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Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China. You can also search for this author in PubMed Google Scholar.

Correspondence to Xia Liu. This work is licensed under a Creative Commons Attribution 4. Reprints and permissions. Wan, Jj. et al. Muscle fatigue: general understanding and treatment. Exp Mol Med 49 , e Download citation. Received : 19 February Revised : 20 May Accepted : 23 May Published : 06 October Issue Date : October Anyone you share the following link with will be able to read this content:.

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Abstract Muscle fatigue is a common complaint in clinical practice. Introduction Fatigue is a common non-specific symptom experienced by many people and is associated with many health conditions. Factors that affect muscle contraction and fatigue The production of skeletal muscle force depends on contractile mechanisms, and failure at any of the sites upstream of the cross-bridges can contribute to the development of muscle fatigue, including nervous, ion, vascular and energy systems.

Neural contributions Central neurotransmitters, especially 5-HT, DA and NA, play important role during whole-body exercise and fatigue. Transcranial magnetic stimulation Transcranial magnetic stimulation involves applying magnetic stimulation to the motor cortex and is optimized to activate the muscle of interest.

Peripheral nerve high-intensity electrical stimulation High-intensity stimulation of the peripheral nerve directly activates the α-motoneuron, evoking a motor response m-wave from the muscle.

Biomarker for the diagnosis of muscle fatigue At present, there are still no specific factors that have been consistently associated with a particular type of fatigue.

Oxidative stress biomarkers Reactive oxygen species ROS remain at a low level in resting skeletal muscle but increase in response to contractile activity. Potential treatment for muscle fatigue Improper exercise, long time combat, military training and some related diseases for example, cancer and stroke can cause muscle fatigue, which negatively affects athletic achievement, military combat ability and patient recovery.

Synthetic products Amphetamine, ephedrine, caffeine, for example, are all synthetic products that excite the central nervous system or sympathetic nervous system and promote resistance to muscle fatigue.

Amphetamine Amphetamine is a phenethylamine-type stimulant and antidepressant that is highly addictive and produces euphoria and an elevated mood. Araliaceae ginseng species American ginseng, panax ginseng C.

Others Enhancing the energy metabolism effectively helps to improve exercise capacity. Nutritional supplements Several nutritional factors that may limit exercise performance have been identified, thus leading to the widespread use of nutritional strategies.

Red bull Red bull contains a mixture of carbohydrates, taurine, glucuronolactone, vitamin B and caffeine, and it is a commonly used energy drink. Others Carnitine plays an essential role in fatty acid oxidation in muscle.

Conclusions Muscle force production involves a sequence of events, extending from cortical excitation to motor unit activation to excitation—contraction coupling, and ultimately leading to muscle activation. References Gruet M, Temesi J, Rupp T, Levy P, Millet GY, Verges S.

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Darías Holgado , Centro de Investigación, Mente, Cerebro y Comportamiento CIMCYC , Universidad de Granada; Departamento de Psicología Experimental, Universidad de Granada, Spain ORCID. Daniel Sanabria , Centro de Investigación, Mente, Cerebro y Comportamiento CIMCYC , Universidad de Granada; Departamento de Psicología Experimental, Universidad de Granada, Spain.

José C. Perales , Centro de Investigación, Mente, Cerebro y Comportamiento CIMCYC , Universidad de Granada; Departamento de Psicología Experimental, Universidad de Granada, Spain.

Miguel A. Similar to cognitive performance fatigue, it was proposed that perceived cognitive fatigue may arise as the consequence of the analysis of the costs and benefits of expending energy in a certain cognitive task [ ], and would depend on modification in neurotransmitter release [ 21 ].

Perceived cognitive fatigue would thus serve as a mechanism that would stop or change ongoing behavior when no longer beneficial. Of note, an alternative view on the origin and role of perceived cognitive fatigue is that of an anticipatory protection mechanism, akin to theories of motor task-induced fatigue [ , , ].

According to this view, perceived cognitive fatigue would act in anticipation of future functional alterations induced by prolonged task performance, to divert behavior away from the taxing activity [ 23 ]. It is assumed that several factors contribute to perceived cognitive fatigue.

As mentioned above, one of the most relevant factors thought to contribute to perceived cognitive fatigue is the cognitive or mental effort invested in the task [ 9 , ]. It is thought that cognitive effort is associated with cognitive control, meaning that non-automated cognitive control-dependent processes, like the execution of difficult cognitive tasks, require cognitive effort [ ].

As mentioned earlier, cognitive effort is perceived as costly as well as aversive and is only maintained or increased if it is expected to be beneficial.

The costs of prolonged cognitive effort investment comprise the intrinsic costs related to cognitive control allocation per se as well as the opportunity costs that arise from forgoing other more rewarding behavior [ , ].

However, there is also evidence that effort is not necessarily perceived as costly and can add value, meaning that the same outcome can be more rewarding when more and not less effort was invested [ ]. It has been shown that several brain areas are activated when cognitive control and effort are exerted, which include the dorsal anterior cingulate cortex, anterior insula, lateral prefrontal cortex, and lateral parietal cortex [ , , , ].

Similar to the perceived effort induced by motor tasks, cognitive effort perception and objective measures of effort investment during the same task can be modulated by homeostatic perturbations such as sleep deprivation [ ] and heat stress [ ], respectively.

It was argued that the costs of effort have a considerable impact on motivation, which drives the behavior of humans [ 9 ].

This interaction is intuitive, since motivation is not only directed towards a specific goal but also refers to the intensity i. Müller and Apps [ 9 ] proposed that the psychophysiological processes associated with activity-induced state fatigue have an impact on motivation in two ways: they would cause direct changes in brain structures that motivate behaviors or would induce alterations in other systems, which are connected to or influenced by these brain areas.

Tasks that require sustained cognitive effort typically increase indices of sympathetic nervous system activity [ , , ], which is interpreted to reflect an aversive affective response [ ]. Indeed, it has been postulated that core affect, comprising affective valence pleasure-displeasure and arousal activation-deactivation , changes during sustained cognitive tasks.

Alternatively, 2 repeated conflicts and errors induce negative affective valence signaling that the current task is unrewarding. The latter is associated with perceived cognitive fatigue, which is thought to direct the individual to other more rewarding activities or to reduce effortful conflict monitoring, especially during externally mandated cognitive tasks [ ].

This view is in line with the notion that negative affect signalizes inadequate progress towards goal achievement [ ], which was also discussed in the context of perceived cognitive fatigue [ ].

Furthermore, it was proposed that the increasingly aversive sensation with time-on-task results from the effort-induced accumulation of opportunity costs that arise from forgoing other and more rewarding behavior [ 22 ].

Similar to motor tasks, performing sustained cognitive tasks requires self-regulation [ ], which describes the dynamic process of bringing thinking and behavior in line with the desired goal [ ]. During sustained cognitive tasks, individuals have to continuously self-regulate different aversive sensations e.

Self-regulation per se requires effort and relies on the integrity of executive functioning and in particular on the core executive functions, which can be classified into inhibitory control i. There are several ways in which people can self-regulate themselves to modify their sensations, feelings, thoughts, and behaviors in service of a personal goal including effortful self-control [ ].

Although self-regulation and self-control are often used interchangeably [ ], it was proposed that they refer to distinct processes [ 64 ]. While self-regulation refers to more general processes of goal-directed thoughts and behaviors, self-control can be defined as the process of overcoming predominant pre-potent, automatic response tendencies in favor of the desired goal [ 65 ].

Self-control is exerted during the execution of sustained cognitive tasks and requires motivation as well as attention [ 64 ]. This is in line with the view that performing a sustained cognitive task competes with motivational options e.

In addition to these key-determinants, there are further important aspects that contribute to the psychophysiological state of an individual with potential consequences for perceived cognitive fatigue.

For instance, it has been revealed that greater interest in a cognitive task resulted in less perceived cognitive fatigue despite a higher willingness to exert cognitive effort [ ]. In the same manner, it was argued that the level of controllability modulates the aversive responses and perceived cognitive fatigue during sustained cognitive activities [ ].

Furthermore, the execution of sustained cognitive tasks can be associated with changes in mood as well as with feelings like stress, anxiety, frustration, hopelessness, tension, and boredom [ , , , ]. Some of these were shown to be related to cognitive task performance [ ] and to modulate perceived cognitive fatigue [ 64 , , ].

For example, it was found that a task requiring the passive observation of strings of numbers resulted in higher boredom ratings, a steeper decline in affective valence, and higher perceived cognitive fatigue ratings compared to a cognitive task that consisted of adding three to each digit of a four-digit number [ ].

Interestingly, passively watching strings of numbers was also rated as effortful, which was interpreted as the effort to keep paying attention. It was also proposed that boredom, caused by the low intrinsic attractiveness of the task itself, can also be responsible for a decrease in cognitive task performance [ ], highlighting the interdependence between determinants of perceived cognitive fatigue and cognitive performance fatigue.

Moreover, it was assumed that expectations based on previous experiences might influence the psychophysiological state and the psychophysiological adjustments during sustained cognitive tasks [ ]. For instance, this was shown in response to heat stress [ , ], sleep deprivation [ ], and mouth rinsing with caffeine-maltodextrin [ ].

These sources of influence also highlight the similarity between the constructs of sleepiness and fatigue. Confusion between those concepts is very common and it remains unclear to what extent the subjective assessment measures allow researchers to clearly tease them apart [ ]. Besides these, there are further factors contributing to perceived cognitive fatigue that are increasingly studied and should be added to the list of potential determinants in the future.

