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Mathematical modeling of myelinated axons in a large-scale model of the neuromuscular system for the study of demyelinating diseases

Grant number: 19/09885-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): November 01, 2019
Effective date (End): August 31, 2021
Field of knowledge:Engineering - Biomedical Engineering - Bioengineering
Principal Investigator:André Fábio Kohn
Grantee:Marina Cardoso de Oliveira
Host Institution: Escola Politécnica (EP). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Large-scale computational models of the neuromuscular system have been shown to be very useful in the study of motor control in healthy subjects. However, these models have practically not been used for the study of neuromuscular pathologies. The present project intends to investigate pathologies that cause demyelination of the motor and sensory axons by means of a large-scale computational model of the neuromuscular system. For this to be possible, an already implemented and validated system of motor neuron pools of the Triceps Surae and Anterior Tibial muscles, as well as their afferent pathways, should be expanded with the implementation of computational models of motor and sensory axons. As the available large-scale model is of leg muscles, the pathologies to be studied will be demyelinating axonal pathologies that affect mainly the lower limbs, such as Charcot-Marie-Tooth disease, Guillain-Barré syndrome and demyelinating polyneuropathies. After the addition of models of the motor and sensory axons to the already modeled neuromuscular system, and the introduction of appropriate changes that characterize the different pathologies, simulations of the proposed model will be performed. Existing experimental data in the literature of patients, such as those of H and tendon reflexes, as well as data obtained during the accomplishment of motor tasks (for example, unipodal in a seated position) will be used to validate the model as a whole. The use of the complete system model will allow analyzing signals not available experimentally, such as the firing of the motoneurons and the afferents, which will provide subsidies to analyze the mechanisms involved in the pathologies and the relationship between the degree of axonal involvement and the degree of motor impairment. Therefore, it is hoped that the obtained results will lead to advances in the understanding of these pathologies. In addition, the results may serve as a basis for proposing approaches for early diagnosis and follow-up of treatment evolution. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE OLIVEIRA, MARINA CARDOSO; WATANABE, RENATO NAVILLE; KOHN, ANDRE FABIO. Electrophysiological and functional signs of Guillain-Barre syndrome predicted by a multiscale neuromuscular computational model. JOURNAL OF NEURAL ENGINEERING, v. 19, n. 5, p. 17-pg., . (19/09885-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
OLIVEIRA, Marina Cardoso de. Effects of peripheral demyelinating polyneuropathies in motor control tasks studied with a multiscale neuromuscular model.. 2021. Master's Dissertation - Universidade de São Paulo (USP). Escola Politécnica (EP/BC) São Paulo.

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