Acute neuromuscular, cardiovascular, and muscle oxygenation responses to low-intensity aerobic interval exercises with blood flow restriction.

We investigated the influence of short- and long-interval cycling exercise with blood flow restriction (BFR) on neuromuscular fatigue, shear stress and muscle oxygenation, potent stimuli to BFR-training adaptations. During separate sessions, eight individuals performed short- (24 × 60 s/30 s; SI) or long-interval (12 × 120 s/60 s; LI) trials on a cycle ergometer, matched for total work. One leg exercised with (BFR-leg) and the other without (CTRL-leg) BFR. Quadriceps fatigue was quantified using pre- to post-interval changes in maximal voluntary contraction (MVC), potentiated twitch force (QT) and voluntary activation (VA). Shear rate was measured by Doppler ultrasound at cuff release post-intervals. Vastus lateralis tissue oxygenation was measured by near-infrared spectroscopy during exercise. Following the initial interval, significant (P < 0.05) declines in MVC and QT were found in both SI and LI, which were more pronounced in the BFR-leg, and accounted for approximately two-thirds of the total reduction at exercise termination. In the BFR-leg, reductions in MVC (-28 ± 15%), QT (-42 ± 17%), and VA (-15 ± 17%) were maximal at exercise termination and persisted up to 8 min post-exercise. Exercise-induced muscle deoxygenation was greater (P < 0.001) in the BFR-leg than CTRL-leg and perceived pain was more in LI than SI (P < 0.014). Cuff release triggered a significant (P < 0.001) shear rate increase which was consistent across trials. Exercise-induced neuromuscular fatigue in the BFR-leg exceeded that in the CTRL-leg and was predominantly of peripheral origin. BFR also resulted in diminished muscle oxygenation and elevated shear stress. Finally, short-interval trials resulted in comparable neuromuscular and haemodynamic responses with reduced perceived pain compared to long-intervals.

The Effect of Duration on Performance and Perceived Fatigability During Acute High-Intensity Interval Exercise in Young, Healthy Males and Females.

Few studies have explored the kinetics of performance and perceived fatigability during high-intensity interval training, despite its popularity. We aimed to characterize the kinetics of fatigability and recovery during an 8 × 4-min HIIT protocol, hypothesizing that most muscle function impairment would occur during the initial four intervals. Fifteen healthy males and females (mean ± standard deviation; age = 26 ± 5 years, V̇O2max = 46.8 ± 6.1 mL·kg-1·min-1) completed eight, 4-min intervals at 105% of critical power with 3 min of rest. Maximal voluntary knee extension contractions (MVCs) coupled with electrical nerve stimulation were performed at baseline and after the first, fourth, and eighth intervals. MVC, potentiated twitch force (Pt), and Db10:100 ratio all declined throughout HIIT (p < 0.05). MVC sharply declined after interval 1 (-15 ± 9% relative to baseline; p < 0.05) and had only further declined after interval 8 (-26 ± 11%; p < 0.05), but not interval 4 (-19 ± 13%; p > 0.05). Pt and Db10:100 also sharply declined after interval 1 (Pt: -18 ± 13%, Db10:100: -14 ± 20%; p < 0.05) and further declined after interval 4 (Pt: -35 ± 19%, Db10:100: -30 ± 20%; p < 0.05) but not interval 8 (Pt: -41 ± 19%; Db10:100: -32 ± 18%; p > 0.05). Voluntary activation did not significantly change across the HIIT protocol (p > 0.05). Evoked force recovery was significantly blunted as more intervals were completed: after interval 1, Pt recovered by 7 ± 11% compared to -6 ± 7% recovery after interval 8 (p < 0.05). Ratings of perceived effort, fatigue, and leg pain rose throughout the session (p < 0.05 for each) and were greater (effort and fatigue) for females (p < 0.05). Otherwise, males and females exhibited similar performance fatigability kinetics, with contractile function declines blunted in response to additional intervals.

Effects of hemp supplementation during resistance training in trained young adults.

