Maximal motor unit firing rates decline with amyotrophic lateral sclerosis progression

• Maximal motor unit firing rates were measured longitudinally in individuals with amyotrophic lateral sclerosis over ∼ 18 months. • Tibialis anterior maximal firing rates declined over time, even in muscles that remained clinically strong. • Maximal firing rates is a sensitive, non-invasive clinical biomarker of neuromotor system deterioration in ALS. Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of upper and lower motor neurons and their motor units (MUs). MU loss is compensated by collateral sprouting and reinnervation of muscle fibres. There is limited information about the properties of these surviving MUs as these processes take place. High-density surface electromyography (HD-sEMG) decomposition enables non-invasive analysis of individual MU firing behaviour during maximal voluntary contractions and assess their changes with ALS progression. Thirty-nine individuals with ALS (24 men; mean age 63 ± 16 years) completed up to five visits (interval 20.0 ± 7.9 weeks). Tibialis anterior HD-sEMG recordings during maximal contractions were decomposed into individual MU spike trains, from which maximal firing rates were quantified. Muscle strength was assessed with the Medical Research Council (MRC) scale, and global function with the revised ALS Functional Rating Scale (ALSFRS-R). Maximal MU firing rates declined significantly over time [–0.32 Hz/month, (95%CI–0.44;–0.19)], regardless of MRC scores. Across participants, maximal firing rates decreased by 2.38 Hz (1.78; 2.98) for each 1-point reduction in MRC and by 0.54 Hz for each ALSFRS-R point (–0.83;–0.26). These findings demonstrate that maximal MU firing rates decline as ALS progresses, suggesting that the surviving motor unit undergo progressive pathophysiological changes as motor neurons degenerate. HD-sEMG MU firing-rates analysis appeared more sensitive than MRC in detecting early deterioration in muscle decline. Maximal firing rates analysis has the potential to serve as a quantitative clinical biomarker of neuromotor system degeneration, complementing global functional scales in clinical monitoring.