Markus Amann  & Jerome A Dempsey
The John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin Medical School, Madison, WI, USA

https://doi.org/10.36866/pn.66.28

How does the central nervous system (CNS) regulate athletic performance in different environmental conditions from below sea level exercise to exercise at moderate altitudes? What is the role of peripheral muscle ‘fatigue’ in endurance performance – is it a major determinant?

Fatigue is defined as the reduction in force/power generating capacity of the neuromuscular system that occurs during sustained exercise and is subclassified into a ‘peripheral’ and a ‘central’ element. It is generally agreed that much of the loss of force/power results from biochemical changes within the working muscle (i.e. peripheral fatigue) (Fig. 1A). However, the loss of force/power can also result from inadequate muscle activation – often, but not exclusively, in combination with failure of contractile mechanisms – resulting from a reduced motor drive by the CNS to the working muscle (i.e. central fatigue) (Fig. 1B). Several mechanisms which are not mutually exclusive have been suggested to underlie central fatigue (Gandevia, 2001). For example, afferent neural feedback mechanisms originating in various peripheral organs (Fig. 1C), including the working muscles (Fig. 1D) might affect brain cortical processes and the CNS might in turn modulate central motor output accordingly to ensure a specific level of organ system homeostasis and protect the organism from damage. Alternatively, exercise-induced changes in cerebral neurotransmitter activities (i.e. serotonin) (Fig. 1E) (Meeusen & De Meirleir, 1995) and/or the effects of various environmental/physiological conditions (e.g. heat stress or hypoxia) (Gandevia, 2001) (Fig. 1F), per se, might affect the control of motor activity in the brain and thus whole body exercise performance, independent of any peripheral sensory feedback mechanism.

Peripheral muscle fatigue can be assessed objectively and reproducibly using, for example, supra-maximal motor nerve stimulation. However, the evaluation of central motor output (and central fatigue) during dynamic whole body exercise, must rely on more indirect measures of the muscle electromyogram, which are prone to artifacts.

We have previously demonstrated a highly sensitive effect of arterial oxygen content (CaO2) on the rate of development of peripheral muscle fatigue during dynamic whole body exercise (Amann et al. 2006a) (Fig. 1G). Even relatively small reductions in hemoglobin saturation (SaO2) below resting levels (as occurs during heavy sustained exercise at sea level or at moderate altitudes (-6 to -10% SaO2)) exaggerated the rate of development of peripheral muscle fatigue, whereas increases of CaO2 significantly attenuated this rate. In a subsequent investigation (Amann et al. 2006b) we varied levels of CaO2 via changes in the inspired O2 fraction (FIO2 0.15 to 1.0) to manipulate the rate of fatigue accumulation during bicycle ergometer time trial performance tests in which trained athletes attempt to cover 5 km in the shortest time possible. This type of exercise performance test mimics real-life competitions wherein the performer must make second by second decisions concerning the magnitude of his power output. Average central motor drive, estimated by integrative electromyography of the locomotor muscles, was strongest during the high CaO2 time trial (FIO2 1.0) and weakest during the condition of reduced CaO2 (FIO2 0.15). Accordingly, the highest average power output and the best exercise performance (i.e. shortest time to finish the time trial) was achieved in the high CaO2 trial and vice versa. The striking finding of this study was that, despite marked differences in central motor output, power output and exercise performance time, the level of peripheral muscle fatigue induced by the various time trials was almost identical (Amann et al. 2006a). Together, these data indicate that as the level of arterial oxygenation was altered during exercise the CNS received sensory input which was used to up- or down-regulate central motor drive to adjust for the respective rates of peripheral muscle fatigue accumulation. Therefore, an ‘excessive’ development of end-exercise peripheral muscle fatigue beyond a critical threshold or ‘sensory tolerance limit’ (Gandevia, 2001) was prevented. We then tested (and confirmed) this hypothesis in the same subjects using a high intensity constant load exercise test to exhaustion at varying FIO2 (Amann et al. 2006a; Romer et al. 2006).

