The effects of biological sex on estimates of persistent inward currents in the human lower limb

Non-invasive recordings of motor unit (MU) spike trains help us understand how neural drive is modulated by various motor commands and/or physiological conditions. The majority of study participants in human and non-human animal physiology studies are male, and it is assumed mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes by quantifying ΔF. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed effects models to determine if peak discharge rate and ΔF were predicted by the fixed effects of sex, muscle, and their interaction. Despite similar peak discharge rates across all muscles, ΔF was larger (χ2(1) = 6.26, p = 0.012) in females (4.73 [0.242 pps]) than males (3.81 [0.240 pps]). These findings suggest that neuromodulatory drive and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns. KEY POINTS Sex differences have been revealed in motor unit studies as inclusion of female participants becomes more common, however, mechanisms for these differences are not yet clear. Levels of sex hormones differ in concentration between females and males, and these hormones are known to affect monoaminergic signaling throughout the central nervous system. Estimates of persistent inward currents (i.e., ΔF) were observed to be greater in females than males in the tibialis anterior, medial gastrocnemius, and soleus muscles. This suggests that neuromodulatory drive, monoaminergic signaling, or descending control may differ between the sexes, likely due to differences in sex hormone concentrations.