Fatigue?

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From muscle to brain or vice versa?

http://jap.physiology.org/cgi/eletters/00976.2009v1?ck=nck

Point-Counterpoint:
Markus Amann, Niels Henry Secher, and Samuele Maria Marcora
Point: Counterpoint - Afferent feedback from fatigued locomotor muscles is / is not an important determinant of endurance exercise performance.

Fatigue can be defined in several ways and depending on the emphasis that has been taken (peripheral or central), can be explained from different angles (5). This point – counterpoint debate nicely illustrates that depending on the `angle' the problem is attacked, each author can find clear arguments to get his statement through (1,3). Afferent feedback (not only from muscles) is important, but there will always be an integration of the signals at the central level, where the perception of effort is computed (5).

It is therefore not only the translation of peripheral input, but also the interpretation of incoming signals that will determine fatigue. This is illustrated by experiments in which brain neurotransmission is manipulated during exercise in the heat. When the dopaminergic system is manipulated (in human and rat models) performance is improved, fatigue is postponed without changes in the perception of effort, but simultaneously, core and brain temperature will increase above 40°C (2,5,6).

Probably both authors are right because one must not forget that we are dealing with a disturbance of homeostasis of `basic' physiological systems where integrative physiology is necessary for the interpretation of incoming peripheral signals. But in this case, also non-homeostatic pathways will be involved in the (regulation of) effort perception.

It should be noted, however, that homeostatic and non-homeostatic pathways are probably not two completely separate (neural) systems : significant interaction at different levels might exist (4), it might therefore be interesting approach this problem from a more `gestalt' viewpoint.

References

1.Amann M & Secher NH. Afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance. J Appl Physiol, in press 2009.

2.Hasegawa H, Piacentini MF, Sarre S, Michotte Y, Ishiwata T, Meeusen R. Effect of a dopamine/ noradrenaline reuptake inhibitior on exercise performance and thermoregulation of the rat in a warm environment. J Physiol 586: 141-149, 2008

3.Marcora SM. Afferent feedback from fatigued locomotor muscles is not an important determinant of endurance exercise performance. J Appl Physiol, in press 2009.

4.Meeusen R. Perception of effort: it is what we think we know that keeps us from learning. J Appl Physiol. 106(6):2063; 2009.

5.Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF. Central Fatigue, the serotonin hypothesis and beyond. Sports Med. 36(10): 881-909, 2006.

6.Roelands B, Hasegawa H, Watson P, Piacentini M, Buyse L, De Schutter G, and Meeusen R. The Effects of Acute Dopamine Reuptake Inhibition on Performance Med Sci Sports exerc; 40(5): 879-885, 2008.



The arguments proffered by Amann and Secher (1) as well as Marcora (4) each have merit when considering the complex factors regulating exercise performance. Clearly, acute adjustments in autonomic nervous system activity are requisite for increasing cardiac output, blood pressure and ventilation to adequately deliver oxygen to exercising muscle. Muscle work could not be sustained at all without these cardiorespiratory adjustments. While important, afferent feedback from metabolically sensitive fibers in locomotor muscle is not the sole determinant of these autonomic changes (3). Mechanically sensitive afferent fibers in muscle, central command (feed forward central cortical control) and the arterial baroreflex all contribute significantly to autonomic regulation during exercise (2,5,6). The fact that these neural inputs may also inhibit central motor output during strenuous exercise is not surprising. Like many "finely-tuned" processes within the body, it is logical for a system to protect its performance by inhibiting outputs that could exceed its functional capacity. However, it seems naïve to suggest that human consciousness does not also play a role in limiting exercise performance. Who among us has not ended an exercise session prematurely due to perceived exhaustion or overestimated task difficulty? It is unlikely that the physiological capacity for exercise is exceeded in such situations, yet exercise performance is limited. Only through learned behaviors or during activation of instinctive survival mechanisms can the physiological limits of performance be approached. A more relevant model of the features determining endurance exercise performance would include both autonomic inputs as well as psychobiological factors.

1. Amann M, and Secher NH. Afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance. J Appl Physiol, in press, 2009.

2. Fisher JP, Bell MP, and White MJ. Cardiovascular responses to human calf muscle stretch during varying levels of muscle metaboreflex activation. Exp Physiol 90(5): 733-781, 2005.

3. Kaufman MP, and Hayes SG. The exercise pressor reflex. Clin Auton Res 12: 429-439, 2002.

4. Marcora S. Afferent feedback from fatigued locomotor muscles is not an important determinant of endurance exercise performance. J Appl Physiol, in press, 2009.

5. Mitchell JH. Cardiovascular control during exercise: central and reflex neural mechanisms. Am J Cardiol 55(10): 34D-41D, 1985.

6. Potts JT, Shi XR, and Raven PB. Carotid baroreflex responsiveness during dynamic exercise in humans. Am J Physiol 265: H1928-H1938, 1993.



Obviously exercise is function of motor unit recruitment – and derecruitment – and the brain is therefore where exercise begins, is regulated and ends (Kayser 2003). The question is how this happens. Studies in extreme conditions like hypoxia suggest a role for muscle afferent feedback limiting exercise intensity/duration (Amann, in press). But, as also suggested by Marcora (in press), other mechanisms may be involved, depending on the experimental conditions. Consider high temperature, when muscle afferents are presumably not an important determinant of endurance exercise performance, as performance seems limited by the CNS when core temperature rises beyond some threshold (Nybo, 2008) and intrinsic skeletal muscle properties are unaffected during repeated contractions performed at 43°C (Place et al 2009) . Another example is a recent rigorously controlled study (Chambers et al 2009) showing that mouth rinsing only (no ingestion) with a carbohydrate solution (but not saccharine) activates selective brain areas, distinctive from areas activated by the sensation of sweetness. Such carbohydrate induced brain activation by mouth rinsing in fasting conditions – probably mediated by specific oral pharyngeal receptors –allowed greater power output compared to saccharin and a substantial improvement of a ~1h time trial that cannot be ascribed to changes in muscle afferent influx. It thus would seem that multiple mechanisms operate, depending on the specific experimental conditions, eventually leading to an `appropriate' pacing strategy. Regulation of exercise performance thus seems complex and only partly understood, even though many athletes and coaches share a clear view: "Performance? 50% in the legs and 50% in the head".

