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Quantification of Neuromuscular Fatigue: What Do We Do Wrong and Why?

Abstract

Neuromuscular fatigue (NMF) is usually assessed non-invasively in healthy, athletic or clinical populations with the combination of voluntary and evoked contractions. Although it might appear relatively straightforward to magnetically or electrically stimulate at different levels (cortical/spinal/muscle) and to measure mechanical and electromyographic responses to quantify neuromuscular adjustments due to sustained/repeated muscle contractions, there are drawbacks that researchers and clinicians need to bear in mind. The aim of this opinion paper is to highlight the pitfalls inevitably faced when NMF is quantified. The first problem might arise from the definition of fatigue itself and the parameter(s) used to measure it; for instance, measuring power vs. isometric torque may lead to different conclusions. Another potential limitation is the delay between exercise termination and the evaluation of neuromuscular function; the possible underestimation of exercise-induced neural and contractile impairment and misinterpretation of fatigue etiology will be discussed, as well as solutions recently proposed to overcome this problem. Quantification of NMF can also be biased (or not feasible) because of the techniques themselves (e.g. results may depend on stimulation intensity for transcranial magnetic stimulation) or the way data are analyzed (e.g. M wave peak-to-peak vs first phase amplitude). When available, alternatives recently suggested in the literature to overcome these pitfalls are considered and recommendations about the best practices to assess NMF (e.g. paying attention to the delay between exercise and testing, adapting the method to the characteristics of the population to be tested and considering the limitations associated with the techniques) are proposed.

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References

  1. Lou JS. Techniques in assessing fatigue in neuromuscular diseases. Phys Med Rehabil Clin N Am. 2012;23(1):11–22 (ix).

    PubMed  Article  Google Scholar 

  2. Twomey R, Aboodarda SJ, Kruger R, Culos-Reed SN, Temesi J, Millet GY. Neuromuscular fatigue during exercise: methodological considerations, etiology and potential role in chronic fatigue. Neurophysiol Clin. 2017;47(2):95–110.

    PubMed  Article  Google Scholar 

  3. Kluger BM, Krupp LB, Enoka RM. Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology. 2013;80(4):409–16.

    PubMed  PubMed Central  Article  Google Scholar 

  4. Enoka RM, Duchateau J. Translating fatigue to human performance. Med Sci Sports Exerc. 2016;48(11):2228–38.

    PubMed  PubMed Central  Article  Google Scholar 

  5. Millet GY, Bachasson D, Temesi J, Wuyam B, Feasson L, Verges S, et al. Potential interests and limits of magnetic and electrical stimulation techniques to assess neuromuscular fatigue. Neuromuscul Disord. 2012;22(Suppl 3):S181–6.

    PubMed  Article  Google Scholar 

  6. Millet GY, Martin V, Martin A, Verges S. Electrical stimulation for testing neuromuscular function: from sport to pathology. Eur J Appl Physiol. 2011;111(10):2489–500.

    PubMed  Article  Google Scholar 

  7. Place N, Yamada T, Bruton JD, Westerblad H. Muscle fatigue: from observations in humans to underlying mechanisms studied in intact single muscle fibres. Eur J Appl Physiol. 2010;110(1):1–15.

    PubMed  Article  Google Scholar 

  8. Asmussen E. Muscle fatigue. Med Sci Sports. 1979;11(4):313–21.

    CAS  PubMed  Google Scholar 

  9. Neyroud D, Maffiuletti NA, Kayser B, Place N. Mechanisms of fatigue and task failure induced by sustained submaximal contractions. Med Sci Sports Exerc. 2012;44(7):1243–51.

    PubMed  Article  Google Scholar 

  10. Place N, Lepers R, Deley G, Millet GY. Time course of neuromuscular alterations during a prolonged running exercise. Med Sci Sports Exerc. 2004;36(8):1347–56.

    PubMed  Article  Google Scholar 

  11. Temesi J, Arnal PJ, Rupp T, Feasson L, Cartier R, Gergele L, et al. Are females more resistant to extreme neuromuscular fatigue? Med Sci Sports Exerc. 2015;47(7):1372–82.

    PubMed  Article  Google Scholar 

  12. Bigland-Ritchie B, Woods JJ. Changes in muscle contractile properties and neural control during human muscular fatigue. Muscle Nerve. 1984;7(9):691–9.