Various modulating factors can influence the extent of cognitive performance fatigue and perceived cognitive fatigue Fig. The main subject-specific factors include age, sex, the existence of diseases, and cognitive fitness.

The extent of fatigue in the different domains is further determined by the characteristics of the cognitive task e. In the following sections, we will only discuss the most important subject- and cognitive task-specific factors that can modulate cognitive performance fatigue and perceived cognitive fatigue.

Cognitive abilities, such as processing speed and executive functioning, decline with advancing age due to structural and functional changes within the brain e.

It is thought that these age-related changes contribute to the increased compensatory brain activation observed during the execution of cognitive tasks [ ], which was assumed to accelerate cognitive performance fatigue development [ ].

However, the results of studies that have investigated the effect of age on cognitive performance fatigue are mixed and do not allow for a definite conclusion. For instance, it was found that reaction times remained constant in young and old adults after the execution of a working memory task performed for 60 min, while accuracy even increased in the elderly.

The authors proposed that the potential decline in cognitive performance was countered by the learning effect [ ].

This is in line with the results of Behrens et al. In contrast, Terentjeviene et al. However, reaction times and intra-individual variability of reaction times only increased in young males indicating higher cognitive performance fatigue compared to the older males. Since brain activation differs between sexes depending on the type of cognitive task [ , ], it might be assumed that the extent of cognitive performance fatigue after a sustained cognitive activity is different between males and females.

However, the results of experiments on that topic are inconclusive. For instance, there were no sex-differences in the error rate and reaction times, which remained constant over time, after performing a continuous performance test for 51 min [ ]. This is consistent with the results of Wang et al.

The authors did not observe differences in the number of errors and completed subtractions between males and females. However, the task lasted only 12 min and was possibly not long enough to induce cognitive performance fatigue.

In contrast to these studies, Noreika et al. They have revealed that accuracy increased, and response times decreased to a larger extent in males compared to females with time-on-task.

However, since cognitive performance increased over time, these results did not indicate cognitive performance fatigue and might be biased by the learning or practice effect.

Since the extent of cognitive performance fatigue strongly depends on the structural and functional integrity of the central nervous system, it might be assumed that cognitive performance fatigue development is accelerated in patient populations, especially in those with neurological diseases affecting the central nervous system.

However, studies investigating cognitive performance fatigue in different patient populations e. Despite similar increases in cognitive task performance, patients showed heightened cerebral activation in specific areas and an increased perceived cognitive fatigue [ 10 , , ] indicating a lower efficiency.

In contrast, a decrease in cognitive performance measures was revealed during the execution of a four-block paced auditory serial addition test with an earlier drop in performance in people with multiple sclerosis compared to healthy controls [ ].

Analogous results were obtained by other studies that investigated the effects of sustained cognitive tasks on cognitive performance fatigue in multiple sclerosis and healthy controls [ , ]. A decrease in cognitive task performance was also found in stroke survivors while performing a min inhibition task, which was, however, comparable to the cognitive task performance reduction of the healthy control group [ ].

Moreover, Jordan et al. The discrepant findings presented above indicate that the effect of age, sex, and diseases on cognitive performance fatigue seems to be strongly influenced by the task characteristics e.

The occurrence and evaluation of cognitive performance fatigue strongly depend on the type of task e. For instance, Smith et al. While the first task required only vigilance, the other two tasks additionally relied on response inhibition.

Cognitive performance i. Interestingly, cognitive performance monitored during the respective tasks deteriorated only for the psychomotor vigilance task i. In contrast, pre- and post-cognitive performance assessments with the 3-min psychomotor vigilance task revealed increased reaction times only after the AX-continuous performance task and the Stroop task.

These data indicate that the detection and extent of cognitive performance fatigue strongly depend on the type of task as well as the task used to assess the potential change in performance.

Besides the effect of the type of cognitive task, other task characteristics e. Although several studies have not found a decline in cognitive performance with time-on-task, it was demonstrated that cognitive task performance decreased with increasing task duration [ 21 , , ]. Furthermore, it was proposed that the cognitive load induced by the task determines the extent of cognitive performance fatigue [ , , ].

Studies on this topic manipulated the cognitive load either by increasing the difficulty of the task e. However, the results of these studies are inconsistent. For instance, during a min working memory task, Shigihara et al.

The authors have additionally tested the effect of the sustained cognitive tasks on the advanced trail making test performance and have found that the number of errors increased from pre to post for both conditions. Moreover, the results of Borragàn et al. However, irrespective of the task characteristics, there is a general critique that laboratory cognitive tasks are not ecologically valid and exhibit low intrinsic motivational value.

Therefore, controllability of these tasks is low, people experience them as increasingly aversive, and might disengage from the tasks because they are not sufficiently important for them [ 22 , 64 , , ]. Subject-specific factors like age, sex, and the presence of diseases might also modulate perceived cognitive fatigue and its potential determinants.

For example, Wascher et al. Interestingly, young adults showed also a concomitant larger decrease in self-reported motivation. This is in line with the results of Terentjeviene et al. This was accompanied by a higher perceived cognitive effort and temporal demand in the young participants during task execution.

The young adults additionally reported increases in tension and confusion as well as a decrease in vigor, which were not found for the older participants.

These data collectively suggest that younger adults perceive sustained cognitive tasks as more effortful, demanding, and fatiguing than older adults, which is corroborated by the larger decreases in motivation and vigor as well as the increased tension and confusion.

Since laboratory cognitive tasks are often performed using a computer and older adults have less experience with digital technology [ ], these differences might be related to the higher intrinsic attractiveness of the task for older people.

Nevertheless, it was also shown that older people with a low frequency of technology use have higher levels of computer anxiety [ ]. Contrary to the findings of age-related differences, it has also been observed that the increase in perceived cognitive fatigue induced by a min inhibitory control task was not different between young and old adults [ 11 ].

Studies on sex-differences in perceived cognitive fatigue also revealed partially inconsistent results. Some studies have not found differences in perceived cognitive fatigue between males and females after performing a min Stroop task and a min continuous performance test, which require response inhibition and sustained attention.

Similarly, no sex-differences in the changes in cognitive effort, vigor, energy, tiredness, tension, calmness, and further self-reported data recorded during these tasks were reported [ , ]. Nevertheless, others have observed higher increases in fatigue ratings during a min mental rotation task in females compared to males, which depended on the menstrual cycle phase [ ].

It was additionally revealed that perceived cognitive effort and perceived task difficulty were higher in females compared to males during both a high and low cognitive load condition involving arithmetic tasks [ ].

There is evidence that perceived cognitive fatigue development in response to sustained cognitive tasks is higher in some diseases, especially those affecting the central nervous system [ 10 , , , ].

Higher increases in fatigue ratings during cognitive tasks have particularly been observed in people with multiple sclerosis [ , , ]. It was further reported that the perceived workload e. In contrast, studies on other patient populations, such as people with chronic fatigue syndrome, depression, and myasthenia gravis, have not found differential changes in perceived cognitive fatigue ratings compared with healthy controls during sustained cognitive tasks [ , ].

It has been shown that perceived cognitive fatigue and its determinants can be influenced by the type of task e. The results of studies that have examined the effect of the type of cognitive task on perceived cognitive fatigue are inconclusive.

The latter was applied with constant processing intervals and with shorter individualized processing intervals based on the maximal performance determined during an incremental TloadDback task.

Although the task duration differed greatly, all cognitive tasks induced perceived cognitive fatigue, assessed with a visual analog scale, with the highest increase in the individualized TloadDback task condition.

However, the AX continuous performance test induced a higher increase in perceived cognitive fatigue and a larger decrease in vigor assessed with the Brunel Mood Scale. These results were accompanied by higher sleepiness ratings and a larger drop in task motivation compared to the TloadDback task condition.

Another study on this topic has compared perceived cognitive fatigue as well as its recovery in response to a psychomotor vigilance task, an AX-continuous performance task, and a Stroop task each performed for 45 min [ ]. The tasks differed regarding their demands on vigilance and response inhibition.

Although all tasks increased perceived cognitive fatigue, the authors concluded that tasks requiring response inhibition appeared to induce perceived cognitive fatigue for a longer duration than a simple vigilance task. With regard to other task characteristics, it was often found that perceived cognitive fatigue progressively increases with time-on-task [ , ].

Moreover, it was shown that altering the cognitive load by the difficulty of the task i. In line with this, Borragàn et al. However, when cognitive load was modulated by decreasing the processing interval for the stimuli, the high cognitive load condition induced a higher increase in perceived cognitive fatigue compared to the low cognitive load condition.

The authors concluded that the processing time interval during cognitive tasks is more relevant for perceived cognitive fatigue development than the number of processed items. In contrast to this, it was also shown that perceived cognitive fatigue cannot only result from performing a sustained cognitive task i.

More specifically, perceived cognitive fatigue was even higher in the boredom condition compared with the cognitive task condition despite lower cognitive effort ratings. This might be related to the steeper decline in affective valence ratings and the lower task interest ratings in the boredom condition.

Indeed, higher interest in a task has been shown to induce less perceived cognitive fatigue [ ]. These data highlight the importance of the characteristics of the cognitive task for the development of perceived cognitive fatigue and its determinants.

The updated framework covers the different dimensions of task-induced state fatigue and the involved mechanisms Fig. Thereby, the interdependence of performance fatigue and perceived fatigue as well as their determinants is acknowledged and highlighted.

