Differences in muscle performance during fatigue may explain the differences in motoneurone excitability between acute and chronic hypoxia

We have with great interest read the paper by Ruggiero and colleagues, which explored the effects of acclimatization to hypoxia on motoneurone excitability during fatigue (Ruggiero et al. 2018). Cervicomedullary evoked potentials (CMEPs), an index of motoneurone excitability, were reported during fatiguing submaximal contractions in normoxia, acute hypoxia (environmental chamber), and after 7–14 days of chronic hypoxic exposure at altitude in Nepal. The study shows that the normal decline in CMEPs that occurs during fatigue of the elbow flexor muscles does not occur after chronic exposure to hypoxia. The paper suggests that after acclimatization, there is heightened motoneurone responsiveness during fatiguing exercise, particularly when compared to acute hypoxia. The authors attributed the heightened motoneurone responsiveness to increased noradrenaline release.

We wish to point out that this interpretation may be problematic and that the differences in CMEP behaviour between acute and chronic hypoxia may simply be due to a difference in motoneurone activity, brought about by different amounts of peripheral fatigue (i.e. fatigue due to processes within the muscle fibres) during the task in each condition.

In the study by Ruggiero et al. (2018) the same fatiguing protocol was used in each condition, and in each condition, as fatigue developed, additional motor units were recruited to maintain the target force level of 25% of maximal force. However, more fatigue occurred in acute hypoxia, as shown by a greater fall in maximal torque. Consistent with greater peripheral fatigue, the rise in EMG over the 16 min fatigue protocol was greatest in acute hypoxia (+58%), compared to normoxia (+22%) and chronic hypoxia (+11%) (see Table 2 of Ruggiero et al. 2018). The recruitment of more motor units (or increased firing rates) during the fatiguing contractions in acute hypoxia than in chronic hypoxia means that motoneurone activity was not well matched between conditions.

Different levels of motoneurone recruitment between conditions are crucial when interpreting the CMEP results because activity‐dependent mechanisms contribute substantially to reductions in CMEP size during fatiguing elbow flexor contractions (McNeil et al. 2011). McNeil et al. (2011) compared the fatigue‐related declines in CMEPs of two sizes (15% and 50% of maximal M‐wave; elicited during a TMS‐induced silent period as in Ruggiero et al. (2018)) during a sustained submaximal contraction of 20% maximal EMG. The smaller CMEP declined more than the larger. As the motoneurones tested by the smaller CMEP were active in the contraction whereas the larger CMEP contained additional motoneurones which were not active, the differential decline was taken as evidence of an activity‐dependent depression of motoneurone excitability. Independent evidence of activity‐dependent depression of human motoneurone excitability comes from single motor unit studies (Johnson et al. 2004; Heroux et al. 2016).

Given the above evidence, we believe that the finding of Ruggiero and colleagues of a greater decline in CMEP during acute hypoxia compared to chronic hypoxia may be the result of the CMEP having tested a greater proportion of active motoneurones when compared to chronic hypoxia. With a baseline CMEP of ∼33% of the maximal M‐wave, it is likely that, at the start of each fatigue protocol, this evoked response included motoneurones that were not active during the 25% contraction. With progressive motor unit recruitment as fatigue developed, the number of active motoneurones would increase. With greater recruitment in acute hypoxia, the proportion of motoneurones that remained inactive would be smaller in acute hypoxia than in chronic hypoxia and normoxia.

Of course, we cannot rule out that chronic exposure to hypoxia causes motoneuronal adaptations. However, we urge caution with regard to the interpretation by Ruggiero et al. (2018) given the differences in fatigue and associated differences in motoneurone activity across the experimental conditions. An experimental approach that would reduce the differences in motoneurone activity between conditions would be to perform contractions to only an EMG target instead of a force target.

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Competing interests

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