Neurophysiology of endurance exercise

Question 1

Define muscle fatigue

Answer 1

decrease in force or power production in response to contractile activity

Question 2

Describe the actomyosin cross-bridge cycle.

Answer 2

• Myosin + actin –> Given ATP –> “power stroke” –> ADP + Pi –> Pi released

Question 3

Why is muscle is unable to provide same amount of power as the action is repeated?

Answer 3

o	Some metabolites change in concentration.
o	Phosphocreatine dec.
o	Inorganic phosphate inc.
o	Lactate inc.
o	ATP pretty stable

Question 4

Does lactate accumulation affect muscle force?

Answer 4

In humans exercising at different work intensities, lactate levels were found not to correlate well with muscle fatigue. In skinned muscle fibers at constant ionic strength have shown that lactate, at concentration even up to 50 mM, has relatively little effect on force production by the contractile apparatus.

Question 5

Which study demonstrated that lactate is not causing muscle fatigue?

Answer 5

• Study looked at time to exhaustion with a supplement that includes (G) glucose and fructose and (C) lactate
• C drink (with lactate) significantly increased time to exhaustion
• This shows that it can actually be a source of energy and spare glycogen

Question 6

How do [ATP], [ADP] and [Pi] change in fatiguing muscles?

Answer 6

• When [Pi] raises, the reaction is favored in the other direction (back to ATP), so ATP gives less energy as Pi concentration increases.
• In fatiguing muscle, the increase in [Pi] and [ADP] leads to a less negative ΔGATP and, therefore, to a decrease of the energy yield per unit of hydrolyzed ATP
• When ADP is elevated, it is further hydrolyzed by the adenylate kinase reaction to AMP, which is then rapidly deaminated to IMP.
o This helps reduce the rise in [ADP] and consequent decrease in free energy for ATP hydrolysis.
o During intense exercise, average cytoplasmic free [ADP] still rises from ∼10 to ∼200 μM (despite mechanisms trying to decrease [ADP])

Question 7

What is ΔGATP in the muscles at rest and how does it change with exercise?

Answer 7

• At rest, ΔGATP is ~ -65 kJ/mol

* With exercise, ΔGATP changes to ~ -50 to -40 kJ/mol

Question 8

During isometric contractions, what are the contributions of the myosin ATPase, SERCA, and Na+/K+-ATPase towards ATP consumption?

Answer 8

Myosin: ~65%
SERCA: ~30%,
Na-K: ~5%

Question 9

What is the activation energy of myosin ATPase?

Answer 9

approximately 40 kJ/mol (>22°C)

Question 10

At which point of ΔGATP does the SERCA ATPase stop working properly?

Answer 10

The minimum ΔGATP required to maintain steady-state SERCA ATPase function has been estimated to be approximately −52 kJ/mol

Question 11

What happens to VO2 for power output as the lactate threshold is reached?

Answer 11

After reaching the lactate threshold (when aerobic exercise can’t meet demands), more O2 is needed, and VO2 max is reached at a lower power output.
• Increased Pi and ADP reduces ∆GATP, which makes the transformation of chemical energy into mechanical work less efficient

Question 12

Describe the effects of H+ accumulation on muscle velocity

Answer 12

Increase in H+ (or decrease in pH) causes a decrease in maximum muscle velocity (Vmax) by 16% and a decrease in maximum isometric force (Po) by 12%.

Question 13

Describe the effects of Pi accumulation on muscle velocity (same pH)

Answer 13

Decreases velocity at a given force

Same Vmax; but 19% decrease in max isometric force (Po)

Question 14

Describe the effects of combined H+ and Pi on muscle velocity

Answer 14

Further decrease in velocity than individually (15% decrease in Vmax, 36% decrease in Po)

Question 15

Describe the effects of H+ accumulation on muscle peak power.

Answer 15

Decreases peak power (ppw) by 34%

Question 16

Describe the effects of Pi accumulation on muscle peak power.

Answer 16

Decreases PPW by 26%

Question 17

Describe the effects of combined H+ and Pi on muscle peak power.

Answer 17

Further decrease in PPW (decrease by 63%)

Question 18

What do Pi and H+ do to affect muscle velocity and power?

Answer 18

It seems like the combined effects of Pi and H+ alter the crossbridge cycling, leading to a slower shortening velocity and decreased power output.

Question 19

Which muscle fiber type(s) is/are affected by Pi and H+?

Answer 19

Similar trend is seen in both types

Question 20

In isolated muscle fibers, how do Pi and H+ affect muscle velocity and power?

Answer 20

Inorganic phosphate decreases sensitivity to Ca2+
• The combined effects of acidosis, phosphate ion accumulation and low Ca2+ interfere with cross-bridge cycling and hence muscle performance.
• Increased Pi and ADP reduces ∆GATP, which makes the transformation of chemical energy into mechanical work less efficient.

Question 21

What is the discharge rate and how does it change with fatigue?

Answer 21

• Discharge rate: Change in frequency of % unit
• During fatigue the slowing of muscle contractile speed shifts the force/frequency relation towards the lower frequency range.
• This allows motor units to remain fully activated despite a substantial reduction in motoneuron discharge rates. …, the reduction in discharge rate probably provides a safeguard against failure of neuromuscular transmission.
• More importantly, it must also serve to optimize force regulation by limiting the range of discharge rates to correspond closely to those in which force production can be modulated.
• Frequency decreases with fatigue
• % of total units recruited increases, possibly to maintain optimal organization

Question 22

How does fatigue at the neuromuscular junction work?

Answer 22

• During fatiguing exercise, change in the frequency of contractions are observed, resulting in lower frequency but greater motor units’ recruitment.
• Therefore, fatigue influences the function of the neuromuscular junction. This adaptation initially maintains the force but may impact fiber type recruitment (depending on the muscle) and the development of skeletal muscle fatigue.

Question 23

What is Hill’s model of exercise fatigue?

Answer 23

• “Shortly before the termination of maximal exercise the oxygen demands of the exercising muscles exceed the (limiting) capacity of the heart to supply that oxygen. This causes skeletal muscle anaerobiosis with the accumulation of “poisonous” lactate (lactic acid) in the muscles.”
• Therefore: athletes stop exercising at VO2max due to what ultimately is a limitation in convective oxygen transport.

Question 24

Do we stop exercising at VO2max due to the limit in our O2 capacity, as stated by Hill’s model of fatigue? Why or why not?

Answer 24

This hypothesis was evaluated bu the effects of a novel ‘reverse’ testing protocol in which the exercise began at a high running speed and then slowed progressively.
• No difference between groups at baseline (incremental)
• Decremental shows significantly higher VO2max in this group. Interestingly, when coming back to incremental at the end, the VO2max stayed at the same high value (sig higher from control group)
• This shows that this idea that we stop exercise at our limit of O2 capacity is not true.

Question 25

Does fatigue develop after complete skeletal muscle recruitment ?

Answer 25

No. Fatigue during exercise develops before there is complete skeletal muscle recruitment.

Question 26

Which 2 factors should be taken into account to study fatigue?

Answer 26

• The first is of central origin and purely nervous in character – namely, the will;
• The second is peripheral, and is the chemical force which is transformed into mechanical work…”

Question 27

How does deception impact fatigue? What does it suggest re: fatigue?

Answer 27

In a study where a group was given accurate feedback, and the other group was given feedback given that makes them think they are slower.
The group with deception had an improved performance.

This suggests that cyclists operate with a metabolic reserve even during maximal time trials and that this reserve can be accessed after deception.

Question 28

Is it possible to reduce fatigue with a placebo?

Answer 28

• Placebo group and control group –> Placebo is given a coffee-like substance (but not coffee); and control group is given the same drink but does not look/taste like coffee.
• Even by being given the same drink, both groups did differently.
o Placebo group had a lower RPE (effort perception) in the third series than the control group.

Question 29

What is central nervous system fatigue?

Answer 29

CNS fatigue is a subset of fatigue, i.e. a failure to maintain the required or expected force or power output, associated with specific alterations in CNS function that cannot reasonably be explained by dysfunction within the muscle itself.

The unwillingness to generate and maintain adequate CNS drive to the working muscle is the most likely explanation of fatigue in most people during normal activities.

