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Time Course of Performance Fatigability during Exercise below, at, and above the Critical Intensity in Females and Males
Authors : Rafael de Almeida Azevedo, Jonas Forot, Danilo Iannetta, Saied Jalal Aboodarda, Guillaume Y Millet, Juan M Murias
Published: May 2022 – Med Sci Sports Exerc.


Purpose: to investigate the time course and amplitude of performance fatigability during cycling at intensities around the maximal lactate steady state (MLSS) until task failure (TTF).

Methods: 10 females and 11 males were evaluated in 8 visits: 1) ramp incremental test; 2-3) 30-min constant power output (PO) cycling for MLSS determination; 4-8) cycling to TTF at PO relative to the MLSS of (i) -15%; (ii) -10 W; (iii) at MLSS; and (iv) +10 W; (v) +15%. Performance fatigability was characterized by femoral nerve electrical stimulation of knee extensors at baseline, min 5, 10, 20, 30, and TTF. Oxygen uptake, blood lactate concentration, muscle oxygen saturation, and perceived exertion were evaluated.

Results: ~75% of the total performance fatigability occurred within 5 min of exercise, independently of exercise intensity, followed by a further change at min 30. Contractile function declined more in males than females (all p < 0.05). At task failure, exercise duration declined from MLSS-15% to MLSS+15% (all p < 0.05), accompanied by greater rate of decline following MLSS+15% and MLSS+10 compared to MLSS, MLSS-10 and MLSS-15% for voluntary activation (-0.005 and -0.003 vs -0.002, -0.001 and -0.001 %·min-1, respectively) and contractile function (potentiated single twitch force, -0.013 and -0.009 vs -0.006, -0.004 and -0.004 %·min-1, respectively).

Conclusions: whereas the time course of performance fatigability responses was similar regardless of exercise intensity and sex, the total amplitude and rate of change were affected by the distinct metabolic disturbances around the MLSS, leading to different performance fatigability aetiologies at task failure.

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Mechanisms of Neuromuscular Fatigability in People with Cancer-related Fatigue
Authors : Callum G Brownstein, Rosemary Twomey, John Temesi, Mary E Medysky, S Nicole Culos-Reed, Guillaume Y Millet
Published: Apr 2022 – Med Sci Sports Exerc.


Introduction: Cancer-related fatigue (CRF) is a debilitating symptom that affects around one-third of people for months or years after cancer treatment. In a recent study, we found that people with post-treatment CRF have greater performance fatigability. The aim of this secondary analysis was to examine the aetiology of performance fatigability in people with post-treatment CRF.

Methods: Ninety-six people who had completed cancer treatment were dichotomized into two groups (fatigued and non-fatigued) based on a clinical cut-point for fatigue. Alterations in neuromuscular function (maximal voluntary contraction peak force, MVC; voluntary activation, VA; potentiated twitch force, Qtw,pot; electromyography, EMG) in the knee extensors were assessed across three common stages of an incremental cycling test. Power outputs during the fatigability test were expressed relative to gas exchange thresholds to assess relative exercise intensity.

Results: The fatigued group had a more pronounced reduction in MVC peak force and Qtw,pot throughout the common stages of the incremental cycling test (main effect of group: p < 0.001, ηp2 = 0.18 and p = 0.029, ηp2 = 0.06, respectively). Electromyography was higher during cycling in the fatigued group (main effect of group: p = 0.022, ηp2 = 0.07). Although the relative intensity of cycling was higher in the fatigued group at the final common stage of cycling, this was not the case during the initial two stages, despite the greater impairments in neuromuscular function.

Conclusions: Our results suggest that the rapid impairments in performance fatigability in people with CRF was primarily due to disturbances at the level of the muscle, rather than the central nervous system. This could impact the ability to tolerate daily physical activities.

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Prevalence of self-reported fatigue in intensive care unit survivors 6 months-5 years after discharge
Authors : Jérôme Morel, Pascal Infantino, Laurent Gergelé, Thomas Lapole, Robin Souron, Guillaume Y Millet
Published: Apr 2022 – Sci Rep


Prolonged stays in intensive care units (ICU) are responsible for long-lasting consequences, fatigue being one of the more debilitating. Yet, fatigue prevalence for patients that have experienced ICU stays remains poorly investigated. This study aimed to evaluate fatigue prevalence and the level of physical activity in ICU survivors from 6 months to 5 years after ICU discharge using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) and Godin questionnaires, respectively. Data from 351 ICU survivors (out of 1583 contacted) showed that 199 (57%) and 152 (43%) were considered as fatigued and non-fatigued, respectively. The median FACIT-F scores for fatigued versus non-fatigued ICU survivors were 21 (14-27) and 45 (41-48), respectively (p < 0.001). Time from discharge had no significant effect on fatigue prevalence (p = 0.30) and fatigued ICU survivors are less active (p < 0.001). In multivariate analysis, the only risk factor of being fatigued that was identified was being female. We reported a high prevalence of fatigue among ICU survivors. Sex was the only independent risk factor of being fatigued, with females being more prone to this symptom. Further studies should consider experimental approaches that help us understand the objective causes of fatigue, and to build targeted fatigue management interventions.

