Integrating Mechanistic and Data-Driven Models for Neurological Disorders through Differentiable Programming
Authors: Shah Pallav Dhanendrakumar, Saikat Pal, Sitikantha Roy
Organizations: Department of Applied Mechanics, Indian Institute of Technology Delhi, New Delhi-110016, India · Yardi School of Artificial Intelligence, Indian Institute of Technology Delhi, New Delhi-110016, India
Abstract
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.
Hybrid mechanistic/data-driven models, which combine first-principles with learned components, are increasingly used in process engineering and scientific machine learning. Common hybrid modeling designs are specified primarily through their architectures and training losses, which offers a limited basis for a shared semantic interface to compare or verify them across domains, with comparatively little attention paid to epistemic uncertainty in the mechanistic part. We bridge hybrid modeling and neuro-symbolic (NeSy) AI by reconstructing these designs as instances of NeSy interface. The resulting translation, Hybrid-to-NeSy (H2N), places mechanistic knowledge on the language side, learned modules on the belief side, and validity domains together with constraints on the logic side. For each design, H2N then yields an explicit NeSy inference functional and a logic-belief decomposition. From this decomposition we derive two metrics: structural violation rate (SVR), measuring whether the learned belief respects the mechanistic structure; and belief dispersion (BD), measuring how concentrated the learned plausibility is, serving as a hybrid model's epistemic uncertainty in its mechanistic part. We instantiate H2N on a case study of a structured hybrid model for binary classification under label noise and show that models with higher SVR and BD exhibit greater variability in held-out accuracy. Under structural distribution shift, H2N further quantifies a model's uncertainty during extrapolations, whereas test accuracy reveals the same shift only post hoc.
Forecasting longitudinal brain lesion evolution is critical for disease monitoring and treatment planning. Existing approaches typically learn a direct mapping from a baseline image to a future observation, without explicitly modeling the physical mechanisms underlying the lesion progression. Such an entangled modeling of structural deformation and image intensity variation limits physical plausibility, model generalization, and interpretability. To address this, we propose PDF, a Physics-grounded Disentangled Flow matching framework for longitudinal brain disease forecasting. We explicitly decompose the longitudinal modeling of lesion growth into two processes, each learned by a dedicated flow matching network: morphology evolution, which captures lesion growth and structural deformation; and intensity evolution, which models signal changes driven by variations in lesion concentration. To enforce physics-grounded constraints, we introduce a PDE-regularized loss based on lesion growth dynamics, that enforces a diffusion-reaction-advection formulation for morphological evolution. Experiments on three public longitudinal datasets spanning diverse brain diseases demonstrate state-of-the-art performance, validating the effectiveness of the disentangled modeling framework and physics-grounded learning design. Code is publicly available at https://github.com/jhuldr/PDF.
Brain tumors such as glioma, meningioma, and pituitary adenoma alter the mechanical behavior of soft brain tissue, yet common diagnostic methods rely on static imaging that cannot capture tumor growth, tissue displacement, or changes in stiffness over time. Deep learning models for this task typically require pooling patient data at one site, which conflicts with privacy rules such as GDPR and HIPAA and limits generalization across institutions, a challenge that is pronounced in neuro oncology given patient diversity. This study presents a federated physics informed neural network combining federated learning with a physics informed loss built on the equations of linear elasticity. Three simulated clinical sites each train a local network on patient specific MRI data using a physics informed loss, and only model weights are shared with a central server through the FedAvg protocol over one hundred rounds, keeping raw data at its site of origin. The federated model reached an overall accuracy of 91.4%, against 90.0% for a non federated baseline trained on pooled data, an average AUC of 0.985 across tumor classes, and a rise in pituitary tumor accuracy from 85.6 to 94.5%. Training produced smooth, divergence free displacement fields consistent with expected tissue deformation, showing that federated training can be paired with physics based constraints without a meaningful loss in performance.