PURPOSE: Hemp contains protein with high concentrations of the branched-chain amino acids leucine, isoleucine, and valine and oils that have anti-inflammatory properties. Our purpose was to investigate the effects of hemp supplementation during resistance training in trained young adults. METHODS: Males (n = 22, 29 ± 8y) and females (n = 12, 30 ± 9y) were randomized (double-blind) to receive 60 g/d of hemp (containing 40 g protein and 9 g oil) or 60 g/d of soy (matched for protein and calories) during eight weeks of resistance training (~  4x/week). Before and after the intervention, participants were assessed for whole-body lean tissue and fat mass (dual-energy X-ray absorptiometry), regional muscle hypertrophy (ultrasound), strength (1-repetition maximum leg press, bench press, biceps curl), voluntary activation (interpolated twitch technique), resting twitch properties (single pulse; 0.5 ms) (before and after a fatigue test), markers of inflammation (Interleukin 6 and C-reactive protein), and bone resorption (urinary N-telopeptides). RESULTS: Hemp supplementation increased elbow flexor muscle thickness in females (2.6 ± 0.4-3.1 ± 0.5 cm, p = 0.012) while soy supplementation increased elbow flexor muscle thickness in males (3.7 ± 0.4-4.0 ± 0.5 cm, p < 0.01). Twitch torque and rate of torque development were preserved after a fatigue test in males consuming hemp compared to males on soy (p < 0.001). CONCLUSION: Overall, hemp provides some sex-specific beneficial effects on measures of muscle accretion and torque under fatiguing conditions in resistance trained young adults. CLINICALTRIALS: gov Identifier: NCT02529917, registered August 11, 2015.

Effects of α-lactalbumin on strength, fatigue and psychological parameters: a randomised double-blind cross-over study.

PURPOSE: The neurotransmitter serotonin has a strong effect on behaviour and motor control. Regarding motor control, serotonin contributes to the development of fatigue and is also involved in the ability of motor neurones to operate across a large range of forces (gain control). The consumption of tryptophan-rich supplements (such as α-lactalbumin) is of interest because this amino acid is the only precursor for brain serotonin synthesis. Therefore, the purpose of this study was to determine the effects of α-lactalbumin supplementation on neuromuscular performance. METHODS: Using a randomised double-blind cross-over design, 16 healthy participants performed plantar flexor and handgrip maximal voluntary contractions, a 30-s submaximal handgrip contraction, and a plantar flexor fatigue protocol before and 90 min after consuming either 40 g of α-lactalbumin, an isonitrogenous beverage (Zein) or an isocaloric beverage (corn-starch). Sleepiness, mood, and cognition were assessed to evaluate any psychological effects. RESULTS: α-Lactalbumin decreased force steadiness by 25% during the sustained submaximal handgrip contraction (p < 0.01) and induced greater fatigue (15% reduction in total torque-time integral, p = 0.01) during the fatigue protocol. These effects were not observed for the other control beverages. No effects were found for maximal or explosive strength, or psychological measurements. CONCLUSIONS: 40 g of α-lactalbumin increased handgrip force variability and reduced performance during fatiguing muscle contractions but did not influence brief maximal contractions or psychological parameters in healthy individuals. These findings support the hypothesis that the consumption of α-lactalbumin can increase motor neurone input-output gain and exacerbate central fatigue during sustained maximal exercise.

Knee position sense and knee flexor neuromuscular function are similarly altered after two submaximal eccentric bouts.

PURPOSE: This study examined eccentric-induced fatigue effects on knee flexor (KF) neuromuscular function and on knee position sense. This design was repeated across two experimental sessions performed 1 week apart to investigate potential repeated bout effects. METHODS: Sixteen participants performed two submaximal bouts of KF unilateral eccentric contractions until reaching a 20% decrease in maximal voluntary isometric contraction force. Knee position sense was evaluated with position-matching tasks in seated and prone positions at 40° and 70° of knee flexion so that KF were either antagonistic or agonistic during the positioning movement. The twitch interpolation technique was used to assess KF neuromuscular fatigue. Perceived muscle soreness was also assessed. Measurements were performed before, immediately (POST) and 24 h after (POST24) each eccentric bout. RESULTS: No repeated bout effect on neuromuscular function and proprioceptive parameters was observed. At POST, central and peripheral factors contributed to the force decrement as shown by significant decreases in voluntary activation level (- 3.8 ± 4.8%, p < 0.01) and potentiated doublet torque at 100 Hz (- 10 ± 15.8%, p < 0.01). At this time point, position-matching errors significantly increased by 1.7 ± 1.9° in seated position at 40° (p < 0.01). At POST24, in presence of muscle soreness (p < 0.05), although KF neuromuscular function had recovered, position-matching errors increased by 0.6 ± 2.6° in prone position at 40° (p < 0.01). CONCLUSION: These results provide evidence that eccentric-induced position sense alterations may arise from central and/or peripheral mechanisms depending on the testing position.

Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue.

