The Role of the Nervous System in Neuromuscular Fatigue Induced by Ultra-Endurance Exercise

Ultra-endurance events are not a recent development but they have only become very popular in the last two decades, particularly ultra-marathons run on trails. The present paper reviews the role of the central nervous system (CNS) in neuromuscular fatigue induced by ultra-endurance exercise. Large decreases in voluntary activation are systematically found in ultra-endurance running but are attenuated in ultra-endurance cycling for comparable intensity and duration. This indirectly suggests that afferent feedback, rather than neurobiological changes within the CNS, is determinant in the amount of central fatigue produced. Whether this is due to inhibition from type III and IV afferent fibres induced by inflammation, disfacilitation of Ia afferent fibers due to repeated muscle stretching or other mechanisms still needs to be determined. Sleep deprivation per se does not seem to play a significant role in central fatigue although it still affects performance by elevating ratings of perceived exertion. The kinetics of central fatigue and recovery, the influence of muscle group (knee extensors vs plantar flexors) on central deficit as well as the limitations related to studies on central fatigue in ultra-endurance exercise are also discussed in the present article. To date, no study has quantified the contribution of spinal modulations to central fatigue in ultra-endurance events. Future investigations utilizing spinal stimulation (i.e. thoracic stimulation) must be conducted to assess the role of changes in motoneuronal excitability on the observed central fatigue. Recovery after ultra-endurance events and the effect of sex on neuromuscular fatigue must also be studied further

Utilisation de la stimulation magnétique transcrânienne dans l'évaluation de la fonction motrice : aspects méthodologiques et application à l'exercice extrême

Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. TMS is now being used in the investigation of fatigue to help partition the effects of central fatigue. Few studies have utilized this technique to evaluate the effects of locomotor exercise and none in conditions of extreme exercise. Therefore, the purpose of this thesis was twofold; first, to answer methodological questions pertaining to the use of TMS in fatigue evaluation, particularly of the quadriceps, and second, to investigate the effects of extreme exercise conditions on the development of central and supraspinal fatigue and corticospinal excitability and inhibition. In Studies 1 and 2, the effect of approaching a target force in different ways before the delivery a TMS pulse and the difference between commonly-employed methods of determining TMS intensity on the selection of optimal TMS intensity were investigated. In Study 3, the effect of one night sleep deprivation on cognitive and exercise performance and central parameters was investigated. The effect of a 110-km ultra-trail on the supraspinal component of central fatigue was evaluated in Study 4. The principal findings from this thesis are that during TMS evaluation during brief voluntary contractions, it is essential to deliver the TMS pulse once the force has stabilized at the target and that a stimulus-response curve at 20% MVC is appropriate for determining optimal TMS intensity in exercise and fatigue studies. Furthermore, while sleep deprivation negatively-impacted cognitive and exercise performance, it did not influence neuromuscular parameters nor result in greater central fatigue. Supraspinal fatigue develops and corticospinal excitability increases during endurance/ultra-endurance running and cycling, while the effects on inhibitory corticospinal mechanisms are equivocal and probably depend on exercise characteristics and TMS intensityLa stimulation magnétique transcrânienne (TMS) est une technique d'investigation classiquement utilisée dans l'évaluation du cortex moteur. La TMS est utilisée dans l'étude de la fatigue afin de distinguer sa composante centrale. Peu d'études ont utilisé cette technique pour évaluer les effets de l'exercice locomoteur et aucune dans des conditions extrêmes. Ainsi, l'objectif de cette thèse était double: d'abord, répondre à certaines questions méthodologiques concernant l'utilisation de la TMS dans l'évaluation de la fatigue, en particulier du muscle quadriceps, et deuxièmement, étudier les effets de l'exercice en conditions extrêmes sur le développement de la fatigue centrale et supraspinal ainsi que sur l’excitabilité et l'inhibition corticospinales. Dans les Etudes 1 et 2, l'effet de différentes approches d'une force cible avant l’application d'une impulsion TMS ainsi que les différences entre les principales méthodes utilisées pour déterminer l'intensité optimale de TMS ont été étudiés. Dans l'Etude 3, l'effet d'une nuit de privation de sommeil sur les performances cognitives et physiques et les paramètres centraux a été étudié. L'effet d'un ultra-trail de 110 km sur la composante supraspinale de la fatigue centrale a été évalué dans l'Etude 4. Les conclusions principales de cette thèse sont, sur le plan méthodologique, i) que lors de l'évaluation par TMS pendant de brèves contractions volontaires, il est essentiel d’appliquer l'impulsion de TMS après que la force produite par le sujet se soit stabilisée à la valeur cible et ii) qu'une courbe stimulus-réponse à 20% de la force maximale volontaire est appropriée pour déterminer l'intensité de TMS optimale dans les études portant sur l'exercice et la fatigue. De plus, bien que la privation de sommeil ait des impacts négatifs sur les performances cognitives et à l'exercice, elle n'a pas d'influence sur des paramètres neuromusculaires ni ne provoque une plus grande fatigue centrale. Une fatigue supraspinale se développe et l’excitabilité corticospinale augmente au cours d’exercices d'endurance/ultra-endurance en course à pied et ne vélo, tandis que les effets sur les mécanismes inhibiteurs corticospinaux sont équivoques et probablement dépendent des caractéristiques de l'exercice et de l'intensité de la TM

