Comprehensive review/Revue généraleNeuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigueLa fatigue neuromusculaire au cours de l’exercice : considérations méthodologiques, étiologie et rôle potentiel dans la fatigue chronique
Introduction
The term fatigue is defined by the Oxford Dictionaries as “extreme tiredness resulting from mental or physical exertion or illness” and originates from the Latin fatigare–“to weary, to tire out” [182]. In this context, the effects of fatigue have received attention in occupations where extreme tiredness can have serious consequences, such as in pilots [79], military personnel [205], fire-fighters [39] and surgeons [183]. In addition, the term fatigue is used to describe a non-specific but debilitating symptom in a range of chronic diseases and disorders such as cancer [129], multiple sclerosis [101], stroke [32] and depression [11]. The subjective nature and severity of fatigue in healthcare is assessed using psychometric tools such as self-report questionnaires and scales [48], [207]. There is no all-inclusive definition of clinical fatigue but the distinction from other uses of the term is that the symptom is the result of an underlying pathophysiology or its associated treatment. The term fatigue is also used in relation to a decline in performance induced by exercise, where exercise is defined inclusively as muscle activity with the potential to disrupt homeostasis [209]. Understanding fatigue in the context of the limitations to exercise performance has been a major research agenda for exercise physiologists for over a century [78], [133]. Lively debate continues to enrich the literature and has provoked consideration across the entire discipline of exercise science [9], [19], [112], [144].
The relative merit of objective and subjective measures of fatigue is dependent on the theoretical framework of study. For example, in a clinical population where fatigue may be chronic and have a devastating impact on quality of life (QoL) and/or physical function, a multidimensional approach is clearly warranted. In contrast, investigation of the mechanisms of fatigue following a specific exercise task may primarily rely on objective physiological measures [125]. It follows that generic use of the term fatigue without explicit definition or consideration of fatigue-related phenomena in different populations or contexts can be problematic. This highlights the inadequacy of the single term “fatigue” for concepts which are readily acknowledged by both exercise scientists and clinicians as being multifactorial, interactive and complex. A taxonomy was suggested for use in clinical research using two domains: perceptions of fatigue and performance fatigability [97] and it was recently proposed that this framework should be implemented as a foundation to unify research in human performance [50]. There is certainly value in adopting a cohesive nomenclature and the emphasis in this review is on describing fatigue according to the application and the techniques used to measure it.
An early model of exercise-induced fatigue proposed that exercise is limited by muscle lactate accumulation secondary to an inadequate supply of oxygen due to a limited cardiac output [78]. In opposition to this model where exercise termination was considered the result of skeletal muscle anaerobiosis, the central governor/complex systems model proposes that exercise is regulated in an anticipatory manner, to ensure exercise terminates before catastrophic biological failure [102], [142]. The latter model involves feed forward motor output to recruit an appropriate number of motor units (based on numerous physiological and psychological factors), continuous modification of pace via feedback from conscious sources and allows for the presence of an end-spurt in closed-loop tasks [143]. There are multiple models of fatigue [1], [141] but a crucial divide is whether fatigue is studied with respect to a change in motor performance (for example, a decrease in the ability to produce force), or as a conscious perception of a sensation [147] with or without a change in motor performance. It has been proposed that fatigue includes both an increase in the perceived effort necessary to exert a desired force and an eventual inability to produce said force [51]. In contrast, some research groups consider fatigue to be an emotion rather than a physical event [143], [179], derived and used by the brain to regulate exercise performance [201].
