Development Of Central Fatigue Research Articles

Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?

It has been suggested that improper post-exercise recovery or improper sequence of training may result in an 'accumulation' of fatigue. Despite this suggestion, there is a lack of clarity regarding which physiological mechanisms may be proposed to contribute to fatigue accumulation. The present paper explores the time course of the changes in various fatigue-related measures in order to understand how they may accumulate or lessen over time following an exercise bout or in the context of an exercise program. Regarding peripheral fatigue, the depletion of energy substrates and accumulation of metabolic byproducts has been demonstrated to occur following an acute bout of resistance training; however, peripheral accumulation and depletion appear unlikely candidates to accumulate over time. A number of mechanisms may contribute to the development of central fatigue, postulating the need for prolonged periods of recovery; however, a time course is difficult to determine and is dependent on which measurement is examined. In addition, it has not been demonstrated that central fatigue measures accumulate over time. A potential candidate that may be interpreted as accumulated fatigue is muscle damage, which shares similar characteristics (i.e., prolonged strength loss). Due to the delayed appearance of muscle damage, it may be interpreted as accumulated fatigue. Overall, evidence for the presence of fatigue accumulation with resistance training is equivocal, making it difficult to draw the conclusion that fatigue accumulates. Considerable work remains as to whether fatigue can accumulate over time. Future studies are warranted to elucidate potential mechanisms underlying the concept of fatigue accumulation.

Peripheral Modulators of the Central Fatigue Development and Their Relationship with Athletic Performance in Jumper Horses.

Simple SummaryPhysical exercise induces various stress responses leading to a disturbance of homeostasis and a number of regulatory systems are called upon to return the body to a new level of equilibrium. The aim of this study was to evaluate the peripheral modulators of serotoninergic function and neurohumoral factors’ changes in athletic horses during an official jumping competition, and to evaluate their relationship with the physical performance of competing horses. The findings obtained in the current survey showed that jumping exercise influenced the levels of tryptophan, leucine, valine, non-esterified fatty acids (NEFAs), dopamine, and prolactin and that these changes are related to the physical performance of competing horses. These findings suggest that the serotoninergic system may be involved in fatigue during jumping exercise.The current study aimed to investigate whether peripheral modulators of serotoninergic function and neurohumoral factors’ changes in athletic horses during an official jumping competition, and to evaluate their relationship with the physical performance of competing horses. From 7 Italian Saddle mares (6–9 years; mean body weight 440 ± 15 kg), performing the same standardized warm-up and jumping course during an official class, heart rate (HR) was monitored throughout the competition. Rectal temperature (RT) measurement, blood lactate and glucose concentration, serum tryptophan, leucine, valine, the tryptophan/branched-chain amino-acids ratio (Try/BCAAs), dopamine, prolactin, and non-esterified fatty acids (NEFAs) were assessed before the exercise event (T0), at the end of the competition stage (5 min ± 10 s following the cessation of the exercise, TPOST5), and 30 min after the end of competition (TPOST30). Highest HR values were recorded during the course and at the outbound (p < 0.0001); blood lactate concentration and RT increased after exercise with respect to the rest condition (p < 0.0001). Lower leucine and valine levels (p < 0.01), and higher tryptophan, Try/BCAAs ratio, and NEFAs values were found at TPOST5 and TPOST30 with respect to T0 (p < 0.0001). A higher prolactin concentration was found at TPOST5 and TPOST30 compared to T0 (p < 0.0001), whereas dopamine showed decreased values after exercise compared to rest (p < 0.0001). Statistically significant correlations among the peripheral indices of serotoninergic function, neurohumoral factors, and athletic performance parameters were found throughout the monitoring period. The findings provide indirect evidence that the serotoninergic system may be involved in fatigue during jumper exercise under a stressful situation, such as competition, in which, in addition to physical effort, athletic horses exhibit more passive behavior.

Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice.

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-β1 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-β1. Intracranial injection of TGF-β1 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.

