The science of fatigue: how to move beyond perception

Fatigue is a complex issue, rarely noted beyond athlete complaints of feeling tired. Alejandro Nino explains why an athlete or patient stops exercising and how to influence variables for improved performance.

Two of the main theories of exercise regulation are the peripheral model and the central governor model of fatigue⁽¹⁾. These two models are mostly based on physiological reflexes and mental constructs and do not appear to give much importance to the role of psychological factors. However, why would the rate of perceived exertion (RPE) score be different during a world cup soccer final than an early league match? Or even, why would an athlete compete to a life-threatening point? Although researchers have yet to come up with a definite answer to these questions, recent studies by researcher Samuele M. Marcora on his newly-developed biopsychosocial model of fatigue seem to be getting closer to uncovering the so-called “cardinal exercise stopper⁽²⁾ _­­­.”

Exhaustion versus fatigue

Exhaustion is the inability to maintain the required physical task⁽¹⁾. The definition of fatigue, on the other hand, varies with the source. Some physiologists opt for the simplest definition:  a decrease in force production⁽³⁾. Others clarify that fatigue is the inability to generate the original force in the presence of an increased perception of effort⁽³⁾. Another noteworthy definition of fatigue involves a process leading to an exercise-induced reduction in the maximal force capacity of the muscle⁽¹⁾. Regardless of its meaning, most exercise physiologists agree that the origins of fatigue can be central or peripheral⁽³⁾.

Peripheral fatigue is a decrease in the capacity of the skeletal muscle to produce force due to physiological causes, such as excitation-contraction coupling failure, an action potential failure, or impairment of the cross bridge-cycling⁽³⁾. The definition of central fatigue is not completely clear. It is believed that an altered efferent command from the brain results in a decrease in force production that is independent of changes in muscle contractility^(2-4). In other words, central fatigue is a sensation of fatigue that is not always directly related to exercise intensity⁽³⁾.

Previous models of fatigue

The peripheral model of fatigue is based on the foundational studies by British Nobel laureates A.V. Hill and F.G. Hopkins in the 1920s and persists as the predominant way of thinking about fatigue ^{(3, 5, 6)}. This model predicts that exercise always stops at an absolute endpoint that is temporarily irreversible. For instance, a person who begins to fatigue during training will continue until they reach a complete endpoint of physiological and metabolic exhaustion, independent of any regulation by the central nervous system⁽³⁾.

Hill and Hopkins suggested that fatigue develops when the oxygen requirement of the active skeletal muscles exceeds the heart’s capacity to further supplement oxygen delivery to exercising muscle, and the energy generation comes only from anaerobic metabolism^(5,6). There are a few limitations to this model. First, not one study has yet clearly established a direct link between any single physiological variable and the perception of effort⁽³⁾. Several studies have shown the contrary. For example, a patient with chronic fatigue syndrome experiences fatigue even at rest and is unwilling to participate in any physical activity, so the physiological bases for their symptoms remain unknown⁽³⁾. Moreover, patients with fever also tend to experience symptoms of fatigue at rest. This fatigue is likely due to cytokines released from the immune cells during fevers that activate the conscious perception of fatigue to speed up recovery by avoiding exercise⁽³⁾.

The mismatch between a person’s perception of effort and their unimpaired exercise capacity leads researchers to believe that fatigue must originate in the area of the brain responsible for the conscious perception of effort⁽³⁾. Second, and most interestingly, human subjects instructed to voluntarily exercise a muscle to exhaustion do not recruit all skeletal muscle fibers before stopping^{(3, 5)}. Dynamic magnetic resonance imaging techniques detected that only 71% of the available motor units are recruited during a 100% maximal voluntary isometric contraction^{(3, 7)}. Another study suggested that a maximal voluntary isometric contraction uses only one-half of the force-generating capacity of the quadriceps muscle⁽⁸⁾. Therefore, a protective central inhibitory mechanism must exist, which limits the maximum forces produced. Even under optimal conditions,⁽⁸⁾ an absolute physiological endpoint to exercise may not be possible⁽³⁾.