Resting and active motor thresholds versus stimulus–response curves to determine transcranial magnetic stimulation intensity in quadriceps femoris

Background: Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. Recently, there has been a surge in TMS studies evaluating lower-limb fatigue. TMS intensity of 120-130% resting motor threshold (RMT) and 120% active motor threshold (AMT) and TMS intensity determined using stimulus-response curves during muscular contraction have been used in these studies. With the expansion of fatigue research in locomotion, the quadriceps femoris is increasingly of interest. It is important to select a stimulus intensity appropriate to evaluate the variables, including voluntary activation, being measured in this functionally important muscle group. This study assessed whether selected quadriceps TMS stimulus intensity determined by frequently employed methods is similar between methods and muscles.Methods: Stimulus intensity in vastus lateralis, rectus femoris and vastus medialis muscles was determined by RMT, AMT (i.e. during brief voluntary contractions at 10% maximal voluntary force, MVC) and maximal motor-evoked potential (MEP) amplitude from stimulus-response curves during brief voluntary contractions at 10, 20 and 50% MVC at different stimulus intensities.Results: Stimulus intensity determined from a 10% MVC stimulus-response curve and at 120 and 130% RMT was higher than stimulus intensity at 120% AMT (lowest) and from a 50% MVC stimulus-response curve (p 0.05).Conclusions: Similar optimal stimulus intensity and maximal MEP amplitudes at 20 and 50% MVC and the minimal risk of residual fatigue at 20% MVC suggest that a 20% MVC stimulus-response curve is appropriate for determining TMS stimulus intensity in the quadriceps femoris. The higher selected stimulus intensities at 120-130% RMT have the potential to cause increased coactivation and discomfort and the lower stimulus intensity at 120% AMT may underestimate evoked responses. One muscle may also act as a surrogate in determining optimal quadriceps femoris stimulation intensity

Effect of exercise before and/or during taxane-containing chemotherapy treatment on chemotherapy-induced peripheral neuropathy symptoms in women with breast cancer: systematic review and meta-analysis

Purpose To systematically review and meta-analyse the efficacy of exercise interventions delivered before and/or during taxane-containing chemotherapy regimens on chemotherapy-induced peripheral neuropathy (CIPN), fatigue, and health-related quality of life (HR-QoL), in women with breast cancer.Methods Seven electronic databases were systematically searched for randomised controlled trials (RCTs) reporting on the effects of exercise interventions in women with breast cancer receiving taxane-containing chemotherapeutic treatment. Meta-analyses evaluated the effects of exercise on CIPN symptoms, fatigue, and HR-QoL.Results Ten trials involving exercise interventions ranging between 2 and 12 months were included. The combined results of four RCTs consisting of 171 participants showed a reduction in CIPN symptoms following exercise compared with usual care (standardised mean difference − 0.71, 95% CI − 1.24 to − 0.17, p = 0.012; moderate-quality evidence, I2 = 76.9%). Pooled results from six RCTs with 609 participants showed that exercise interventions before and/or during taxane-containing chemotherapy regimens improved HR-QoL (SMD 0.42, 95% CI 0.07 to 0.76, p = 0.03; moderate-quality evidence, I2 = 49.6%). There was no evidence of an effect of exercise on fatigue (− 0.39, 95% CI − 0.95 to 0.18, p = 0.15; very low-quality evidence, I2 = 90.1%).Conclusions This systematic review found reduced levels of CIPN symptoms and an improvement in HR-QoL in women with breast cancer who exercised before and/or during taxane-based chemotherapy versus usual care controls.Implications for Cancer Survivors This evidence supports the role of exercise as an adjunctive treatment for attenuating the adverse effects of taxane-containing chemotherapy on CIPN symptoms and HR-QoL

Utilisation de la stimulation magnétique transcrânienne dans l'évaluation de la fonction motrice (aspects méthodologiques et application à l'exercice extrême)