    CAS  PubMed  Article  Google Scholar 

  13. Sogaard K, Gandevia SC, Todd G, Petersen NT, Taylor JL. The effect of sustained low-intensity contractions on supraspinal fatigue in human elbow flexor muscles. J Physiol. 2006;573(Pt 2):511–23.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  14. Simonson E, Weiser PC. Psychological aspects and physiological correlates of work and fatigue. Springfield, IL: CC Thomas; 1976. p. 336–405.

    Google Scholar 

  15. Bigland-Ritchie B, Johansson R, Lippold OC, Woods JJ. Contractile speed and EMG changes during fatigue of sustained maximal voluntary contractions. J Neurophysiol. 1983;50(1):313–24.

    CAS  PubMed  Article  Google Scholar 

  16. Edwards RH, Hill DK, Jones DA, Merton PA. Fatigue of long duration in human skeletal muscle after exercise. J Physiol. 1977;272(3):769–78.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Bruton JD, Place N, Yamada T, Silva JP, Andrade FH, Dahlstedt AJ, et al. Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice. J Physiol. 2008;586(1):175–84.

    CAS  PubMed  Article  Google Scholar 

  18. MacIntosh BR, Rassier DE. What is fatigue? Can J Appl Physiol. 2002;27(1):42–55.

    CAS  PubMed  Article  Google Scholar 

  19. Bachasson D, Millet GY, Decorte N, Wuyam B, Levy P, Verges S. Quadriceps function assessment using an incremental test and magnetic neurostimulation: a reliability study. J Electromyogr Kinesiol Off J Int Soc Electrophysiol Kinesiol. 2013;23(3):649–58.

    Article  Google Scholar 

  20. Bachasson D, Guinot M, Wuyam B, Favre-Juvin A, Millet GY, Levy P, et al. Neuromuscular fatigue and exercise capacity in fibromyalgia syndrome. Arthritis Care Res (Hoboken). 2013;65(3):432–40.

    PubMed  Article  Google Scholar 

  21. Bankole LC, Millet GY, Temesi J, Bachasson D, Ravelojaona M, Wuyam B, et al. Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: a randomized controlled trial. Medicine (Baltimore). 2016;95(31):e4497.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Cheng AJ, Rice CL. Fatigue and recovery of power and isometric torque following isotonic knee extensions. J Appl Physiol. 2005;99(4):1446–52.

    PubMed  Article  Google Scholar 

  23. Kruger RL, Aboodarda SJ, Jaimes LM, MacIntosh BR, Samozino P, Millet GY. Fatigue and recovery measured with dynamic properties vs isometric force: effects of exercise intensity. J Exp Biol. 2019;222:jeb197483 (in press).

    PubMed  Article  Google Scholar 

  24. Kruger RL, Aboodarda SJ, Samozino P, Rice CL, Millet GY. Isometric versus dynamic measurements of fatigue: does age matter? A meta-analysis. Med Sci Sports Exerc. 2018;50(10):2132–44.

    PubMed  Article  Google Scholar 

  25. Millet GY, Tomazin K, Verges S, Vincent C, Bonnefoy R, Boisson RC, et al. Neuromuscular consequences of an extreme mountain ultra-marathon. PLoS One. 2011;6(2):e17059.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. Enoka RM, Stuart DG. Neurobiology of muscle fatigue. J Appl Physiol. 1992;72(5):1631–48.

    CAS  PubMed  Article  Google Scholar 

  27. Enoka RM, Baudry S, Rudroff T, Farina D, Klass M, Duchateau J. Unraveling the neurophysiology of muscle fatigue. J Electromyogr Kinesiol Off J Int Soc Electrophysiol Kinesiol. 2011;21(2):208–19.

    Article  Google Scholar 

  28. Amann M, Dempsey JA. Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance. J Physiol. 2008;586(1):161–73.

    CAS  PubMed  Article  Google Scholar 

  29. Amann M, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J Physiol. 2009;587(1):271–83.

    CAS  PubMed  Article  Google Scholar 

  30. Jubeau M, Rupp T, Perrey S, Temesi J, Wuyam B, Levy P, et al. Changes in voluntary activation assessed by transcranial magnetic stimulation during prolonged cycling exercise. PLoS One. 2014;9(2):e89157.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  31. Thomas K, Elmeua M, Howatson G, Goodall S. Intensity-dependent contribution of neuromuscular fatigue after constant-load cycling. Med Sci Sports Exerc. 2016;48(9):1751–60.

