Learning High-dimensional Ionic Model Dynamics Using Fourier Neural Operators

Ionic models, described by systems of stiff ordinary differential equations, are fundamental tools for simulating the complex dynamics of excitable cells in both Computational Neuroscience and Cardiology. Approximating these models using Artificial Neural Networks poses significant challenges due to their inherent stiffness, multiscale nonlinearities, and the wide range of dynamical behaviors they exhibit, including multiple equilibrium points, limit cycles, and intricate interactions. While in previous studies the dynamics of the transmembrane potential has been predicted in low dimensionality settings, in the present study we extend these results by investigating whether Fourier Neural Operators can effectively learn the evolution of all the state variables within these dynamical systems in higher dimensions. We demonstrate the effectiveness of this approach by accurately learning the dynamics of three well-established ionic models with increasing dimensionality: the two-variable FitzHugh-Nagumo model, the four-variable Hodgkin-Huxley model, and the forty-one-variable O'Hara-Rudy model. To ensure the selection of near-optimal configurations for the Fourier Neural Operator, we conducted automatic hyperparameter tuning under two scenarios: an unconstrained setting, where the number of trainable parameters is not limited, and a constrained case with a fixed number of trainable parameters. Both constrained and unconstrained architectures achieve comparable results in terms of accuracy across all the models considered. However, the unconstrained architecture required approximately half the number of training epochs to achieve similar error levels, as evidenced by the loss function values recorded during training. These results underline the capabilities of Fourier Neural Operators to accurately capture complex multiscale dynamics, even in high-dimensional dynamical systems.

Learning cardiac activation and repolarization times with operator learning

Solving partial or ordinary differential equation models in cardiac electrophysiology is a computationally demanding task, particularly when high-resolution meshes are required to capture the complex dynamics of the heart. Moreover, in clinical applications, it is essential to employ computational tools that provide only relevant information, ensuring clarity and ease of interpretation. In this work, we exploit two recently proposed operator learning approaches, namely Fourier Neural Operators (FNO) and Kernel Operator Learning (KOL), to learn the operator mapping the applied stimulus in the physical domain into the activation and repolarization time distributions. These data-driven methods are evaluated on synthetic 2D and 3D domains, as well as on a physiologically realistic left ventricle geometry. Notably, while the learned map between the applied current and activation time has its modelling counterpart in the Eikonal model, no equivalent partial differential equation (PDE) model is known for the map between the applied current and repolarization time. Our results demonstrate that both FNO and KOL approaches are robust to hyperparameter choices and computationally efficient compared to traditional PDE-based Monodomain models. These findings highlight the potential use of these surrogate operators to accelerate cardiac simulations and facilitate their clinical integration.

Learning the Hodgkin-Huxley Model with Operator Learning Techniques

We construct and compare three operator learning architectures, DeepONet, Fourier Neural Operator, and Wavelet Neural Operator, in order to learn the operator mapping a time-dependent applied current to the transmembrane potential of the Hodgkin- Huxley ionic model. The underlying non-linearity of the Hodgkin-Huxley dynamical system, the stiffness of its solutions, and the threshold dynamics depending on the intensity of the applied current, are some of the challenges to address when exploiting artificial neural networks to learn this class of complex operators. By properly designing these operator learning techniques, we demonstrate their ability to effectively address these challenges, achieving a relative L2 error as low as 1.4% in learning the solutions of the Hodgkin-Huxley ionic model.