Introduction
During high-intensity exercise, especially, in the case of a graded exercise treadmill protocol, an individual develops an overwhelming sensation which may be aptly described as the “I need to stop” phenomenon. Although this sensation is prevalent during maximal oxygen testing, the root cause has been heavily debated for years (4,8,18,44,45,77). It has been postulated that the mechanisms which initiate ultimate failure lie within one of 2 distinct camps: peripheral (encompassing skeletal muscle, including enzymatic, and mitochondrial function) (12,23,60) or central (pertaining to cardiopulmonary system including heart, lungs, and blood) (14,40,58,65,67). More recently, however, an additional hypothesis suggests that such maximal limitations may be located within the central nervous system (CNS) (51,64) or another related central governor of the brain (42,44,47). Although conclusive evidence directly supports the notion that central or peripheral mechanisms limit maximal exercise, definitive research which establishes grounds for a central governor model (CGM) has been heavily refuted (13,22,69). Since the early 1920s, Nobel laureate Archibald Vivian Hill's research on oxygen uptake during maximal intensity exercise (31–33) has proven to be a staple of the information which is taught today. Because this hallmark work was conducted in 1923, the root cause of maximal oxygen uptake (V̇o2max) has been routinely visited (5,35,55). Although nearly 100 years have passed, researchers have yet to pinpoint a single determining factor for fatigue during maximal exercise (44,45,50,70). The cause of fatigue during volitional failure has led to the recent inquiry: does exercise truly start and end in the brain? This review will examine the historical and modern propositions pertaining to what limits human performance during maximal intensity exercise including a focused look at AV Hill's original “catastrophic” model as well as Timothy David Noakes' CGM. Those familiar with both models presented in this review may better integrate practice-based evidence into evidence-based practice when working with athletes who seek peak performance when operating at or near maximal intensity. Practitioners who recognize that the cause of fatigue may not be limited to one single factor can address other areas of limitation by tailored exercise regimens. In this regard, identification of potential insufficiencies should mandate the development of a training purview for peak human performance.
Historical Perspective
It is not clear whether the initial intentions of AV Hill were to establish evidence of an absolute V̇o2max value. However, a graded exercise protocol initiated on a grass track with an observer calling out times to keep a steady pace ultimately established maximal oxygen consumption values leveling at 4 L·min−1; making “it obvious that no useful purpose would be served by investigating higher speeds in this way” (p. 157) (31). Although, Hill does suggest that speeds greater than 5 m·s−1 were not comfortable on their small 90-meter grass track (31). Nonetheless, this research pioneered the foundation for the use of an exercise protocol of progressively increasing workloads to determine V̇o2max in exercising participants (10,54). In addition, Hill's research (4) rationalized what would later be referred to as the “plateau phenomenon” for oxygen consumption during maximal exercise. Taylor et al are credited as the first to establish the “plateau” concept by continually increasing speed (stage duration 3 minutes) until the oxygen intake had reached a plateau (75). Their novel interpretation concluded that if V̇o2max values differed less than 150 cc·min−1 or 2.1 cc·kg−1·min−1 despite an increase in intensity, then a true maximal value had been attained.
Hill's Classic Model of Fatigue
Hill's classic theory, recently described as the cardiovascular/anaerobic/catastrophic model of fatigue (46), holds that fatigue develops as a result of skeletal muscle lactic acid accumulation resulting when oxygen supply fails to match oxygen demand (33). This theory argues that fatigue occurs because of peripheral metabolic changes in the muscle and is thus not regulated by the CNS or any CGM. This model explains that the governing role of lactic acid directly impairs muscle function, induces fatigue (as lactic acid moves into the blood and circulates to other tissues) and causes involuntary termination of exercise (32). However, it has since been determined that lactate accumulation in and of itself may not act as Hill suggested (61). Another understanding of Hill's model establishes that a peripheral regulator activates to prevent skeletal muscle adenosine triphosphate concentrations from falling to such a level that muscle rigor occurs (43). Although the interpretations are slightly different, given a more current understanding of metabolic acidosis, the end result remains that Hill's model expresses a peripheral governor which induces fatigue to avoid catastrophic muscle failure. Further investigation by AV Hill resulted in the conclusion that a governor lies in the “heart muscle itself or in the nervous system… some mechanism which causes a slowing of the circulation as soon as a serious degree of (blood) unsaturation occurs, and vice versa” (p 163) (31). Therefore, when myocardial ischemia develops, the workload of the heart is reduced to avoid subsequent cardiac cell damage.