Although there is evidence that 5-HT acts as an excitatory neuromodulator to enhance maximal force generation, it is largely unknown how 5-HT activity influences the ability to sustain a constant force during steady-state contractions. A total of 22 healthy individuals participated in the study, where elbow flexion force was assessed during brief isometric contractions at 10% maximal voluntary contraction (MVC), 60% MVC, MVC, and during a sustained MVC. The selective serotonin reuptake inhibitor, paroxetine, suppressed physiological tremor and increased force steadiness when performing the isometric contractions. In particular, a main effect of drug was detected for peak power of force within the 8-12 Hz range (P = 0.004) and the coefficient of variation (CV) of force (P < 0.001). A second experiment was performed where intermittent isometric elbow flexions (20% MVC sustained for 2 min) were repeatedly performed so that serotonergic effects on physiological tremor and force steadiness could be assessed during the development of fatigue. Main effects of drug were once again detected for peak power of force in the 8-12 Hz range (P = 0.002) and CV of force (P = 0.003), where paroxetine suppressed physiological tremor and increased force steadiness when the elbow flexors were fatigued. The findings of this study suggest that enhanced availability of 5-HT in humans has a profound influence of maintaining constant force during steady-state contractions. The action of 5-HT appears to suppress fluctuations in force regardless of the fatigue state of the muscle.NEW & NOTEWORTHY Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.

Blockade of 5-HT2 receptors suppresses rate of torque development and motor unit discharge rate during rapid contractions.

Serotonin (5-HT) is a neuromodulator that is critical for regulating the excitability of spinal motoneurons and the generation of muscle torque. However, the role of 5-HT in modulating human motor unit activity during rapid contractions has yet to be assessed. Nine healthy participants (23.7 ± 2.2 yr) ingested 8 mg of the competitive 5-HT2 antagonist cyproheptadine in a double-blinded, placebo-controlled, repeated-measures experiment. Rapid dorsiflexion contractions were performed at 30%, 50%, and 70% of maximal voluntary contraction (MVC), where motor unit activity was assessed by high-density surface electromyographic decomposition. A second protocol was performed where a sustained, fatigue-inducing dorsiflexion contraction was completed before undertaking the same 30%, 50%, and 70% MVC rapid contractions and motor unit analysis. Motor unit discharge rate (P < 0.001) and rate of torque development (RTD; P = 0.019) for the unfatigued muscle were both significantly lower for the cyproheptadine condition. Following the fatigue inducing contraction, cyproheptadine reduced motor unit discharge rate (P < 0.001) and RTD (P = 0.024), whereas the effects of cyproheptadine on motor unit discharge rate and RTD increased with increasing contraction intensity. Overall, these results support the viewpoint that serotonergic effects in the central nervous system occur fast enough to regulate motor unit discharge rate during rapid powerful contractions.NEW & NOTEWORTHY We have shown that serotonin activity in the central nervous system plays a role in regulating human motor unit discharge rate during rapid contractions. Our findings support the viewpoint that serotonergic effects in the central nervous system are fast and are most prominent during contractions that are characterized by high motor unit discharge rates and large amounts of torque development.

The relationship between central fatigue and Attention Deficit/Hyperactivity Disorder of the inattentive type.

Chronic fatigue and central fatigue with malaise significantly impair quality of life. Inattention caused by central fatigue is closely related to attention deficit/hyperactivity disorder (ADHD) symptoms, but the neurochemical mechanism of central fatigue remains hypothetical. The serotonin hypothesis of central fatigue was proposed first, serving as the central dogma for the molecular and neural mechanisms of central fatigue, and underpinning many studies. The tryptophan hypothesis was proposed because tryptophan released into the synaptic cleft of neurons in the brain coincides with and responds sensitively to development of fatigue. Tryptophan is highly bioactive, with brain concentrations of 50 to 200 times that of serotonin. The tryptophan-kynurenic acid-synergy hypothesis posits that central fatigue is not monocausal but a synergistic effect between tryptophan itself and its catabolite kynurenic acid. Central fatigue is associated with mental health problems and is a cause of inattention, thereby warranting scrutiny for its relationship with ADHD. Fatigability in ADHD is mediated by tryptophan, in which abnormal enhancement of the tryptophan-kynurenine-kynurenic acid pathway causes an imbalance in monoamine nervous system function. Notably, noradrenergic neuronal dysfunction is associated with the characteristic inattention of ADHD. Neutral amino acids such as branched-chain amino acids (BCAAs) can assist recovery from attentional and cognitive decline caused by central fatigue. Since they are transported by the same L-amino acid transporter as tryptophan, BCAAs compete with tryptophan to inhibit its brain uptake. Controlling central fatigue this way may improve attentional cognitive performance.