Question 30

Describe the central governor theory

Answer 30

the brain uses two conscious sensations to regulate that exercise – the physical symptoms produced by the exercise and measured by the RPE and the sense of effort, which is a gauge of the psychic effort required to sustain a given work output. Thus “The direct consequence of the increasing sense of effort will be an altered behaviour, specifically a voluntary reduction in the exercise intensity. Conversely, exercise intensities that do not pose a threat to homeostatic control produce no or little sense of effort”

Question 31

Name some centrally-acting exercise -modifiers based on the Central Governor Model of Exercise Regulation

Answer 31

	Emotional state
	State of mental fatigue
	Sleep deprivation
	Recovery from prior exercise
	Level of motivation
	Degree of self-belief
	Superstitious beliefs
	Rewards (monetary or not)
	Presence of competitors
	Knowledge of endpoints
	Amphetamines, caffeine, …
	Cytokines
	Placebos, nocebos
	Psychological skills training
	Accurate or deceptive conscious feedback
	Body cooling before or during exercise
	CHO mouth rinsing (brain tricked into thinking nutrients are coming in)
	Prior experience (feel threatened by experience?)
	Visual feedback
	Analgesics

Question 32

How does anticipation affect exercise regulation?

Answer 32

o Begin exercise at different intensities

o Rate of increase in RPE predicts exercise duration also during VO2max testing

Question 33

How does reserve affect exercise regulation?

Answer 33

o Submaximal muscle recruitment at exhaustion
o Submaximal blood [La] and CO at altitude
o VO2max occurs at suboptimal VO2 and muscle recruitment

Question 34

How do afferent sensory feedbacks affect exercise regulation?

Answer 34

o	Rate of heat accumulation
o	Arterial or cerebral oxygenation
o	Thirst/extent of fluid loss
o	Muscle soreness or damage
o	Running downhill
o	Level of skeletal muscle fatigue

Question 35

Define exercise fatigue (updated definition)

Answer 35

Fatigue is a physical manifestation of a change in pacing strategy to ensure that internal body homeostasis is maintained (muscles do not develop ATP depletion, the hearth does not develop myocardial ischemia, body temperature does not become excessive, and the brain maintains an adequate glucose supply).

Question 36

Is fatigue a physical event?

Answer 36

Fatigue is a central perception (a sensation or emotion) and not a direct physical event. Exhaustion results from changes in central (brain) command to muscles rather than changes in the muscle themselves.

Question 37

Which 2 areas of the brain are activated during fatiguing exercise?

Answer 37

Fatigue‐induced increase in intracortical communication between mid/anterior insular and motor cortex during cycling exercise

Question 38

How does mental fatigue (stroop test) impact endurance performance?

Answer 38

• Doing inhibition task before self-paced endurance training:
o Decreases speed
o Increases RPE
o Decreases HR

Question 39

How do encouragements affect perfoemance?

Answer 39

It improves performance

Question 40

How does self-talk affect performance?

Answer 40

Participants trained to give themselves positive feedback improved more in edurance performance

Question 41

Name one hormone associated with runner’s high

Answer 41

Beta-endorphins: Endorphin levels rise with the length of exercise and with exhaustion
 Endorphins are associated with a sense of euphoria and happiness

Question 42

Which part of the brain is important in the feeling of euphoria (“will” to do exercise)?

Answer 42

o Anterior cingulate complex (ACC) –> Important area with opiodergic binding (reward feeling that encourages to keep exercising)
o Others as well, including OFC and INS parts of brain

Question 43

Which feelings are associated with beta-endorphin levels?

Answer 43

Endorphins are associated with a sense of euphoria and happiness

Question 44

What are the 2 mechanisms in which endocannabinoids lead to “runner’s high”?

Answer 44

A- Hedonic signals acting on the mesolimbic dopamine running system

a. 1- activation of the endocannabinoid receptor 1 (eCB1) relieves the inhibition of GABAergic neurons.
b. 2- This loss of inhibition results in dopamine release in the nucleus accumbens region (reward)

B- Analgesics (exercise-induced analgesia): Analgesia occurs in both the CNS and PNS via eCB receptors expressed on peripheral nerve fibres.

Question 45

What do opioid analgesics do for exercise performance?

Answer 45

They inhibit central motor drive and limit peripheral muscle fatigue development in humans

Analgesic group = VERY high power at the beginning, then goes down by a lot, significantly under other 2 groups.
• This shows that their perception of effort was low but short-lived.