Central Governor Model: A Contrasting Perspective
The original Hill model also explains that a plateau in oxygen consumption is reached as a result of gradual humoral factor accumulation (lactate) which reduces muscle capacity and therefore effort ceases (33). Noakes concurs; a governor which regulates maximal exertion does indeed exist. However, the governor is not limited to myocardial ischemia alone (47). Noakes' CGM states that the CNS determines the work rate that can be sustained for the anticipated duration of exercise and thus regulates the number of motor units that are recruited during exercise, setting metabolic demand (48). As a result, cerebral control maintains homeostasis for all organ systems, not simply myocardial tissue. Interestingly, Noakes' hypothesis refutes Hill's classic model which posited a peripheral governor of volitional fatigue. Although AV Hill may have agreed that the possibility of nervous system involvement in fatigue was a possibility, evidence was unavailable to support the hypothesis at that time.
“It is hypothesized that physical activity is controlled by a central governor in the brain and that the human body functions as a complex system during exercise. Using feed forward control in response to afferent feedback from different physiological systems, the extent of skeletal muscle recruitment is controlled as part of a continuously altering pacing strategy, with the sensation of fatigue being the conscious interpretation of these homoeostatic, central governor control mechanisms”
∼Timothy Noakes (p. 120) (43).
Evidence of a Central Governor Model
The CGM develops an understanding of fatigue based on the subconscious brain which establishes exercise intensity by regulation of the size/number of motor units activated (49). The degree of motor neuron excitation necessary is relayed as a feedback from peripheral organs. With respect to system homeostasis in light of increasing exercise intensity, Noakes suggests that the conscious brain receives input from the subconscious brain regarding increasing neural requirements (73). Information (increased sensation of fatigue) is then interpreted by the brain which may facilitate additional control pertaining to subconscious brain regulation processes (73). Therefore, in light of subconscious feedback, the conscious brain may initiate alterations in subconscious functioning which, in turn, alters the feedback continuing to return to the brain (negative feedback loop). This mechanism acts to maintain optimal performance in light of increased exercise intensity.
Certainly, the brain is involved in the voluntary initiation of skeletal muscle contraction; this has been well documented (17,20,28,66). However, more importantly, the brain regulates power output based on anticipated demand or duration (3). This is to say that previous experiences (pertaining to known exercise durations) will impact maximal power output because the brain initiates an orchestrated pacing strategy. Pacing strategies have been shown to be a key component of performance in continuous exercise (25,39,52,72). As an example, if one group of participants is expecting a 30-second maximal sprint, but the sprint time is deceptively set at 36 seconds, participants in the group expecting 36 seconds will generate a greater power output than participants expecting 30 seconds. This is because there is a significant reduction in the last 6 seconds of the group that was expecting a 30-second sprint (3). Pacing strategies are cognitively implemented when a known exercise duration is established before the onset of the event. As such, when individuals are asked to exercise for an unknown duration at maximal effort (as conducted during some sprint exercises), the work accumulated is lowest compared with either groups who (a) know the intended duration or (b) are deceived with a shorter duration which is later extended (11). A known exercise duration, therefore, allows (through cerebral initiation) appropriate neural recruitment and thus maximized performance (42,72). Trained athletes adopt an optimal pace from the start of exercise which varies from day to day. As such, the best performances are associated with higher pacing and power output compared with those paces which begin slower at the start of an exercise (30). Given this understanding of pacing and the associated potential benefit, it may be inferred that maximal testing, as is conducted during a V̇o2max test, cannot produce truly maximal results. In such instances, traditional maximal testing (where speed and grade are controlled – pacing is not feasible) is conducted in the absence of conscious or subconscious pacing strategies as an unknown duration of effort will initiate volitional fatigue and test conclusion (48).
