High-Density Surface Electromyography Reveals Shared Baseline Spatial Organization and Heterogeneous Fatigue Responses in Amyotrophic Lateral Sclerosis

Introduction/Aims Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, denervation, collateral reinnervation, and altered motor unit organization. Clinical assessments track functional decline but provide limited information about the physiological remodeling that precedes or accompanies weakness. High-density surface electromyography (HD-sEMG) can noninvasively measure motor unit morphology, fatigue-related signal behavior, and spatial patterns of muscle activation. Methods We recorded HD-sEMG from the biceps brachii and tibialis anterior in participants with ALS and healthy controls during sustained isometric contractions at 30% and 50% maximum voluntary contraction. Features were extracted from four domains: fatigue dynamics, motor unit morphology, propagation, and spatial organization. Principal component analysis (PCA) was used to test whether the dominant HD-sEMG feature structure was shared or reorganized differently between groups at baseline and during fatigue. Results Baseline PCA showed highly similar HD-sEMG structure in healthy and ALS muscles. Baseline loading profiles were strongly spatial in both groups, with spatial features contributing 91.1% of loading weight in healthy observations and 89.9% in ALS observations. During fatigue, the composite did not significantly separate groups, but ALS showed a larger shift in loading structure and greater score variability than controls. The fatigue-change composite did not scale linearly with limb function. Exploratory binned analysis showed the greatest variability in the moderate impairment group. Discussion HD-sEMG captured strong spatial organization in both groups during baseline contraction. Sustained contraction exposed more variable ALS responses involving amplitude and spectral dynamics, rather than a single uniform fatigue pattern.