What causes CNS fatigue during exercise?

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Central nervous system (CNS) fatigue has been observed during exercise, as well as in the days following exercise. It is often assumed that CNS fatigue that is observed during exercise is the same CNS fatigue that occurs after exercise. However, this is certainly not true, because the CNS fatigue that arises during exercise is caused by a completely different set of mechanisms from the CNS fatigue that arises in the days after a workout. In this article, I explain how CNS fatigue arises during exercise.

What is CNS fatigue (and why does it matter)?

Fatigue refers to a transitory and reversible reduction in maximum strength (or more accurately exercise performance) due to a preceding bout of exercise. Consequently, CNS fatigue refers to a transitory and reversible reduction in maximum strength due to a preceding bout of exercise that is caused by mechanisms inside the brain or spinal cord.

CNS fatigue is not a feeling, nor is it a perception of being tired or fatigued. It is a reduction in the ability to send a sufficiently large electrical signal to the muscle (in the form of a central motor command). By reducing the size of the central motor command for a given level of perceived effort, CNS fatigue prevents maximal levels of motor unit recruitment from being attained, even when we are exerting a maximal effort.

A gradual increase in the amount of CNS fatigue present during exercise causes a gradual reduction in the magnitude of the central motor command, and this steadily reduces the number of high-threshold motor units that are recruited, starting with the highest high-threshold motor unit and working downwards from there. In other words, CNS fatigue affects motor units from the top downwards.

At this point, it is important to recognize that the fitness industry frequently (and incorrectly) refers to CNS fatigue in the context of overtraining. Yet, it is a completely normal part of any fatiguing exercise, including aerobic exercise as well strength training. It really should be discussed more regularly, at least as often as we discuss the role of metabolites in contributing to fatigue. Indeed, CNS fatigue is likely a more common type of fatigue than metabolite-related fatigue, at least if we consider all types of physical activity.

Nevertheless, the presence of CNS fatigue during exercise is not a good thing, because it prevents the recruitment of all of the accessible high-threshold motor units (and in fact preferentially affects the highest high-threshold motor units). Since increasing the ability to recruit high-threshold motor units is a key mechanism that underpins gains in maximum strength and since this adaptation is caused by reaching very high levels of motor unit recruitment during exercise, it is likely that the presence of CNS fatigue during exercise stops this adaptation from happening. Thus, CNS fatigue is a very detrimental phenomenon if we want to stimulate gains in maximum strength. Additionally, since the level of motor unit recruitment during exercise is a key determinant of the hypertrophy that is stimulated (since the higher the level of motor unit recruitment, the more muscle fibers are activated and therefore trained), the presence of CNS fatigue during exercise likely also reduces the amount of muscle growth that is stimulated after a workout. Thus, CNS fatigue is also likely to be detrimental for bodybuilding.

So what causes CNS fatigue during exercise?

Does reaching a high level of motor unit recruitment cause CNS fatigue during exercise?

It is often suggested that CNS fatigue is caused by exercise that involves a high level of effort, and therefore a high level of central motor command. Indeed, some researchers have implicitly assumed that it is the high level of central motor command that causes fatigue within the brain or spinal cord. Similarly, example, have sometimes suggested that CNS fatigue occurs after training with highly-fatiguing drop sets, and powerlifters frequently assume that CNS fatigue occurs after 1RM efforts.

Despite the popularity of these ideas, nothing could be further from the truth.

Indeed, dozens of research studies have shown that CNS fatigue accumulates during low-intensity aerobic exercise that involves submaximal levels of motor unit recruitment, as well as during low-force isometric contractions that do not involve reaching muscular failure. In fact, the amount of CNS fatigue that is present during submaximal contractions is typically much greater than the amount of CNS fatigue present during high-intensity exercise bouts.

This demonstrates that reaching a high level of motor unit recruitment does not cause CNS fatigue, as is often assumed.

These studies also tell us quite a bit about how the process of CNS fatigue works, since it seems that CNS fatigue is actually increased by exercise duration and not by exercise intensity. Indeed, studies that have directly compared different durations of exercise have shown that the amount of CNS fatigue present during exercise increases with increasing exercise duration, and not with increasing exercise intensity. Similarly, when CNS fatigue has been measured at multiple time-points during a long-duration bout of exercise, it has been shown to increase steadily and gradually over time.

Indeed, this gradual increase in CNS fatigue with increasing exercise duration is likely why exercise order matters during strength training. Several studies have shown that muscles that are trained earlier in a workout experience greater gains in strength and size than muscles that are trained later in the same workout. This probably occurs due to the gradual accumulation of CNS fatigue over the course of the workout, such that the later exercises are performed with a higher level of CNS fatigue than the earlier exercises.

So what are the mechanisms that cause CNS fatigue to appear during exercise, and why do they increase with increasing exercise duration?

What mechanisms do cause CNS fatigue during exercise?

CNS fatigue mechanisms all reduce the size of the central motor command that reaches the muscle during maximal efforts. Yet, these reductions can occur at two very different points: the brain and the spinal cord.

Supraspinal CNS fatigue takes place inside the brain. It reduces the size of the central motor command that is created. Spinal CNS fatigue takes place in the spinal cord. It reduces the size of the central motor command that can be transmitted to the muscle (this mechanism still causes CNS fatigue, even if the brain has managed to generate a sufficiently large signal). Although some commentators have denied the existence of one or other of these two types of CNS fatigue, there is evidence that CNS fatigue during exercise can be caused by both supraspinal and spinal mechanisms.

In terms of spinal CNS fatigue, it is usually accepted that the simple act of repeatedly causing a motor neuron to fire is responsible for some kind of fatigue response, such that the longer that the motor neuron spends firing, the greater the spinal CNS fatigue that occurs. While several investigations have been carried out to identify the exact nature of this mechanism, no clear picture has yet emerged. Even so, it does make sense in the context of the observation that increasing exercise duration increases the amount of CNS fatigue that is present.

In terms of supraspinal CNS fatigue, there is evidence that this can be caused by multiple mechanisms.

One important mechanism is afferent feedback. Afferent feedback refers to information that is collected by receptors at various places inside the body, including within the muscles, and which is then sent along afferent nerves back to the brain. This afferent feedback can be produced by several effects inside muscles or within the bloodstream, including metabolite accumulation and inflammatory mediators.

During exercise, working muscles produce metabolites. These metabolites are detected by receptors inside the muscles, and that information is sent to the brain, which causes us to experience burning and fatiguing sensations. Several studies have shown that the presence of these fatiguing sensations can cause supraspinal CNS fatigue. Conversely, blocking these fatiguing sensations can lead to a reduction in the amount of supraspinal CNS fatigue that is present. Therefore, it seems clear that metabolite accumulation can cause CNS fatigue. Even so, a metabolite-based mechanism does not fit well with the observation that CNS fatigue increases with increasing exercise duration, rather than with increasing exercise intensity, because metabolite accumulation is greater during shorter, higher-intensity types of exercise.

Inflammatory mediators are also produced during exercise, and seem to increase with increasing exercise duration. Also, the presence of these inflammatory mediators appears to cause CNS fatigue during exercise, after exercise, and also as a result of sleep deprivation. Based upon these observations, researchers have developed an explanatory model that links the presence of these inflammatory mediators to supraspinal CNS fatigue through two mechanisms. One mechanism involves afferent feedback, since the inflammatory mediators are produced inside exercising muscles, and can be detected by receptors inside the muscles. Another mechanism involves the inflammatory mediators entering the bloodstream and being detected by the circumventricular organs of the brain, which can be accessed without crossing the blood-brain barrier. Even so, both mechanisms probably work in ultimately the same way, which is to increase the perception of effort (I explain how this works in the next section).

In summary, there are therefore at least four different mechanisms that can cause CNS fatigue during exercise: (1) spinal CNS fatigue due to repetitive motor neuron firing, (2) afferent feedback due to metabolites (albeit likely only during high-intensity exercise), (3) afferent feedback due to inflammatory mediators, and (4) inflammatory mediators directly affecting the brain by entering into the bloodstream. It is likely that spinal CNS fatigue and/or inflammatory mediators are the best explanations for how CNS fatigue builds up with increasing exercise duration, since these mechanisms also increase in importance with increasing time.

At this point, it makes sense to take a moment to explain why an increase in the perception of effort causes supraspinal CNS fatigue.

How do changes in the perception of effort bring about supraspinal CNS fatigue?

According to the psychobiological model of exercise, the brain produces a signal that creates movement. As explained above, this signal is called the “central motor command” and it is sent to the muscles to stimulate motor unit recruitment. Large signals create a high level of motor unit recruitment, and small signals create a low level of motor unit recruitment. Importantly, this central motor command also produces a secondary signal (called the corollary discharge), which is what causes our perception of effort.

This perceived level of effort therefore increases progressively as the size of the central motor command (and the level of motor unit recruitment) both increase. Yet, we can only tolerate a certain level of perceived effort for a given bout of exercise (but the exact level might vary according to our level of motivation). In this way, the level of perceived effort limits the maximum level of central motor command.

CNS fatigue therefore arises when either [A] the level of perceived effort is increased by other factors (which do not simultaneously increase the size of the central motor command), or [B] the level of motivation is reduced. When motivation is maintained at a constant level, increasing the level of perceived effort without increasing the level of central motor command causes us to reach our maximum level of perceived effort earlier than we would normally, such that we are unable to achieve maximal levels of central motor command or maximal levels of motor unit recruitment.

Importantly, afferent feedback (and inflammatory mediators exerting direct effects on the brain) increases the perception of effort, without altering the level of central motor command. Therefore, when afferent feedback is present, the level of perceived effort at any given level of central motor command is increased. For this reason, when the level of perceived effort reaches its maximum tolerable limit in the presence of afferent feedback, the level of central motor command is not maximal, which means that the level of motor unit recruitment is also not maximal. We describe this inability to achieve a maximal level of motor unit recruitment despite the production of a maximal effort as CNS fatigue.

But is CNS fatigue during exercise really that important?

How much does CNS fatigue contribute to overall fatigue during exercise?

CNS fatigue has traditionally been shown to be responsible for 50% of the total fatigue that occurs during aerobic exercise, but only 10% of the total fatigue that occurs in strength training. However, until recently, all tests of CNS fatigue have been conducted after a short rest following exercise, and it seems likely that this short rest has been causing us to underestimate the role played by CNS fatigue during exercise to a large extent.

An important recent study compared the traditional way of testing for CNS fatigue with a novel test that did not allow any rest after exercise. The novel test showed that the CNS fatigue after a short bout of maximal effort strength training was responsible for 30% of the total fatigue, and this was much greater than was reported by the traditional testing method, which found that CNS fatigue contributed just 10% of the total fatigue. Previous research has similarly found that CNS fatigue contributes approximately 5–10% to overall fatigue during heavy strength training.

So this suggests that we have been hugely underestimating the contribution of CNS fatigue to overall fatigue during exercise.

Nevertheless, we should have guessed that this underestimation was taking place. Previous research has often shown that when total fatigue is measured by a strength test after long-duration exercise to task failure, the reduction in strength is much smaller than would have been necessary to cause task failure. This suggests that a very rapid recovery of strength is taking place before the measurement is normally taken.

For example, when performing isometric contractions with 10% of maximum force to task failure, it is logical that strength must reduce by 90% during exercise. Otherwise, task failure would not be reached. Yet, when this has been tested, research has found that the reductions in strength (when they are tested a couple of minutes after exercise) are only 50%. Therefore, there is a further reduction in muscular force of 40% during exercise (the reduction is 90%, which is from 100% down to 10%) that is not mirrored by the reduction in strength during the post-exercise strength test.

It seems likely that this additional fatigue is caused by CNS fatigue that dissipates almost immediately after exercise has terminated, and so is not detected by a post-exercise test that is performed a couple of minutes after exercise. Indeed, even the most rapidly-dispersing peripheral fatigue mechanisms take more than several minutes to dissipate after exercise, so it is highly likely that this extra fatigue has a central origin. This suggests that rather than accounting for 5-10% of overall fatigue during strength training and 40–50% of overall fatigue during aerobic exercise, CNS fatigue probably accounts for 20–30% of overall fatigue during strength training, and 60–70% of overall fatigue during aerobic exercise.

So CNS fatigue during exercise is really important!

Which CNS fatigue mechanisms contribute during exercise but not immediately afterwards?

Which particular CNS fatigue mechanism is responsible for the extremely large fatigue effect that is present during an exercise task but which is not present several minutes afterwards is not clear. As I will explain in the next section, it is unlikely to be either inflammation-related afferent feedback or metabolite-related afferent feedback, because neither of those mechanisms dissipate quickly enough.

This suggests that it could be a spinal mechanism. Unfortunately, there is little research to date into the rate of recovery of spinal CNS fatigue after exercise.

Alternatively, it could be an entirely different mechanism, involving the processing of information gathered from various sources, including the afferent feedback and inflammatory mediators, as well as from cognitive deductions. This is where CNS fatigue starts to require discussion of central governors, which I generally do not discuss, because they are not relevant to testing CNS fatigue by voluntary activation during maximal strength tests.

This psychological mechanism may involve an erosion of self-control. New research has shown that the apparent erosion of self-control (which has traditionally been called “ego depletion”) is probably caused by a task-specific switching of priorities instead of a reduction in resources. This psychological mechanism may bring about a reduction in the ability to exert force during a long-duration task that is not then apparent in a maximum strength test (because the perceived task constraints are different), which then gives the appearance of a rapid recovery of CNS fatigue. It is possible that CNS fatigue is not actually dissipating from the end of the exercise to the strength test, but rather than the CNS fatigue is only apparent in the exercise task, since it involves a longer perceived duration.

Do the various elements of CNS fatigue during exercise recover at different rates?

N.B. Once again, I want to emphasize that the CNS fatigue that is present the following day after exercise is totally different from the CNS fatigue that occurs during exercise, because it is probably caused by the development of muscle damage rather than by the mechanisms listed above. The fact that these CNS fatigue mechanisms recover relatively rapidly should not be taken as an indicator that CNS fatigue is not present in the days following a workout.

There are probably multiple mechanisms of CNS fatigue that are present during exercise. For various reasons, we might expect that these mechanisms will recover at different rates after a bout of exercise. We can identify at least three main elements of CNS fatigue: [A] supraspinal CNS fatigue caused by afferent feedback due to inflammatory mediators or by inflammatory mediators working released into the bloodstream, [B] supraspinal CNS fatigue caused by metabolite-related afferent feedback, and [C] spinal CNS fatigue caused by repetitive motor neuron firing.

By taking this information into account, we can see that the effects of CNS fatigue are likely underestimated during a bout of exercise itself (because of the rapidly-dissipating spinal CNS fatigue mechanism), that strength training techniques that involve high levels of metabolite accumulation (such as the use of pre-exhaustion, drop sets, and short rest periods) are not a great idea for maximizing adaptations (because of the high levels of supraspinal CNS fatigue caused by afferent feedback), and that long workouts are likely to cause diminishing returns, with later sets and exercises being ineffective (due to the accumulation of supraspinal CNS fatigue due to inflammatory mediators). This is why understanding the mechanisms of CNS fatigue during exercise is so important for strength training programming.

Nevertheless, we can also learn more from these mechanisms.

Does the CNS fatigue that occurs during exercise have a systemic effect or a localized effect?

Although voluntary activation levels are the gold-standard method for assessing the presence of CNS fatigue, CNS fatigue is also often inferred by the presence of non-local fatigue.

Non-local fatigue refers to the existence of fatigue in a muscle that was not used during an exercise bout. This non-local fatigue is frequently used as an indicator that CNS fatigue is present (especially since voluntary activation is very difficult and time-consuming to measure, while non-local fatigue is not). Nevertheless, if we use non-local fatigue to test for the presence of CNS fatigue, we are assuming that CNS fatigue is systemic (insofar as it affects all muscles in the body equally) rather than localized (insofar as it affects only the muscle or motor pathway that was trained).

Interestingly, there is evidence that an element of CNS fatigue may be localized, although much of it is certainly systemic.

When non-local fatigue is measured, there seems to be greater non-local fatigue in muscles that are directly contralateral to the one used during the exercise bout, compared to other muscles in the body. For example, when exercising with the index finger muscle of one arm, there is more non-local fatigue in the index finger muscle of the other arm compared to in the biceps muscles of that other arm. Since contralateral muscles share motor pathways, this suggests that CNS fatigue is greater in those motor pathways that are used during exercise in comparison with those that are not. In other words, there seems to be localized CNS fatigue as well as systemic CNS fatigue.

So what mechanisms might cause this localized CNS fatigue?

What mechanisms might cause a localized CNS fatigue effect (and why does this matter)?

We already know that some of the CNS fatigue mechanisms have systemic effects. Clearly, the inflammation pathway that involves the bloodstream will cause systemic effects, as it works by communicating through the circulation. Similarly, afferent feedback also seems to cause systemic effects. Indeed, recent research has shown that afferent feedback (due to the metabolites produced during exercise) from one muscle causes CNS fatigue in another muscle, as measured during a maximum strength test. Similarly, any indirect CNS fatigue mechanism in the brain caused by a shift in priorities is likely to have systemic effects.

Therefore, spinal CNS fatigue seems to be the only factor that might produce localized effects, since only the motor neurons of the working muscle will be affected by the repeated firing. Cross-over fatigue effects as a result of motor unit firing in the same motor pathway can in this way explain the greater non-local fatigue that seems to occur in the exact contralateral muscles.

Since spinal CNS fatigue likely dissipates very quickly after stopping a bout of exercise, this means that the localized element of CNS fatigue during exercise is probably very short-lived, while the systemic element of CNS fatigue is likely more long-lived. Unfortunately, this means that performing lots of different exercises in a single workout (as during whole-body strength training) will likely not circumvent the problem of increasing CNS fatigue over the course of a strength training workout, since most of the CNS fatigue that builds up over the course of a workout is probably systemic and not localized. It also suggests that when single-leg strength training is performed, appropriate rest periods should be allowed between training each leg, and one leg should not be trained immediately after the other.

What is the takeaway?

CNS fatigue is the name given to the types of fatigue that cause reductions in the ability to send a sufficiently large electrical signal to the muscle (in the form of a central motor command) so as to cause a maximal level of motor unit recruitment during exercise. Supraspinal CNS fatigue during exercise can occur in the brain as a result of afferent feedback from metabolites (during high-intensity exercise) or inflammatory mediators (during low-intensity exercise), as well as a result of inflammatory mediators communicating with the brain via the bloodstream (during low-intensity exercise). Spinal CNS fatigue can occur during exercise as a result of the repetitive firing of motor neurons (during exercise of all intensities).

By reducing the size of the central motor command that reaches the muscle to produce motor unit recruitment, the presence of CNS fatigue during exercise likely prevents gains in maximum strength from occurring by means of increases in the ability to recruit high-threshold motor units. Similarly, it likely reduces the amount of hypertrophy that occurs after training. Therefore, it should ideally be reduced or avoided.

By looking more closely at the mechanisms that underpin CNS fatigue during exercise, we can see that avoiding CNS fatigue during exercise involves: reducing the amount of metabolite accumulation during exercise (such as by avoiding short rest periods, advanced techniques such as pre-exhaustion and drop sets), reducing the exposure to inflammatory mediators (by avoiding very long workouts and too many exercises), and by reducing the duration of each set of exercise to avoid long periods of motor neuron firing (by using heavy or moderately-heavy loads, depending on the training goal).

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