There is no single factor primarily determining performance fatigue and perceived fatigue in response to motor and cognitive tasks. Instead, the relative weight of each determinant and their interaction depends on several modulating factors e.

Although the mechanisms of motor performance fatigue are not yet fully elucidated, there are extensive data on the changes in the nervous system and muscle during motor tasks contributing to the decline in motor performance [ 16 , 17 , 25 , 26 ].

In contrast, the mechanisms underlying perceived motor fatigue and their interactions with motor performance fatigue received less attention. Therefore, future research should not only investigate the neural and muscular mechanisms driving motor performance fatigue but also aspects of perceived motor fatigue and the corresponding neuro physiological correlates in detail.

This approach can assist in investigating the motor task-induced perceptual differences between individuals and exercise protocols e. This is of special importance for clinical populations suffering from an increased prevalence of motor performance fatigue and perceived motor fatigue e.

There are a few studies available that have assessed neural and muscular contributions to motor performance fatigue in parallel with ratings of perceived motor fatigue, effort perception, and affective valence to study their interactions [ 42 , ]. For instance, Greenhouse-Tucknott et al.

They have shown that prior submaximal hand grip exercise reduced the time to exhaustion during a submaximal isometric contraction of the knee extensors without altering neuromuscular function. Thereby, effort perception and affective valence were correlated with time to exhaustion and the ratings of perceived motor fatigue.

These findings indicate that prior handgrip exercise limited single-joint endurance performance of the knee extensors primarily by the interactions between perceived motor fatigue, effort perception, as well as affective valence and not by a decreased neuromuscular function.

Similar approaches should be adopted in the future to investigate the interactions between motor performance fatigue and perceived motor fatigue in different populations, particularly in those suffering from diseases.

Besides the combined investigation of motor performance fatigue, perceived motor fatigue, and the underlying mechanisms, the determining factors can be manipulated to elucidate their causal involvement in the development of state fatigue in different populations and in response to various motor tasks.

For that purpose, different interventions can be used aiming to modify the physiological and psychological regulatory processes during fatiguing motor exercise. For instance, neuromodulation techniques like tDCS are suitable to alter cortical excitability and to investigate the effects of changed neural properties on motor performance fatigue and perceived motor fatigue [ 67 ].

Furthermore, other interventions can be applied to modify neural as well as muscular properties e. Interventions aiming to modulate the psychological determinants of endurance performance have also been shown to induce changes in motor performance and the perceptual responses to fatiguing exercise [ 48 ].

These strategies could be used to investigate the role of cognitive processes in the interpretation of perceptual responses and the change in affective valence emerging during fatiguing motor exercise.

Motor performance fatigue can be assessed using maximal and submaximal motor performance measures. Maximal performance tasks e. In addition, the variation of submaximal motor performance is also an indication of motor performance fatigue e. The neural and muscular mechanisms contributing to motor performance fatigue can be investigated with different non-invasive techniques.

Neural adjustments i. Moreover, functional magnetic resonance imaging is suitable to monitor changes within cortical and subcortical structures during motor exercise [ ]. The contractile function of muscles can be validly quantified using peripheral nerve stimulation [ ], while changes in muscle oxygenation and muscle metabolism can be measured with near-infrared spectroscopy and phosphorus magnetic resonance spectroscopy, respectively [ , ].

In addition to these measures, perceived motor fatigue as well as the contributing factors should be comprehensively assessed before, during, and after fatiguing exercise. For this purpose, different scales and questionnaires can be used according to the focus of the respective study.

These measures should be applied together with standardized wording as described elsewhere [ 5 , 38 ]. Furthermore, the attentional focus during fatiguing motor exercise should be recorded as an index for the motor task intensity-dependent attentional shift from an external focus on the surrounding to an internal focus on the bodily sensations [ ].

These aspects should be quantified in conjunction with affective valence and arousal, recorded with the feeling scale and felt arousal scale, respectively, as indicators of the motor task-dependent homeostatic perturbations [ 40 , 60 ].

It has been shown that these aspects can influence perceived motor fatigue and performance during fatiguing motor tasks. Moreover, they reflect the motor task-induced homeostatic perturbations in various physiological subsystems and are thus indicators of the physical demands.

Besides these core measures of perceived motor fatigue, additional scales and tests should be used according to the aim of the respective study.

This should be done to investigate the role of self-regulation capacity, executive functioning [ 41 , , ], and other determinants for motor performance fatigue as well as perceived motor fatigue. The interactions between cognitive performance fatigue and perceived cognitive fatigue have been investigated more comprehensively and in greater detail compared to those between motor performance fatigue and perceived motor fatigue.

Accordingly, many studies in this field have recorded both changes in cognitive performance as well as in the perception of fatigue during and after sustained cognitive tasks. However, it must be pointed out that in studies which have measured cognitive performance on the same task as the one used to induce fatigue, evidence for a decline in cognitive task performance was frequently missing [ , ].

The lack of a systematic decline in cognitive performance with time-on-task was often attributed to an increased compensatory cognitive effort or to a learning effect that would lead to a performance increase overcoming the performance decline induced by fatigue [ , , , ].

In contrast, increases in perceived cognitive fatigue with time-on-task have been shown very consistently across many different conditions e.

Therefore, future studies should use separate cognitive tasks to induce and measure cognitive performance fatigue as already done by some studies [ 23 , 24 , , , ]. This approach might bypass the influence of a decreased motivation or learning effect and has typically led to more consistent correlations between the cognitive performance decline and perceived cognitive fatigue [ 24 , ].

Furthermore, the effect of distinct types e. There is evidence that different cognitive tasks induce specific declines in performance measures depending on the assessment task. On the contrary, pre and post cognitive performance assessments with a 3-min psychomotor vigilance task revealed only increased reaction times after the AX-continuous performance task and the Stroop task.

However, perceived cognitive fatigue increased in all conditions, even though it tended to persist longer after the tasks requiring more response inhibition.

Moreover, cognitive performance fatigue and perceived cognitive fatigue measures were also shown to be sensitive to the manipulation of the cognitive load [ , ]. Consequently, future studies on this topic should not only examine the effects of diverse types of tasks on cognitive performance fatigue, perceived cognitive fatigue, and their neural correlates but also the influence of varying cognitive loads.

Furthermore, it is likely that the level of overlap between the fatiguing and the assessment tasks, in terms of the cognitive processes involved, is also crucial [ ]. Therefore, it appears essential that future studies assess performance before and after the fatiguing cognitive task not only with cognitive tasks requiring similar cognitive processes, but also with tasks that involve different processes.

These experiments should further take the impact of the cognitive load, the nature of the cognitive processes involved, and the degree of process overlap with the fatiguing task into account. As stated above, other important sources of influence are mood and emotional variables, like stress, anxiety, frustration, hopelessness, tension, and boredom [ , , , ], which were shown to modulate perceived cognitive fatigue [ , , ] and cognitive task performance [ ].

Therefore, it seems mandatory to quantify these aspects and to analyze their effects on cognitive performance fatigue, perceived cognitive fatigue, and their neural correlates.

Due to the discrepant findings, the influence of subject-specific factors i. Nevertheless, it seems that cognitive task-induced perceived cognitive fatigue is higher in some patient populations [ , , ].

To address the causal relationships, neurophysiological and psychophysiological determinants of cognitive performance fatigue as well as perceived cognitive fatigue can also be modulated experimentally.

For instance, it was shown that anodal tDCS applied to the right parietal cortex counteracted the cognitive performance decline during a min visual vigilance task in healthy controls and people with multiple sclerosis but had no effect on perceived cognitive fatigue [ ].

Similar effects were observed in multiple sclerosis patients after stimulating the left dorsolateral prefrontal cortex with anodal tDCS [ ]. In addition, investigating the effects of different neuromodulatory substances such as caffeine on cognitive performance fatigue, perceived cognitive fatigue [ ], and its neurophysiological correlates can help to unravel their interdependence.

As outlined above, the detection and quantification of cognitive performance fatigue strongly depend on the assessment task and the considered variables e. These measures should be combined with techniques suitable to record brain activity e. Ample evidence points to the interactions between the different dimensions of activity-induced state fatigue.

For instance, Marcora et al. However, effort perception during exercise was higher after performing the sustained cognitive task leading the authors to the conclusion that the participants reached their maximal tolerable effort level earlier and subsequently disengaged from exercise.

These data indicate that fatiguing cognitive or motor activities seem to modulate the performance and perceptions during a subsequent fatiguing motor or cognitive task, respectively.

Evidence for the interactions between the different dimensions of activity-induced state fatigue also arises from experiments that have investigated the psychophysiological adjustments and performance changes in response to sustained motor-cognitive dual tasks [ , , ].

These studies have found a decreased time to exhaustion during submaximal motor tasks when a concurrent cognitive task had to be executed e. Additionally, time to exhaustion during a fatiguing motor-cognitive dual task tended to be shorter for a high compared to a low cognitive load condition.

This was accompanied by a higher reduction in muscle activation of the knee extensors i. As expected, cognitive effort perception scaled with the level of cognitive load, but, surprisingly, effort perception associated with the motor task was greater in the high cognitive load condition compared to that recorded during the single motor task condition [ ].

These data have impressively shown that the different domains of activity-induced state fatigue interact with each other. Since there is an overlap of brain structures involved during the execution of fatiguing motor and cognitive tasks e.

Thereby, the degree of overlap between cognitive processes required for the respective motor and cognitive task might mediate the detrimental effects on performance and perceptions [ 9 , , ].

Consequently, future studies should investigate the effects of diverse types e. These effects should also be studied in relation to various motor tasks e.

Conversely, the impact of different fatiguing motor tasks performed prior to various fatiguing cognitive tasks relying on distinct cognitive processes should be examined.

The mechanistic basis for the interactions between motor performance fatigue, perceived motor fatigue, cognitive performance fatigue, and perceived cognitive fatigue can be probed with the methods mentioned in the respective paragraphs above. However, the quantification of some perceptual responses to motor and cognitive tasks requires specific scales and a clear description with standardized wording.

This is of particular importance for the measurement of perceived fatigue and effort in response to motor, cognitive, or motor-cognitive dual tasks. Although it was proposed that the feeling of fatigue arising from exertion might be similarly induced by motor and cognitive tasks [ 9 ], results of studies indicated that perceived motor fatigue and perceived cognitive fatigue represent different perceptual domains [ , ].

The same applies to effort perception, which can be related to either to the motor or the cognitive task [ ]. Performance fatigue and perceived fatigue as well as their determinants are interdependent and should not be considered in isolation.

Consequently, there is no single factor primarily determining performance fatigue and perceived fatigue in response to motor and cognitive tasks. Instead, the relative weight of each determinant and their interaction depend on body homeostasis e. Therefore, a combined assessment of performance fatigue and perceived fatigue measures as well as its neuro physiological correlates is required to unravel the psychophysiology of motor and cognitive task-induced state fatigue.

This will help to better understand the interactions between the different dimensions of fatigue and their impact on human performance, which is necessary to design effective interventions for increasing exercise tolerance and human performance in healthy and clinical populations.

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Neuropharmacology ; 17 : — Morozova E, Yoo Y, Behrouzvaziri A, Zaretskaia M, Rusyniak D, Zaretsky D et al. Stress due to employment or study pressure is another known precursor of fatigue, as is the temptation to continue training or playing sport while carrying an existing injury.

Most episodes of fatigue can be mitigated by first identifying the cause, followed by adjustments to training or activity schedules. The symptoms of fatigue will usually disappear quickly, however, in cases where fatigue symptoms persist a medical review will be necessary.

Anaemia and iron deficiency are common causes of fatigue, as are some infections. Fatigue is a symptom of major illnesses including heart disease, diabetes, sleep apnoea and thyroid problems.

A visit to your Doctor or Sports and Exercise Medicine Physician will help rule out these possibilities while honing in on the actual cause of fatigue. Muscle fatigue takes place when there is a decrease in power of the muscle, and is experienced in different ways according to the activity performed.

Fatigue can set in when muscle tension cannot be maintained. They will often be sore days later as a result of acute muscle breakdown. Interval training helps by conditioning muscle fibres to respond more adequately for longer periods.

Here, we performed a meta-analysis to investigate these inconsistent findings. However, a three-parameter selection model also revealed evidence of publication or reporting biases, suggesting that the bias-corrected estimates might be substantially lower 0.

In sum, current evidence does not provide conclusive support for the claim that mental fatigue has a negative influence on exercise performance. Review Article. Mental Fatigue Might Be Not So Bad for Exercise Performance After All: A Systematic Review and Bias-Sensitive Meta-Analysis.

Authors: Darías Holgado Email Darías Holgado.

Although self-regulation and self-control are often used interchangeably [ ], it was proposed that they refer to distinct processes [ 64 ]. While self-regulation refers to more general processes of goal-directed thoughts and behaviors, self-control can be defined as the process of overcoming predominant pre-potent, automatic response tendencies in favor of the desired goal [ 65 ].

Self-control is exerted during the execution of sustained cognitive tasks and requires motivation as well as attention [ 64 ]. This is in line with the view that performing a sustained cognitive task competes with motivational options e.

In addition to these key-determinants, there are further important aspects that contribute to the psychophysiological state of an individual with potential consequences for perceived cognitive fatigue. For instance, it has been revealed that greater interest in a cognitive task resulted in less perceived cognitive fatigue despite a higher willingness to exert cognitive effort [ ].

In the same manner, it was argued that the level of controllability modulates the aversive responses and perceived cognitive fatigue during sustained cognitive activities [ ]. Furthermore, the execution of sustained cognitive tasks can be associated with changes in mood as well as with feelings like stress, anxiety, frustration, hopelessness, tension, and boredom [ , , , ].

Some of these were shown to be related to cognitive task performance [ ] and to modulate perceived cognitive fatigue [ 64 , , ]. For example, it was found that a task requiring the passive observation of strings of numbers resulted in higher boredom ratings, a steeper decline in affective valence, and higher perceived cognitive fatigue ratings compared to a cognitive task that consisted of adding three to each digit of a four-digit number [ ].

Interestingly, passively watching strings of numbers was also rated as effortful, which was interpreted as the effort to keep paying attention. It was also proposed that boredom, caused by the low intrinsic attractiveness of the task itself, can also be responsible for a decrease in cognitive task performance [ ], highlighting the interdependence between determinants of perceived cognitive fatigue and cognitive performance fatigue.

Moreover, it was assumed that expectations based on previous experiences might influence the psychophysiological state and the psychophysiological adjustments during sustained cognitive tasks [ ]. For instance, this was shown in response to heat stress [ , ], sleep deprivation [ ], and mouth rinsing with caffeine-maltodextrin [ ].

These sources of influence also highlight the similarity between the constructs of sleepiness and fatigue. Confusion between those concepts is very common and it remains unclear to what extent the subjective assessment measures allow researchers to clearly tease them apart [ ]. Besides these, there are further factors contributing to perceived cognitive fatigue that are increasingly studied and should be added to the list of potential determinants in the future.

Various modulating factors can influence the extent of cognitive performance fatigue and perceived cognitive fatigue Fig. The main subject-specific factors include age, sex, the existence of diseases, and cognitive fitness.

The extent of fatigue in the different domains is further determined by the characteristics of the cognitive task e. In the following sections, we will only discuss the most important subject- and cognitive task-specific factors that can modulate cognitive performance fatigue and perceived cognitive fatigue.

Cognitive abilities, such as processing speed and executive functioning, decline with advancing age due to structural and functional changes within the brain e. It is thought that these age-related changes contribute to the increased compensatory brain activation observed during the execution of cognitive tasks [ ], which was assumed to accelerate cognitive performance fatigue development [ ].

However, the results of studies that have investigated the effect of age on cognitive performance fatigue are mixed and do not allow for a definite conclusion. For instance, it was found that reaction times remained constant in young and old adults after the execution of a working memory task performed for 60 min, while accuracy even increased in the elderly.

The authors proposed that the potential decline in cognitive performance was countered by the learning effect [ ]. This is in line with the results of Behrens et al. In contrast, Terentjeviene et al. However, reaction times and intra-individual variability of reaction times only increased in young males indicating higher cognitive performance fatigue compared to the older males.

Since brain activation differs between sexes depending on the type of cognitive task [ , ], it might be assumed that the extent of cognitive performance fatigue after a sustained cognitive activity is different between males and females. However, the results of experiments on that topic are inconclusive.

For instance, there were no sex-differences in the error rate and reaction times, which remained constant over time, after performing a continuous performance test for 51 min [ ].

This is consistent with the results of Wang et al. The authors did not observe differences in the number of errors and completed subtractions between males and females.

However, the task lasted only 12 min and was possibly not long enough to induce cognitive performance fatigue.

In contrast to these studies, Noreika et al. They have revealed that accuracy increased, and response times decreased to a larger extent in males compared to females with time-on-task.

However, since cognitive performance increased over time, these results did not indicate cognitive performance fatigue and might be biased by the learning or practice effect. Since the extent of cognitive performance fatigue strongly depends on the structural and functional integrity of the central nervous system, it might be assumed that cognitive performance fatigue development is accelerated in patient populations, especially in those with neurological diseases affecting the central nervous system.

However, studies investigating cognitive performance fatigue in different patient populations e. Despite similar increases in cognitive task performance, patients showed heightened cerebral activation in specific areas and an increased perceived cognitive fatigue [ 10 , , ] indicating a lower efficiency.

In contrast, a decrease in cognitive performance measures was revealed during the execution of a four-block paced auditory serial addition test with an earlier drop in performance in people with multiple sclerosis compared to healthy controls [ ].

Analogous results were obtained by other studies that investigated the effects of sustained cognitive tasks on cognitive performance fatigue in multiple sclerosis and healthy controls [ , ].

A decrease in cognitive task performance was also found in stroke survivors while performing a min inhibition task, which was, however, comparable to the cognitive task performance reduction of the healthy control group [ ]. Moreover, Jordan et al.

The discrepant findings presented above indicate that the effect of age, sex, and diseases on cognitive performance fatigue seems to be strongly influenced by the task characteristics e. The occurrence and evaluation of cognitive performance fatigue strongly depend on the type of task e.

For instance, Smith et al. While the first task required only vigilance, the other two tasks additionally relied on response inhibition. Cognitive performance i. Interestingly, cognitive performance monitored during the respective tasks deteriorated only for the psychomotor vigilance task i.

In contrast, pre- and post-cognitive performance assessments with the 3-min psychomotor vigilance task revealed increased reaction times only after the AX-continuous performance task and the Stroop task. These data indicate that the detection and extent of cognitive performance fatigue strongly depend on the type of task as well as the task used to assess the potential change in performance.

Besides the effect of the type of cognitive task, other task characteristics e. Although several studies have not found a decline in cognitive performance with time-on-task, it was demonstrated that cognitive task performance decreased with increasing task duration [ 21 , , ].

Furthermore, it was proposed that the cognitive load induced by the task determines the extent of cognitive performance fatigue [ , , ]. Studies on this topic manipulated the cognitive load either by increasing the difficulty of the task e.

However, the results of these studies are inconsistent. For instance, during a min working memory task, Shigihara et al. The authors have additionally tested the effect of the sustained cognitive tasks on the advanced trail making test performance and have found that the number of errors increased from pre to post for both conditions.

Moreover, the results of Borragàn et al. However, irrespective of the task characteristics, there is a general critique that laboratory cognitive tasks are not ecologically valid and exhibit low intrinsic motivational value.

Therefore, controllability of these tasks is low, people experience them as increasingly aversive, and might disengage from the tasks because they are not sufficiently important for them [ 22 , 64 , , ].

Subject-specific factors like age, sex, and the presence of diseases might also modulate perceived cognitive fatigue and its potential determinants. For example, Wascher et al. Interestingly, young adults showed also a concomitant larger decrease in self-reported motivation.

This is in line with the results of Terentjeviene et al. This was accompanied by a higher perceived cognitive effort and temporal demand in the young participants during task execution. The young adults additionally reported increases in tension and confusion as well as a decrease in vigor, which were not found for the older participants.

These data collectively suggest that younger adults perceive sustained cognitive tasks as more effortful, demanding, and fatiguing than older adults, which is corroborated by the larger decreases in motivation and vigor as well as the increased tension and confusion.

Since laboratory cognitive tasks are often performed using a computer and older adults have less experience with digital technology [ ], these differences might be related to the higher intrinsic attractiveness of the task for older people.

Nevertheless, it was also shown that older people with a low frequency of technology use have higher levels of computer anxiety [ ]. Contrary to the findings of age-related differences, it has also been observed that the increase in perceived cognitive fatigue induced by a min inhibitory control task was not different between young and old adults [ 11 ].

Studies on sex-differences in perceived cognitive fatigue also revealed partially inconsistent results. Some studies have not found differences in perceived cognitive fatigue between males and females after performing a min Stroop task and a min continuous performance test, which require response inhibition and sustained attention.

Similarly, no sex-differences in the changes in cognitive effort, vigor, energy, tiredness, tension, calmness, and further self-reported data recorded during these tasks were reported [ , ].

Nevertheless, others have observed higher increases in fatigue ratings during a min mental rotation task in females compared to males, which depended on the menstrual cycle phase [ ]. It was additionally revealed that perceived cognitive effort and perceived task difficulty were higher in females compared to males during both a high and low cognitive load condition involving arithmetic tasks [ ].

There is evidence that perceived cognitive fatigue development in response to sustained cognitive tasks is higher in some diseases, especially those affecting the central nervous system [ 10 , , , ].

Higher increases in fatigue ratings during cognitive tasks have particularly been observed in people with multiple sclerosis [ , , ]. It was further reported that the perceived workload e. In contrast, studies on other patient populations, such as people with chronic fatigue syndrome, depression, and myasthenia gravis, have not found differential changes in perceived cognitive fatigue ratings compared with healthy controls during sustained cognitive tasks [ , ].

It has been shown that perceived cognitive fatigue and its determinants can be influenced by the type of task e. The results of studies that have examined the effect of the type of cognitive task on perceived cognitive fatigue are inconclusive. The latter was applied with constant processing intervals and with shorter individualized processing intervals based on the maximal performance determined during an incremental TloadDback task.

Although the task duration differed greatly, all cognitive tasks induced perceived cognitive fatigue, assessed with a visual analog scale, with the highest increase in the individualized TloadDback task condition. However, the AX continuous performance test induced a higher increase in perceived cognitive fatigue and a larger decrease in vigor assessed with the Brunel Mood Scale.

These results were accompanied by higher sleepiness ratings and a larger drop in task motivation compared to the TloadDback task condition. Another study on this topic has compared perceived cognitive fatigue as well as its recovery in response to a psychomotor vigilance task, an AX-continuous performance task, and a Stroop task each performed for 45 min [ ].

The tasks differed regarding their demands on vigilance and response inhibition. Although all tasks increased perceived cognitive fatigue, the authors concluded that tasks requiring response inhibition appeared to induce perceived cognitive fatigue for a longer duration than a simple vigilance task.

With regard to other task characteristics, it was often found that perceived cognitive fatigue progressively increases with time-on-task [ , ]. Moreover, it was shown that altering the cognitive load by the difficulty of the task i.

In line with this, Borragàn et al. However, when cognitive load was modulated by decreasing the processing interval for the stimuli, the high cognitive load condition induced a higher increase in perceived cognitive fatigue compared to the low cognitive load condition. The authors concluded that the processing time interval during cognitive tasks is more relevant for perceived cognitive fatigue development than the number of processed items.

In contrast to this, it was also shown that perceived cognitive fatigue cannot only result from performing a sustained cognitive task i. More specifically, perceived cognitive fatigue was even higher in the boredom condition compared with the cognitive task condition despite lower cognitive effort ratings.

This might be related to the steeper decline in affective valence ratings and the lower task interest ratings in the boredom condition.

Indeed, higher interest in a task has been shown to induce less perceived cognitive fatigue [ ]. These data highlight the importance of the characteristics of the cognitive task for the development of perceived cognitive fatigue and its determinants. The updated framework covers the different dimensions of task-induced state fatigue and the involved mechanisms Fig.

Thereby, the interdependence of performance fatigue and perceived fatigue as well as their determinants is acknowledged and highlighted. There is no single factor primarily determining performance fatigue and perceived fatigue in response to motor and cognitive tasks. Instead, the relative weight of each determinant and their interaction depends on several modulating factors e.

Although the mechanisms of motor performance fatigue are not yet fully elucidated, there are extensive data on the changes in the nervous system and muscle during motor tasks contributing to the decline in motor performance [ 16 , 17 , 25 , 26 ].

In contrast, the mechanisms underlying perceived motor fatigue and their interactions with motor performance fatigue received less attention. Therefore, future research should not only investigate the neural and muscular mechanisms driving motor performance fatigue but also aspects of perceived motor fatigue and the corresponding neuro physiological correlates in detail.

This approach can assist in investigating the motor task-induced perceptual differences between individuals and exercise protocols e. This is of special importance for clinical populations suffering from an increased prevalence of motor performance fatigue and perceived motor fatigue e.

There are a few studies available that have assessed neural and muscular contributions to motor performance fatigue in parallel with ratings of perceived motor fatigue, effort perception, and affective valence to study their interactions [ 42 , ].

For instance, Greenhouse-Tucknott et al. They have shown that prior submaximal hand grip exercise reduced the time to exhaustion during a submaximal isometric contraction of the knee extensors without altering neuromuscular function.

Thereby, effort perception and affective valence were correlated with time to exhaustion and the ratings of perceived motor fatigue. These findings indicate that prior handgrip exercise limited single-joint endurance performance of the knee extensors primarily by the interactions between perceived motor fatigue, effort perception, as well as affective valence and not by a decreased neuromuscular function.

Similar approaches should be adopted in the future to investigate the interactions between motor performance fatigue and perceived motor fatigue in different populations, particularly in those suffering from diseases. Besides the combined investigation of motor performance fatigue, perceived motor fatigue, and the underlying mechanisms, the determining factors can be manipulated to elucidate their causal involvement in the development of state fatigue in different populations and in response to various motor tasks.

For that purpose, different interventions can be used aiming to modify the physiological and psychological regulatory processes during fatiguing motor exercise.

For instance, neuromodulation techniques like tDCS are suitable to alter cortical excitability and to investigate the effects of changed neural properties on motor performance fatigue and perceived motor fatigue [ 67 ].

Furthermore, other interventions can be applied to modify neural as well as muscular properties e. Interventions aiming to modulate the psychological determinants of endurance performance have also been shown to induce changes in motor performance and the perceptual responses to fatiguing exercise [ 48 ].

These strategies could be used to investigate the role of cognitive processes in the interpretation of perceptual responses and the change in affective valence emerging during fatiguing motor exercise.

Motor performance fatigue can be assessed using maximal and submaximal motor performance measures. Maximal performance tasks e. In addition, the variation of submaximal motor performance is also an indication of motor performance fatigue e.

The neural and muscular mechanisms contributing to motor performance fatigue can be investigated with different non-invasive techniques. Neural adjustments i. Moreover, functional magnetic resonance imaging is suitable to monitor changes within cortical and subcortical structures during motor exercise [ ].

The contractile function of muscles can be validly quantified using peripheral nerve stimulation [ ], while changes in muscle oxygenation and muscle metabolism can be measured with near-infrared spectroscopy and phosphorus magnetic resonance spectroscopy, respectively [ , ].

In addition to these measures, perceived motor fatigue as well as the contributing factors should be comprehensively assessed before, during, and after fatiguing exercise. For this purpose, different scales and questionnaires can be used according to the focus of the respective study.

These measures should be applied together with standardized wording as described elsewhere [ 5 , 38 ]. Furthermore, the attentional focus during fatiguing motor exercise should be recorded as an index for the motor task intensity-dependent attentional shift from an external focus on the surrounding to an internal focus on the bodily sensations [ ].

These aspects should be quantified in conjunction with affective valence and arousal, recorded with the feeling scale and felt arousal scale, respectively, as indicators of the motor task-dependent homeostatic perturbations [ 40 , 60 ].

It has been shown that these aspects can influence perceived motor fatigue and performance during fatiguing motor tasks. Moreover, they reflect the motor task-induced homeostatic perturbations in various physiological subsystems and are thus indicators of the physical demands.

Besides these core measures of perceived motor fatigue, additional scales and tests should be used according to the aim of the respective study. This should be done to investigate the role of self-regulation capacity, executive functioning [ 41 , , ], and other determinants for motor performance fatigue as well as perceived motor fatigue.

The interactions between cognitive performance fatigue and perceived cognitive fatigue have been investigated more comprehensively and in greater detail compared to those between motor performance fatigue and perceived motor fatigue.

Accordingly, many studies in this field have recorded both changes in cognitive performance as well as in the perception of fatigue during and after sustained cognitive tasks. However, it must be pointed out that in studies which have measured cognitive performance on the same task as the one used to induce fatigue, evidence for a decline in cognitive task performance was frequently missing [ , ].

The lack of a systematic decline in cognitive performance with time-on-task was often attributed to an increased compensatory cognitive effort or to a learning effect that would lead to a performance increase overcoming the performance decline induced by fatigue [ , , , ].

In contrast, increases in perceived cognitive fatigue with time-on-task have been shown very consistently across many different conditions e. Therefore, future studies should use separate cognitive tasks to induce and measure cognitive performance fatigue as already done by some studies [ 23 , 24 , , , ].

This approach might bypass the influence of a decreased motivation or learning effect and has typically led to more consistent correlations between the cognitive performance decline and perceived cognitive fatigue [ 24 , ].

Furthermore, the effect of distinct types e. There is evidence that different cognitive tasks induce specific declines in performance measures depending on the assessment task. On the contrary, pre and post cognitive performance assessments with a 3-min psychomotor vigilance task revealed only increased reaction times after the AX-continuous performance task and the Stroop task.

However, perceived cognitive fatigue increased in all conditions, even though it tended to persist longer after the tasks requiring more response inhibition. Moreover, cognitive performance fatigue and perceived cognitive fatigue measures were also shown to be sensitive to the manipulation of the cognitive load [ , ].

Consequently, future studies on this topic should not only examine the effects of diverse types of tasks on cognitive performance fatigue, perceived cognitive fatigue, and their neural correlates but also the influence of varying cognitive loads.

Furthermore, it is likely that the level of overlap between the fatiguing and the assessment tasks, in terms of the cognitive processes involved, is also crucial [ ].

Therefore, it appears essential that future studies assess performance before and after the fatiguing cognitive task not only with cognitive tasks requiring similar cognitive processes, but also with tasks that involve different processes. These experiments should further take the impact of the cognitive load, the nature of the cognitive processes involved, and the degree of process overlap with the fatiguing task into account.

As stated above, other important sources of influence are mood and emotional variables, like stress, anxiety, frustration, hopelessness, tension, and boredom [ , , , ], which were shown to modulate perceived cognitive fatigue [ , , ] and cognitive task performance [ ].

Therefore, it seems mandatory to quantify these aspects and to analyze their effects on cognitive performance fatigue, perceived cognitive fatigue, and their neural correlates. Due to the discrepant findings, the influence of subject-specific factors i.

Nevertheless, it seems that cognitive task-induced perceived cognitive fatigue is higher in some patient populations [ , , ]. To address the causal relationships, neurophysiological and psychophysiological determinants of cognitive performance fatigue as well as perceived cognitive fatigue can also be modulated experimentally.

For instance, it was shown that anodal tDCS applied to the right parietal cortex counteracted the cognitive performance decline during a min visual vigilance task in healthy controls and people with multiple sclerosis but had no effect on perceived cognitive fatigue [ ].

Similar effects were observed in multiple sclerosis patients after stimulating the left dorsolateral prefrontal cortex with anodal tDCS [ ]. In addition, investigating the effects of different neuromodulatory substances such as caffeine on cognitive performance fatigue, perceived cognitive fatigue [ ], and its neurophysiological correlates can help to unravel their interdependence.

As outlined above, the detection and quantification of cognitive performance fatigue strongly depend on the assessment task and the considered variables e.

These measures should be combined with techniques suitable to record brain activity e. Ample evidence points to the interactions between the different dimensions of activity-induced state fatigue.

For instance, Marcora et al. However, effort perception during exercise was higher after performing the sustained cognitive task leading the authors to the conclusion that the participants reached their maximal tolerable effort level earlier and subsequently disengaged from exercise.

These data indicate that fatiguing cognitive or motor activities seem to modulate the performance and perceptions during a subsequent fatiguing motor or cognitive task, respectively. Evidence for the interactions between the different dimensions of activity-induced state fatigue also arises from experiments that have investigated the psychophysiological adjustments and performance changes in response to sustained motor-cognitive dual tasks [ , , ].

These studies have found a decreased time to exhaustion during submaximal motor tasks when a concurrent cognitive task had to be executed e.

Additionally, time to exhaustion during a fatiguing motor-cognitive dual task tended to be shorter for a high compared to a low cognitive load condition. This was accompanied by a higher reduction in muscle activation of the knee extensors i. As expected, cognitive effort perception scaled with the level of cognitive load, but, surprisingly, effort perception associated with the motor task was greater in the high cognitive load condition compared to that recorded during the single motor task condition [ ].

These data have impressively shown that the different domains of activity-induced state fatigue interact with each other. Since there is an overlap of brain structures involved during the execution of fatiguing motor and cognitive tasks e. Thereby, the degree of overlap between cognitive processes required for the respective motor and cognitive task might mediate the detrimental effects on performance and perceptions [ 9 , , ].

Consequently, future studies should investigate the effects of diverse types e. These effects should also be studied in relation to various motor tasks e.

Conversely, the impact of different fatiguing motor tasks performed prior to various fatiguing cognitive tasks relying on distinct cognitive processes should be examined.

The mechanistic basis for the interactions between motor performance fatigue, perceived motor fatigue, cognitive performance fatigue, and perceived cognitive fatigue can be probed with the methods mentioned in the respective paragraphs above.

However, the quantification of some perceptual responses to motor and cognitive tasks requires specific scales and a clear description with standardized wording. This is of particular importance for the measurement of perceived fatigue and effort in response to motor, cognitive, or motor-cognitive dual tasks.

Although it was proposed that the feeling of fatigue arising from exertion might be similarly induced by motor and cognitive tasks [ 9 ], results of studies indicated that perceived motor fatigue and perceived cognitive fatigue represent different perceptual domains [ , ].

The same applies to effort perception, which can be related to either to the motor or the cognitive task [ ].

Performance fatigue and perceived fatigue as well as their determinants are interdependent and should not be considered in isolation. Consequently, there is no single factor primarily determining performance fatigue and perceived fatigue in response to motor and cognitive tasks.

Instead, the relative weight of each determinant and their interaction depend on body homeostasis e. Therefore, a combined assessment of performance fatigue and perceived fatigue measures as well as its neuro physiological correlates is required to unravel the psychophysiology of motor and cognitive task-induced state fatigue.

This will help to better understand the interactions between the different dimensions of fatigue and their impact on human performance, which is necessary to design effective interventions for increasing exercise tolerance and human performance in healthy and clinical populations.

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Within the family of HSPs, HSP25 protein is abundantly expressed in skeletal muscle and increases with muscle contractile activity. have reported that a widespread HSP25 response to fatigue in a single hindlimb muscle is responsible for a global adaptive response to acute localized stress and have demonstrated that group III and IV muscle afferents play an important role in the fatigue-induced p-HSP25 response; moreover, the sympathetic nerve supply to the muscles and kidney comprises the efferent arm of the p-HSP25 activation.

Orosomucoid ORM is an acute-phase protein, with a very low pI of 2. It is predominantly synthesized in the liver, and many extra-hepatic tissues have also been reported to produce ORM under physiological and pathological stress. Interestingly, exogenous ORM increases muscle glycogen and enhances muscle endurance, whereas ORM deficiency results in decreased muscle endurance, thus indicating that ORM is an endogenous anti-fatigue protein.

Further studies have demonstrated that ORM binds to C—C chemokine receptor type 5 CCR5 on muscle cells and activates AMPK, thus promoting glycogen storage and enhancing muscle endurance, and representing a positive feedback mechanism for resisting fatigue and maintaining homeostasis.

Muscle fatigue is manifested most naturally in the intact organism. Non-invasive techniques of site-specific stimulation can now be used to evaluate the potential sites of the entire system for force production in human studies.

All evoked muscle responses are recorded via electromyography EMG electrodes placed on the muscle. Transcranial magnetic stimulation involves applying magnetic stimulation to the motor cortex and is optimized to activate the muscle of interest.

MEP is influenced not only by cortical excitability but also by spinal cord motor neuron excitability and muscle factors.

MEP depression can occur in the relaxed muscle after a fatiguing exercise, possibly as a result of afferent input from the fatigued muscle. MEP is increased in the upper- and lower-limb muscles during sustained submaximal isometric contractions and is regarded as an augmentation of the central drive to the lower motoneuron pool that allows a constant level of force to be maintained despite the development of peripheral fatigue.

During sustained MVC, MEP has been reported to increase during the first seconds and then to level off, increase linearly or remain stable, depending on the protocol used that is, continuous vs intermittent and the muscle investigated.

Electrical stimulation in the cervicomedullary region aims to activate the corticospinal tract at a subcortical level, thereby eliminating cortical contributions to the evoked muscle response. The muscular response recorded by EMG is known as the cervicomedullary motor-evoked potential CMEP.