La stimulation magnétique transcrânienne (TMS) est une technique d'investigation classiquement utilisée dans l'évaluation du cortex moteur. La TMS est utilisée dans l'étude de la fatigue afin de distinguer sa composante centrale. Peu d'études ont utilisé cette technique pour évaluer les effets de l'exercice locomoteur et aucune dans des conditions extrêmes. Ainsi, l'objectif de cette thèse était double: d'abord, répondre à certaines questions méthodologiques concernant l'utilisation de la TMS dans l'évaluation de la fatigue, en particulier du muscle quadriceps, et deuxièmement, étudier les effets de l'exercice en conditions extrêmes sur le développement de la fatigue centrale et supraspinal ainsi que sur l excitabilité et l'inhibition corticospinales. Dans les Etudes 1 et 2, l'effet de différentes approches d'une force cible avant l application d'une impulsion TMS ainsi que les différences entre les principales méthodes utilisées pour déterminer l'intensité optimale de TMS ont été étudiés. Dans l'Etude 3, l'effet d'une nuit de privation de sommeil sur les performances cognitives et physiques et les paramètres centraux a été étudié. L'effet d'un ultra-trail de 110 km sur la composante supraspinale de la fatigue centrale a été évalué dans l'Etude 4. Les conclusions principales de cette thèse sont, sur le plan méthodologique, i) que lors de l'évaluation par TMS pendant de brèves contractions volontaires, il est essentiel d appliquer l'impulsion de TMS après que la force produite par le sujet se soit stabilisée à la valeur cible et ii) qu'une courbe stimulus-réponse à 20% de la force maximale volontaire est appropriée pour déterminer l'intensité de TMS optimale dans les études portant sur l'exercice et la fatigue. De plus, bien que la privation de sommeil ait des impacts négatifs sur les performances cognitives et à l'exercice, elle n'a pas d'influence sur des paramètres neuromusculaires ni ne provoque une plus grande fatigue centrale. Une fatigue supraspinale se développe et l excitabilité corticospinale augmente au cours d exercices d'endurance/ultra-endurance en course à pied et ne vélo, tandis que les effets sur les mécanismes inhibiteurs corticospinaux sont équivoques et probablement dépendent des caractéristiques de l'exercice et de l'intensité de la TMSTranscranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. TMS is now being used in the investigation of fatigue to help partition the effects of central fatigue. Few studies have utilized this technique to evaluate the effects of locomotor exercise and none in conditions of extreme exercise. Therefore, the purpose of this thesis was twofold; first, to answer methodological questions pertaining to the use of TMS in fatigue evaluation, particularly of the quadriceps, and second, to investigate the effects of extreme exercise conditions on the development of central and supraspinal fatigue and corticospinal excitability and inhibition. In Studies 1 and 2, the effect of approaching a target force in different ways before the delivery a TMS pulse and the difference between commonly-employed methods of determining TMS intensity on the selection of optimal TMS intensity were investigated. In Study 3, the effect of one night sleep deprivation on cognitive and exercise performance and central parameters was investigated. The effect of a 110-km ultra-trail on the supraspinal component of central fatigue was evaluated in Study 4. The principal findings from this thesis are that during TMS evaluation during brief voluntary contractions, it is essential to deliver the TMS pulse once the force has stabilized at the target and that a stimulus-response curve at 20% MVC is appropriate for determining optimal TMS intensity in exercise and fatigue studies. Furthermore, while sleep deprivation negatively-impacted cognitive and exercise performance, it did not influence neuromuscular parameters nor result in greater central fatigue. Supraspinal fatigue develops and corticospinal excitability increases during endurance/ultra-endurance running and cycling, while the effects on inhibitory corticospinal mechanisms are equivocal and probably depend on exercise characteristics and TMS intensityST ETIENNE-Bib. électronique (422189901) / SudocSudocFranceF

Use of transcranial magnetic stimulation to assess relaxation rates in unfatigued and fatigued knee-extensor muscles

We examined whether transcranial magnetic stimulation (TMS) delivered to the motor cortex 13 allows assessment of muscle relaxation rates in unfatigued and fatigued knee extensors (KE). 14 We assessed the ability of this technique to measure time course of fatigue-induced changes 15 in muscle relaxation rate and compared relaxation rate from resting twitches evoked by 16 femoral nerve stimulation. Twelve healthy men performed maximal voluntary isometric 17 contractions (MVC) twice before (PRE) and once at the end of a 2-min KE MVC and five 18 more times within 8 min during recovery. Relative (intraclass correlation coefficient; ICC2,1) 19 and absolute (repeatability coefficient) reliability and variability (coefficient of variation) 20 were assessed. Time course of fatigue-induced changes in muscle relaxation rate was tested 21 with generalized estimating equations. In unfatigued KE, peak relaxation rate coefficient of 22 variation and repeatability coefficient were similar for both techniques. Mean (95% CI) 23 ICC2,1 for peak relaxation rates were [0.933 (0.724-0.982)] and [0.889 (0.603-0.968)] for 24 TMS and femoral nerve stimulation, respectively. TMS-induced normalized muscle 25 relaxation rate was -11.5 ± 2.5 s-1 at PRE, decreased to -6.9 ± 1.2 s-1 (-37 ± 17%, P < 0.001), 26 and recovered by 2 min post-exercise. Normalized peak relaxation rate for resting twitch did 27 not show a fatigue-induced change. During fatiguing KE exercise, the change in muscle 28 relaxation rate as determined by the two techniques was different. TMS provides reliable 29 values of muscle relaxation rates. Furthermore, it is sufficiently sensitive and more 30 appropriate than the resting twitch evoked by femoral nerve stimulation to reveal fatigue-31 induced changes in KE