Although the Hill model relies heavily on feedback mechanisms and therefore potential CNS integration, Noakes' CGM expresses an additional feed forward mechanism for explaining the root cause of fatigue (73). This feed forward mechanism may be the next avenue of research necessary to further understand the complexity of the human body (38). Noakes' model expresses the important role the brain plays in modulating power output (performance) based on a set endpoint. Thus, this model is directly applicable to athletes who seek optimal performance for the entire duration of their respective event (63) while seeking to “leave everything on the field.” In this case, all efforts are expended during the event and the athlete does not conclude their activity with large energy reserves. This aspect of sport requires a feed forward mechanism which can anticipate energy remaining along with event duration to ensure maximal output through completion; something the Hill model simply cannot address (49). In this manner, the Hill model may not adequately address the inherent complexity of sport, even if relevance is linked to maximal exercise testing in a laboratory or other controlled setting.
Central Nervous System Regulation
During maximal testing protocol, participants are asked to begin exercise at a low intensity which gradually increases over time. In such instances, participants cannot initiate a feed forward anticipation of the duration of the testing protocol as maximal exercise testing ceases at volitional fatigue. Maximal oxygen testing has therefore produced a “brainless” model of human exercise performance (48) in which results may not generalize to performance under race conditions (where a known intended duration is available). Activation of the neural component is initiated by the higher brain by motor unit recruitment in working muscles. This occurs in the absence of a pacing strategy during maximal testing protocols which control the intensity during a test (speed and grade etc.). In addition, athletes competing in their respective sport are rarely, if ever, provided with an exercise regimen in which they cannot themselves control the speed/power. Thus, maximal testing is deemed unnatural as the brain is excluded from regulating intensity to maximize performance at the end of the event (48). Therefore, a rudimentary understanding of physiology suggests that it is the responsibility of the CNS to initiate voluntary exercise which sequentially starts and ends in the brain (36).
The understanding of traditional central or peripheral fatigue does not account for psychological factors associated with exercise performance. Feedback typically initiates downregulation of systems to preserve functional capacity. However, the CGM incorporates a possible explanation for exercise performance which can be altered by music (37,71), placebos (6,7,24), previous experience (39), deception (41), and financial compensation (15). Provided the previously mentioned studies discovered improved markers (V̇o2max, power output, performance etc.) after external factors were applied, which they did, a cognitive component deserves further investigation.
Furthermore, a simplistic perspective of voluntary motor unit activation recognizes that a conscious decision initiates contraction and again a conscious decision precedes termination of exercise. However, at maximal exercise, the cause of muscle derecruitment at exhaustion is unknown (36), although the sensation of perceived exertion is believed to play a role (74). At exhaustion, stroke volume and systemic oxygen delivery may fall, whereas the brain elicits enhanced oxygen, glucose, and lactate uptake (27). In addition, increased and decreased brain serotonin activity has been shown to accelerate and prolong the onset of fatigue, respectively (21). During intense activity, regions of the brain which are more active tend to consume greater quantities of glycogen (19). Depleting glycogen reserves in such areas of the brain could demonstrate a link to central fatigue (19) as the information is afferently relayed to the CGM to modulate motor control (36).
The brain requires elevated oxygen at high intensities of exercise, therefore, the CGM may control peak performance or workload to avoid damage because of ischemia in vital organs such as the brain and heart (42,44,47,49). Two possible conclusions may be drawn from this: (a) the CGM is directly affected by brain blood flow and oxygen consumption and (b) the anticipation or feed forward mechanism is less important than physical determinants within the brain.
