CNS Fatigue - The Muscle PhD

CNS Fatigue

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If you’ve spent even minimal amounts of time in the gym over the past few years, I’m certain you’ve heard someone complain that their central nervous system (CNS) is fatigued, burnt out, exhausted, etc. What exactly does this mean? Are these dramatic gym bros actually experiencing CNS fatigue?

Most would likely assume that the whole-body fatigue, mentally tired feeling that you get from super hard workouts is CNS fatigue. That’s actually not the case. CNS fatigue has a much smaller definition and is even more difficult to accurately assess without unique (and expensive) machinery. Since this is a topic that’s more complicated than meets the eye, let’s get started.

Peripheral vs Central Fatigue

When considering exercise-induced fatigue, there’s two main contributors to this phenomenon:

1) Peripheral Fatigue:

Peripheral fatigue is localized to the muscle. As the muscle fatigues during exercise, metabolites accumulate in the muscle. Each metabolite that accumulates has unique effects on fatigue which includes things like reducing excitability, reducing calcium release from the sarcoplasmic reticulum, reducing calcium sensitivity in the contractile proteins, and even reducing force production of individual cross bridges during muscle contraction (4,5,10,29). All of this is, essentially, a complicated way of saying that metabolite accumulation can reduce force production of a working muscle. This leads to greater effort being expended and a greater need for oxygen delivery to the muscle which is why you get tired and out-of-breath during exhaustive exercise.

Now, for the most part, none of these peripheral issues have anything to do with the central nervous system – AKA the brain and spinal cord. Before we touch on central fatigue, we need to outline a simplified schematic of how a signal for movement travels from the brain to the muscle (9):

Brain (Motor Cortex) -> Spinal Cord -> Motor Neuron -> Muscle Fibers

This map can also run in reverse through afferent or sensory neurons when considering feedback loops. There’s a constant flow of information from the brain to the muscle and vice-versa. The brain needs these feedback loops so that it knows when or how to modulate body motions to adapt to the environment (9) or, in terms of exercise, increasing difficulty during a lift.

Okay, with that out of the way, let’s move onto central fatigue.

2) Central Fatigue:

Central fatigue is not the feeling of physical and mental exhaustion following training. Central fatigue is simply an inability to maximally recruit a muscle (4,5). This is due to a few reasons: decreased input to motor neurons (22), increased afferent inhibitory feedback (5,11,29), and reduced responsiveness of individual motor neurons (16). From the schematic above, we can deduce that:

1) Decreased input to motor neurons is likely localized in the brain as the inputs for movement are formed in the motor cortex (29).

2) Increased afferent inhibitory feedback likely stems from the muscle as this would be a feedback loop to the spinal cord (4,5,29).

3) Reduced responsiveness of individual motor neurons is likely a combination of factors from both the spinal cord and feedback loops preventing some of these motor neurons from firing (29).

Now, these are all complicated ways of saying that, when we are centrally fatigued, we cannot maximally activate a muscle. Why is this important for training?

CNS Fatigue and Training

Before we get too in-depth, it’s worth reminding everyone that CNS fatigue can happen from heavy training (23,24), light-weight high-volume training (5,23), and even cardio (4,5,23). CNS fatigue will develop throughout a set working to failure and can persist for up to 30-mins after a set to failure (4,5). Therefore, if you perform a set to failure and then try to repeat that set after say, 3-5 minutes of rest, you won’t be able to maximally activate your muscle during the second set (4,5). Why is this important?

We know that mechanical tension is the main stimulus of muscle growth (26). Muscle fibers primarily experience tension through producing force, and the amount of tension that a muscle experiences is dependent on its contraction speed (5). When CNS fatigue is present, muscle activation decreases – especially in the motor units that control the larger muscle fibers that grow the most in response to training (5). If you can’t activate these fibers in your next few sets, how are they supposed to grow? Working out with high levels of CNS fatigue, then, probably isn’t best for growth. Does the research confirm this idea?

We see some evidence from studies in which set volume decreases significantly when performing each set to failure (13) – i.e. say you perform a 10RM on set 1, you’ll maybe get 8 reps on set 2, and likely only 5-6 reps on set 3. A reduction in muscle activation due to CNS fatigue likely plays a major role here. We also see long term evidence showing that training programs with short rest periods produce less muscle growth than training programs with longer rest periods (18). Since CNS fatigue accumulates during a workout, using shorter rest periods will actually reduce muscle activation and the overall stimulus for growth from that workout (5). This can also explain why super high rep sets below 30% 1RM do not produce as much growth as using weights 30% and up (12)– super high rep sets will accumulate more CNS fatigue throughout the set which means that your large, growth-happy motor units may not actually get much of a growth signal (5).