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Central models of fatigue

Early models of central fatigue hypothesized that altered output commands from the brain skeletal cause muscle fatigue⁽³⁾. One of these models suggests that changes in concentrations of certain brain neurotransmitters are responsible for creating fatigue⁽¹²⁾. An alternative central model claims that central fatigue is not caused by inhibitory metabolic processes in the brain, but by an active neural process that prevents the development of absolute fatigue and organ damage⁽⁵⁾. Kay et al.⁽¹⁰⁾ asked eleven athletes to complete, under warm and humid conditions, the greatest distance possible in a 60 min self-paced cycling time trial, which included a one minute maximal-effort sprint every 10 minutes. Efferent neural output during each sprint was measured using EMG data obtained from the belly of the rectus femoris. Rate of perceived exertion, peak power output, and peak oxygen consumption were also measured.

The outcomes of this study were noteworthy for exercise physiologists. There was a decrease in efferent activity and power output starting in the early phases of the exercise. However, they increased both neural drive to the muscle and power output during the final sprint. This renewed effort despite prolonged muscle activation, indicates the existence of a subconsciously-controlled motor unit recruitment reserve during the initial five sprints, and the ability to recruit that reserve during the final sprint^{(3, 10)}.

The researchers theorized that if substrate depletion or metabolite accumulation was the cause of the decrease in force output and EMG activity, as is predicted by the peripheral fatigue model, the athletes couldn’t increase their power output in the last sprint⁽³⁾. Also, despite encouragement to exert themselves as hard as possible during each sprint, the cyclists maintained a submaximal rate of perceived exertion ranging from 14 to 18 on the Borg (0-20) scale. This contradiction led South African scientist Professor Tim Noakes and colleagues to postulate that the regulation of effort must occur at a subconscious level, or through a central governor, that overrules the conscious desire of the subject to exercise as hard as possible⁽³⁾. This central-governor model of fatigue suggests that a central region of the brain controls exercise regulation by integrating afferent sensory signals and information from the environment to produce a sustainable exercise intensity. This level of activity allows homeostasis and a sensation of fatigue that the individual finds acceptable⁽³⁾. This model may be an effective evolutionary survival mechanism to prevent complete exhaustion after physical activity, thus maintaining an activity reserve that would allow escape from further predatory attacks⁽³⁾.

Figure 1: Central Governor Model*

*Adapted from  

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Biopsychosocial model of fatigue in rehabilitation

Similar to the biopsychosocial model of pain, a deep understanding of the biopsychosocial model of fatigue may offer sports specialists an additional framework on which to structure rehab⁽¹⁾. Emotional responses to exercise, such as displeasure or discomfort, in addition to the perception of effort and physiological stresses, can make the exercise experience aversive, especially for beginners⁽¹⁵⁾. By highlighting the importance of neuroscience and exercise psychology, physical therapists may be able to directly influence the ability of a patient to resist higher levels of perceived effort⁽¹⁾. For example, interventions can modulate potential motivation and impact the motivational and cognitive elements during exercise.

A clinician can influence the patient’s RPE by using Morgan and Pollock’s⁽¹⁶⁾ associative/dissociative cognitive strategies and manipulating teleoanticipatory expectations⁽¹⁴⁾. Dissociation strategies involve shifting one’s focus towards environmental stimuli with the aim of blocking sensations of pain or discomfort related to the physical effort⁽¹⁵⁾. This strategy may be useful in situations where pain is not a threat to tissue homeostasis⁽¹⁶⁾.­ Association strategies involve focusing on one’s physical perceptions stem­­ming from changes in temperature, respiration, and muscular fatigue⁽¹⁵⁾. Use this technique to avoid overuse injuries when there is a risk of an athlete doing too much too soon⁽¹⁶⁾. Be aware that the effects of attention to physical symptoms are also affected by the context in which the sensation occurs⁽¹⁷⁾. Lastly, teleoanticipatory expectations may be manipulated by assuring exercisers that they still have a long way before finishing, rather than the usual, “ You are nearly there!” encouragement.

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