    PubMed  Article  Google Scholar 

  32. Mira J, Lapole T, Souron R, Messonnier L, Millet GY, Rupp T. Cortical voluntary activation testing methodology impacts central fatigue. Eur J Appl Physiol. 2017;117:1845–57.

    PubMed  Article  Google Scholar 

  33. Taylor JL, Allen GM, Butler JE, Gandevia SC. Supraspinal fatigue during intermittent maximal voluntary contractions of the human elbow flexors. J Appl Physiol. 2000;89(1):305–13.

    CAS  PubMed  Article  Google Scholar 

  34. Vernillo G, Temesi J, Martin M, Millet GY. Mechanisms of fatigue and recovery in upper versus lower limbs in men. Med Sci Sports Exerc. 2018;50(2):334–43.

    PubMed  Article  Google Scholar 

  35. Levenez M, Kotzamanidis C, Carpentier A, Duchateau J. Spinal reflexes and coactivation of ankle muscles during a submaximal fatiguing contraction. J Appl Physiol. 2005;99(3):1182–8.

    PubMed  Article  Google Scholar 

  36. Froyd C, Millet GY, Noakes TD. The development of peripheral fatigue and short-term recovery during self-paced high-intensity exercise. J Physiol. 2013;591(Pt 5):1339–46.

    PubMed  Article  Google Scholar 

  37. Neyroud D, Kayser B, Place N. Are there critical fatigue thresholds? Aggregated vs. individual data. Front Physiol. 2016;7:376.

    PubMed  PubMed Central  Google Scholar 

  38. Ducrocq GP, Hureau TJ, Meste O, Blain GM. Increased fatigue response to augmented deceptive feedback during cycling time trial. Med Sci Sports Exerc. 2017;49(8):1541–51.

    PubMed  Article  Google Scholar 

  39. Monks MR, Compton CT, Yetman JD, Power KE, Button DC. Repeated sprint ability but not neuromuscular fatigue is dependent on short versus long duration recovery time between sprints in healthy males. J Sci Med Sport. 2017;20(6):600–5.

    PubMed  Article  Google Scholar 

  40. Doyle-Baker D, Temesi J, Medysky ME, Holash RJ, Millet GY. An innovative ergometer to measure neuromuscular fatigue immediately after cycling. Med Sci Sports Exerc. 2017;50:375–87.

    Article  Google Scholar 

  41. Aboodarda SJ, Mira J, Floreani M, Jaswal R, Moon SJ, Amery K, et al. Effects of endurance cycling training on neuromuscular fatigue in healthy active men. Part II: corticospinal excitability and voluntary activation. Eur J Appl Physiol. 2018;118(11):2295–305.

    CAS  PubMed  Article  Google Scholar 

  42. Mira J, Aboodarda SJ, Floreani M, Jaswal R, Moon SJ, Amery K, et al. Effects of endurance training on neuromuscular fatigue in healthy active men. Part I: strength loss and muscle fatigue. Eur J Appl Physiol. 2018;118(11):2281–93.

    CAS  PubMed  Article  Google Scholar 

  43. Temesi J, Mattioni Maturana F, Peyrard A, Piucco T, Murias JM, Millet GY. The relationship between oxygen uptake kinetics and neuromuscular fatigue in high-intensity cycling exercise. Eur J Appl Physiol. 2017;117(5):969–78.

    PubMed  Article  Google Scholar 

  44. Dekerle J, Ansdell P, Schäfer L, Greenhouse-Tucknott A, Wrightson J. Methodological issues with the assessment of voluntary activation using transcranial magnetic stimulation in the knee extensors. Eur J Appl Physiol. 2019;119(4):991–1005.

    PubMed  Article  Google Scholar 

  45. Button DC, Behm DG. The effect of stimulus anticipation on the interpolated twitch technique. J Sports Sci Med. 2008;7(4):520–4.

    PubMed  PubMed Central  Google Scholar 

  46. Peyrard A, Sawh P, Fan S, Temesi J, Millet GY. Anticipation of magnetic and electrical stimuli does not impair maximal voluntary force production. Neurosci Lett. 2016;15(628):128–31.

    Article  CAS  Google Scholar 

  47. Bampouras TM, Reeves ND, Baltzopoulos V, Jones DA, Maganaris CN. Is maximum stimulation intensity required in the assessment of muscle activation capacity? J Electromyogr Kinesiol Off J Int Soc Electrophysiol Kinesiol. 2012;22(6):873–7.