Brain Blood Flow During Exercise
Consequently, decreased supraspinal activation of motor neurons occurs during prolonged or strenuous exercise (26). Higher cerebral regulation may result, concomitantly, with a rise in brain serotonin activity and ammonia levels, as well as a drop in brain glycogen and dopamine, in addition to inherent inhibitory feedback relayed from the working muscles (1,2,21,68). As exercise intensity nears maximum, exhaustion begins. Similarly, cardiac output may slightly fall, resulting in reduced brain blood flow. As the brain continues to demand high oxygen content, the supply may be outpaced by demand and this may lead to reduced motor unit recruitment (62). This is further explained in a meta-analysis which found untrained individuals to exhibit reduced oxygen delivery to the frontal cortex, insufficient for demand, causing cerebral blood oxygen levels to decline, when compared to trained individuals (62). Trained athletes exposed to repeated bouts of high-intensity exercise may, therefore, reduce afferent signaling to the CGM, thus allowing greater overall work to be accomplished. Yet, another hypothesis states that trained individuals incur repeated CNS neuronal input and the CGM may desensitize to arriving stimuli allowing greater intensity effort and consequently greater “homeostatic challenge to cerebral homeostasis” to occur (62).
Over a range of low-to-high intensity exercise, it is generally accepted that global cerebral oxygenation follows a quadratic trend (62). As such, oxygen levels increase from low to moderate intensity, level-off from moderate to high intensity, and then fall during maximal/exhaustive intensities (62). Interestingly, the regional cerebral blood flow within the thalamic region, insular cortex and anterior cingulate cortex, or the medial prefrontal region increases in response to perceived exertion, which is noted when heart rate and blood pressure elevate (78). These regions may, therefore, be assumed to play a role in the regulation of central command of cardiovascular-mediated changes in response to exercise. Further assumptions may implicate the structures as a pivotal afferent relay to the CGM which supersedes motor unit recruitment.
In addition, insular cortex activation has been shown to increase during imagined effort when a cardiovascular response occurred (79). The dorsal posterior insula accumulates afferent sensory information from body tissues which relay their homeostatic state, whereas the anterior insula fabricates a sensation based on that information (30). Therefore, because of the quadratic trend for cerebral oxygen level, it is possible that such structures receive inadequate oxygen based on the increased demand and, as such, provide relay to the CGM to downregulate “performance” before catastrophic failure, organ ischemia, or injury. Because a change in the rating of perceived exertion is responsible for insular structure activation, this may elude to a feed forward mechanism which initiates adaptation of optimum pacing strategies in trained/experienced athletes (30). Furthermore, the rating of perceived exertion has been directly tied to pacing strategy (53). Therefore, it must be understood that real-time perception alters feed forward anticipatory pacing to optimize performance. This cannot be explained by the classic Hill model. During maximal intensity exercise, brain deoxygenated hemoglobin content continues to rise, whereas cerebral oxygen falls in the prefrontal cortex (34). This supports the theory that the prefrontal cortex sends neural input to the premotor areas which decrease muscle function in the presence of decreased prefrontal oxygenation (57). In such cases, cerebral oxygen desaturation occurs before voluntary exhaustion (76). This leads to the hypothesis that the brain may recall oxygenation levels at various intensities. The anticipation of an exercise bout duration then demands recollection of the motor unit recruitment necessary to complete the event. This demands the question: does the brain remember the blood oxygen supply at a given intensity (one necessary to complete the work bout at maximal performance), and does this lend to the pacing strategy required to avoid catastrophic failure before exercise conclusion? A feed forward mechanism may support such inquiry.
Present Understanding of AV Hill's Classic Model
With an understanding of Hill's model of fatigue, it is necessary to determine the validity of the proposed theory. If the theory can withstand research-based criticism, certainly some degree of credibility should be recognized. However, if such a theory cannot refute opposition, it may be necessary to retire or revise theoretical understanding.