Lastly, CNS fatigue may also explain why exercises that are done at the end of a workout produce less growth and strength gains than exercises done in the beginning of a workout (21). Since CNS fatigue accumulates throughout a workout, performing too many additional sets or exercises at the end may not net much benefit (5). Therefore, it’s probably a good idea to avoid training to failure multiple times in a workout, using short rest periods, and doing a bunch of “junk” volume at the end of your workout. However, using isolation exercises at the end of your workout will likely net more benefits than compound exercises as isolation movements are less likely to be affected by CNS fatigue (read here).

Now that we know how CNS fatigue can affect training (and since we have your attention now), let’s move on to the exact causes of CNS fatigue. We touched on that a little bit before but let’s get into the nitty gritty now.

What Causes CNS Fatigue?

We know from above that CNS fatigue can develop from heavy lifting, light/high volume lifting, and even cardio. Why can all of these things cause CNS fatigue?

The main determinant of CNS fatigue is probably afferent inhibitory feedback loops (2,4,5,29). Afferent neurons in the muscle are separated into 4 groups – group III and group IV afferent neurons can detect both mechanical loading and metabolite accumulation in the muscle (2,5,29). If these nerves detect that mechanical loading is too extreme, or metabolite accumulation is progressing too quickly, they will send feedback signals to the spinal cord which results in decreased input to the target motor neuron and reduced muscle activation. This is likely some type of defense mechanism to prevent injury or damage to the muscle.

The signals from afferent nerves can differ in both intensity and duration. This is why things like super high rep training and even cardio can cause greater CNS fatigue than normal strength training (25). The duration of inhibitory feedback is likely a greater predictor of CNS fatigue than just the intensity of the signal itself (4,5). An easy way to experience this is by performing a single set of 100 reps on curls, bench press, etc. with a super light weight. What do you think the odds are that you could repeat that set within a few minutes?

In addition, both lifting weights (heavy and light) and cardio can cause muscle damage. Since muscle damage results in muscle soreness, this can also increase afferent inhibitory feedback from the muscle due to activation of pain receptors in the muscle (17). The resulting inflammation from muscle damage can also play a role in CNS fatigue as inflammation can increase muscle soreness and further activate these pain receptors (5).

Afferent inhibitory feedback loops mostly covers the motor neuron and spinal cord aspects of CNS fatigue, but how can the brain also become fatigued?

As you exercise, branched chain amino acid (BCAA) uptake and metabolism in the muscle increases which reduces BCAA levels in the blood (20). Reducing blood levels of BCAAs can increase the amount of unbound tryptophan in the blood. This results in more tryptophan passing through the blood-brain barrier and increases the serotonin concentration in the brain (14). Serotonin accumulation in the brain can reduce motor signals and overall performance (6) and can also give you that “mentally exhausted” feeling.

So, now that we have a decent idea of what causes CNS fatigue, let’s get into a more interesting and more applicable debate: is CNS fatigue local to the trained muscle or is it systemic?

Is CNS Fatigue Local or Systemic?

What we mean by this question is – since CNS fatigue reduces muscle activation, does this only occur in the muscle you just trained? Or does the CNS fatigue stemming from, say, a high-volume chest workout, also affect the legs? If CNS fatigue was just local, only the chest would be affected. On the other hand, if CNS fatigue is systemic, then every other muscle group would be affected by that chest workout. Let’s discuss.

A common assumption is that CNS fatigue is local (5). This is why things like push-pull supersets are convenient to perform, however, they do get more difficult the heavier you go or the higher in reps that you go. This could be evidence of CNS fatigue being systemic (5) but it could also just mean that your conditioning is crap.

In addition, studies show that CNS fatigue, as measured by quad activation, is similar between squats and deadlifts (3). This is interesting support for CNS fatigue being systemic since the squat will activate and fatigue the quads to a much greater degree than the deadlift will. However, we see quad activation being reduced similarly from both exercises.

Interestingly enough, we have some evidence showing that non-local fatigue (CNS fatigue) may be dependent on what exercises you pair. Studies show that performing upper body movements to fatigue/failure can reduce activation in the lower body muscles (1,10). This is likely because the lower body muscles (like the quads, glutes, and hamstrings) are typically much larger than upper body muscles and also have more overall motor units. Any kind of CNS fatigue triggered by upper body training, then, is probably more likely to affect the legs (10) than the contrary – i.e. leg training affecting upper body muscle activation.

Afferent inhibitory feedback would likely result in local CNS fatigue, however, CNS fatigue in the brain would likely affect the body in a systemic manner rather than local. Ammonia production during fatiguing exercise can also impair neurotransmission in a systemic fashion (15) so there certainly seems to be more evidence leaning towards the systemic side. This can be a key takeaway as CNS fatigue in the brain seems to be caused by increased BCAA metabolism in the muscle – this would occur during highly fatiguing/high volume workouts and may even be influenced by training fasted. Therefore, super high volume workouts are probably more likely to induce systemic CNS fatigue rather than local.