Comparison of MEP and CMEP is helpful for the localization of excitability at the cortical or subcortical level. Low-intensity electrical stimulation of the peripheral nerve preferentially activates the Ia sensory fibers, which synapse with the α-motoneuron in the spinal cord. The signal is then carried along the motor neurons to the muscle, generating a response in the muscle known as the Hoffmann reflex H-reflex.

The H-reflex is used to assess spinal excitability and inhibition. Although there are several of an increase 65 or no change, 66 the general consensus is that there is an overall decline in the amplitude of the H-reflex with the development of muscle fatigue, thus indicating a decrease in spinal excitability.

High-intensity stimulation of the peripheral nerve directly activates the α-motoneuron, evoking a motor response m-wave from the muscle.

The m-wave is a compound action potential recorded with surface EMG and is used to assess peripheral excitability of the muscle membrane and transmission at the neuromuscular junction.

A change in the twitch force without a change in the m-wave indicates a failure of excitation-contraction coupling. At present, there are still no specific factors that have been consistently associated with a particular type of fatigue. According to the mechanism and metabolic changes during muscle fatigue, three categories of biomarkers have been determined: 1 ATP metabolism biomarkers, such as lactate, ammonia and hypoxanthine; 2 Oxidative stress biomarkers ROS , such as lipid peroxidation, protein peroxidation, and antioxidative capacity; and 3 Inflammatory biomarkers, such as TNF-α, leukocytes, and interleukins.

When the ATP supply fails to meet the consumption of ATP during exercise, fatigue occurs. AMP is subsequently degraded by AMP-deaminase to IMP and ammonia. The best-known biomarkers of muscle fatigue from ATP metabolism include lactate, ammonia, and hypoxanthine. Hypoxanthine is usually analyzed in the serum or urine.

Serum lactate increases with exercise intensity in healthy and diseased subjects. Under the conditions of workload standardization, serum lactate appears to be a promising biomarker of muscle fatigue. Serum ammonia is not associated with age 77 and remains low in physical fitness, but is higher in men than in women.

Reactive oxygen species ROS remain at a low level in resting skeletal muscle but increase in response to contractile activity. ROS products lead to protein, lipid or nucleic acid oxidation accompanied by a marked decrease in the antioxidant capacity, 81 thus ultimately inducing fatigue.

Promising biomarkers to assess oxidative damage in muscle fatigue include lipid peroxidation biomarkers that is, thiobarbituric acid-reactive substances TBARS and isoprostanes , and protein oxidation biomarkers that is, protein carbonyls PCs.

Biomarkers to evaluate the antioxidant capacity include glutathione GSH , glutathione peroxidase GPX , catalase, and the total antioxidant capacity TAC. TBARS are indicators of lipid peroxidation and oxidative stress, which form during the decomposition of lipid peroxidation products that react with thiobarbituric acid and form a fluorescent red adduct.

Isoprostanes are prostaglandin-like compounds derived from the peroxidation of essential fatty acids catalyzed by ROS. PCs are mainly derived from the oxidation of albumin or other serum proteins and are regarded as markers of oxidative protein injury.

GSH is a pseudotripeptide that is present in nearly all cells and plays an important role in ROS scavenging. GPX and catalase are both enzymes that scavenge hydrogen peroxide into water and oxygen. TAC is defined as the sum of the antioxidant activities of the nonspecific pool of antioxidants.

TBARS, PC, catalase and TAC are usually determined in the serum, but TBARS are also detectable in the saliva.

Isoprostanes are usually measured in the serum, urine, or other body fluids and blood cells. GSH and GPX are present in cells and are detectable in serum and saliva.

In addition to the depletion of ATP and ROS production, exercise and fatigue also induce local or systemic inflammatory reaction. Promising biomarkers to evaluate inflammation in muscle fatigue include leukocytes, IL-6 and TNF-α.

These changes represent a nonspecific immune response induced by ischemia in a stressed tissue, while there is a lack of a real injury.

Generally, IL-6 and TNF-α levels are determined in the serum. IL-6 levels can also be determined in the saliva. With age, the change in T-cells expressing CD8 remains controversial, , whereas the change in IL-6 is age independent. Sex differences in T-cell immune responses are particularly evident in graft-versus-host disease, with a stronger effect in females, and IL-6 levels are also markedly lower in females.

There are still many potential immunological biomarkers, including C-reactive protein CRP , IL-8, IL, IL, HSP27, HSP70, plasma DNA and orosomucoid ORM. Improper exercise, long time combat, military training and some related diseases for example, cancer and stroke can cause muscle fatigue, which negatively affects athletic achievement, military combat ability and patient recovery.

At present, there are still no official or semi-official recommendations for the treatment of muscle fatigue. However, some nonspecific treatments, such as synthetic products for example, amphetamine and caffeine , natural products for example, American ginseng and rhodiola rosea and nutritional supplements for example, vitamins and minerals and creatine , have been used clinically or experimentally, and have shown some effects in various studies.

Amphetamine, ephedrine, caffeine, for example, are all synthetic products that excite the central nervous system or sympathetic nervous system and promote resistance to muscle fatigue. Almost half of the stimulant abuse in sport involves amphetamines and ephedrine, as reported by WADA World Anti-Doping Agency in The use of amphetamines, amphetamine derivatives, propanolamine and ephedrine remains illegal in competition.

However, caffeine and pseudoephedrine have been accepted at any level since Amphetamine is a phenethylamine-type stimulant and antidepressant that is highly addictive and produces euphoria and an elevated mood.

Amphetamine at low to moderate doses enhances the physical performance of humans and animals. High body temperature is one of the strongest exhaustion signals. Recently, Morozova E has reported that amphetamine may mask or delay fatigue in rats by slowing down the exercise-induced elevation in core body temperature.

Although amphetamine usage is prohibited during competitions, it may be used in some situations, such as in combat, to improve performance by delaying exhaustion. The use of caffeine as a sports-related enhancement drug is well documented.

High caffeine dose consumption enhances performance during extended periods of exercise. Other sympathomimetic stimulants, such as ephedrine, pseudoephedrine and phenylpropanolamine, are several times less potent than amphetamines in improving performance.

In addition, taltirelin, a synthetic thyrotropin-releasing hormone TRH analog, effectively improves sports activity. Benzamide derivatives, such as 1- 1, 3-benzodioxolylcarbonyl piperidine 1-BCP , significantly prolong the time of forced swimming in mice, through an unclear mechanism.

More than half of the drugs introduced worldwide are derived from or are inspired by natural products. In the past few decades, health scholars and athletic physiologists have been searching for natural products that can improve athletic ability and resist or eliminate fatigue in human beings.

Now, more and more natural products and their extracts have been revealed as potentially anti-fatigue agents. American ginseng, panax ginseng C. Meyer and radix notoginseng all belong to the araliaceae ginseng species. American ginseng is the root of panax quinquefolium, which is currently grown in Canada and eastern USA.

Panax ginseng C. ginseng is an edible and medicinal Chinese herb that is often used in Asian countries. Panax notoginseng Burk. Chen is cultivated throughout Southwest China, Burma, and Nepal. The root, a commonly used part of this plant, is called radix notoginseng or Sanchi.

All of them contain multiple active components, such as saponins, polysaccharides, flavonoids, vitamins and microelements, which are responsible for the effects in the improvement of physical fatigue in humans and animals.

For example, saponins or protein extracted from American ginseng significantly lengthens the swimming time in mice via increasing the levels of liver glycogen and muscle glycogen.

Meyer, have all been reported to have marked anti-fatigue activity in mice swimming or grasping test. Meyer, including enhancing lactate dehydrogenase LDH activity, increasing hepatic glycogen levels, retarding the accumulation of serum urea nitrogen SUN and blood lactic acid BLA , inhibiting oxidative stress and improving mitochondrial function in skeletal muscles.

Regarding panax notoginseng, a single dose has been reported to enhance aerobic capacity, endurance and mean blood pressure MAP in young adults.

Rhodiola rosea R. rosea , belonging to the family Crassulaceae and genus Rhodiola, is a commonly used plant in folk medicine in Eastern Europe and China. It is also an important resource against fatigue. The ingredients of rhodiola rosea include salidroside and rosavin.

Rosavin is the only constituent unique to R. rosea from the Rhodiola genus, and salidroside is common to most other Rhodiola species. The natural ratio of rosavins to salidrosides in R. rosea is approximately Salidroside has been identified as the main anti-fatigue ingredient in Rhodiola rosea.

rosea extract has also been found to significantly increase swimming time, hepatic superoxide dismutase content, and serum lactate dehydrogenase in mice. Garlic Allium sativum is an herb that is used mainly as a food in many countries. Garlic was given to soldiers and athletes as a tonic in ancient Rome.

Recently, the anti-fatigue effect of garlic has been reported by many researchers. Garlic-processing methods affect the anti-fatigue effects.

have examined the effect of raw garlic juice, heated garlic juice, dehydrated garlic powder and AGE on physical strength and recovery from fatigue. They have found that raw garlic and AGE prolongs the treadmill running time of mice and enhances the speed of recovery of rectal temperature after immersion in cool water.

These effects are related to the improvement of peripheral circulation, an action of anti-stress, and improvement of nutrition. have investigated the effects of garlic oil on cardiac performance and exercise tolerance in 30 patients with coronary artery disease.

After an initial treadmill stress test, the subjects were administered garlic oil for 6 weeks, and treadmill stress tests were repeated. In comparison with the initial test, garlic significantly decreased the heart rate at peak exercise and work load on the heart, thus leading to the better exercise tolerance.

