Sex- and Task-dependent Modulation of Spinal and Cortical Motor Neuron Excitability During Fatigue

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Muscle activation during fatiguing activity is modulated by supraspinal, spinal, and peripheral factors that contribute to or compensate for failure at multiple points along the pathway from brain to muscle. Two potential compensatory mechanisms include, i) increased gain of cortical motor neurons or “intracortical facilitation” (ICF), and ii) increased gain of spinal motor neurons via “persistent inward current” (PIC). It is unclear how these two compensatory mechanisms function together to maintain motor output and reduce sense of effort during fatigue. Earlier work suggests that cortical gain increases to offset failure as fatiguing activity continues. It is possible spinal motor neuron gain increases to offset fatigue, and that fatigue-resistance observed in females compared to males, may be due a compensatory increase in PIC. Caffeine is a central nervous system stimulant that can be used to assess central contributions to neuromuscular fatigue and could be used to assess the relationship between PIC and fatigue. However, very little is known about caffeine-induced changes in neuromuscular function and fatigue in females, and it is unclear how such effects might change across the menstrual cycle. These questions must be answered before caffeine can be used to investigate sex-dependent relationships between spinal motor neuron gain and subjective sense of fatigue. Finally, fatigue-induced changes in the gain of spinal motor neurons that control locomotion may be modulated by changing sensory information from the sole of the foot. To date, the role of plantar cutaneous afferents in the modulation of PIC is unknown. Work in this area advances slowly because estimates of motor neuron PIC in humans rely on invasive intramuscular recording methods that yield a small sample of data. New technologies are now emerging that extract a large sample of data via “decomposition” of a noninvasive surface recording. Although, this high-yield technology has the potential to be a game-changer in human neurophysiological research, work is required to validate the approach. The proposed program of research aims to, 1) demonstrate the role that cortical and spinal motor neuron gain play in offsetting fatigue in males and females, 2) investigate the relationship between fatigue-associated changes in PIC and force sensation using caffeine after establishing effects of caffeine on neuromuscular function across the menstrual cycle, and 3) explore the role of regionalized cutaneous afferent input that may contribute to the modulation of spinal MN PIC during functional movement using both conventional intramuscular recordings as well as high-yield decomposition.