Neurological disorders leading to mechanical dysfunction of the esophagus: an emergent behavior of a neuromechanical dynamical system

Fuente: arXiv
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Autores principales: Elisha, Guy, Halder, Sourav, Liu, Xinyi, Carlson, Dustin A., Kahrilas, Peter J., Pandolfino, John E., Patankar, Neelesh A.
Formato: Preprint
Publicado: 2024
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author Elisha, Guy
Halder, Sourav
Liu, Xinyi
Carlson, Dustin A.
Kahrilas, Peter J.
Pandolfino, John E.
Patankar, Neelesh A.
author_facet Elisha, Guy
Halder, Sourav
Liu, Xinyi
Carlson, Dustin A.
Kahrilas, Peter J.
Pandolfino, John E.
Patankar, Neelesh A.
contents An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive wall. Such neuromechanical insights could be crucial to eventually develop targeted pharmacological interventions.
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id arxiv_https___arxiv_org_abs_2402_18103
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Neurological disorders leading to mechanical dysfunction of the esophagus: an emergent behavior of a neuromechanical dynamical system
Elisha, Guy
Halder, Sourav
Liu, Xinyi
Carlson, Dustin A.
Kahrilas, Peter J.
Pandolfino, John E.
Patankar, Neelesh A.
Neurons and Cognition
Biological Physics
An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive wall. Such neuromechanical insights could be crucial to eventually develop targeted pharmacological interventions.
title Neurological disorders leading to mechanical dysfunction of the esophagus: an emergent behavior of a neuromechanical dynamical system
topic Neurons and Cognition
Biological Physics
url https://arxiv.org/abs/2402.18103