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

Abstract Introduction 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.引言 借助神经肌肉骨骼系统（neuromusculoskeletal system）的计算模型，可大幅深化对运动控制背后神经生理机制的理解。基于生物学原理的多尺度神经肌肉骨骼模型（multi-scale neuromusculoskeletal model）具备巨大潜力，可在分子、细胞、突触乃至系统层面为肌肉力量产生的相关机制提供全新理论与阐释。尽管已有部分研究探索了神经退行性疾病（neurodegenerative disease）如何改变神经肌肉系统各组成部分的动力学特性，但目前尚未有研究从系统视角出发，利用多尺度模型对这类疾病展开分析。 概述与展望 本展望性综述文章梳理了当前多尺度神经肌肉系统发育领域的已有研究成果，并指明了若干可拓展该类模型的研究方向，以期未来可借助这些模型挖掘神经退行性疾病的早期预测标志物，同时提出全新的定量临床神经生理学（clinical neurophysiology）方法，用于追踪不同疗法（药物或其他干预手段）相关的病情改善进程。 结语 因此，本文将阐述如何对现有的基于生物学原理的多尺度神经肌肉骨骼模型进行拓展与适配，以应用于临床场景；同时将指明在模型开发过程中需重点考量的不同层级的运作机制，并探讨解读神经系统疾病患者实验数据的相关思路。