    Article  Google Scholar 

  48. Martin V, Millet GY, Martin A, Deley G, Lattier G. Assessment of low-frequency fatigue with two methods of electrical stimulation. J Appl Physiol. 2004;97(5):1923–9.

    CAS  PubMed  Article  Google Scholar 

  49. Rodriguez-Falces J, Maffiuletti NA, Place N. Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve. Muscle Nerve. 2013;48(5):752–61.

    PubMed  Article  Google Scholar 

  50. Giroux C, Roduit B, Rodriguez-Falces J, Duchateau J, Maffiuletti NA, Place N. Short vs. long pulses for testing knee extensor neuromuscular properties: does it matter? Eur J Appl Physiol. 2018;118(2):361–9.

    PubMed  Article  Google Scholar 

  51. Neyroud D, Temesi J, Millet GY, Verges S, Maffiuletti NA, Kayser B, et al. Comparison of electrical nerve stimulation, electrical muscle stimulation and magnetic nerve stimulation to assess the neuromuscular function of the plantar flexor muscles. Eur J Appl Physiol. 2015;115(7):1429–39.

    PubMed  Article  Google Scholar 

  52. Verges S, Maffiuletti NA, Kerherve H, Decorte N, Wuyam B, Millet GY. Comparison of electrical and magnetic stimulations to assess quadriceps muscle function. J Appl Physiol. 2009;106(2):701–10.

    PubMed  Article  Google Scholar 

  53. Tomazin K, Verges S, Decorte N, Oulerich A, Maffiuletti NA, Millet GY. Fat tissue alters quadriceps response to femoral nerve magnetic stimulation. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2011;122(4):842–7.

    Article  Google Scholar 

  54. Tomazin K, Verges S, Decorte N, Oulerich A, Millet GY. Effects of coil characteristics for femoral nerve magnetic stimulation. Muscle Nerve. 2010;41(3):406–9.

    PubMed  Article  Google Scholar 

  55. Jason LA, Evans M, Brown M, Porter N. What is fatigue? Pathological and nonpathological fatigue. PMR. 2010;2(5):327–31.

    Article  Google Scholar 

  56. Eldadah BA. Fatigue and fatigability in older adults. PMR. 2010;2(5):406–13.

    Article  Google Scholar 

  57. Behm DG, St-Pierre DM, Perez D. Muscle inactivation: assessment of interpolated twitch technique. J Appl Physiol. 1996;81(5):2267–73.

    CAS  PubMed  Article  Google Scholar 

  58. Bickel CS, Gregory CM, Dean JC. Motor unit recruitment during neuromuscular electrical stimulation: a critical appraisal. Eur J Appl Physiol. 2011;111(10):2399–407.

    PubMed  Article  Google Scholar 

  59. Place N, Casartelli N, Glatthorn JF, Maffiuletti NA. Comparison of quadriceps inactivation between nerve and muscle stimulation. Muscle Nerve. 2010;42(6):894–900.

    PubMed  Article  Google Scholar 

  60. Rodriguez-Falces J, Place N. Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation. Eur J Appl Physiol. 2013;113(12):3069–77.

    PubMed  Article  Google Scholar 

  61. Ruggiero L, Bruce CD, Cotton PD, Dix GU, McNeil CJ. Prolonged low-frequency force depression is underestimated when assessed with doublets compared to tetani in the dorsiflexors. J Appl Physiol. 2019;126(5):1352–9.

    PubMed  Article  PubMed Central  Google Scholar 

  62. Han TR, Shin HI, Kim IS. Magnetic stimulation of the quadriceps femoris muscle: comparison of pain with electrical stimulation. Am J Phys Med Rehabil. 2006;85(7):593–9.

    PubMed  Article  Google Scholar 

  63. Bachasson D, Temesi J, Bankole C, Lagrange E, Boutte C, Millet GY, et al. Assessement of quadriceps strength, endurance and fatigue in FSHD and CMT: benefits and limits of femoral nerve magnetic stimulation. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2014;125(2):396–405.

    CAS  Article  Google Scholar 

  64. Harris ML, Luo YM, Watson AC, Rafferty GF, Polkey MI, Green M, et al. Adductor pollicis twitch tension assessed by magnetic stimulation of the ulnar nerve. Am J Respir Crit Care Med. 2000;162(1):240–5.