Since CNS fatigue is probably more so systemic than local, what are some ways you can measure your CNS readiness? Are there any ways you can recover your CNS? Let’s get into that next.

CNS Fatigue Assessment and Recovery

The most common way that coaches and professionals track or assess CNS fatigue is by testing vertical jump height (7,8,27,28). If you’re interested in tracking your own CNS fatigue, perform your first vertical jump test after a few days of rest and then assess it before and after every workout. If you’re more than 10% off of your initial jump (for example, <27 inches instead of 30), odds are your CNS is pretty fatigued.

Other researchers have used handgrip strength tests to assess CNS fatigue as handgrip strength is highly reliant on maximum muscle activation (8,17). However, we understand that not everyone has a handgrip dynamometer at the ready, so vertical jumps may be an easier assessment for the masses.

One issue with vertical jumps, however, is that they likely do not isolate CNS fatigue as the lone cause of reductions in performance (28). Muscle damage is a great example to use here as muscle damage is both a form of peripheral (muscle) fatigue and can influence CNS fatigue. If you perform a vertical jump while you’re sore, it’s tough to say how much of a role both types of fatigue are playing in your terrible jump.

One last way you can track CNS fatigue is by assessing your rating of perceived exertion (RPE) on various lifts (27). Pay attention to how a specific weight feels or moves. I’d assume most people here have a pretty routine warm-up for big lifts like squats, bench press, and deadlifts. During your warm-up, pay attention to how the weight feels; does 225lbs feel like a house? Did 185 move much slower than usual? If you’re noticing any of these issues, it’s very possible that you’re still experiencing some CNS fatigue from a previous workout.

So, we have most of the assessments nailed down and now it’s time to talk about CNS recovery. Like we stated early, CNS fatigue arising from afferent inhibitory feedback likely lasts for about 30-minutes following a set to failure (5). The majority of your CNS fatigue following this 30-minute period is due to muscle damage and inflammation. Therefore, you really wouldn’t focus specific recovery efforts for your central nervous system; but, rather, just focus recovery on repairing muscle damage. This is the typical advice of eating plenty of protein, moderate carbs to replenish glycogen losses, getting at least 8-hours of sleep, and drinking plenty of fluids to maintain hydration. Really nothing special here!


So, after this long, drawn-out discussion, what conclusions can we make?

1) CNS fatigue is a real thing. It is not the sensation of mental exhaustion following a heavy workout but, rather, it is defined as a reduced ability to maximally activate a muscle.

2) CNS fatigue is mostly caused by afferent inhibitory feedback loops. Afferent neurons can detect mechanical loading and metabolite accumulation in the muscle and can send signals to the spinal cord when one of these issues becomes sketchy.

3) All types of training can cause CNS fatigue; however, super high rep training and long cardio sessions may cause more CNS fatigue than traditional bodybuilding-style training. Therefore, plan your cardio days accordingly so that your CNS is not fried for a heavy leg day the next day.

4) If you’re planning on lifting to failure in a given workout, doing more than 1-2 sets to failure for a given exercise/muscle group will not have any additional benefits due to CNS fatigue onset.

5) Since CNS fatigue can accumulate during a workout, place your most important exercises at the beginning of the workout and your least important ones towards the end. This is entirely dependent on your goals and what you want to achieve with that specific workout.

6) The time-course of CNS recovery following a high-volume session is going to be similar to muscle soreness and inflammation. Therefore, your CNS can be fatigued for 48-72 hours following training. Adopting good recovery habits, like proper nutrition and sleep, may help accelerate this process slightly.

7) CNS fatigue is likely more systemic than local; however, upper body training appears to influence lower body training more than vice-versa. This is a good reason to always start your week off with a lower body workout before upper body rather than upper body before lower body. That way your lower body workout isn’t impaired by systemic CNS fatigue from the upper body workout. Super high volume workouts or fasted workouts are also probably more likely to induce systemic CNS fatigue.

8) Since increased BCAA metabolism can be a precursor to CNS fatigue in the brain, consuming protein/BCAAs/or even carbohydrates before/during training may be a way to slow the progression of CNS fatigue during a workout (6,29).

Okay, I think that’s about it. I would encourage everyone to re-read this article a second time. A lot of the topics here are pretty complicated and difficult to break down into layman’s terms, so now that you’re slightly more familiar with the concepts, a second read may help you absorb more info. If you made it all the way to the end of this one, give yourself a pat on the back!

Easter Eggs

If you’re interested in a more in-depth discussion, check out these articles from Dr. Chris Beardsley here and here.


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