The effect of elevated muscle pain on neuromuscular fatigue during exercise.

PURPOSE: Muscle pain can impair exercise performance but the mechanisms for this are unknown. This study examined the effects of muscle pain on neuromuscular fatigue during an endurance task. METHODS: On separate visits, twelve participants completed an isometric time-to-task failure (TTF) exercise of the right knee extensors at ~ 20% of maximum force following an intramuscular injection of isotonic saline (CTRL) or hypertonic saline (HYP) into the vastus lateralis. Measures of neuromuscular fatigue were taken before, during and after the TTF using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation. RESULTS: The mean pain intensity was 57 ± 10 in HYP compared to 38 ± 18 in CTRL (P < 0.001). TTF was reduced in HYP (4.36 ± 0.88 min) compared to CTRL (5.20 ± 0.39 min) (P = 0.003). Maximum voluntary force was 12% lower at minute 1 (P = 0.003) and 11% lower at minute 2 in HYP (P = 0.013) compared to CTRL. Voluntary activation was 4% lower at minute 1 in HYP compared to CTRL (P = 0.006) but not at any other time point (all P > 0.05). The TMS silent period was 9% longer at 100 s during the TTF in HYP compared to CTRL (P = 0.026). CONCLUSION: Muscle pain reduces exercise performance through the excacerbation of neuromuscular fatigue that is central in origin. This appears to be from inhibitory feedback from group III/IV nociceptors which acts to reduce central motor output.

Effects of induced local ischemia during a 4-km cycling time trial on neuromuscular fatigue development.

The present study analyzed the effects of local ischemia during endurance exercise on neuromuscular fatigue (NMF). Nine cyclists performed, in a counterbalanced order, two separate 4-km cycling time trials (TT) with (ISCH) or without (CONTR) induced local ischemia. NMF was characterized by using isometric maximal voluntary contractions (IMVC), whereas central [voluntary activation (VA)] and peripheral fatigue [peak torque of potentiated twitch (TwPt)] of knee extensors were evaluated using electrically evoked contractions performed before (PRE) and 1 min after (POST) the TT. Electromyographic activity (EMG), power output (PO), oxygen uptake (V̇o2), and rating of perceived exertion (RPE) were also recorded. The decrease in IMVC (-15 ± 9% vs. -10 ± 8%, P = 0.66), VA (-4 ± 3% vs. -3 ± 3%, P = 0.46), and TwPt (-16 ± 7% vs. -19 ± 14%, P = 0.67) was similar in ISCH and CONTR. Endurance performance was drastically reduced in ISCH condition (512 ± 29 s) compared with CONTR (386 ± 17 s) (P < 0.001), which was accompanied by lower EMG, PO, and V̇o2 responses (all P < 0.05). RPE was greater in ISCH compared with CONTR (P < 0.05), but the rate of change was similar throughout the TT (8.19 ± 2.59 vs. 7.81 ± 2.01 RPE.% of total time-1, P > 0.05). These results indicate that similar end-exercise NMF levels were accompanied by impaired endurance performance in ISCH compared with CONTR. These novel findings suggest that the local reduced oxygen availability affected the afferent feedback signals to the central nervous system, ultimately increasing perceived effort and reducing muscle activity and exercise intensity to avoid surpassing a sensory tolerance limit before the finish line.

Central fatigue aetiology in prolonged trail running races.

NEW FINDINGS: What is the central question of this study? Are spinal and/or supraspinal perturbations implicated in central fatigue induced in the plantar flexor muscles following prolonged trail running races? What is the main finding and its importance? The study confirmed the presence of central fatigue following various trail running distances from 40 to 170 km. The reduction in the V-wave in conjunction with the lack of change in the H-reflex suggests that a major component of this central fatigue may arise from supraspinal mechanisms in the plantar flexor muscles. ABSTRACT: Trail running races are known to induce considerable impairments in neuromuscular function of which central mechanisms are a substantial component. However, the loci of this central fatigue (i.e. supraspinal and/or spinal) is not well identified. The aim of this study was to better understand central fatigue aetiology induced in the plantar flexor muscles by various trail running distances from 40 to 170 km. Eighteen runners participated in the study and neuromuscular function of their plantar flexors was tested before (PRE) and after (POST) various races during the Ultra-Trail du Mont Blanc. Neuromuscular function was evaluated with voluntary and evoked contractions using electrical tibial nerve stimulation. H-reflex and V-wave responses were also measured during submaximal and maximal voluntary contraction, respectively. Reductions in maximal voluntary contraction torque (-29%; P < 0.001) and voluntary activation level (-12%; P < 0.001) were observed after trail running races. The V-wave was reduced in soleus (-35%; P = 0.003) and gastrocnemius medialis (-28%; P = 0.031), with no changes for the H-reflex in soleus (P = 0.577). The present study confirmed the presence of central fatigue following trail running exercise. The reduction in the V-wave in conjunction with the lack of change in the H-reflex suggests that a major component of this central fatigue may arise from supraspinal mechanisms.