It is often difficult to extrapolate the findings from one approach to another since different experimental designs provide information about different processes. The approach taken to study exercise-induced fatigue also varies between research groups due to techniques used by diverse specialist fields, e.g. magnetic peripheral stimulation in respiratory medicine vs. electrical stimulation in neurology and sport sciences. In view of the recent suggestions in regards to clarity, the focus of this review is on both a decline in objective physiological measures over a discrete period of time and the subjective experience of fatigue (termed “performance fatigability” and “perceptions of fatigue”, respectively [50], [97]). A somewhat underexplored area for consideration is the relationship between mechanisms of exercise-induced fatigue and the chronic fatigue present in many clinical populations. As previously highlighted, establishing the relationship between these distinct and often independent concepts, is a priority for future research [97]. In particular, we will provide two examples of clinical populations (cancer survivors and people with multiple sclerosis, PwMS), where objective physiological measures related to a reduced fatigue resistance may be associated with increased perceptions of fatigue during exercise and/or activities of daily living. In other words, neurophysiological measures to determine central and peripheral factors during acute exercise may aid in the understanding of chronic fatigue.
Where data are available, this review will primarily consider mechanisms of neuromuscular fatigue in the lower limbs during single-joint and whole-body exercise (mainly running and cycling), where whole-body exercise is considered to be bilateral, dynamic and that which involves large muscle groups. This is due to the functional relevance to locomotion, rehabilitation and activities of daily living in clinical populations. Within this review, exercise-induced fatigue is considered to be a deficit originating in the nervous and/or muscular system, in relation to the integration of mechanisms and regulatory functions at a number of biological levels. As such, a number of fascinating topics broadly related to fatigue or exercise performance fall outside of the scope of this review. In particular, the reader is directed to examples elsewhere in regards to the conscious perception of effort [145], [177], mental fatigue [114], exercise-induced pain [117], overtraining [118], automonic nervous system changes [171] and deteriorated metabolic/mechanical cost of locomotion [65].
Section snippets
Part 1: acute fatigue as a reduction in maximal performance
Historically, fatigue was defined as a failure to maintain the required force to maintain a task [47]. It is now well established that this definition is invalid: fatigue develops gradually during sustained physical activity, not solely at the point of task failure [62]. A more accurate definition should reflect this and also distinguish fatigue from muscle damage or muscle weakness (which persists over longer time periods and can be independent from exercise [203]), in that it is reversible by
Part 2: etiology of acute lower limb fatigue
Some studies have investigated lower limb fatigue using the classic 2-min sustained isometric MVC (e.g. [90]) and showed that both central (decrease in VA) and peripheral (twitch reduction by ∼ 70%, personal unpublished data) factors can explain the large decrease in MVC. However, while these studies are of interest to examine the fundamental causes of fatigue in a well-controlled environment, the present paper focuses on fatiguing tasks more relevant to daily living in humans. Another
Potential role of low acute fatigue resistance in subjective chronic fatigue
The sections above have underlined the complexity of exercise-induced fatigue etiology, especially when considering the task dependency of fatigue. Yet, chronic fatigue experienced by athletes (i.e. overtraining) or patients is even more complex. Indeed, in addition to the objective and direct physiological and biological causes of fatigue (e.g. anemia), other indirect causes of fatigue such as psychological (e.g. depression, anxiety), nutritional, social and behavioural (in particular sleep
Conclusion
In clinical populations where chronic fatigue is particularly pervasive, debilitating and mechanistically complex, we propose that the relationship between the central and peripheral contributions to neuromuscular fatigue and the perceptions of fatigue measured using self-report questionnaires warrants further investigation. There are a number of alternatives to the classical measurement of exercise-induced fatigue, which could be utilised in this framework to overcome some of the enduring
Declaration of interest
The authors declare that they have no competing interest.
References (214)
- et al.
Knee extensors neuromuscular fatigue changes the corticospinal pathway excitability in biceps brachii muscle
Neuroscience
(2017) - et al.
Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors
Ann Oncol
(2016) Understanding fatigue in major depressive disorder and other medical disorders
Psychosomatics
(2008)- et al.
Quadriceps function assessment using an incremental test and magnetic neurostimulation: a reliability study
J Electromyogr Kinesiol
(2013) - et al.
Exercise and rehabilitation for individuals with multiple sclerosis
Phys Med Rehabil Clin N Am
(2005) - et al.
