Learning Cardiac Electrophysiology Digital Twins Through Agentic Discovery of Hybrid Structure

Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.

Integrating Mechanistic and Data-Driven Models for Neurological Disorders through Differentiable Programming

Advances in computational modeling, neuroimaging, and artificial intelligence are revolutionizing the modeling of neurological disorders for improved diagnostics, prognosis, and treatment planning. Mechanistic models provide valuable scientific insight into the disorders, but in practice they are often simplified with assumptions or computationally expensive and slow to solve. However, while purely data driven approaches provide speed and scalability, they require large, high quality data to train and generally suffer from interpretability and generalization issues. This perspective paper presents a structured overview of hybrid modeling strategies, which combine deep learning models with physics based solvers, and are categorized into parallel, series, and parallel-series architectures. Three main approaches that have been emphasized are residual modeling for missing or incomplete physics, Neural Ordinary Differential Equations (NODEs) for continuous time dynamics approximation, and solver in the loop that accelerates traditional solvers with neural approximations. These hybrid models integrate the governing differential equation based formulations and deep learning to characterize the evolution of neurological disorders, and promise advanced personalized neurological modeling. In addition, the study explores and proposes different hybrid configurations to improve diagnosis accuracy, predict disease progression, and inform treatment strategies across a range of neurological disorders. These capabilities outperform standalone mechanistic or purely data driven approaches, making hybrid modeling a powerful tool, especially in applications involving modeling the progression and treatment responses in neurological conditions such as brain tumors, Alzheimer's disease, and stroke.