures the short-time behavior and provides better predictions of the statistical moments of the number density when compared against the solution of the Markovian baseline, regularized DK equation.
Bhargav Sriram Siddani, John B. Bell, Alejandro L. Garcia +1