Multiscale modeling of the neuromuscular system: Coupling neurophysiology and skeletal muscle mechanics

Abstract

Mathematical models and computer simulations have the great potential to substantially increase our understanding of the biophysical behavior of the neuromuscular system. This, however, requires detailed multiscale, and multiphysics models. Once validated, such models allow systematic in silico investigations that are not necessarily feasible within experiments and, therefore, have the ability to provide valuable insights into the complex interrelations within the healthy system and for pathological conditions. Most of the existing models focus on individual parts of the neuromuscular system and do not consider the neuromuscular system as an integrated physiological system. Hence, the aim of this advanced review is to facilitate the prospective development of detailed biophysical models of the entire neuromuscular system. For this purpose, this review is subdivided into three parts. The first part introduces the key anatomical and physiological aspects of the healthy neuromuscular system necessary for modeling the neuromuscular system. The second part provides an overview on state‐of‐the‐art modeling approaches representing all major components of the neuromuscular system on different time and length scales. Within the last part, a specific multiscale neuromuscular system model is introduced. The integrated system model combines existing models of the motor neuron pool, of the sensory system and of a multiscale model describing the mechanical behavior of skeletal muscles. Since many sub‐models are based on strictly biophysical modeling approaches, it closely represents the underlying physiological system and thus could be employed as starting point for further improvements and future developments. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

Combining Ultrafast Ultrasound and High-Density EMG to Assess Local Electromechanical Muscle Dynamics: A Feasibility Study

“…Still, mechanical waves could be detected in these trials. CMAP conduction velocities were found to be within the physiological range, as reported in literature [1], [31]. The highly repeatable EMG recordings were comparable to other studies that used transcutaneous muscle stimulation [31]- [34].…”

“…3). However, (surface) EMG measures potential differences caused by the AP [1], which will initiate the calcium dynamics, resulting in the formation of crossbridges and thus force generation (i.e. the E-C coupling).…”

“…Muscles generate force through a series of fast electrochemical and electromechanical processes, enabling movement [1]. Muscle contraction is initiated by spinal motor neu-rons, which generate action potentials (APs).…”

“…A fiber consists of multiple myofibrils in parallel, and myofibrils consist of multiple sarcomeres in series. The sarcomeres are the smallest contractile units of a muscle, and following AP arrival, calcium will be released, allowing cross-bridges to form between actin and myosin filaments in a sarcomere [1]. As the AP propagates longitudinally along the fiber, more sarcomeres will be activated and start to form cross-bridges.…”

A Systematic Review and Meta-Analysis on the Longitudinal Effects of Unilateral Knee Extension Exercise on Muscle Strength

“…Using models to reveal the underlying principles of training do not necessarily exist on the musculoskeletal system level yet. However, such models can be integrated into multi-muscle forward-dynamics models (e.g., Röhrle et al, 2017;Valentin et al, 2018), in neuromuscular system models (e.g., Röhrle et al, 2019) and linked to homogenization techniques aiming to describe macroscopic muscle behavior based on microscopic constituents (e.g., Bleiler et al, 2019). Such models can then be used to investigate the musculoskeletal system in more detail.…”