Central and peripheral muscle fatigue following repeated-sprint running in moderate and severe hypoxia.

NEW FINDINGS: What is the central question of this study? Increasing severity of arterial hypoxaemia induces a shift towards greater central, relative to peripheral, mechanisms of fatigue during exhaustive exercise. Does a similar pattern exist for 'all-out' repeated-sprint running? What is the main finding and its importance? Severe normobaric hypoxia [fraction of inspired oxygen ( FI,O2 ) = 0.13] did not induce a greater contribution from central fatigue, but indices of muscle fatigue were elevated compared with normoxia ( FI,O2  = 0.21) and moderate hypoxia ( FI,O2  = 0.17). This suggests a different fatigue response to repeated-sprint running versus other exercise modalities and, consequently, that task specificity might modulate the effect of hypoxia on the central versus peripheral contribution to fatigue. ABSTRACT: We examined the effects of increasing hypoxia severity on repeated-sprint running performance and neuromuscular fatigue. Thirteen active males completed eight sprints of 5 s (recovery = 25 s) on a motorized sprint treadmill in normoxia (sea level, SL; FI,O2  = 0.21), in moderate hypoxia (MH; FI,O2  = 0.17) and in severe hypoxia (SH; FI,O2  = 0.13). After 6 min of passive recovery, in all conditions a second set of four sprints of 5 s was conducted in normoxia. Neuromuscular function of the knee extensors was assessed at baseline (Pre-) and 1 min after set 1 (Post-set 1) and set 2 (Post-set 2). In set 1, the mean distance covered in SL (22.9 ± 1.2 m) was not different to MH (22.7 ± 1.3 m; P = 0.71) but was greater than in SH (22.3 ± 1.3 m; P = 0.04). No significant differences between conditions for mean distance occurred in set 2. There was a decrease in maximal voluntary contraction torque (Δ = -31.4 ± 18.0 N m, P < 0.001) and voluntary activation (%VA; Δ = -7.1 ± 5.1%, P = 0.001) from Pre- to Post-set 1, but there was no effect of hypoxia. No further change from Post-set 1 to Post-set 2 occurred for either maximal voluntary contraction or %VA. The decrease in potentiated twitch torque in SL (Δ = -13.3 ± 5.2 N m) was not different to MH (Δ = -13.3 ± 6.3 N m) but was lower than in SH (Δ = -16.1 ± 4 N m) from Pre- to Post-set 1 (interaction, P < 0.003). Increasing severity of normobaric hypoxia, up to an equivalent elevation of 3600 m, can increase indices of peripheral fatigue but does not impact central fatigue after 'all-out' repeated-sprint running.

Brain function during central fatigue induced by intermittent high-intensity cycling.

BACKGROUND: The central governor model putatively explains the mechanism of endurance exercise-induced central fatigue, however high-intensity exercise-induced central fatigue strategies have not been investigated yet. This study aimed to examine how central fatigue affects neural response alterations, as measured by electroencephalographic (EEG) recordings, in intermittent high-intensity cycling. METHODS: Neural responses were assessed by measuring the alteration of brainwaves based on spectral energy band estimates during an intermittent, high-intensity, 60-min exercise bout on a cycle ergometer. The cycle ergometer incline was changed every 10 min in an intermittent pattern (10-20-5-20-5-10°). EEG was used to analyze altering brain function. Heart rate (HR), blood lactate (BL), and rating of perceived exertion (RPE) were measured after the participants completed each change in incline. RESULTS: The results showed that HR, BL, and RPE increased at an incline of 20° in comparison to a 5° incline. The spectral power of EEG was significantly increased (P Ë‚ 0.01) in the alpha and beta frequency ranges with a change in inclines between 5 and 20°. The spectral power of the EEG was significantly increased (P Ë‚ 0.01) over the whole frequency range from rest (theta + 251%, alpha + 165%, beta + 145%). CONCLUSION: Higher, relative intensities (10 and 20°) increased brain function, regardless of fatigue occurrence. HIIT (high-intensity interval training) led to an alteration in the neural response. Further work investigating the usefulness of HIIT to improve brain function is warranted.

Fatigue development and perceived response during self-paced endurance exercise: state-of-the-art review.

Performance in self-paced endurance exercises results from continuous fatigue symptom management. While it is suggested that perceived responses and neuromuscular fatigue development may determine variations in exercise intensity, it is uncertain how these fatigue components interact throughout the task. To address the fatigue development in self-paced endurance exercises, the following topics were addressed in the present review: (1) fatigue development during constant-load vs. self-paced endurance exercises; (2) central and peripheral fatigue and perceived exertion interconnections throughout the self-paced endurance exercises; and (3) future directions and recommendations. Based on the available literature, it is suggested (1) the work rate variations during a self-paced endurance exercise result in transitions between exercise intensity domains, directly impacting the end-exercise central and peripheral fatigue level when compared to constant-load exercise mode; (2) central and peripheral fatigue, as well as perceived exertion response contribute to exercise intensity regulation at the different stages of the trial. It seems that while neuromuscular fatigue development might be relevant at beginning of the trial, the perceived exertion might interfere in the remaining parts to achieve maximal values only at the finish line; (3) future studies should focus on the mechanisms underpinning fatigue components interactions throughout the task and its influence on exercise intensity variations.

Neuromuscular Fatigue After Long-Duration Adventure Racing in Adolescent Athletes.

PURPOSE: To characterize the acute effects of a long-duration adventure race on knee extensor (KE) fatigue and the knee functional ratio in adolescent athletes. METHODS: Twenty trained male adolescents (aged 14-17 y) performed an adventure race of 68.5 km. Maximal voluntary isometric contraction (MVIC) KE and knee flexor torques were measured before and immediately after the race. Central and peripheral components of neuromuscular fatigue were quantified from the maximal voluntary activation level and the doublet peak torque (Tw100), respectively. The peak eccentric knee flexor torque to concentric KE torque ratio was also measured to determine functional ratio. RESULTS: The race completion time was 05:38 (00:20) hours. Significant reductions in MVICKE (-14.7%, P < .001) and MVICKF (-17.0%, P < .01) were observed after the race. Voluntary activation level decreased by 8.3% (P < .001) while Tw100 remained unchanged. Peak eccentric knee flexor torque decreased 16.0% (P < .001) while peak concentric KE torque did not change. This resulted in a significant reduction in functional ratio (-12.0%, P < .01). CONCLUSION: The adventure race induced a moderate fatigue, which was mainly explained by central factors without significant peripheral fatigue. However, particular attention should be paid to the knee muscular imbalance incurred by the race, which could increase the risk of ligament injury in adolescent athletes.

High-volume intermittent maximal intensity isometric exercise caused great stress, although central motor fatigue did not occur.

To establish whether very high-volume, high-intensity isometric exercise causes stress to the body and how it affects peripheral and central fatigue. Nineteen physically active healthy male subjects (21.2 ± 1.7 years; height - 1.82 ± 0.41 m, body weight - 79.9 ± 4.5 kg; body mass index - 24.3 ± 2.1 kg/m2) volunteered to participate in this study. They participated in two experiments 3-5 days apart. Each experiment comprised six series of 60-s maximum voluntary contraction (MVC) force (knee extension) achieved as rapidly as possible. This very high-volume, high-intensity exercise (HVHIE) was performed at different quadriceps muscle lengths: short (SL) and long (LL). The MVC and the electrically stimulated contractile properties of the muscle were measured prior to HVHIE, immediately after and 3 min after each series, and at 3, 10, and 30 min after the end of HVHIE. We found that HVHIE caused high levels of stress (cortisol levels approximately doubled, heart rate and the root mean square successive difference of interval (RMSSD) decreased by about 75%); lactate increased to 8-11 mmol/L, voluntary and 100 Hz stimulation-induced force (recorded immediately after HVHIE) decreased by 55% at LL and 40% at SL. However, the central activation ratio during MVC did not change after either exercise. Isometric HVHIE performed using one leg caused high levels of stress (RMSSD decreased, cortisol increased after HVHIE equally at SL and LL; La increased more while exercising at LL) and the voluntary and electrostimulation-induced muscle force significantly decreased, but muscle central activation during MVC did not decrease.