Contralateral fatigue during severe-intensity single-leg exercise: influence of acute acetaminophen ingestion.

Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P < 0.05). There were no differences in intramuscular phosphorus-containing metabolites and substrates or muscle activation between Leg1ACT and Leg1PL and between Leg2ACT-CONTRA and Leg2PL-CONTRA (all P > 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.

Fatigue-related group III/IV muscle afferent feedback facilitates intracortical inhibition during locomotor exercise.

This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise. Firing of these interneurons probably contributes to the development of central fatigue during physical activity. We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n=11) cycled at a comparable vastus-lateralis EMG signal (∼0.26mV) before (PRE; 100W) and immediately after (POST; 90±2W) fatiguing constant-load cycling exercise (80% Wpeak; 221±10W; ∼8min). During, PRE and POST cycling, single and paired-pulse (100ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P<0.05). This paralleled a reduction in conditioned MEP (P<0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P>0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.

Low-Carbohydrate-High-Fat Diet: Can it Help Exercise Performance?

Low-carbohydrate-high-fat (LCHF) diets have been used as a means of weight loss and control of symptoms in several clinical conditions. There is emerging evidence that the metabolic changes induced by LCHF diets enhance endurance performance. The aims of this review are to examine the evidence of LCHF diets in improving various aspects of athletic performance. Long-term LCHF dietary intake may help control body weight and fat mass while maintaining lean body mass in athletes in weight-sensitive sports. LCHF-adapted endurance athletes can reach the maximal fat oxidation rate of approximately 1.5 g/min, with a lower carbohydrate oxidation rate and similar muscle glycogen content and a resynthesis rate compared to their counterparts consuming high-carbohydrate-low-fat (HCLF) diets. The elevated fat oxidation rate and glycogen sparing effect may improve performance in ultra-endurance events. These metabolic changes may also prevent the decline in performance in later stages of repeated high-intensity movements, in which the aerobic metabolism becomes more important. However, elevated blood concentrations of non-esterified fatty acids and ammonia during exercise after LCHF diets may lead to early development of central fatigue. It appears that at least several months of adaptation to a LCHF diet are required for the metabolic changes and restoration of muscle glycogen to occur. Further investigations on LCHF diets are needed regarding (1) performance after weight loss in weight-categorized sports; (2) repeated high-intensity exercise performance; (3) development of central fatigue during endurance events; (4) perceptual-motor performance during prolonged intermittent sports; and (5) ideal dietary fatty acid compositions.

Hyperthermia and supraspinal fatigue.

Hyperthermia and supraspinal fatigue.

Repeated sprint ability but not neuromuscular fatigue is dependent on short versus long duration recovery time between sprints in healthy males.

During maximal intensity leg cycling sprints, previous research has shown that central and peripheral fatigue development occurs with various (<30s) short-duration recovery periods between sprints. The aim of the current study was to compare the development of neuromuscular fatigue during maximal intensity lower-body sprints interspersed with short and longer duration recovery periods. Crossover study. Ten participants completed 10, 10s sprints interspersed with either 30 or 180s of recovery. Peak power outputs were measured for each sprint. Maximal force, voluntary activation (VA) and evoked contractile properties of the knee extensors were measured at pre-sprint 1, post-sprint 5 and post-sprint 10. Perceived pain was also measured immediately following each sprint. Peak power output was significantly lower by 16.1±4.2% (p<0.001) during sprint 10 with 30 compared to 180s of recovery. Irrespective of recovery time, maximal force, VA and potentiated twitch force decreased by 26.7±7.2% (p<0.005), 5.8±1.2% (p=0.025), 38.7±6.1% (p=0.003) respectively, from pre-sprint 1 to post-sprint 10. MVC and PT decreased by 17±4% (p<0.003) and 23±9% (p<0.002) respectively, from pre-sprint 1 to post-sprint 5. Although decreases in peak power and increases in perceived pain were greater when sprints were interspersed with 30 compared to 180s of recovery, the development of neuromuscular fatigue of the knee extensors was similar. The results illustrate that peripheral fatigue developed early whereas central fatigue developed later in the sprint protocol, however the effect of recovery time on neuromuscular fatigue could be task specific.

Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise.

To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13±3% higher (P<0.05), resulting in a decrease in MEP/CMEP (P<0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (-53±3% vs. -39±3%; P<0.01), the reduction in voluntary muscle activation was smaller (-2±2% vs. -10±2%; P<0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13±3% and 25±6% in FENT (P<0.05). During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans.

Does cerebral hypoxia facilitate central fatigue?

What is the topic of this review? This review addresses whether a mismatch between cerebral O2 demand and delivery accelerates the development of central fatigue during endurance-type exercise. What advances does it highlight? The difficulty with studying the importance of cerebral O2 availability for exercise performance is to manipulate cerebral O2 availability independently of muscular O2 availability. The different approaches to overcome this limitation indicate that cerebral oxygenation is not a major limiting factor in normoxia, but may limit performance in submaximal exercise tasks in hypoxia. Central fatigue originates within the central nervous system and is characterized by a decrease in voluntary muscle activation. Reduced systemic O2 availability can facilitate central fatigue by enhancing the afferent input of the chemosensitive nerves that play a pivotal role in development of central fatigue. There is accumulating evidence that, in some situations, inadequate O2 availability to the brain itself promotes central fatigue. This short review presents some of the recent findings supporting a direct effect of inadequate cerebral O2 availability on central fatigue and addresses the persisting limitations.

Peripheral and Central Fatigue Development during All-Out Repeated Cycling Sprints.

We investigated the development and recovery of peripheral and central fatigue during repeated cycling sprints and its influence on power output. On six separate days, 12 healthy males performed the following tests: 1, 4, 6, 8, and 10 × 10 s sprints with 30 s of passive recovery between sprints, as well as 8 × 10 s sprints with 10 s of passive recovery. Peripheral and central fatigue levels were quantified via changes in preexercise- to postexercise-potentiated quadriceps twitch force, as evoked by supramaximal electrical stimulation of the femoral nerve (30 s through 6 min recovery), and quadriceps voluntary activation (VA), respectively. Root mean square of the vastus lateralis and the vastus medialis electromyogram during sprints were normalized by maximal M wave amplitude (RMS·Mmax). From the first to the sixth sprint, we found significant and gradual reductions in power output (-25% ± 7%), RMS·Mmax (-7% ± 4%), twitch force (-47% ± 11%) and VA (-11% ± 6%). During the subsequent sprints, no additional reduction in power output, RMS·Mmax, twitch force or VA, was found. Reduction in between-sprints recovery duration led to a significant reduction in power output and RMS·Mmax but no change in peripheral and central fatigue. These findings are consistent with the hypothesis that central motor command and power output during all-out repeated sprints are limited in order to prevent excessive locomotor muscle fatigue. They also demonstrate that both the peripheral and central fatigue contribute significantly to the decline in power output elicited via repeated sprints.

Neuromuscular fatigue during hypoxia is mediated by the hypoxic ventilatory response

Neurons of the corticospinal tract are inherently sensitive to oxygen availability and, in response to hypoxia, reduce their metabolic requirements and activity [1]. Consequently, hypoxia is associated with neuromuscular fatigue, attributed in part to central (i.e., CNS) mechanisms [2]. Although changes in cerebral blood flow (CBF), mediated by the ratio of hypoxia induced vasodilation to hypoxic ventilatory response (HVR) induced hypocapnia (i.e., PETCO2) [3], may be implicated in the development of central fatigue, the contribution from the chemoreflex control of HVR and CBF vs. reductions in CBF per se has yet to be isolated.