Fatigue risk management by volunteer fire-fighters: use of informal strategies to augment formal policy
Accid Anal Prev
(2015) - et al.
Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans
Electroencephalogr Clin Neurophysiol Electromyogr Mot Control
(1998) - et al.
Methodological issues with the interpolated twitch technique
J Electromyogr Kinesiol
(2007) - et al.
Neuromuscular complications in cancer
J Neurol Sci
(2016) - et al.
A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee
Clin Neurophysiol
(2012)
Stimulation of the motor cortex and corticospinal tract to assess human muscle fatigue
Neuroscience
Fatiguing effect of multiple take-offs and landings in regional airline operations
Accid Anal Prev
Fatigue in multiple sclerosis – a brief review
J Neurol Sci
Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue
J Pain Symptom Manage
Neuroscience needs behavior: correcting a reductionist bias
Neuron
Models to explain fatigue during prolonged endurance cycling
Sport Med
Unilateral elbow flexion fatigue modulates corticospinal responsiveness in non-fatigued contralateral biceps brachii
Scand J Med Sci Sports
Twitch interpolation of the elbow flexor muscles at high forces
Muscle Nerve
Skeletal muscle fatigue: cellular mechanisms
Physiol Rev
A biobehavioral model for the study of exercise interventions in cancer-related fatigue
Biol Res Nurs
Central and peripheral fatigue: interaction during cycling exercise in humans
Med Sci Sports Exerc
Point: afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance
J Appl Physiol
Peripheral fatigue limits endurance exercise via a sensory feedback-mediated reduction in spinal motoneuronal output
J Appl Physiol
Non-invasive magnetic stimulation of human motor cortex
Lancet
Recommendations for high-priority research on cancer-related fatigue in children and adults
J Natl Cancer Inst
Cancer-related fatigue version 2.2015
J Natl Compr Cancer Netw
The uses and interpretations of the motor-evoked potential for understanding behaviour
Exp Brain Res
Central and peripheral fatigue in sustained maximum voluntary contractions of human quadriceps muscle
Clin Sci Mol Med
Effects of induced metabolic alkalosis on prolonged intermittent-sprint performance
Med Sci Sport Exerc
The evolutionary significance of fatigue
Front Physiol
Fatigue in breast cancer survivors: occurrence, correlates and impact on quality of life
J Clin Oncol
Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation
J Clin Oncol
Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis
Cancer Epidemiol Biomarkers Prev
Muscle electrophysiology in patients with advanced breast cancer
J Natl Cancer Inst
Extracellular Ca2 ± induced force restoration in K ± depressed skeletal muscle of the mouse involves an elevation of [K + ]i: implications for fatigue
J Appl Physiol
Canadian Cancer Society's Advisory Committee on Cancer Statistics
Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients
Mult Scler J
Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation
Front Cell Neurosci
Mechanism of the silent period following transcranial magnetic stimulation
Exp Brain Res
Fatigue and recovery of power and isometric torque following isotonic knee extensions
J Appl Physiol
Isometric torque and shortening velocity following fatigue and recovery of different voluntary tasks in the dorsiflexors
Appl Physiol Nutr Metab
Poststroke fatigue: an emerging, critical issue in stroke medicine
Int J Stroke
Instantaneous quantification of skeletal muscle activation, power production and fatigue during cycle ergometry
J Appl Physiol
Is the notion of central fatigue based on a solid foundation?
J Neurophysiol
Exercise for the management of cancer-related fatigue in adults
Older men are more fatigable than young when matched for maximal power and knee extension angular velocity is unconstrained
Age (Omaha)
Physiological responses to prolonged exercise in ultramarathon athletes
J Appl Physiol
Delayed recovery of leg fatigue symptoms lowing a maximal exercise session in people with multiple sclerosis
Neurorehabil Neural Repair
Changes in velocity of shortening, power output and relaxation rate during fatigue of rat medial gastrocnemius muscle
Pflugers Arch
Recent insights into muscle fatigue at the cross-bridge level
Front Physiol
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