How did the CNS know how to regulate motor drive and match contractile activity to the functional capacity – which was determined by CaO2? How might CaO2-dependent effects on the rate of development of peripheral muscle fatigue be ‘sensed’ and in turn impact central motor output? In other words, what provides feedback to the working athlete allowing him to exercise close to his highest endurable rate of fatigue development without significantly exceeding it which would result in premature ‘excessive’ peripheral fatigue and jeopardize his maximal performance? We propose that metabolite accumulation (e.g. inorganic phosphate) whose rate of accumulation in contracting muscle is CaO2 dependent (Hogan et al. 1999) activates sensory nerve endings which project the rate of fatigue accumulation in the peripheral muscle to higher areas of the CNS (Taylor et al. 2000). Based on this afferent feedback the CNS will modulate central motor drive to optimize exercise performance while concurrently ensuring locomotor muscle homeostasis. The data point to the rate of peripheral muscle fatigue development as an important determinant of central motor drive and of exercise performance. Thus, the classical view which emphasizes the direct effect of peripheral fatigue on contractile performance is now extended by showing a connection between peripheral locomotor muscle fatigue and central motor output during whole body exercise.

It is important to emphasize that the rate of peripheral fatigue accumulation is certainly not the only potential source of inhibitory influences on central motor output and thus exercise performance. Significant influences of, for example, cerebral hypoxia on central drive have been indirectly implicated in several investigations. Based on these reports, we predict that the relative influence of our proposed feedback effect from fatiguing muscle on central motor output (Fig. 1A) will diminish as CaO2 is reduced below normoxic levels (i.e. exposure to higher and higher altitudes) and CNS hypoxia, per se, gradually increases its inhibitory influence (see Fig. 1F). Furthermore, there are surely systemic sources of inhibitory feedback – other than from fatiguing limb locomotor muscles. For example, in situations where expiratory flow limitation and lung hyperinflation occur during sustained exercise (highly trained subjects at maximum exercise, fit elderly and COPD patients), excessive respiratory muscle work or respiratory muscle fatigue are also likely to occur. In turn, reflex-induced supra-spinal sensory feedback occurs which will not only intensify cortical perceptions of effort but may also influence blood flow and O2 transport to exercising limbs thereby exacerbating limb fatigue (Fig. 1H). We are currently investigating the relative influence of hypoxemia severity and respiratory muscle work on central and peripheral fatigue during exercise in health and in COPD patients.

In conclusion we need to emphasize that the physiologic determinants of central and peripheral fatigue and exercise performance are highly complex and controversial and certainly situation- and subject-dependant. Our correlative findings in healthy humans have provided only a first indication – albeit we believe a strong one – that exercise-induced peripheral muscle fatigue is likely to play a significant role in this process under many circumstances in health and in certain disease states.

References

Amann M, Romer LM, Pegelow DF, Jacques AJ, Hess CJ & Dempsey JA (2006a). Effects of arterial oxygen content on peripheral locomotor muscle fatigue. J Appl Physiol 101, 119-127.

Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF & Dempsey JA (2006b). Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue. J Physiol 575, 937-952.

Gandevia SC (2001). Spinal and supraspinal factors in human muscle fatigue. Physiol Rev 81, 1725-1789.

Hogan MC, Richardson RS & Haseler LJ (1999). Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a 31P-MRS study. J Appl Physiol 86, 1367-1373.

Meeusen R & De Meirleir K (1995). Exercise and brain neurotransmission. Sports Med 20, 160-188.

Romer LM, Haverkamp HC, Amann M, Lovering AT, Pegelow DF & Dempsey JA (2006). Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans. 10.1152/ajpregu. Am J Physiol Regul Integr Comp Physiol, 00269.02006.

Taylor JL, Petersen N, Butler JE & Gandevia SC (2000). Ischaemia after exercise does not reduce responses of human motoneurones to cortical or corticospinal tract stimulation. J Physiol 525, 793-801.