The interaction between cooling and hypoxia on the rate of peripheral and central fatigue development of the knee extensors

The interaction between cooling and hypoxia on the rate of peripheral and central fatigue development of the knee extensors

Augmented supraspinal fatigue following constant-load cycling in the heat.

The development of central fatigue is prominent following exercise-induced hyperthermia, but the contribution of supraspinal fatigue is not well understood. Seven endurance-trained cyclists (mean ± SD peak O2 uptake, 62.0 ± 5.6 mL/kg/min) completed two high-intensity constant-load cycling trials (296 ± 34 W) to the limit of tolerance in a hot (34 °C, 20% relative humidity) and, on a separate occasion, for the same duration, a control condition (18 °C, 20% relative humidity). Core body temperature (Tc ) was measured throughout. Before and immediately after each trial, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation were obtained from the knee extensors to assess neuromuscular and corticospinal function, respectively. Exercise time was 11.4 ± 2.6 min. Peak Tc was higher in the hot compared with control (38.36 ± 0.43 °C vs 37.86 ± 0.36 °C; P = 0.035). Post-exercise reductions in maximal voluntary contraction force (13 ± 9% vs 9 ± 5%), potentiated twitch force (16 ± 12% vs 21 ± 13%) and voluntary activation (9 ± 7% vs 7 ± 7%) were similar in hot and control trials, respectively. However, cortical voluntary activation declined more in the hot compared with the control (8 ± 3% vs 3 ± 2%; P = 0.001). Exercise-induced hyperthermia elicits significant central fatigue of which a large portion can be attributed to supraspinal fatigue. These data indicate that performance decrements in the heat might initially originate in the brain.

Peripheral And Central Fatigue Development And Short-term Recovery During All-out Repeated Sprints

Recent evidence suggests that power output during repeated sprints of short duration is adjusted by the central nervous system to restrain the development of locomotor muscle fatigue to a critical threshold. This adjustment of power output might involve a complex interplay between peripheral and central determinants of muscle fatigue. The rate of peripheral and/or central fatigue development and its influence on the pattern of power output during repeated sprints remain however largely unknown. PURPOSE:We aimed to determine the contribution of peripheral and central fatigue to power output reduction during repeated sprints and whether power output levels off when a critical threshold of peripheral fatigue is reached. METHODS: On separate days, twelve healthy subjects performed the following tests: 1, 4, 6, 8 and 10, 10 s all-out sprints, each with 30 s of passive recovery between sprints, as well as 8, 10 s sprints, each with 10 s of passive recovery to test the influence of varying the work / recovery ratio on our hypotheses. Peripheral fatigue was quantified via changes in pre- to post-exercise potentiated quadriceps twitch force evoked by supramaximal electrical stimulation of the femoral nerve (ΔQtw, 0.5 through 6 min recovery). Central fatigue was estimated via changes in pre- to post-exercise voluntary quadriceps activation (ΔVA). EMG during sprints was normalized by maximal M-wave amplitude (ΔRMS.Mmax-1). RESULTS: From the 1st to the 6th sprint, we found a significant and gradual reduction in ΔQtw (- 47 ± 3 %), ΔRMS.Mmax-1 (- 7 ± 1 %) and power output (- 25 ± 2 %). During the 4 subsequent sprints, no additional reduction of quadriceps fatigue, RMS.Mmax-1 or power output was found but VA was significantly reduced compared to baseline (- 11 ± 2 %). Recovery of Qtw, post-sprints (0.5 through 6 min), was reduced progressively following sprint #1 through #6, with no further reduction thereafter (through sprint #10). CONCLUSIONS: Both peripheral and central fatigue contribute to the reduction of power output during repeated sprints. The leveling off of power output and RMS.Max-1 when the same degree of peripheral fatigue was reached, independently of the work / recovery duration ratio, suggest that central motor drive was restricted to limit excessive development of peripheral muscle fatigue.

