The fatigue-induced failure of the motor cortex to drive muscles maximally increases in acute hypoxia (AH) compared to normoxia (N) but improves with acclimatization (chronic hypoxia; CH). Despite their importance to muscle output, it is unknown how locomotor motoneurones in humans are affected by hypoxia and acclimatization. Eleven participants performed 16 min of submaximal [25% maximal torque (maximal voluntary contraction, MVC)] intermittent isometric elbow flexions in N, AH (environmental chamber) and CH (7-14 days at 5050 m) (P O = 140, 74 and 76 mmHg, respectively). For each minute of the fatigue protocol, motoneurone responsiveness was measured with cervicomedullary stimulation delivered 100 ms after transcranial magnetic stimulation (TMS) used to transiently silence voluntary drive. Every 2 min, cortical voluntary activation (cVA) was measured with TMS. After the task, MVC torque declined more in AH (∼20%) than N and CH (∼11% and 14%, respectively, P < 0.05), with no differences between N and CH. cVA was lower in AH than N and CH at baseline (∼92%, 95% and 95%, respectively) and at the end of the protocol (∼82%, 90% and 90%, P < 0.05). During the fatiguing task, motoneurone excitability in N and AH declined to ∼65% and 40% of the baseline value (P < 0.05). In CH, motoneurone excitability did not decline and, late in the protocol, was ∼40% higher compared to AH (P < 0.05). These novel data reveal that acclimatization to hypoxia leads to a heightened motoneurone responsiveness during fatiguing exercise. Positive spinal and supraspinal adaptations during extended periods at altitude might therefore play a vital role for the restoration of performance after acclimatization to hypoxia.

Based on H-reflex data, spinal mechanisms are proposed to be responsible for the first 50-80 ms of the transcranial magnetic stimulation (TMS)-induced silent period. As several methodological issues can compromise H-reflex validity as a measure of motoneuron excitability, this study used transmastoid stimulation to elicit cervicomedullary motor evoked potentials (CMEPs) during the silent period. Eleven subjects made 1-3 visits which involved 32 or 44 brief (~3 s) isometric elbow flexor contractions at 25 % of maximal torque. During each contraction, transmastoid stimulation was delivered in isolation to elicit an unconditioned CMEP and at interstimulus intervals (ISIs) ranging from 50 to 150 ms after TMS to elicit a conditioned CMEP. Stimulus intensities for TMS and transmastoid stimulation were set to elicit a silent period of ~200 ms and an unconditioned CMEP of 15, 50, or 85 % of the maximal compound muscle action potential (M ), respectively. At all ISIs and intensities of transmastoid stimulation, the conditioned CMEP was significantly smaller than the unconditioned CMEP (p< 0.001). However, suppression of the conditioned CMEP was significantly less at 85 % compared to 15 or 50 % M (p = 0.001). Contrary to published H-reflex data, the conditioned CMEP did not recover within 50-80 ms, remaining significantly suppressed at the longest ISI tested (150 ms). These data suggest the spinal portion of the TMS-evoked silent period is considerably longer than reported previously. Transmastoid stimulation, unlike peripheral nerve stimulation, does not impact proprioceptive inflow to motoneurons. Hence, relative to the H-reflex, the CMEP will be subjected to greater afferent-mediated disfacilitation and inhibition due to the TMS-induced muscle twitch.

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Data are scant on sex-related differences for electrically-evoked contractions, which assess intrinsic contractile properties while limiting spinal and supraspinal adaptations to mitigate fatigue. Furthermore, the few studies that exist use stimulus frequencies considerably higher than the natural motor unit discharge rate for the target force. The purpose of this study was to compare force loss to electrically-evoked contractions at a physiological stimulus frequency among young females (n=12), young males (n=12), old females (n=11) and old males (n=11). The quadriceps of the dominant leg were fatigued by 3 min of intermittent transcutaneous muscle belly stimulation (15 Hz stimulus train to initially evoke 25% of maximal voluntary force). Impairment of tetanic contractile impulse (area under the curve) did not differ between sexes for young or old adults or between age groups, with a pooled value of 55.2±12.4% control at the end of fatigue. These data contrast with previous findings at 30 Hz, when the quadriceps of females had greater fatigue resistance than males for young and old adults. The present results highlight the impact stimulus frequency has on intrinsic fatigability of muscle; the findings have implications for future fatigue paradigms and treatment approaches when utilizing electrical stimulation for rehabilitation. Novelty bullets: • Fatigue was not different between sexes with a stimulation frequency comparable to discharge rates during voluntary contractions • These results highlight that stimulus frequency not only influences fatigue development but also between-group differences