Amann M & Secher NH. Afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance. J Appl Physiol, in press, 2009.

Chambers ES, Bridge MW, Jones DA. Carbohydrate sensing in the human mouth: effects on exercise performance and brain activity. J Physiol 587:1779-1794, 2009.

Kayser B. Exercise starts and ends in the brain. Eur J Appl Physiol, 90:411-419, 2003.

Marcora SM. Afferent feedback from fatigued locomotor muscles is not an important determinant of endurance exercise performance. J Appl Physiol, in press, 2009.

Nybo L. Hyperthermia and fatigue. J Appl Physiol, 104:871-878, 2008.

Place N, Yamada T, Zhang SJ, Westerblad H, Bruton JD. High temperature does not alter fatigability in intact mouse skeletal muscle fibres. J Physiol, 587:4717-4124, 2009.



The scientific literature has a fairly complete discussion of why muscles fail to contract when worked to exhaustion (2). However, failure of contraction is not what most people mean when they say "I am fatigued". Rather, they mean, "I feel tired and don't want to continue physical/mental work." What causes this feeling of fatigue? We propose that Group III and IV sensory neurons in skeletal muscle, heart and brain [the same afferents refered to by (1) and (6)] detect increases in specific metabolites, and signal the brain causing the cognitive sensory experience of fatigue.

We characterized this group of muscle afferent neurons in the mouse as well as another afferent group more suited to signal muscle pain (5). We determined likely molecular receptors that mediate their ability to detect muscle contraction produced metabolites.

We do not know the properties of these "fatigue" signaling afferents. Do these afferents contact the sympathetic nervous system to increase blood flow to the working muscles (thus decreasing the metabolites) as part of the exercise pressor response (3, 4)? What changes their responsiveness (exercise, injury, nutrition, drugs, etc.)? How and what alters their signaling in the spinal cord, brainstem, cerebrum? Can inputs from these receptors alter motivation, mental states? How can these inputs best be used during strength vs. endurance exercise? Moreover, what is the real relationship between the sensation of fatigue, and the ultimate failure of motor command signals? Without this knowledge it is too early to determine their real role in endurance exercise.

1.Amann M and Secher NH. Afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance. J Appl Physiol(in Press) 2009.

2.Bellinger AM, Reiken S, Dura M, Murphy PW, Deng SX, Landry DW, Nieman D, Lehnart SE, Samaru M, LaCampagne A, and Marks AR. Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci 105: 2198-2202, 2008.

3.Hayes SG, McCord JL, Rainier J, Liu Z, and Kaufman MP. Role played by acid-sensitive ion channels in evoking the exercise pressor reflex. Am J Physiol Heart Circ Physiol 295: H1720-H1725, 2008.

4.Kaufman MP and Hayes SG. The exercise pressor reflex. Clin Auton Res 12: 429-439, 2002.

5.Light AR, Hughen RW, Zhang J, Rainier J, Liu Z, and Lee J. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. J Neurophysiol 100: 1184-1201, 2008.

6.Marcora SM. Afferent feedback from fatigued locomotor muscles is not an important determinant of endurance exercise performance. . J Appl Physiol (in Press)2009.


Physiological models can explain the average speed/power during an endurance competition (2). However, they can not explain the end-spurt and many other phenomena well-known to endurance athletes and their coaches but often snubbed by exercise physiologists. For instance, a detrimental effect upon endurance performance is observed under mental fatigue conditions (3). The reduced endurance performance can be explained by the increased perception of effort, probably related to the increased mental effort to cycle. It is important to notice that no musculo-energetic or cardiorespiratory changes that could explain reduced performance were detected. Conversely, listening to music at fast tempo improved cycling performance by means of increased pedal cadence. It has occurred parallel to increased heart rate, thermal discomfort and perception of effort at isotimes when compared to slow and normal tempo of a music track (4). The greater performance while listening to the fast tempo music can be explained by change in potential motivation (1), which can influence the conscious self-paced cycling strategy. These results cannot be explained by feedback models. The psychobiological model proposed by Marcora provides us with a single model that can integrate both perspectives. The influence of traditional physiological factors (e.g., VO2max and heat) can be explained by their effects on perception of effort, whilst the influence of psychological factors such as the presence of a competitor (5) is directly explained by motivational intensity theory. Therefore, the psychobiological model should be preferred to the supraspinal reflex inhibition model proposed by Amann and Secher and other physiological models of endurance performance. We need a paradigm shift which provides us with a more integrative (psychology + biology) and powerful way of explaining endurance performance.

References

1. Brehm JW, Self EA. The intensity of motivation. Annu Rev Psychol. 40:109-31, 1989.

2. Joyner MJ, Coyle EF. Endurance exercise performance: the physiology of champions. J Physiol. 586: 35-44, 2008.

3. Marcora SM, Staiano W, Manning V. Mental fatigue impairs physical performance in humans. J Appl Physiol. 106: 857-64, 2009.

4. Waterhouse J, Hudson P, Edwards B. Effects of music tempo upon submaximal cycling performance. Scand J Med Sci Sports. in press

5. Wilmore JH. Influence of motivation on physical work capacity and performance. J Appl Physiol. 24: 459-63, 1968.