Delineating the Role of Cerebral Blood Flow and Hypocapnia on Neuromuscular Function

Neuromuscular fatigue, defined as the inability of a muscle to maintain a given level of force regardless of whether or not a task can be sustained, has been attributed, in part, to central mechanisms. Although reductions in cerebral blood flow (CBF) may be implicated in the development of central fatigue, the contribution from hypocapnic-reductions (i.e., PETCO2) in CBF versus reductions in CBF per se has yet to be isolated. PURPOSE: To examine the hypothesis that hypocapnia, independent of concomitant reductions in CBF, cause impairments in neuromuscular function. METHODS: Neuromuscular function, as indicated by motor evoked potentials (MEP), M-waves and cortical voluntary activation (cVA) of the flexor carpal radialis muscle during isometric wrist flexion, was assessed in 8 males (31±12 y) during 3 separate conditions: 1) cyclooxygenase inhibition using Indomethacin (Indo) to selectively reduce CBF; 2) controlled hyperventilation-induced hypocapnia (Hypocapnia); and 3) isocapnic hyperventilation (Isocapnia). CBF was estimated using transcranial Doppler ultrasound velocity measurements of the middle cerebral artery. Change from baseline and comparison of the 3 conditions was assessed using two-way repeated measures ANOVA. Relationships between variables were assessed using Pearson‘s correlations. RESULTS: The experimental conditions successfully isolated CBF and PETCO2. MEP amplitude (% M-wave amplitude) increased in hypocapnia (14.6±9.5%, p < 0.01) in comparison to Indo (-2.0±2.8%) and Isocapnia (0.6±1.8%); however, no significant changes were observed in M wave (p = 0.666) or cVA (p = 0.117). Correlation analysis revealed that MEP amplitude was inversely associated with PETCO2 (r = -0.54, p < 0.01) and cVA was weakly associated with CBF (r = 0.30, p < 0.05). CONCLUSIONS: Increased motor cortex excitability appears to be exclusive to hypocapnia but not reductions in CBF per se. However, a weak relationship between reductions in CBF and cVA exists, such that further research is required to confirm this finding and explore the potential implications. Supported by NSERC Discovery 227912-2012.

Improved tolerance of peripheral fatigue by the central nervous system after endurance training

The purposes of this study were to evaluate the effect of endurance training on central fatigue development and recovery. A control group was compared to a training group, which followed an 8-week endurance-training program, consisting in low-force concentric and isometric contractions. Before (PRE) and after (POST) the training period, neuromuscular function of the knee extensor (KE) muscles was evaluated before, immediately after and during 33 min after an exhausting submaximal isometric task at 15 % of the maximal voluntary contraction (MVC) force. After training, the trained group performed another test at iso-time, i.e., with the task maintained until the duration completed before training was matched (POST2). The evaluation of neuromuscular function consisted in the determination of the voluntary activation level during MVCs, from peripheral nerve electrical (VAPNS) and transcranial magnetic stimulations (VATMS). The amplitude of the potentiated twitch (Pt), the evoked [motor evoked potentials, cortical silent period (CSP)] and voluntary EMG activities were also recorded on the KE muscles. Before training, the isometric task induced significant reductions of VAPNS, VATMS and Pt, and an increased CSP. The training period induced a threefold increase of exercise duration, delayed central fatigue appearance, as illustrated by the absence of modification of VAPNS, VATMS and CSP after POST2. At POST, central fatigue magnitude and recovery were not modified but Pt reduction was greater. These results suggest that central fatigue partially adapts to endurance training. This adaptation principally translates into improved tolerance of peripheral fatigue by the central nervous system.

Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

Purpose: To outline how hypoxia profoundly affects neuronal functionality and thus compromises exercise performance. Methods: Investigations were reviewed and evaluated that used electroencephalography (EEG) and transcranial magnetic stimulation (TMS) to detect neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH). Results: At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral fatigue; as the severity of hypoxia increases, mechanisms of peripheral fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral fatigue observed in AH; however, it attenuates the development of central fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions: The attenuated development of central fatigue in CH might explain the improvements in locomotor exercise performance commonly observed after acclimatisation to high altitude.