Enhancing the energy metabolism effectively helps to improve exercise capacity. Chinese yam and fructus aurantii have been reported to improve muscle glycogen, liver glycogen and other indicators. However, most of them still require extensive studies to determine their anti-fatigue effects and mechanisms.

Several nutritional factors that may limit exercise performance have been identified, thus leading to the widespread use of nutritional strategies. Nutritional supplementation is regarded as legal by the International Olympic Committee IOC and, therefore, has gained popularity as a way to achieve performance enhancement.

Despite their relative paucity in the diet and the body, vitamins and minerals are key regulators of health and function, including work performance. They are not direct sources of energy but facilitate energy metabolism. Water-soluble vitamins include B vitamins thiamin, riboflavin, niacin, pyridoxine, folate, biotin, pantothenic acid, vitamin B12 and choline and vitamin C.

Fat-soluble vitamins include vitamin A, D, E, and K. Vitamin A, C and E are also antioxidants. Twelve minerals are designated essential nutrients. Magnesium, iron, zinc, copper and chromium have the potential to affect physical performance. For example, severe deprivation of folate and vitamin B12 result in anemia and decrease endurance work performance.

Iron supplementation improves progressive fatigue resistance in iron-depleted, nonanemic women. Fish oil, a dietary supplement, has been shown to have beneficial effects on performance. Fish oil is rich in omega-3 fatty acids, specifically docosahexaenoic acid DHA and eicosapentaenoic acid EPA , which have been found to improve cardiac energy efficiency, fat metabolism and immunomodulatory responses.

Creatine Cr , a nitrogen-containing compound synthesized in the body from glycine, arginine and methionine, is also found in the diet, primarily in red meat and seafood. Therefore, creatine supplementation is a potential ergogenic strategy to improve muscle endurance. Red bull contains a mixture of carbohydrates, taurine, glucuronolactone, vitamin B and caffeine, and it is a commonly used energy drink.

Several small studies have reported that carbohydrate and caffeine consumption improves aerobic and anaerobic performance as well as cognitive functions such as concentration, alertness and reaction time.

Carnitine plays an essential role in fatty acid oxidation in muscle. However, there is a lack of definite evidence regarding its beneficial role in performance as a supplement.

Protein supplements have been demonstrated to be ineffective except in rare cases in which dietary protein intake is inadequate. Individual amino acids, especially ornithine, arginine and glutamine, are also commonly used as supplements.

However, their effects on performance are not supported by documented evidence. Acute-phase protein ORM has been reported to enhance muscle endurance after vein or intraperitoneal injection in rodents, 60 but it is not convenient for daily supplementation.

In theory, the use of antioxidant vitamins and glutamine during periods of intensive training should be beneficial, but further evidence is still needed before they are recommended as supplements.

Muscle force production involves a sequence of events, extending from cortical excitation to motor unit activation to excitation—contraction coupling, and ultimately leading to muscle activation. Changes at any level in this pathway, including changes in the nervous, ion, vascular, and energy systems, impair force generation and contribute to the development of muscle fatigue.

Site-specific stimulation via non-invasive techniques provides a method to gain systemic insight into the fatigue process under physiological conditions. Although there is a lack of consensus, a sex- and age-specific distribution in muscle fatigue has been observed, in which children, older adults and males are more resistant to fatigue than adults and females.

Biomarkers of ATP metabolism, oxidative stress and inflammatory reactions are helpful for the diagnosis of muscle fatigue. Despite the lack of official or semi-official recommendations, muscle fatigue has been reported to be improved by some nonspecific treatments, including CNS-exciting drugs, natural products and nutritional supplements.

More potential mechanisms, biomarkers, targets and related drugs for muscle fatigue— for example, ORM—still need to be explored in the future. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Call or Chat now! Simply defined, yet physiologically quite complex, fatigue refers to the inability to continue exercise at a given intensity. This article provides a brief overview of the various types of fatigue and examines the role gender plays in fatigue.

Also covered are training recommendations for combatting fatigue. Fatigue is a process that develops over time, and is largely dependent on the duration and intensity of exercise. The three dominant exercise scenarios leading to fatigue are short-term intense exercise, repeated-sprint exercise and extended submaximal exercise Girard et al.

Following is an overview of the key metabolic and system events that contribute to fatigue under these circumstances.

During activities such as sprinting and high-intensity resistance exercise, continued muscle contraction is dependent on the formation of adenosine triphosphate ATP for the demanding energy needs. Under these exercise conditions, creatine phosphate CrP , which resynthesizes ATP, and glucose breakdown called glycolysis are primarily responsible for maintaining ATP levels.

Skeletal muscle concentrations of CrP are quite limited; in fact, resting CrP stores can be depleted within approximately 10 seconds Powers and Howley, Historically, it was thought that lactate was principally a dead-end waste product that caused muscle soreness and fatigue.

Conversely, proton accumulation contributes to a decreased cellular pH acidosis , which interferes with normal skeletal muscle contraction through a number of mechanisms:.

Activity of the enzyme myosin ATPase is impaired. This enzyme is responsible for the breakdown of ATP in skeletal muscle and the release of energy to support muscle contraction. Other enzymes involved in the cellular regulation of sodium and potassium during muscle contraction become impaired.

Training can partially mitigate these negative events. Check out the box below for advice on how to combat fatigue during short-term, intense exercise.

Fatigue-fighting Training Tip 1. Improvements to the buffering-capacity system of the cellular environment will permit better tolerance of increased acidosis and, as a result, delay fatigue when performing short-term intense exercise.

Interestingly, past research has shown that eliciting acidosis i. Repeated-sprint exercise RSE is a fitness attribute required for success in many team and racquet sports Girard et al. RSE is characterized by numerous short-duration sprints generally lasting less than 10 to 15 seconds interspersed with brief and incomplete recovery typically less than 60 seconds.

Many of the sources of fatigue for RSE are similar to those encountered in short-term intense exercise, including proton accumulation and a finite CrP supply.

Exercise conditions, such as RSE, that extensively tax the phosphagen system ultimately lead to depletion in the primary fuel i. Therefore, recovery from CrP degradation becomes critical if the later bouts of RSE are to be maintained at a high performance.

Fatigue-fighting training tip 2 below highlights how combatting fatigue during RSE can be augmented. A neural fatigue also exists during RSE. Each single motor nerve which are under your voluntary control activates a group of muscle fibers ranging from a few to several hundred or more , and is collectively referred to as a motor unit.

Fatigue-fighting Training T ip 2. Research suggests that individuals with higher maximal oxygen uptake VO 2 max values have a greater capacity to resist fatigue during RSE.

The most likely reason is that those with high VO 2 max levels also more rapidly resynthesize CrP stores between brief bouts of intense exercise. Traditionally, increasing cardiorespiratory fitness has been accomplished through the performance of moderate-intensity continuous exercise training.

More contemporary research has shown interval training to also be a great option for quickly improving VO 2 max. This workout should be performed one to two days per week Gormley et al.

During prolonged exercises such as cycling, cross-country skiing and distance running, muscle contraction is also dependent on the ability of metabolic pathways breakdown of a fuel to release energy to continuously regenerate ATP.

Mitochondrial respiration aerobic metabolism in the mitochondrion of the cell becomes the primary supplier of ATP. Many fuels, or substrates from fat, carbohydrates and proteins, are available for mitochondrial respiration; however, the two most important relative to fatigue are blood glucose and muscle glycogen.

Fats in the form of triglycerides are also readily available for ATP production, but their breakdown is much slower than glucose and glycogen.

Decreased levels of blood glucose and low levels of muscle glycogen have been more associated with the onset of fatigue in sustained exercise events.

In terms of optimizing exercise performance, a limiting factor to glycolysis, and maintenance of this maximal rate of ATP regeneration, is the substrate availability of muscle glycogen.

Research has reported that muscle glycogen stores become depleted after approximately two hours of maximal usage Fitts, Prolonged aerobic and resistance exercise eccentric muscle contractions, in particular can lead to substantial disturbances in the skeletal muscle environment, including damage to the sarcolemma, contractile proteins and connective tissue Powers and Howley, These disturbances can impair the ability to transport blood glucose into the skeletal muscle cell, which in turn leads to a decreased capacity to replenish glycogen stores.

As a result, fatigue may continue for numerous days after the workout. Some exercise activities, such as hiking, cross-training events and endurance races, may take place in hot, humid environments that can lead to considerable heat stress and possibly dehydration.

Repeated muscle contractions during prolonged exercise leads to continuous, metabolically generated heat, which can dramatically increase core body temperature a condition known as hyperthermia.

Research suggests that rising core temperatures may cause fatigue in both the contracting muscles and central nervous system Powers and Howley, Failure to maintain fluid balance throughout prolonged sports events and exercise sessions may eventually result in decreased availability of blood flow to both exercising muscles and the skin for dissipation of heat.

The importance of fluid intake for total-body health, sport performance and reduced fatigue cannot be overemphasized. The third training tip, below, explains how to improve exercise tolerance during exposure to hot and humid environments. Fatigue-fighting Training T ip 3. Chronic adaptations associated with heat acclimation include increased plasma volume, earlier onset of sweating during exercise combined with enhanced sweat rate, and decreased electrolyte loss.

The stimulus required for eliciting these favorable adaptations is training in hot environments. The scientific literature has clearly shown, however, that the intensity of these training sessions need not be high.

For example, it was recently reported Lorenzo et al.