A computer simulation study of alpha motor neuron excitability and neurophysiological control of force in amyotrophic lateral sclerosis

Author(s)

Débora Elisa da Costa Matoso

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Elétrica e de Computação
• Defense date: 2022-04-08

Examining board members

Leonardo Abdala Elias; José Wilson Magalhães Bassani; Carina Marconi Germer; Alexandre Leite Rodrigues de Oliveira; Marcus Fraga Vieira

• Advisor: Leonardo Abdala Elias

Abstract

Computational modeling has been crucial for investigating the healthy neuromuscular system but less used to explore pathological conditions. This study aimed to develop a biologically plausible and computational efficient multiscale model of the neuromuscular system representing typical amyotrophic lateral sclerosis (ALS) features. The computational approach allowed accessing information from three essential levels of the motor control system responsible for movement: the motor cortex and descending pathways, the spinal cord, and the motor unit. First, a multiparametric exploration with individual motor neurons (MNs) has expanded our understanding of how changes in intrinsic properties of these nerve cells would modify electrophysiological properties, synaptic efficacy and integration, and responsiveness to L-type calcium current under three conditions of excitability observed in ALS: hyperexcitability, normal excitability, and hypoexcitability. In addition, we explored which MNs parameters could explain other conditions of hyperexcitability and hypoexcitability, namely the bistability and the absence of repetitive MN firing, respectively. Simulation results suggest that changes in persistent inward currents alone could not fully explain these two behaviors, and changes in activation potential and maximal conductance of slow potassium channels are needed. Finally, the implemented multiscale model of the neuromuscular system allowed investigations on how the typical neuromotor alterations of ALS at each level mentioned above could influence the generation and control of muscle force. The simulation results were consistent about the changes in force coefficient of variation (CV) at 2.5% of the maximal voluntary isometric contraction (MVC) before and after alterations in the ability to generate muscle force. These original observations suggest that the CV of low-intensity forces could contribute to future procedures for the early diagnosis of ALS in combination with other measures (AU)

• FAPESP's process: 17/11464-9 - A computer simulation study on the effects of Amyotrophic Lateral Sclerosis in the neurophysiological control of muscle force
• Grantee: Débora Elisa da Costa Matoso
• Support Opportunities: Scholarships in Brazil - Doctorate