Spinal contribution to neuromuscular recovery differs between elbow-flexor and knee-extensor muscles after a maximal sustained fatiguing task

Data from studies of elbow-flexor (EF) or knee-extensor (KE) muscles suggest that a fatigue-related decrease in motoneuron excitability only occurs in EF. It is unknown how motoneuron excitability changes after sustained fatiguing maximal voluntary isometric contractions (MVICs) in EF and KE in the same participants. In two sessions, eight healthy men performed a 2-min MVIC of EF or KE to induce fatigue with brief MVICs before and six times after the 2-min MVIC. Electromyographic responses elicited by corticospinal tract stimulation at the transmastoid [cervicomedullary motor-evoked potential (CMEP)] or thoracic [thoracic motor-evoked potential (TMEP)] level were recorded from EF and KE, respectively. To account for muscle excitability, CMEPs and TMEPs were normalized to maximal M-wave (Mmax) elicited by peripheral nerve stimulation during each brief MVIC. Immediately after the 2-min MVIC, biceps brachii and brachioradialis CMEP/Mmax were 88% (SD 11%) (P = 0.026) and 87% (SD 12%) (P = 0.029) of pre-MVIC values, respectively, and remained lower than PRE after 5 s of recovery [91% (SD 8%), P = 0.036 and 87% (SD 13%), P = 0.046, respectively]. No subsequent time points differed from PRE (all P ³ 0.253). TMEP/Mmax for rectus femoris and vastus lateralis were not different from PRE at any time during the recovery period (all P > 0.050). A different recovery pattern in motoneuron excitability occurred in EF as it recovered by 60 s whereas KE motoneurons were unaffected by the fatiguing task. The present findings may contribute to better understand muscle-specific neurophysiological differences in spinal excitability

Effect of the Fatigue Induced by a 110-km Ultramarathon on Tibial Impact Acceleration and Lower Leg Kinematics

Ultramarathon runners are exposed to a high number of impact shocks and to severe neuromuscular fatigue. Runners may manage mechanical stress and muscle fatigue by changing their running kinematics. Our purposes were to study (i) the effects of a 110-km mountain ultramarathon (MUM) on tibial shock acceleration and lower limb kinematics, and (ii) whether kinematic changes are modulated according to the severity of neuromuscular fatigue. Twenty-three runners participated in the study. Pre- and post-MUM, neuromuscular tests were performed to assess knee extensor (KE) and plantar flexor (PF) central and peripheral fatigue, and a treadmill running bouts was completed during which step frequency, peak acceleration, median frequency and impact frequency content were measured from tibial acceleration, as well as foot-to-treadmill, tibia-to-treadmill, and ankle flexion angles at initial contact, and ankle range of motion using video analysis. Large neuromuscular fatigue, including peripheral changes and deficits in voluntary activation, was observed in KE and PF. MVC decrements of ~35% for KE and of ~28% for PF were noted. Among biomechanical variables, step frequency increased by ~2.7% and the ankle range of motion decreased by ~4.1% post-MUM. Runners adopting a non rearfoot strike pre-MUM adopted a less plantarflexed foot strike pattern post-MUM while those adopting a rearfoot strike pre-MUM tended to adopt a less dorsiflexed foot strike pattern post-MUM. Positive correlations were observed between percent changes in peripheral PF fatigue and the ankle range of motion. Peripheral PF fatigue was also significantly correlated to both percent changes in step frequency and the ankle angle at contact. This study suggests that in a fatigued state, ultratrail runners use compensatory/protective adjustments leading to a flatter foot landing and this is done in a fatigue dose-dependent manner. This strategy may aim at minimizing the overall load applied to the musculoskeletal system, including impact shock and muscle stretch

Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy

Background: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-based exercise training program on fitness, muscle, and motor function in FSHD patients. Methods: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n = 8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35 minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO 2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention. Results: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO 2 peak (+19%, P = 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P = 0.008) and 46% (P = 0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG. Conclusions: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated. With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2–1.8); p = 3×10−4). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics. In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance