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This article is part of a series:
→ Part 1 — What is fatigue?
→ Part 2 — Do your muscles slow you down?
→ Part 3 — Does your brain slow you down?
→ Part 4 — Why do you slow down?
→ Part 5 — How to resist slowing down.
→ Part 6 — There’s always something left in the tank.
→ Part 1 — What is fatigue?
→ Part 2 — Do your muscles slow you down?
→ Part 3 — Does your brain slow you down?
→ Part 4 — Why do you slow down?
→ Part 5 — How to resist slowing down.
→ Part 6 — There’s always something left in the tank.
Fatigue in runners. Part 3 of 6:
The causes of fatigue — does your brain slow you down?
Thomas Solomon PhD.
9th April 2022.
In your training to become a Jedi of the Fatigue Resistance, you’ve met fatigue in the muscles, heart, and lungs, and the environmental extremes that can influence it. But, now it's time to head up into your brain. Welcome to “central” fatigue…
Note: This part and the last part of the series (Parts 2 and 3) go pretty deep into the complexities of fatigue. If you wanna get your nerd on you’re in the right place, so stay tuned. However, if you’re less interested in the why and more interested in the what, then you are welcome to skip ahead to Part 4, in which I summarise all the causes of fatigue during exercise.
Reading time ~20-mins.
Or listen to the Podcast version.
Or listen to the Podcast version.
If you’ve followed this series, you will know that fatigue during exercise is slowing down when you don’t expect (or want) to because your muscles produce less force. You will also know that “peripheral” fatigue — what happens in and between your muscles, heart, and lungs — can sometimes explain why you produce less force and slow down and that environmental extremes — heat, cold, and altitude — can accelerate these routes to a visit from Lord Fader, Sith Lord of fatigue . However, at the end of Part 2, you learned that for your muscles to keep producing force, muscle fibres need to be continually activated (or innervated) by electrical nerve impulses (or action potentials) coming from your brain via the spine. Better runners can send larger impulses, recruit more muscle fibres, and can activate muscle fibres more quickly (see here, here and here). Larger electrical impulses activate more fibres and produce more force but, when you fatigue (slow down), the size of these impulses decreases, you activate fewer muscle fibres and produce less force. Simply put,
It has been known for many moons that applying external electrical current to a muscle nerve causes a contraction. Some clever scientists have exploited this phenomenon and realised that firing external electrical impulses into the tibial nerve (which serves the knee extensor muscles) not only causes the quads to contract (an evoked contraction) but that doing so during submaximal and maximal voluntary contractions provides additional information about the true maximal force capacity of the muscles. (Of course, you have to be careful how much electricity to apply because you can snap the femur!)
Several studies have used such methodology to demonstrate the presence of neuromuscular fatigue during trail races and ultra races (e.g. from 40 to 170 km at UTMB) and that the source of this neuromuscular fatigue is supraspinal — above the spine — and therefore beginning in the brain — central fatigue (see here and here). But, this accumulation of neuromuscular (and central) fatigue during trail running is also coupled to improved running (and walking) economy, especially on uphill terrain — i.e. as we fatigue, we adjust our gait/biomechanics to spend less energy for a given pace (see here, here, here, here, & here). We humans are rather adaptable to change. But, you already knew that.
So…
It is difficult to say exactly what causes pain during exercise. Some evidence shows that metabolite accumulation may be the culprit. For example, when injected into the muscles of the thumb, low concentrations of hydrogen ions (H+), lactate and ATP, equivalent to those measured during moderate endurance exercise, can cause sensations of fatigue and higher concentrations of these metabolites, equivalent to vigorous exercise, can cause pain, whereas injection H+ ions, lactate, or ATP on their own causes no sensations of fatigue or pain. No matter the cause, it’s important to acknowledge that pain is simply a perceived “feeling” our brain tells us to experience to avoid danger. Furthermore, muscle pain caused by an injection of hypertonic saline into muscles has been found to reduce endurance performance and maximal strength due to a loss of neuromuscular signals coming from the brain.
Further evidence that pain impairs performance comes from a 2021 systematic review showing a small effect of the painkiller paracetamol (aka acetaminophen) on time-to-exhaustion when consumed 45 to 60-minutes before exercise. Additional evidence from a 2012 systematic review found that athletes have far superior pain tolerance to a range of stimuli than physically-active non-athletes. This has been confirmed in marathon runners and ultrarunners, suggesting that your regular training might alter pain perception.
So, it may not surprise you to hear that…
This model has been replicated many times since but, in 2001, Alan St Clair Gibson from Tim Noakes lab added a clever spin. They included short high-intensity efforts during the ride to exhaustion to examine the time course of muscular fatigue, finding that the electrical signal from the brain/spine to muscles progressively fell during each successive high-intensity effort. I.e. the brain was choosing to reduce the number of muscle fibres being recruited as fatigue set in.
So, neuromuscular fatigue was present but notice how I use the word “choose”, as in “the riders chose to stop riding”. Decisions come from the brain. So, where peripheral fatigue occurs in the time between the muscle receiving the signal and the contraction taking place, central fatigue occurs at the point of the central nervous system (CNS) sending a signal to the muscle.
There are several reasons that central fatigue is a credible cause of fatigue during exercise…
Firstly, rating of perceived exertion (RPE) steadily increases during prolonged exercise to exhaustion until it reaches a maximum value when folks choose to stop. Yes, studies show that starting such exercise with high muscle glycogen enables athletes to exercise for longer but the same maximum RPE is reached no matter whether athletes start out with low or high glycogen — it is the rate of increase in RPE over time that is affected by muscle glycogen status. However, when you examine the rise in RPE as a function of the percentage of time-to-exhaustion, muscle glycogen has no influence. (see data here, here, here, here, and go deep on this topic here).
Secondly, during exercise, even maximal exercise, skeletal muscle fibre recruitment is never maximal — there is always a “skeletal muscle fibre recruitment reserve”. This indicates that your central nervous system is imposing a limit on how many muscles fibres can be activated, probably to prevent a catastrophic failure to maintain homeostasis. The goal of your brain is, after all, to keep the body alive. (Notably, the lungs work in much the same way — during exercise, you never reach your maximal ventilatory capacity, not even close).
Thirdly, mouth rinsing with carbohydrates improves endurance performance.
And, fourthly, loss of peak muscle force persists for several days after a marathon (reviewed here). This cannot be explained by peripheral fatigue mechanisms like a lack of oxygen or nutrients or elevated core body temperature, indicating some form of central fatigue.
So, if it is plausible that your brain gets “tired” during exercise…
Why?
Probably to slow you down before these “things” become critical — to maintain homeostasis. This is why your muscle glycogen levels or blood glucose concentrations never reach zero and why your body temperature never goes so high your blood boils. This is the essence of the “central governor” model.
In 2001, Tim Noakes, Alan St Clair Gibson, and Estelle Lambert proposed that exercise performance is regulated by the central nervous system specifically to ensure that catastrophic physiological failure does not occur during exercise. For example, hypoglycemia will starve the brain of its primary fuel — glucose — while hypoxia — low oxygen — can cause ischemia in the heart, both leading to irreversible damage. The central governor model proposes that the brain subconsciously predicts maximal exercise capacity causing us to slow down during prolonged intense exercise to protect ourselves from harm and that this is all “governed” by a regulated, anticipatory response coordinated in the brain aiming to maintain physiological homeostasis during exercise, regardless of intensity, duration, or environmental conditions.
Pacing behaviour is a key piece of evidence in support of this theory because folks nearly always set off at a pace that is manageable as if we anticipate our capacity in line with what might come down the road. Furthermore, you always seem to know how quick to start a race no matter what distance you’re racing — you never start a marathon at your 1-mile pace or your 400m race at your marathon pace.
Image adapted from Abbiss & Laursen (2005) Sports Med.
The concept of central fatigue during exercise was proposed in the late 1980s by Eric Newsholme and colleagues. They showed that free tryptophan concentrations rise during exercise because increasing free fatty acids levels (released from fat) compete with and prevent tryptophan binding to albumin. Consequently, they hypothesised that the increase in blood tryptophan pushes more tryptophan into the brain increasing the synthesis of 5-hydroxytryptamine (5-HT), aka serotonin, a neurotransmitter with potent effects on mood and sleep. Indeed some work shows that paroxetine, a 5-HT reuptake inhibitor, reduces endurance capacity. But if all this were true, then tryptophan supplementation before or during exercise would reduce exercise performance — it doesn’t (here, here, here, & here) and in some cases (and in horses) may even improve performance (here & here)?! Furthermore, because branched-chain amino acids (BCAAs) compete for the same transporters into the brain as tryptophan, then BCAA supplementation before or during exercise should also improve performance — it doesn’t (here, here, here, here, here and a systematic review here).
This is not to say that the brain is not involved. A whole body of work shows how central nervous system stimulants, like amphetamines, can increase endurance exercise capacity, even in elite athletes. And, noradrenergic pathways in the brain have been implicated with the onset of fatigue during endurance exercise and are associated with a steeper rate of increase of RPE during exercise. While neurotransmitters including serotonin (5-HT), dopamine, and acetylcholine may influence central fatigue during exercise. Furthermore, neuromodulators like inflammatory cytokines, ammonia, and adenosine (which accumulates in the brain during mental fatigue; more on that in a mo) can block the release of neurotransmitters like dopamine, resulting in a greater perception of effort (RPE) and a decrease in motivation to keep going. To go real deep on this topic, there are two excellent reviews by Stephen Bailey and Mark Davis (1997) and Romain Meeusen (2021).
And, besides the complicated neurophysiology of fatigue, there is of course the same thing that limits cardiac functions and muscle contraction — oxygen. At rest, cerebral blood flow increases when arterial oxygen levels drop, protecting the brain against hypoxia. But, during strenuous exercise, cerebral blood flow is blunted, which can lead to inadequate oxygen delivery to the brain and is implicated with fatigue during exercise (go deep on this in a 2007 review by Lars Nybo & Peter Rasmussen).
That your brain might be involved in fatigue during exercise might seem obvious — you can probably relate how you “feel” to how you perform. And, that’s exactly where I’m going next…
In 2010, Sam Marcora and Walter Staiano measured maximal voluntary cycling power in nonathletes before and immediately after a ride-to-exhaustion at 80% of their peak aerobic power (which the subjects who were not trained cyclists could manage for about 10-mins). Unsurprisingly, maximal power dropped (from 1075±214 to 731±206 watts, P<0.001) but the notable finding was that perceived effort (RPE) during the ride-to-exhaustion was lower in subjects who could ride longer (correlation: r=0.82, P=0.003). Marcora and Staiano concluded that muscle fatigue was not the cause of exhaustion and that “exercise tolerance in highly-motivated subjects is ultimately limited by perception of effort”. This idea evolved into a theory that fatigue during exercise is a combination of an athlete’s muscular fatigue (which creates a sense of increasing effort) and the athlete reaching their maximum threshold of perceived effort.
Sounds good and, during exercise performance tests, the feeling of exertion — RPE — is a frequently-stated obstacle. But, the notion that fatigue is solely caused by your perception of effort generated debate because it neglects to take into account the deterioration of the power-velocity relationship, which we now know also “fatigues” with time (here and here). However, the other observation Marcora & Staiano’s 2010 paper was that when subjects had ridden to exhaustion, during the subsequent max power test they could still produce a power output greater than that at which they were “exhausted”. They wrote “We argue that exhaustion is a form of task disengagement, i.e. a conscious decision to withdraw effort when the effort required by exercise is beyond the maximal effort subjects are willing to produce in order to succeed in the task”, ultimately concluding that the main factor causing exhaustion is “mind over muscle”. What this really emphasises is that “there is always something left in the tank” (more on that in Part 5) and that your feelings are involved in your decision to slow down.
Other studies have shown that muscle-damaging protocols (100 drop-jumps in ~30-mins) can increase RPE and decrease pace during a subsequent 15-min cycling time trial without altering folks’ pacing strategies. This suggests that the choice to go slower may be a behavioural response to compensate for the significant increase in perception of effort induced by muscle damage-induced fatigue. Similarly, muscle damage caused highly-trained runners to take longer to complete a 20 km time-trial and poorer running performance was associated with greater RPE, less perceived worth of the time-trial, greater perceived crisis and less flow state. Quite simply, when fatigued, things feel tougher and more pointless and you feel less “in the zone”. These things are all in your mind.
Data adapted from Taylor et al. (2022) Scand J Med Sci Sports.
This is relevant because motivation is a core component of performance — without motivation, there is no behaviour; without behaviour, there is no performance. Among recreational marathoners, large cross-sectional studies find that many factors influence motivation to run (here and here). This can include negative external factors like the guilt of stopping or weight control. In competitive runners, mastery and competition are key drivers of motivation and elite athletes are more likely to be motivated by extrinsic (aka “external”) factors like rewards, prizes, and financial incentives, which have been found to motivate world-class Kenyan athletes. Once again, these things are in your mind.
Being highly motivated is not just about having lots of willpower (or self-control, aka ego). Your willpower (or ego) is not infinite and, like your bank balance, it fluctuates and gets depleted when you spend it. Although the ego-depletion effect has been questioned (see “A Multilab Preregistered Replication of the Ego-Depletion Effect”), meta-analyses find that experimental depletion of folk’s willpower increases feelings of effort, perceived difficulty, and subjective fatigue, while lowering enjoyment (affect) and endurance performance, with medium-sized effects (Cohen’s d = ~0.5; see here and here).
To complicate things further, your motivation can also be shaped by exposure to emotions. In one study, cycling time-trial performance was reduced and feelings of pain were increased after subjects viewed painful images compared to neutral or pleasant images. Meanwhile, priming people with subliminal images of happy faces (vs. sad faces) and “action” words (“go”, “lively”, “energy” vs. inaction words like “stop”, “toil”, “sleep”, and “tired”) has lowered RPE and lengthened cycling time-to-exhaustion. However, these studies were in non-athletes in a laboratory where there are no “real” motivational factors, like medals, prize money, or competitors. In a study pitting endurance cyclists against virtual opponents during 10 km time trials, pursuit of a goal was an important determinant of athletes’ pacing behaviour because they had to balance their effort with their expectation of success. This suggests that athletes in a competitive environment are motivated to maintain their effort perhaps due to greater self-efficacy (aka self-belief).
Pretty darn cool.
Image adapted from Abbiss & Laursen (2005) Sports Med.
Systematic reviews clearly show that mental fatigue caused by cognitively-demanding tasks changes electroencephalographic (EEG) activity (electrical activity in the brain) and impairs cognitive performance and sport-specific skills (see here, here, here, and here). Systematic reviews also show that exposure to environmental extremes (cold, heat, altitude) also impairs cognitive performance. So, if you’re trying to do your best at any task that involves tactics or skill, mental fatigue should be avoided. As for endurance performance, it all started with a 2009 study from Samuele Marcora who had subjects play a mentally-challenging video game or watch emotionally-unprovocative documentaries (“World Class Trains” and “The History of Ferrari”) for 90-minutes prior to a ride to exhaustion. Documentary watching caused folks to report a lower RPE and ride ~15% longer than video game playing suggesting that mental fatigue may directly affect endurance performance. These types of studies have since been compiled in systematic reviews and meta-analysed, concluding that mental fatigue indeed causes physical fatigue.
Earlier meta-analyses found that yes, cognitive fatigue blunts physical performance but with a small effect size (g = -0.27) that is largely driven by random effects. Subsequent meta-analyses found a small to moderate detrimental effect (overall effect size = -0.38) of mental fatigue on exercise performance (effect size = 0.53) and RPE (effect size = 0.32) but with clear evidence of bias in favour of only publishing and/or reporting positive findings (see here and updated here).
Interestingly, the detrimental effect of mental fatigue on endurance performance is not explained by changes in heart rate, lactate accumulation, or neuromuscular function, mental fatigue simply increases your RPE and makes you reach your peak RPE more quickly — it makes things “feel” harder, sooner. So, the next obvious question is:
Earlier I said that several neurotransmitters may influence central fatigue during exercise. Mental fatigue is also thought to involve alterations in several neurotransmitter systems in multiple brain regions and the summation of these alterations might explain how mental fatigue impairs endurance performance (to go deep on this, please see a 2021 review by Romain Meeusen et al.). The most important of these systems may be dopamine and adenosine, which regulate one another and are both implicated with mental fatigue and fatigue during exercise by influencing RPE (see 2018 review by Schiphof-Godart et al.). The role of adenosine is of particular note because not only does accumulation of adenosine in the brain cause mental fatigue but a rise in adenosine blocks dopamine release, increases RPE, and decreases motivation (read about the emergence of this idea here and further reviewed here and here ); and, caffeine is also a potent adeosine receptor inhibitor, which partly explains why caffeine is such a potent performance enhancer.
Phew. Buzzing!
So, when we look at the role of the brain in fatigue, impaired motivation, reduced alertness, and blunted decision-making abilities may render you less able to unleash your true ability on race day. Ultimately, we don’t exactly understand “central” fatigue — there are many possibilities and it is unlikely to be driven by a single mechanism, and there are perhaps unknowns we’ve yet to discover. One thing is for sure: the brain is involved in fatigue during exercise — an exciting frontier for exercise biology.
Next time, I will tie everything together — “peripheral” and “central” — to create a “fatigue checklist” of things you need to address to keep Darth Fader, the Sith Lord of fatigue , away for as long as possible... Until then, stay nerdy and keep empowering yourself to be the best athlete you can be by training smart...
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If your brain sends less signal, you activate less muscle fibres and produce less force.
This is the essence of “central” fatigue — everything happening in the brain/CNS (central nervous system). During a hard race or session, your brain might get tired of sending signals — your brain might get tired of running. To start digging into that, I will say one thing…
Neuromuscular fatigue links the muscles to the brain.
Neuromuscular function is essentially your central nervous system firing a series of controlled and coordinated lightning bolts at your muscle fibres, providing the signal for them to use energy, contract and move you forward. But, like everything in life, it is not infinite and gets “tired”. During a run, you have a pool of “recruitable” muscle fibres that contract to produce force. With time, the amount of force each muscle fibre can produce drops (due to fatigue) and other fibres step in to take their place, like a cycle. But, with time, as fatigue sets in, more force is required to maintain the same running speed. This creates a problem, a collision of sorts, between the decreasing numbers of fibres available to produce force and the increasing number of fibres required to produce the desired force. When these things “collide”, your force drops and you slow down — all fibres are “tired” and there are none left in your pool to take over. This is neuromuscular fatigue — it is sneaky and creeps up on you — you don't notice neuromuscular fatigue until it's too late.
×
The “maximal voluntary contraction (MVC) of the knee extensor” test is a classic test of neuromuscular function. Several studies using this test show that maximal muscle force is blunted following prolonged exercise. When compared to cycling, running causes greater impairment in neuromusclar function, which is likely due to the eccentric contraction-induced muscle damage caused during running (vs. cycling) since muscle damage is strongly associated with loss of peak muscle force (see here and here). Other studies show that measures of peak muscle force (single-leg jump distance and 300m sprint time) and the ability to repeatedly produce force is what separates 10 km running performance among trained athletes with similar V̇O2max. In fact, maximal sprinting, heavy lifting, and intense and/or long workouts (hard intervals or hard long runs) all cause neuromuscular fatigue. Sometimes you can notice it in your stride but for a more objective approach, you can use explosive tests (e.g. a countermovement jump test) or reaction time tests (that measure ground contact time) to monitor your state of neuromuscular fatigue to indicate whether you are recovered from a big effort. But, I’ve gone off piste a little.
It has been known for many moons that applying external electrical current to a muscle nerve causes a contraction. Some clever scientists have exploited this phenomenon and realised that firing external electrical impulses into the tibial nerve (which serves the knee extensor muscles) not only causes the quads to contract (an evoked contraction) but that doing so during submaximal and maximal voluntary contractions provides additional information about the true maximal force capacity of the muscles. (Of course, you have to be careful how much electricity to apply because you can snap the femur!)
Several studies have used such methodology to demonstrate the presence of neuromuscular fatigue during trail races and ultra races (e.g. from 40 to 170 km at UTMB) and that the source of this neuromuscular fatigue is supraspinal — above the spine — and therefore beginning in the brain — central fatigue (see here and here). But, this accumulation of neuromuscular (and central) fatigue during trail running is also coupled to improved running (and walking) economy, especially on uphill terrain — i.e. as we fatigue, we adjust our gait/biomechanics to spend less energy for a given pace (see here, here, here, here, & here). We humans are rather adaptable to change. But, you already knew that.
So…
Neuromuscular function is the link between the brain and the muscles — the link between central and peripheral fatigue mechanisms.
Impaired neuromuscular function is the end point of all causes of fatigue — without an electrical signal, your muscles won’t produce force.
And into your brain we go…
Impaired neuromuscular function is the end point of all causes of fatigue — without an electrical signal, your muscles won’t produce force.
Feelings of soreness and pain can cause fatigue.
A consequence of micro-trauma (damage) occurring to muscle and connective tissue during exercise is soreness and pain, which you have no doubt experienced during a race (or session). Muscle damage and/or soreness induced by repetitive maximal effort eccentric exercise has been shown to impair neuromuscular function. Similarly, in endurance athletes, markers of muscle damage are correlated with the loss of neuromuscular function after a race. Furthermore, exercise-induced muscle damage and pain (caused by 100 drop-jumps in ~30-mins) impair 20 km time-trial performance in highly-trained runners.It is difficult to say exactly what causes pain during exercise. Some evidence shows that metabolite accumulation may be the culprit. For example, when injected into the muscles of the thumb, low concentrations of hydrogen ions (H+), lactate and ATP, equivalent to those measured during moderate endurance exercise, can cause sensations of fatigue and higher concentrations of these metabolites, equivalent to vigorous exercise, can cause pain, whereas injection H+ ions, lactate, or ATP on their own causes no sensations of fatigue or pain. No matter the cause, it’s important to acknowledge that pain is simply a perceived “feeling” our brain tells us to experience to avoid danger. Furthermore, muscle pain caused by an injection of hypertonic saline into muscles has been found to reduce endurance performance and maximal strength due to a loss of neuromuscular signals coming from the brain.
Further evidence that pain impairs performance comes from a 2021 systematic review showing a small effect of the painkiller paracetamol (aka acetaminophen) on time-to-exhaustion when consumed 45 to 60-minutes before exercise. Additional evidence from a 2012 systematic review found that athletes have far superior pain tolerance to a range of stimuli than physically-active non-athletes. This has been confirmed in marathon runners and ultrarunners, suggesting that your regular training might alter pain perception.
So, it may not surprise you to hear that…
Your brain can drive fatigue — central fatigue.
In the early 1980s, Ed Coyle found that fasted elite cyclists rode for about 4-hours when ingesting 100 grams/hour of carbs vs. 3-hours when given a sweetened and flavoured but calorie-free placebo. In that era, scientists were focused on fuel depletion and peripheral fatigue but, when the “carb munchers” chose to stop pedalling, muscle glycogen was not depleted and hypoglycaemia was not present — fuel was available but athletes’ bodies could not or would not use it.This model has been replicated many times since but, in 2001, Alan St Clair Gibson from Tim Noakes lab added a clever spin. They included short high-intensity efforts during the ride to exhaustion to examine the time course of muscular fatigue, finding that the electrical signal from the brain/spine to muscles progressively fell during each successive high-intensity effort. I.e. the brain was choosing to reduce the number of muscle fibres being recruited as fatigue set in.
So, neuromuscular fatigue was present but notice how I use the word “choose”, as in “the riders chose to stop riding”. Decisions come from the brain. So, where peripheral fatigue occurs in the time between the muscle receiving the signal and the contraction taking place, central fatigue occurs at the point of the central nervous system (CNS) sending a signal to the muscle.
There are several reasons that central fatigue is a credible cause of fatigue during exercise…
Firstly, rating of perceived exertion (RPE) steadily increases during prolonged exercise to exhaustion until it reaches a maximum value when folks choose to stop. Yes, studies show that starting such exercise with high muscle glycogen enables athletes to exercise for longer but the same maximum RPE is reached no matter whether athletes start out with low or high glycogen — it is the rate of increase in RPE over time that is affected by muscle glycogen status. However, when you examine the rise in RPE as a function of the percentage of time-to-exhaustion, muscle glycogen has no influence. (see data here, here, here, here, and go deep on this topic here).
×
If that was a bit heavy… what I am trying to say is that the maximal RPE you can sustain might determine the time at which you choose to stop and that the rate at which RPE increases might determine your exercise duration (possibly because it would prevent total energy depletion). This line of thinking is a bit Matrix-like because it indicates the following:
The duration of prolonged exercise might already be set and your brain might already know it at, or shortly after, the start of a race (or session).
Yikes, alright Morpheus, keep your hair on.
Secondly, during exercise, even maximal exercise, skeletal muscle fibre recruitment is never maximal — there is always a “skeletal muscle fibre recruitment reserve”. This indicates that your central nervous system is imposing a limit on how many muscles fibres can be activated, probably to prevent a catastrophic failure to maintain homeostasis. The goal of your brain is, after all, to keep the body alive. (Notably, the lungs work in much the same way — during exercise, you never reach your maximal ventilatory capacity, not even close).
Thirdly, mouth rinsing with carbohydrates improves endurance performance.
And, fourthly, loss of peak muscle force persists for several days after a marathon (reviewed here). This cannot be explained by peripheral fatigue mechanisms like a lack of oxygen or nutrients or elevated core body temperature, indicating some form of central fatigue.
So, if it is plausible that your brain gets “tired” during exercise…
What do we know (or think we know) about central fatigue during exercise?
The brain is constantly monitoring your body — it constantly monitors your heart rate, breathing rate, cardiac output, blood flow, blood pressure, core body temperature, skin temperature, sweat rate, blood concentrations of electrolytes (Na+ and K+), hydrogen ions (H+), glucose, lactate, O2, CO2, free radicals, etc, plus damage and soreness/pain, etc etc. All of these are “internal” signals. But there are also external signals like your pace, time splits, visual cues, support/coaching feedback, and don’t forget your competitors. The brain detects changes in these signals and uses these signals to determine how to change your work rate.
Why?
Probably to slow you down before these “things” become critical — to maintain homeostasis. This is why your muscle glycogen levels or blood glucose concentrations never reach zero and why your body temperature never goes so high your blood boils. This is the essence of the “central governor” model.
In 2001, Tim Noakes, Alan St Clair Gibson, and Estelle Lambert proposed that exercise performance is regulated by the central nervous system specifically to ensure that catastrophic physiological failure does not occur during exercise. For example, hypoglycemia will starve the brain of its primary fuel — glucose — while hypoxia — low oxygen — can cause ischemia in the heart, both leading to irreversible damage. The central governor model proposes that the brain subconsciously predicts maximal exercise capacity causing us to slow down during prolonged intense exercise to protect ourselves from harm and that this is all “governed” by a regulated, anticipatory response coordinated in the brain aiming to maintain physiological homeostasis during exercise, regardless of intensity, duration, or environmental conditions.
Pacing behaviour is a key piece of evidence in support of this theory because folks nearly always set off at a pace that is manageable as if we anticipate our capacity in line with what might come down the road. Furthermore, you always seem to know how quick to start a race no matter what distance you’re racing — you never start a marathon at your 1-mile pace or your 400m race at your marathon pace.
×
So, if central fatigue happens, the obvious question is:
What explains central fatigue during exercise?
While the central governor theory is rather sexy, there is no evidence that a central governor region in the brain exists. The evidence for this theoretical framework comes from observations of athletes’ detonations during exercise.
The concept of central fatigue during exercise was proposed in the late 1980s by Eric Newsholme and colleagues. They showed that free tryptophan concentrations rise during exercise because increasing free fatty acids levels (released from fat) compete with and prevent tryptophan binding to albumin. Consequently, they hypothesised that the increase in blood tryptophan pushes more tryptophan into the brain increasing the synthesis of 5-hydroxytryptamine (5-HT), aka serotonin, a neurotransmitter with potent effects on mood and sleep. Indeed some work shows that paroxetine, a 5-HT reuptake inhibitor, reduces endurance capacity. But if all this were true, then tryptophan supplementation before or during exercise would reduce exercise performance — it doesn’t (here, here, here, & here) and in some cases (and in horses) may even improve performance (here & here)?! Furthermore, because branched-chain amino acids (BCAAs) compete for the same transporters into the brain as tryptophan, then BCAA supplementation before or during exercise should also improve performance — it doesn’t (here, here, here, here, here and a systematic review here).
This is not to say that the brain is not involved. A whole body of work shows how central nervous system stimulants, like amphetamines, can increase endurance exercise capacity, even in elite athletes. And, noradrenergic pathways in the brain have been implicated with the onset of fatigue during endurance exercise and are associated with a steeper rate of increase of RPE during exercise. While neurotransmitters including serotonin (5-HT), dopamine, and acetylcholine may influence central fatigue during exercise. Furthermore, neuromodulators like inflammatory cytokines, ammonia, and adenosine (which accumulates in the brain during mental fatigue; more on that in a mo) can block the release of neurotransmitters like dopamine, resulting in a greater perception of effort (RPE) and a decrease in motivation to keep going. To go real deep on this topic, there are two excellent reviews by Stephen Bailey and Mark Davis (1997) and Romain Meeusen (2021).
And, besides the complicated neurophysiology of fatigue, there is of course the same thing that limits cardiac functions and muscle contraction — oxygen. At rest, cerebral blood flow increases when arterial oxygen levels drop, protecting the brain against hypoxia. But, during strenuous exercise, cerebral blood flow is blunted, which can lead to inadequate oxygen delivery to the brain and is implicated with fatigue during exercise (go deep on this in a 2007 review by Lars Nybo & Peter Rasmussen).
That your brain might be involved in fatigue during exercise might seem obvious — you can probably relate how you “feel” to how you perform. And, that’s exactly where I’m going next…
Your emotions cause fatigue during exercise.
The problem with the original central governor model is its focus on physiological homeostatic control. This led to an update, the “integrative governor” model, proposed in 2017 by Jerone Swart, Alain St Clair Gibson, and Ross Tucker (former students of Noakes) who hypothesise that fatigue during exercise is regulated by the dynamic interaction between physiological and psychological homeostatic drives that generate control. I.e. that it is not about “peripheral” vs. “central” fatigue but that there is a melting pot of many things and the brain protects your physiological and psychological homeostasis. This would mean that “slowing down” is not only the result of your choice of initial pacing strategy but is also influenced by a cauldron full of your subsequent decisions, feedback mechanisms, metabolic limits, external factors (your competitors, the weather, etc), learned experience from prior races, and your awareness of fatigue. But, for the existence of a “central governor” or an “integrative governor” to make any sense, we must acknowledge our emotional feelings, specifically our motivation to continue. This is the essence of the “psychobiological model” of fatigue, which essentially argues that a high perception of effort (aka high RPE) impairs exercise performance and high motivation is the remedy.In 2010, Sam Marcora and Walter Staiano measured maximal voluntary cycling power in nonathletes before and immediately after a ride-to-exhaustion at 80% of their peak aerobic power (which the subjects who were not trained cyclists could manage for about 10-mins). Unsurprisingly, maximal power dropped (from 1075±214 to 731±206 watts, P<0.001) but the notable finding was that perceived effort (RPE) during the ride-to-exhaustion was lower in subjects who could ride longer (correlation: r=0.82, P=0.003). Marcora and Staiano concluded that muscle fatigue was not the cause of exhaustion and that “exercise tolerance in highly-motivated subjects is ultimately limited by perception of effort”. This idea evolved into a theory that fatigue during exercise is a combination of an athlete’s muscular fatigue (which creates a sense of increasing effort) and the athlete reaching their maximum threshold of perceived effort.
Sounds good and, during exercise performance tests, the feeling of exertion — RPE — is a frequently-stated obstacle. But, the notion that fatigue is solely caused by your perception of effort generated debate because it neglects to take into account the deterioration of the power-velocity relationship, which we now know also “fatigues” with time (here and here). However, the other observation Marcora & Staiano’s 2010 paper was that when subjects had ridden to exhaustion, during the subsequent max power test they could still produce a power output greater than that at which they were “exhausted”. They wrote “We argue that exhaustion is a form of task disengagement, i.e. a conscious decision to withdraw effort when the effort required by exercise is beyond the maximal effort subjects are willing to produce in order to succeed in the task”, ultimately concluding that the main factor causing exhaustion is “mind over muscle”. What this really emphasises is that “there is always something left in the tank” (more on that in Part 5) and that your feelings are involved in your decision to slow down.
Other studies have shown that muscle-damaging protocols (100 drop-jumps in ~30-mins) can increase RPE and decrease pace during a subsequent 15-min cycling time trial without altering folks’ pacing strategies. This suggests that the choice to go slower may be a behavioural response to compensate for the significant increase in perception of effort induced by muscle damage-induced fatigue. Similarly, muscle damage caused highly-trained runners to take longer to complete a 20 km time-trial and poorer running performance was associated with greater RPE, less perceived worth of the time-trial, greater perceived crisis and less flow state. Quite simply, when fatigued, things feel tougher and more pointless and you feel less “in the zone”. These things are all in your mind.
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Further evidence that our emotions are involved comes from studies examining enjoyment of effort (aka affect) and self-efficacy (aka the degree to which you “believe” you can successfully achieve your performance goal). A 2022 paper hot off the press from my good friend, Dr Ian Taylor, found that a jargon-filled concept known as the “desire-goal motivational conflict” may influence our choice to slow down. He showed that people’s desire to reduce effort steadily rises and their value of the goal steadily drops during exercise as intensity drifts upward from the easy to moderate to heavy domains. In other words, some folks become less motivated as things get harder.
This is relevant because motivation is a core component of performance — without motivation, there is no behaviour; without behaviour, there is no performance. Among recreational marathoners, large cross-sectional studies find that many factors influence motivation to run (here and here). This can include negative external factors like the guilt of stopping or weight control. In competitive runners, mastery and competition are key drivers of motivation and elite athletes are more likely to be motivated by extrinsic (aka “external”) factors like rewards, prizes, and financial incentives, which have been found to motivate world-class Kenyan athletes. Once again, these things are in your mind.
Being highly motivated is not just about having lots of willpower (or self-control, aka ego). Your willpower (or ego) is not infinite and, like your bank balance, it fluctuates and gets depleted when you spend it. Although the ego-depletion effect has been questioned (see “A Multilab Preregistered Replication of the Ego-Depletion Effect”), meta-analyses find that experimental depletion of folk’s willpower increases feelings of effort, perceived difficulty, and subjective fatigue, while lowering enjoyment (affect) and endurance performance, with medium-sized effects (Cohen’s d = ~0.5; see here and here).
To complicate things further, your motivation can also be shaped by exposure to emotions. In one study, cycling time-trial performance was reduced and feelings of pain were increased after subjects viewed painful images compared to neutral or pleasant images. Meanwhile, priming people with subliminal images of happy faces (vs. sad faces) and “action” words (“go”, “lively”, “energy” vs. inaction words like “stop”, “toil”, “sleep”, and “tired”) has lowered RPE and lengthened cycling time-to-exhaustion. However, these studies were in non-athletes in a laboratory where there are no “real” motivational factors, like medals, prize money, or competitors. In a study pitting endurance cyclists against virtual opponents during 10 km time trials, pursuit of a goal was an important determinant of athletes’ pacing behaviour because they had to balance their effort with their expectation of success. This suggests that athletes in a competitive environment are motivated to maintain their effort perhaps due to greater self-efficacy (aka self-belief).
Pretty darn cool.
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The brain is certainly “alive” during exercise — imaging technologies like fMRI, NIRS, PET-CT, and Doppler ultrasound show that the brain lights up like a neural and metabolic firecracker when we get moving. Plus, a 2022 systematic review and meta-analysis of all known laboratory experiments found that mood disturbances, like cognitive anxiety and depression, and having an “ego climate” have small negative effects (d = -0.21) on endurance performance while self-efficacy (belief) has a large beneficial effect (d = 0.82). But we are far from understanding everything…
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So… Fatigue during a race is very likely driven by how much you’re enjoying the effort but also by how motivated you are to continue the effort (which is influenced by importance and reward) and how much you believe in your ability to sustain the effort — all these things are connected and influence how much you’re willing to push. Why? Because athletes always have a sprint finish, especially when an Olympic Gold medal can be won. But, we’ve also all had races when our head isn’t in the game — the brain says “nope” not “yep”. I’ve dropped out of a couple of races shortly after thinking “why the feck am I here?”. No matter how the laboratory-derived experimental evidence plays out and no matter what the precise biological explanations are for fatigue during exercise, if we gather all our empirical observations into a pot, as coaches and/or athletes, we can confidently state that,
“Our brain can certainly slow us down”.
And, one last thing on that…
Mental fatigue might slow you down.
Mental fatigue is a psychobiological state that you might experience as a feeling of tiredness, exhaustion, or lethargy, etc, caused by prolonged exertion and/or heavy cognitive load. This includes anything that burdens your mind — stressing over your training decisions, your nutrition choices, your recovery choices etc. We all know what it feels like to have a tired brain. I get excessively “brain tired” when I write these articles, when I teach, and when I hang out in crowds or groups of people. Perhaps you can relate to that. But, have you ever linked “brain tiredness” to your physical performance or lack thereof? During training, resting your mind, as well as your body, is essential for optimal recovery (I dug deep on this at veohtu.com/rest) but mental fatigue also impairs performance…Systematic reviews clearly show that mental fatigue caused by cognitively-demanding tasks changes electroencephalographic (EEG) activity (electrical activity in the brain) and impairs cognitive performance and sport-specific skills (see here, here, here, and here). Systematic reviews also show that exposure to environmental extremes (cold, heat, altitude) also impairs cognitive performance. So, if you’re trying to do your best at any task that involves tactics or skill, mental fatigue should be avoided. As for endurance performance, it all started with a 2009 study from Samuele Marcora who had subjects play a mentally-challenging video game or watch emotionally-unprovocative documentaries (“World Class Trains” and “The History of Ferrari”) for 90-minutes prior to a ride to exhaustion. Documentary watching caused folks to report a lower RPE and ride ~15% longer than video game playing suggesting that mental fatigue may directly affect endurance performance. These types of studies have since been compiled in systematic reviews and meta-analysed, concluding that mental fatigue indeed causes physical fatigue.
Earlier meta-analyses found that yes, cognitive fatigue blunts physical performance but with a small effect size (g = -0.27) that is largely driven by random effects. Subsequent meta-analyses found a small to moderate detrimental effect (overall effect size = -0.38) of mental fatigue on exercise performance (effect size = 0.53) and RPE (effect size = 0.32) but with clear evidence of bias in favour of only publishing and/or reporting positive findings (see here and updated here).
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To summarise, the evidence shows that mental fatigue can cause physical fatigue but that neurological tests are often not used to confirm the presence of cognitive fatigue and that the quality of studies is generally poor — perhaps the studies were designed following cognitively-demanding tasks. Overall, the negative effect of mental fatigue includes isometric and dynamic resistance exercise performance and aerobic exercise performance, including running. The only part of sporting performance that appears to be less affected by mental fatigue is maximal anaerobic performance — i.e. you should always be able to unleash the anaerobic beast even when brain dead. Recent evidence also indicates that some elite athletes are immune to the effects of mental fatigue. This possibly indicates that your training and increased situational exposure (to hard sessions and hard races) may play a massive role in negating the effects of mental fatigue.
Interestingly, the detrimental effect of mental fatigue on endurance performance is not explained by changes in heart rate, lactate accumulation, or neuromuscular function, mental fatigue simply increases your RPE and makes you reach your peak RPE more quickly — it makes things “feel” harder, sooner. So, the next obvious question is:
What explains mental fatigue?
If Jermaine Clement, writer of the TV show “What We Do in The Shadows”, was asked this question, he’d probably say that mental fatigue is caused by Energy Vampires who drain your will to live from your brain. Exposing your mind to exhausting people can certainly be a brain drain but what about neurology…
Earlier I said that several neurotransmitters may influence central fatigue during exercise. Mental fatigue is also thought to involve alterations in several neurotransmitter systems in multiple brain regions and the summation of these alterations might explain how mental fatigue impairs endurance performance (to go deep on this, please see a 2021 review by Romain Meeusen et al.). The most important of these systems may be dopamine and adenosine, which regulate one another and are both implicated with mental fatigue and fatigue during exercise by influencing RPE (see 2018 review by Schiphof-Godart et al.). The role of adenosine is of particular note because not only does accumulation of adenosine in the brain cause mental fatigue but a rise in adenosine blocks dopamine release, increases RPE, and decreases motivation (read about the emergence of this idea here and further reviewed here and here ); and, caffeine is also a potent adeosine receptor inhibitor, which partly explains why caffeine is such a potent performance enhancer.
Phew. Buzzing!
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So, when we look at the role of the brain in fatigue, impaired motivation, reduced alertness, and blunted decision-making abilities may render you less able to unleash your true ability on race day. Ultimately, we don’t exactly understand “central” fatigue — there are many possibilities and it is unlikely to be driven by a single mechanism, and there are perhaps unknowns we’ve yet to discover. One thing is for sure: the brain is involved in fatigue during exercise — an exciting frontier for exercise biology.
Next time, I will tie everything together — “peripheral” and “central” — to create a “fatigue checklist” of things you need to address to keep Darth Fader, the Sith Lord of fatigue , away for as long as possible... Until then, stay nerdy and keep empowering yourself to be the best athlete you can be by training smart...
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About the author:
I am Thomas Solomon and I'm passionate about relaying accurate and clear scientific information to the masses to help folks meet their fitness and performance goals. I hold a BSc in Biochemistry and a PhD in Exercise Science and am an ACSM-certified Exercise Physiologist and Personal Trainer, a VDOT-certified Distance running coach, and a Registered Nutritionist. Since 2002, I have conducted biomedical research in exercise and nutrition and have taught and led university courses in exercise physiology, nutrition, biochemistry, and molecular medicine. My work is published in over 80 peer-reviewed medical journal publications and I have delivered more than 50 conference presentations & invited talks at universities and medical societies. I have coached and provided training plans for truck-loads of athletes, have competed at a high level in running, cycling, and obstacle course racing, and continue to run, ride, ski, hike, lift, and climb as much as my ageing body will allow. To stay on top of scientific developments, I consult for scientists, participate in journal clubs, peer-review papers for medical journals, and I invest every Friday in reading what new delights have spawned onto PubMed. In my spare time, I hunt for phenomenal mountain views to capture through the lens, boulder problems to solve, and for new craft beers to drink with the goal of sending my gustatory system into a hullabaloo.
Copyright © Thomas Solomon. All rights reserved.
I am Thomas Solomon and I'm passionate about relaying accurate and clear scientific information to the masses to help folks meet their fitness and performance goals. I hold a BSc in Biochemistry and a PhD in Exercise Science and am an ACSM-certified Exercise Physiologist and Personal Trainer, a VDOT-certified Distance running coach, and a Registered Nutritionist. Since 2002, I have conducted biomedical research in exercise and nutrition and have taught and led university courses in exercise physiology, nutrition, biochemistry, and molecular medicine. My work is published in over 80 peer-reviewed medical journal publications and I have delivered more than 50 conference presentations & invited talks at universities and medical societies. I have coached and provided training plans for truck-loads of athletes, have competed at a high level in running, cycling, and obstacle course racing, and continue to run, ride, ski, hike, lift, and climb as much as my ageing body will allow. To stay on top of scientific developments, I consult for scientists, participate in journal clubs, peer-review papers for medical journals, and I invest every Friday in reading what new delights have spawned onto PubMed. In my spare time, I hunt for phenomenal mountain views to capture through the lens, boulder problems to solve, and for new craft beers to drink with the goal of sending my gustatory system into a hullabaloo.
Copyright © Thomas Solomon. All rights reserved.