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

A. Alexiadis, M. J.H. Simmons, K. Stamatopoulos, H. K. Batchelor, I. Moulitsas

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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.

Original languageEnglish
Article number20201024
JournalJournal of the Royal Society, Interface
Volume18
Issue number177
DOIs
Publication statusPublished - 14 Apr 2021

Bibliographical note

Funding Information:
Data accessibility. All LAMMPS input files and Python code used in the simulations are freely available under the GNU. General Public License v3 and can be downloaded from the repository edata. bham.ac.uk/570/. Authors’ contributions. A.A. had the main idea and wrote the first draft. M.J.H.S. provided expertise in fluid dynamics. K.S. provided expertise on physiology of the intestine. H.K.B. provided expertise on physiology of the intestine. I.M. provided expertise in high-performance computing and computer simulations. All authors revised the paper and participated in the writing of the final manuscript. Competing interests. We declare we have no competing interests. Funding. This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) grant no. EP/S019227/1. Acknowledgements. The computations described in this paper were performed using the University of Birmingham’s BlueBEAR HPC service and the Cranfield University’s Delta HPC service. The authors would also like to acknowledge the help and support of Dr Michael Knaggs at the Cranfield HPC.

Publisher Copyright:
© 2021 The Authors.

Keywords

  • coupling multiphysics with artificial intelligence
  • mathematical modelling of the intestine
  • multiphysics
  • reinforcement learning
  • virtual human

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

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