Voluntary muscle and motor cortical activation during progressive exercise and passively induced hyperthermia

This study examined whether central fatigue was exacerbated by an increase in muscle contractile speed caused by passive hyperthermia (PaH) and whether exercise-induced hyperthermia (ExH) combined with related peripheral fatigue influenced this response. The ExH was induced by cycling at 60% of maximal oxygen uptake in 38°C conditions and the PaH by sitting in a 48°C climate chamber. Ten men performed brief (≈ 5 s) and sustained (30 s) maximal voluntary isometric contractions (MVCs) of the knee extensors at baseline (CON, ∼37.1°C) and during moderate (MOD, ≈ 38.5°C) and severe (SEV, ∼39.5°C) hyperthermia. Motor nerve and transcranial magnetic stimulation were used to assess voluntary muscle and cortical activation level, along with contractile properties. Brief MVC force decreased to a similar extent during SEV-ExH (-8%) and SEV-PaH (-6%; P < 0.05 versus CON). Sustained MVC force also decreased during MOD-ExH (-10%), SEV-ExH (-13%) and SEV-PaH (-7%; P < 0.01 versus CON). Motor nerve and cortical activation were reduced on reaching MOD (≈ 3%) and SEV (≈ 5%) ExH and PaH during the brief and sustained MVCs (P < 0.01 versus CON). Peak twitch force decreased on reaching SEV-ExH and SEV-PaH (P < 0.05 versus CON). Following transcranial magnetic stimulation, during the brief and sustained MVCs the peak muscle relaxation rate increased in ExH and PaH (P < 0.01 versus CON). The increase was greatest during the sustained contraction in SEV-PaH (P < 0.01), but this did not exacerbate central fatigue relative to ExH. These results indicate that during fatiguing cycling exercise in the heat, quadriceps peak relaxation rate increases. However, the centrally mediated rate of activation appears sufficient to overcome even the largest increase in muscle relaxation rate, seen during SEV-PaH.

Supraspinal fatigue after normoxic and hypoxic exercise in humans

Inadequate cerebral O2 availability has been proposed to be an important contributing factor to the development of central fatigue during strenuous exercise. Here we tested the hypothesis that supraspinal processes of fatigue would be increased after locomotor exercise in acute hypoxia compared to normoxia, and that such change would be related to reductions in cerebral O2 delivery and tissue oxygenation. Nine endurance-trained cyclists completed three constant-load cycling exercise trials at ∼80% of maximal work rate: (1) to the limit of tolerance in acute hypoxia; (2) for the same duration but in normoxia (control); and (3) to the limit of tolerance in normoxia. Throughout each trial, prefrontal cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared spectroscopy and transcranial Doppler sonography, respectively. Cerebral O2 delivery was calculated as the product of arterial O2 content and MCAV. Before and immediately after each trial, twitch responses to supramaximal femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and cortical function, respectively. Exercise time was reduced by 54% in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; P < 0.001). Cerebral O2 delivery, cerebral oxygenation and maximum O2 uptake were reduced whereas muscle electromyographic activity was increased in hypoxia compared to control (P < 0.05). Maximum voluntary force and potentiated quadriceps twitch force were decreased below baseline after exercise in each trial; the decreases were greater in hypoxia compared to control (P < 0.001), but were not different in the exhaustive trials (P > 0.05). Cortical voluntary activation was also decreased after exercise in all trials, but the decline in hypoxia (Δ18%) was greater than in the normoxic trials (Δ5–9%) (P < 0.05). The reductions in cortical voluntary activation were paralleled by reductions in cerebral O2 delivery. The results suggest that curtailment of exercise performance in acute severe hypoxia is due, in part, to failure of drive from the motor cortex, possibly as a consequence of diminished O2 availability in the brain.