CNS Fatigue

Introduction
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!

Conclusion
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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