    CAS  PubMed  Article  Google Scholar 

  65. Temesi J, Gruet M, Rupp T, Verges S, Millet GY. Resting and active motor thresholds versus stimulus-response curves to determine transcranial magnetic stimulation intensity in quadriceps femoris. J Neuroeng Rehabil. 2014;21(11):40.

    Article  Google Scholar 

  66. McNeil CJ, Giesebrecht S, Gandevia SC, Taylor JL. Behaviour of the motoneurone pool in a fatiguing submaximal contraction. J Physiol. 2011;589(Pt 14):3533–44.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. Temesi J, Rupp T, Martin V, Arnal PJ, Feasson L, Verges S, et al. Central fatigue assessed by transcranial magnetic stimulation in ultratrail running. Med Sci Sports Exerc. 2014;46(6):1166–75.

    PubMed  Article  Google Scholar 

  68. Bachasson D, Temesi J, Gruet M, Yokoyama K, Rupp T, Millet GY, et al. Transcranial magnetic stimulation intensity affects exercise-induced changes in corticomotoneuronal excitability and inhibition and voluntary activation. Neuroscience. 2016;9(314):125–33.

    Article  CAS  Google Scholar 

  69. Rodriguez-Falces J, Place N. Muscle excitability during sustained maximal voluntary contractions by a separate analysis of the M-wave phases. Scand J Med Sci Sports. 2017;27(12):1761–75.

    CAS  PubMed  Article  Google Scholar 

  70. Gandevia SC, McNeil CJ, Carroll TJ, Taylor JL. Twitch interpolation: superimposed twitches decline progressively during a tetanic contraction of human adductor pollicis. J Physiol. 2013;591(5):1373–83.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. Neyroud D, Cheng AJ, Bourdillon N, Kayser B, Place N, Westerblad H. Muscle fatigue affects the interpolated twitch technique when assessed using electrically-induced contractions in human and rat muscles. Front Physiol. 2016;7:252.

    PubMed  PubMed Central  Google Scholar 

  72. Place N, Yamada T, Bruton JD, Westerblad H. Interpolated twitches in fatiguing single mouse muscle fibres: implications for the assessment of central fatigue. J Physiol. 2008;586(11):2799–805.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. Rodriguez-Falces J, Place N. Determinants, analysis and interpretation of the muscle compound action potential (M wave) in humans: implications for the study of muscle fatigue. Eur J Appl Physiol. 2018;118(3):501–21.

    PubMed  Article  Google Scholar 

  74. Rodriguez-Falces J, Place N. Sarcolemmal membrane excitability during repeated intermittent maximal voluntary contractions. Exp Physiol. 2019;104(1):136–48.

    PubMed  Google Scholar 

  75. Merton PA. Interaction between muscle fibres in a twitch. J Physiol. 1954;124(2):311–24.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. Belanger AY, McComas AJ. Extent of motor unit activation during effort. J Appl Physiol Respir Environ Exerc Physiol. 1981;51(5):1131–5.

    CAS  PubMed  Google Scholar 

  77. de Haan A, Gerrits KH, de Ruiter CJ. Counterpoint: the interpolated twitch does not provide a valid measure of the voluntary activation of muscle. J Appl Physiol. 2009;107(1):355–7.

    PubMed  Article  Google Scholar 

  78. Taylor JL. Point: the interpolated twitch does/does not provide a valid measure of the voluntary activation of muscle. J Appl Physiol. 2009;107(1):354–5.

    PubMed  Article  Google Scholar 

  79. Millet GY. Can neuromuscular fatigue explain running strategies and performance in ultra-marathons?: the flush model. Sports Med. 2011;41(6):489–506.

    PubMed  Article  Google Scholar 

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Acknowledgements

The authors would like to thank Chris Donnelly for editing the English and all co-authors who have worked with them on the topic of the present opinion, in particular S. J. Aboodarda, D. Bachasson, B. Kayser, R. Kruger, V. Martin, D. Neyroud, J. Rodriguez-Falces, T. Rupp, J. Temesi, S. Vergès, H. Westerblad.

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Correspondence to Guillaume Y Millet.

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Nicolas Place and Guillaume Millet declare that they have no conflicts of interest.

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Place, N., Millet, G.Y. Quantification of Neuromuscular Fatigue: What Do We Do Wrong and Why?. Sports Med 50, 439–447 (2020). https://doi.org/10.1007/s40279-019-01203-9

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