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The use of a biologically realistic computational model of the neuromuscular system to the study of neurodegenerative diseases

Grant number: 15/21819-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Engineering - Biomedical Engineering - Bioengineering
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:André Fábio Kohn
Grantee:Renato Naville Watanabe
Host Institution: Escola Politécnica (EP). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The use of multi-scale computational models of the neuromuscular system is becoming common in the study of motor control. Nevertheless, these models have very seldom been used to study neuromuscular diseases. Due to the relevance of complementing clinical studies with computer simulations of biologically inspired models we propose to investigate pathologies that cause the demyelinization of the motor and sensory axons by using a multi-scale computational model of the neuromuscular system. To make this possible, an implemented and validated system of the motoneuron pools of the Triceps Surae and Tibialis Anterior muscles as well as their afferents must be expanded to include computational models of the motor and sensory axons. As the implemented model is for the leg muscles, the pathologies to be studied are the ones that affect mainly the lower limbs: Charcot-Marie-Tooth disease, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. New models for the motor and sensory axons will be added to the existent neuromuscular model and modifications will be developed to the axon models to characterize the different pathologies that we propose to study. Model validation will be based on experimental data available in the literature from patients performing position and force tasks (unipodal and seated), as well as quiet standing postural control. In addition tendinous and H-reflex data will also be used to validate the model. With the use of the model, it is possible to have access to signals not available experimentally, such as spike trains from each of the motoneurons and afferent axons. The model simulations will provide a means to analyze the mechanims involved in the targeted pathologies and the relation between the degree of axonal degradation and the degree of motor deficit. The results of this research have a strong potential of advancing the knowledge on these diseases which will pave the way for more optimized treatment procedures. (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)
LEONARDO ABDALA ELIAS; DÉBORA ELISA DA COSTA MATOSO; RENATO NAVILLE WATANABE; ANDRÉ FABIO KOHN. Perspectives on the modeling of the neuromusculoskeletal system to investigate the influence of neurodegenerative diseases on sensorimotor control. Res. Biomed. Eng., v. 34, n. 2, p. 176-186, . (15/14917-9, 15/21819-3, 17/11464-9)
WATANABE, RENATO NAVILLE; KOHN, ANDRE FABIO. Nonlinear Frequency-Domain Analysis of the Transformation of Cortical Inputs by a Motoneuron Pool-Muscle Complex. IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, v. 25, n. 11, p. 1930-1939, . (15/21819-3, 11/17193-0, 11/21103-7)

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