The virtual physiological human gets nerves! How to account for the action of the nervous system in multiphysics simulations of human organs

Author:

Alexiadis A.1ORCID,Simmons M. J. H.1,Stamatopoulos K.12,Batchelor H. K.3,Moulitsas I.4ORCID

Affiliation:

1. School of Chemical Engineering, University of Birmingham, Birmingham, Edgbaston B15 2TT, UK

2. Biopharmaceutics, Pharmaceutical Development, PDS, MST, RD Platform Technology and Science, GSK, David Jack Centre, Park Road, Ware, Hertfordshire SG12 0DP, UK

3. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK

4. Centre for Computational Engineering Sciences, Cranfield University, Bedford MK43 0AL, UK

Abstract

This article shows how to couple multiphysics and artificial neural networks to design computer models of human organs that autonomously adapt their behaviour to environmental stimuli. The model simulates motility in the intestine and adjusts its contraction patterns to the physical properties of the luminal content. Multiphysics reproduces the solid mechanics of the intestinal membrane and the fluid mechanics of the luminal content; the artificial neural network replicates the activity of the enteric nervous system. Previous studies recommended training the network with reinforcement learning. Here, we show that reinforcement learning alone is not enough; the input–output structure of the network should also mimic the basic circuit of the enteric nervous system. Simulations are validated against in vivo measurements of high-amplitude propagating contractions in the human intestine. When the network has the same input–output structure of the nervous system, the model performs well even when faced with conditions outside its training range. The model is trained to optimize transport, but it also keeps stress in the membrane low, which is exactly what occurs in the real intestine. Moreover, the model responds to atypical variations of its functioning with ‘symptoms’ that reflect those arising in diseases. If the healthy intestine model is made artificially ill by adding digital inflammation, motility patterns are disrupted in a way consistent with inflammatory pathologies such as inflammatory bowel disease.

Funder

Engineering and Physical Sciences Research Council

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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