Perspectives on the modeling of the neuromusculoskeletal system to investigate the influence of neurodegenerative diseases on sensorimotor control

Abstract

The understanding of the neurophysiological mechanisms underlying movement control can be much furthered using computational models of the neuromusculoskeletal system. Biologically based multi-scale neuromusculoskeletal models have a great potential to provide new theories and explanations related to mechanisms behind muscle force generation at the molecular, cellular, synaptic, and systems levels. Albeit some efforts have been made to investigate how neurodegenerative diseases alter the dynamics of individual elements of the neuromuscular system, such diseases have not been analyzed from a systems viewpoint using multi-scale models. Overview and Perspectives: This perspective article synthesizes what has been done in terms of multi-scale neuromuscular development and points to a few directions where such models could be extended so that they can be useful in the future to discover early predictors of neurodegenerative diseases, as well as to propose new quantitative clinical neurophysiology approaches to follow the course of improvements associated with different therapies (drugs or others). Concluding Remarks: Therefore, this article will present how existing biologically based multi-scale models of the neuromusculoskeletal system could be expanded and adapted for clinical applications. It will point to mechanisms operating at different levels that would be relevant to be considered during model development, along with implications for interpreting experimental results from neurological patients.

Methodological advances for studying gamma motor neurons

“…A similar computer model of the proprioceptive circuit was coupled with servo motor control of a cadaver finger to test hypotheses about altering γ motor neuron drive on the stretch reflex using realistic muscle and tendon forces [ 37 , 38 ]. Computer models hold great promise for testing hypotheses about the role of fusimotor control in normal movement and disease, but they would benefit from a greater understanding of the biophysical properties of γ motor neurons [ 39 ]. Future advances in recording techniques, experimental paradigms, and computer models can shed further light on human fusimotor control.…”

Electrophysiological and functional signs of Guillain–Barré syndrome predicted by a multiscale neuromuscular computational model

“…Particularly, studies based on such models have answered many questions on the functioning of pools of spinal cord neurons and how they help control muscle activity as a function of the descending drives from upper centres, the feedback from sensory receptors, and the dynamics of tendons and muscles. With the accumulated knowledge of the fine details that such multiscale models can provide, it is believed that they are ripe to be employed as a tool in the study of neuromuscular diseases [12][13][14][15]. The results of computer simulation studies of such models, when adapted to represent specific diseases, have the potential to: (a) provide relevant insights on how the progression of a specific disease may hamper motor control and affect different quantifiers of electrical and mechanical variables, (b) indicate specific quantitative measurements that could be helpful for neurologic diagnosis as well as for the follow-up during therapy, (c) provide predictions on the levels of success of different treatment approaches.…”

Efeitos de neuropatias periféricas desmielinizantes em tarefas de controle motor estudados por meio de um modelo neuromuscular multiescala.

“…Esses modelos são capazes de gerar dados equivalentes aos observados experimentalmente, com a grande vantagem de possibilitar a análise sistemática da dinâmica de cada um dos subsistemas envolvidos e de suas interações (RÖHRLE et al, 2019). O uso desses modelos para o estudo de neuropatias pode ajudar a elucidar mecanismos por trás do controle postural, controle da força ou da posição em diferentes níveis de desmielinização axonal, de modo a avançar no entendimento dessas neuropatias, e até mesmo servir como base para estratégias de diagnóstico precoce (ELIAS et al, 2018).…”