Effects of pre-induced fatigue vs. concurrent pain on exercise tolerance, neuromuscular performance and corticospinal responses of locomotor muscles.

KEY POINTS: Fatigue and muscle pain induced in a remote muscle group has been shown to alter neuromuscular performance in exercising muscles. Inhibitory neural feedback associated with activation of mechano- and metabo-sensitive muscle afferents has been implicated in this phenomenon. The present study aimed to quantify and compare the effects of pre-induced fatigue and concurrent rising pain (evoked by muscle ischaemia) on the contralateral leg exercise capacity, neuromuscular performance, and corticomotor excitability and inhibition of knee extensor muscles. Pre-induced fatigue in one leg had a greater detrimental effect than the concurrent rising pain on the contralateral limb cycling capacity. Furthermore, pre-induced fatigue, but not concurrent rising pain, reduced corticospinal inhibition recorded from tested contralateral muscles. Regardless of the origin or mechanisms modulating sensory afferents during single-leg cycling exercise (i.e. pre-induced fatigue vs. concurrent rising pain), the limit of exercise tolerance remained the same and exercise was terminated upon achievement of a sensory tolerance limit. ABSTRACT: Individuals often need to maintain voluntary contractions during high intensity exercise in the presence of fatigue and pain. This investigation examined the effects of pre-induced fatigue and concurrent rising pain (evoked by muscle ischaemia) in one leg on motor fatigability and corticospinal excitability/inhibition of the contralateral limb. Twelve healthy males undertook four experimental protocols including unilateral cycling to task failure at 80% of peak power output with: (i) the right-leg (RL); (ii) the left-leg (LL); (iii) RL immediately preceded by LL protocol (FAT-RL); and (iv) RL when blood flow was occluded in the contralateral (left) leg (PAIN-RL). Participants performed maximal and submaximal 5 s right-leg knee extensions during which transcranial magnetic and femoral nerve electrical stimuli were delivered to elicit motor-evoked and compound muscle action potentials, respectively. The pre-induced fatigue reduced the right leg cycling time-to-task failure (mean ± SD; 332 ± 137 s) to a greater extent than concurrent pain (460 ± 158 s), compared to RL (580 ± 226 s) (P < 0.001). The maximum voluntary contraction force declined less following FAT-RL (P < 0.019) and PAIN-RL (P < 0.032) compared to RL. Voluntary activation declined and the corticospinal excitability recorded from knee extensors increased similarly after the three conditions (P < 0.05). However, the pre-induced fatigue, but not concurrent pain, reduced corticospinal inhibition compared to RL (P < 0.05). These findings suggest that regardless of the origin and/or mechanisms modulating sensory afferent feedback during single-leg cycling (e.g. pre-induced fatigue vs. concurrent rising pain), the limit of exercise tolerance remains the same, suggesting that exercise will be terminated upon achievement of sensory tolerance limit.

Enhanced serotonin availability amplifies fatigue perception and modulates the TMS-induced silent period during sustained low-intensity elbow flexions.

KEY POINTS: During maximal effort contractions, intense serotonin release via the raphe-spinal pathway spills over from the somato-dendritic compartment to activate inhibitory 5-HT1A receptors on the axon initial segment of motoneurons to reduce motoneuronal output. We investigated whether the same mechanism of central fatigue is present for low-intensity contractions, whereby weak serotonergic drive over an extended period may cause accumulation of serotonin and exacerbate central fatigue. Enhanced availability of serotonin did not directly influence motor pathways or motor performance during prolonged submaximal contraction. However, perceptions of muscle fatigue were greater, and the fatigue-induced lengthening of the silent period elicited via motor cortical stimulation was reduced with enhanced availability of serotonin. We propose that sustained low-intensity serotonergic neurotransmission influences supraspinal processes associated with fatigue, without directly influencing the output of the motor system during submaximal exercise. ABSTRACT: Enhanced availability of serotonin (5-HT) exacerbates central fatigue that occurs during maximal effort contractions. However, it is unknown if 5-HT release contributes to central fatigue during prolonged submaximal contractions. Hence, we assessed the effect that enhanced availability of 5-HT has on sustained low-intensity fatiguing contractions. Fifteen individuals (22.3 ± 2.1 years) ingested the 5-HT reuptake inhibitor paroxetine in a human, double-blinded, placebo-controlled, repeated-measures design. Participants performed a low-intensity isometric elbow flexion for 30 min (15% of maximal voluntary contraction, MVC). Throughout the protocol, brief MVCs were performed and muscle responses to transcranial magnetic stimulation (TMS) of the motor cortex, electrical stimulation of the brachial plexus, and motor point stimulation of the biceps were obtained. Ratings of perceived fatigue were also acquired. Paroxetine did not influence torque or voluntary activation during brief MVCs performed throughout the low-intensity contraction. However, paroxetine increased the perception of fatigue throughout the contraction (P = 0.005), and shortened the biceps silent period elicited via TMS during sustained submaximal contraction (P = 0.003) and brief MVCs (P = 0.011). Overall, it appears that prolonged low-intensity contractions do not cause intense 5-HT release onto motoneurons, and therefore, 5-HT does not activate inhibitory extra-synaptic 5-HT1A receptors of motoneurons to reduce their output. Although motor performance was unaffected by paroxetine, perceived fatigue was greater and intracortical inhibitory activity was reduced following the enhancement of endogenous concentrations of 5-HT during sustained submaximal contraction. Thus, 5-HT affects supraspinal processes during low-intensity contractions without directly altering motor pathways projecting to the muscle.

Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans.

Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence. Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated. Here, we have assessed the effect of an experimental immune challenge (administration of lipopolysaccharide, LPS) on the development of both fatigue and sleepiness, and the associations between increases in cytokine concentrations, fatigue and sleepiness, in healthy volunteers. In addition, because chronic-low grade inflammation may represent a risk factor for fatigue, we tested whether higher baseline levels of inflammation result in a more pronounced development of cytokine-induced fatigue and sleepiness. Data from four experimental studies was combined, giving a total of 120 subjects (LPS N = 79, 18 (23%) women; Placebo N = 69, 12 (17%) women). Administration of LPS resulted in a stronger increase in fatigue and sleepiness compared to the placebo condition, and the development of both fatigue and sleepiness closely paralleled the cytokine responses. Individuals with stronger increases in cytokine concentrations after LPS administration also suffered more from fatigue and sleepiness (N = 75), independent of gender. However, there was no support for the hypothesis that higher baseline inflammatory markers moderated the responses in fatigue or sleepiness after an inflammatory challenge. The results demonstrate a tight connection between the acute inflammatory response and development of both fatigue and sleepiness, and motivates further investigation of the involvement of inflammation in the pathophysiology of central fatigue.

Effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise.

NEW FINDINGS: What is the central question of the study? What are the effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise? What is the main finding and its importance? In a non-fatigued state, caffeine decreased the duration of the silent period evoked by transcranial magnetic stimulation. Caffeine-induced reduction of inhibitory mechanisms in the central nervous system before exercise was associated with an increased performance. Individuals who benefit from caffeine ingestion may experience lower perception of effort during exercise and an accelerated recovery of M-wave amplitude postfatigue. This study elucidates the mechanisms of action of caffeine and demonstrates that inter-individual variability of its effects on neuromuscular function is a fruitful area for further work. ABSTRACT: Caffeine enhances exercise performance, but its mechanisms of action remain unclear. In this study, we investigated its effects on neuromuscular function in a non-fatigued state and during fatiguing exercise. Eighteen men participated in this randomized, double-blind, placebo-controlled crossover trial. Baseline measures included plantarflexion force, drop jump, squat jump, voluntary activation of triceps surae muscle, soleus muscle contractile properties, M-wave, α-motoneuron excitability (H-reflex), corticospinal excitability, short-interval intracortical inhibition, intracortical facilitation, silent period evoked by transcranial magnetic stimulation (SP) and plasma potassium and caffeine concentrations. Immediately after baseline testing, participants ingested caffeine (6 mg·kg-1 ) or placebo. After a 1-h rest, baseline measures were repeated, followed by a fatiguing stretch-shortening cycle exercise (sets of 40 bilateral rebound jumps on a sledge apparatus) until task failure. Neuromuscular testing was carried out throughout the fatigue protocol and afterwards. Caffeine enhanced drop jump height (by 4.2%) and decreased the SP (by 12.6%) in a non-fatigued state. A caffeine-related decrease in SP and short-interval intracortical inhibition before the fatiguing activity was associated with an increased time to task failure. The participants who benefitted from an improved performance on the caffeine day reported a significantly lower sense of effort during exercise and had an accelerated postexercise recovery of M-wave amplitude. Caffeine modulates inhibitory mechanisms of the CNS, recovery of M-wave amplitude and perception of effort. This study lays the groundwork for future examinations of differences in caffeine-induced neuromuscular changes between those who are deemed to benefit from caffeine ingestion and those who are not.