AV Hill expressed a theory which established maximal oxygen consumption leveled (plateau phenomenon) in the presence of metabolic byproducts. As such, the plateau may be viewed as an external indicator of muscle acidosis. If this is true, then all exercise conducted maximally should initiate a plateau during exhaustive exercise. However, a review of literature by Noakes and Gibson (43) determined only 45% of approximately 1978 individual tests established criteria for a “gradual” as opposed to “abrupt” plateau. As a result, the proposed acidosis as a cause of fatigue cannot explain why, in many cases, V̇o2 values do not plateau at maximal exertion.
Another criticism of Hill's classic model includes the debate suggesting that muscles are ill perfused with oxygen and thus become ischemic/hypoxic or subsequently metabolically anaerobic, inducing fatigue and downregulation during exhaustion. However, the pO2 of blood leaving the muscles (venous) is much higher than that of the heart, which, in healthy individuals does not become ischemic/hypoxic or metabolically anaerobic during maximal exercise (56). As a result, present literature establishing conclusive evidence of muscle hypoxia during voluntary exercise under normobaric conditions is lacking. In fact, “intracellular pO2 remains constant during graded incremental exercise in humans (50–100% of V̇o2max)” and therefore, “…during incremental exercise, skeletal muscle cells do not become anaerobic as lactate levels suddenly rise, as intracellular pO2 is well preserved at a constant level, even at maximal exercise” (p. 631) (59). Thus, anerobiosis cannot suffice as a significant cause of skeletal muscle fatigue. The Hill model also suggests that a governor protects the heart from ischemia and therefore fatigue develops. This, however, does not occur in healthy athletes (56) even during hypoxic conditions of simulated altitude (16).
Hill's model does not suggest regulation by the CNS with respect to motor unit recruitment. Maximal oxygen consumption is supposedly achieved when all motor units in the exercising muscles are recruited (understanding that maximal exercise requires maximal motor activation). Such activation at max is therefore not regulated by a CGM where less than 100% may be advantageous to avoid damage/injury to other organs in the body. The assumption that 100% of motor units are activated is based on the understanding that no peripheral mechanisms of fatigue may be justified if less than 100% of motor units are active at failure (exhaustion). If greater motor units were available in “reserve,” then peripheral limitations would not occur as the other motor units would subsequently turn on. The lack of CNS control does not suggest any regulation of the sort. Studies have demonstrated that less than 100% of muscle recruitment occurs during maximal exercise in a tested muscle/group (9,29). Therefore, afferent sensory information relayed to the brain (by a CGM) allows motor unit recruitment regulation, especially, during the instances of hypoxia (16).
The aforementioned evidence refuting the Hill model would indicate that this model cannot provide sole justification of cause for fatigue. This is, especially, evident as skeletal muscle recruitment is submaximal at maximal intensity effort. In addition, V̇o2max can be limited by a drug, naloxone, which increases perceived exertion. This finding establishes that endogenous opioids affect perceived exertion rather than by physiological limits which are responsible for reduction in V̇o2max. The Hill model, therefore, cannot wholly represent the spectrum of fatigue without the addition of a cognitive integration component.
Practical Applications
The intricacy of proposed mechanisms pertaining to exhaustion/failure during maximal exercise cannot be refined to a single factor. Instead, practitioners should recognize the complexity of the human body during maximal intensity exercise and understand the necessity for targeted training modalities. A number of components, including those from a central or peripheral nature, may conjunctively elucidate the complex nature of fatigue. In addition, a new proposal of a feed forward model (anticipated demand) may concomitantly regulate energy expenditure to enhance performance. Coaches and athletes alike may consider previous experience (and knowledge of the event) to be a powerful tool to enhance performance by improved conscious/subconscious feed forward adjustments in pace/intensity during an event. This highlights the importance of training both the body and mind as mental preparation (knowledge of anticipated event duration, course features—hills, etc.) improves expectations and may alter pacing strategies for peak performance throughout an event. Future research is necessary to foster insight, instigate further debate, cultivate novel ideas, and responsively birth new discovery.
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