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

The findings do not support the concept that equivocal findings regarding sex differences in central fatigue are related to augmented effects of group III/IV afferent feedback in males compared with females.

New Findings r What is the central question of this study?Does the induction of a model of lung injury affect the expiratory time constant (τ E ) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τ E either before or after injury? r What is the main finding and its importance?The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τ E between fastand slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures.Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τ E ). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF 6 ) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O 2 and the remaining 50% as nitrogen (N 2 ), helium (He) or sulfur hexafluoride (SF 6 ). Values for τ E decreased with injury and were more variable after injury than before (P < 0.001). Values for τ E increased throughout expiration both before and after injury, and the rate of increase in τ E was lessened by SF 6 (P < 0.001 when compared with N 2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF 6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N 2 and He mixtures.

Elbow flexor force steadiness is less with the forearm pronated (PRO) compared with neutral (NEU) or supinated (SUP) and may relate to neural excitability. Although not tested in a force steadiness paradigm, lower spinal and cortical excitability was observed separately for biceps brachii in PRO, possibly dependent on contractile status at the time of assessment. This study aimed to investigate position-dependent changes in force steadiness as well as spinal and cortical excitability at a variety of contraction intensities. Thirteen males (26 ± 7 yr; means ± SD) performed three blocks (PRO, NEU, and SUP) of 24 brief (~6 s) isometric elbow flexor contractions (5, 10, 25 or 50% of maximal force). During each contraction, transcranial magnetic stimulation or transmastoid stimulation was delivered to elicit a motor-evoked potential (MEP) or cervicomedullary motor-evoked potential (CMEP), respectively. Force steadiness was lower in PRO compared with NEU and SUP ( P ≤ 0.001), with no difference between NEU and SUP. Similarly, spinal excitability (CMEP/maximal M wave) was lower in PRO than NEU (25 and 50% maximal force; P ≤ 0.010) and SUP (all force levels; P ≤ 0.004), with no difference between NEU and SUP. Cortical excitability (MEP/CMEP) did not change with forearm position ( P = 0.055); however, a priori post hoc testing for position showed excitability was 39.8 ± 38.3% lower for PRO than NEU at 25% maximal force ( P = 0.006). The data suggest that contraction intensity influences the effect of forearm position on neural excitability and that reduced spinal and, to a lesser extent, cortical excitability could contribute to lower force steadiness in PRO compared with NEU and SUP. NEW & NOTEWORTHY To address conflicting reports about the effect of forearm position on spinal and cortical excitability of the elbow flexors, we examine the influence of contraction intensity. For the first time, excitability data are considered in a force steadiness context. Motoneuronal excitability is lowest in pronation and this disparity increases with contraction intensity. Cortical excitability exhibits a similar pattern from 5 to 25% of maximal force. Lower corticospinal excitability likely contributes to relatively poor force steadiness in pronation.

Transcranial magnetic stimulation (TMS) of the motor cortex during a maximal voluntary contraction (MVC) permits functionally relevant measurements of muscle group relaxation rate (i.e., when muscles are actively contracting under voluntary control). This study's purpose was twofold: (1) to explore the impact of muscle length on TMS‐induced plantar flexor relaxation rate; and (2) to incorporate ultrasonography to measure relaxation‐induced lengthening of medial gastrocnemius (MG) fascicles and displacement of the muscle–tendon junction (MTJ). Eleven males (24.8 ± 7.0 years) performed 21 brief isometric plantar flexor MVCs. Trials were block‐randomized every three MVCs among 20° dorsiflexion (DF), a neutral ankle position, and 30° plantar flexion (PF). During each MVC, TMS was delivered and ultrasound video recordings captured MG fascicles or MTJ length changes. Peak relaxation rate was calculated as the steepest slope of the TMS‐induced drop in plantar flexor torque or the rate of length change for MG fascicles and MTJ. Torque relaxation rate was slower for PF (−804 ± 162 Nm·s−1) than neutral and DF (−1896 ± 298 and −2008 ± 692 Nm·s−1, respectively). Similarly, MG fascicle relaxation rate was slower for PF (−2.80 ± 1.10 cm·s−1) than neutral and DF (−5.35 ± 1.10 and −4.81 ± 1.87 cm·s−1, respectively). MTJ displacement rate showed a similar trend (P = 0.06), with 3.89 ± 1.93 cm·s−1 for PF compared to rates of 6.87 ± 1.55 and 6.36 ± 2.97 cm·s−1 for neutral and DF, respectively. These findings indicate muscle length affects the torque relaxation rate recorded after TMS during an MVC. Comparable results were obtained from muscle fascicles, indicating ultrasound imaging is suitable for measuring evoked contractile properties during voluntary contraction.