Uncovering Sex-Specific Mechanisms of Neuromuscular Fatigue Under Cognitive and Motor Perturbations via Neuromodulation and Brain Network Analysis

Abstract

Fatigue is a significant workplace concern which has shown to exacerbate worker health, injury risk, safety, and productivity, and accounts for $136 Billion in lost productivity and healthcare costs. Exercise-induced neuromuscular fatigue can increase work-related musculoskeletal injuries and is impacted by several individual factors, such as sex and age. Neuromuscular fatigue is modulated by the brain that determines the perceptions of fatigue or exhaustion through proprioceptive and affective inputs that may be sex specific. Stress is a cognitive perturbation of the brain and can therefore influence fatigue development. Despite the occupational relevance of stress and cognitive demands in high-risk work domains (e.g., healthcare, emergency response, manufacturing), their potential contributions to neuromuscular fatigue and associated underlying mechanisms among men and women are not well documented. This dissertation investigates the sex-specific mechanisms of neuromuscular performance and fatigue under stress for young and old adults and the subsequent role of the cognitive brain in modulating fatigue. Here results from three studies are presented that investigate 1) the sex-specific mechanisms of neuromuscular performance under the influence of stress, 2) the sex-specific neural and physiological mechanisms of fatigue for handgrip exercise, and 3) investigate the central mechanisms of fatigue under stress. Collectively, this work highlights key demographic differences in vulnerability to fatigue under stress, emphasizes the role of the prefrontal cortex during neuromuscular fatigue manifestation, and illuminates how stress further affects motor performance and fatigability using integrated neuromodulation and neuroimaging methods.