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The repeated bout effect influences lower-extremity biomechanics during a 30-min downhill run
Authors : Arash Khassetarash, Michael Baggaley, Gianluca Vernillo, Guillaume Y Millet, W Brent Edwards
Published: Feb 2022 – Eur J Sport Sci.


The repeated bout effect in eccentric-biased exercises is a well-known phenomenon, wherein a second bout of exercise results in attenuated strength loss and soreness compared to the first bout. We sought to determine if the repeated bout effect influences changes in lower-extremity biomechanics over the course of a 30-min downhill run. Eleven male participants completed two bouts of 30-min downhill running (DR1 and DR2) at 2.8 m.s-1 and -11.3° on an instrumented treadmill. Three-dimensional kinematics and ground reaction forces were recorded and used to quantify changes in spatiotemporal parameters, external work, leg stiffness, and lower extremity joint-quasi-stiffness throughout the 30-min run. Maximum voluntary isometric contraction (MVIC) and perceived quadriceps pain were assessed before-after, and throughout the run, respectively. DR2 resulted in attenuated loss of MVIC (= 0.004), and perceived quadriceps pain (< 0.001) compared to DR1. In general, participants ran with an increased duty factor towards the end of each running bout; however, increases in duty factor during DR2 (+5.4%) were less than during DR1 (+8.8%, < 0.035). Significant reductions in leg stiffness (-11.7%, = 0.002) and joint quasi-stiffness (up to -25.4%, all < 0.001) were observed during DR1 but not during DR2. Furthermore, DR2 was associated with less energy absorption and energy generation than DR1 (< 0.004). To summarize, the repeated bout effect significantly influenced lower-extremity biomechanics over the course of a downhill run. Although the mechanism(s) underlying these observations remain(s) speculative, strength loss and/or perceived muscle pain are likely to play a key role.

Highlights A 30-min downhill running bout increased contact time and reduced flight time transitioning to an increased duty factor.Lower-extremity stiffness also decreased and mechanical energy absorption increased over the course of the first 30-min downhill running bout.When the same bout of 30-min downhill running was performed three weeks later, the observed changes to lower extremity biomechanics were significantly attenuated.The findings from this study demonstrated, for this first time, a repeated bout effect for lower extremity biomechanics associated with downhill running.

Keywords: 3D analysis; Biomechanics; exercise.

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Performance Determinants in Trail-Running Races of Different Distances
Authors : Frederic Sabater Pastor, Thibault Besson, Giorgio Varesco, Audrey Parent, Marie Fanget, Jérôme Koral, Clément Foschia, Thomas Rupp, Diana Rimaud, Léonard Féasson, Guillaume Y Millet
Published: June 2022 – Int J Sports Physiol Perform.


Purpose: While the physiological determinants of road running have been widely studied, there is a lack of research in trail-running racing performance. The aim of our study was to determine the physiological predictors of trail-running performance in races of different distances in similar terrain and weather conditions.

Methods: Seventy-five trail runners participating in one of the races of the Ultra-Trail du Mont-Blanc were recruited. Previous to the race, each runner was evaluated with (1) an incremental treadmill test to determine maximal oxygen uptake, ventilatory thresholds, cost of running, and substrate utilization; (2) a power-force-velocity profile on a cycle ergometer; (3) maximal voluntary contractions of the knee extensors and plantar flexors; and (4) anthropometric characteristics. Neuromuscular fatigue was evaluated after the races. Twenty-four runners finished a SHORT (<55 km), 16 finished a MEDIUM (101 km), and 14 finished a LONG (>145 km) race. Correlations and multiple linear regressions were used to find the determinants of performance in each race distance.

Results: Performance in SHORT was explained by maximal oxygen uptake and lipid utilization at 10 km/h (r2 = .825, P < .001). Performance in MEDIUM was determined by maximal oxygen uptake, maximal isometric strength, and body fat percentage (r2 = .917, P < .001). A linear model could not be applied in LONG, but performance was correlated to peak velocity during the incremental test.

Conclusions: Performance in trail running is mainly predicted by aerobic capacity, while lipid utilization also influences performance in races <60 km and performance in approximately 100 km is influenced by muscle strength and body composition.

Keywords: off-road running; performance predictors; prolonged exercise; ultramarathon.

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Disparate Mechanisms of Fatigability in Response to Prolonged Running versus Cycling of Matched Intensity and Duration
Authors : Callum G Brownstein, Mélanie Metra, Frederic Sabater Pastor, Robin Faricier, Guillaume Y Millet
Published: Jan 2022 – Med Sci Sports Exerc.


Introduction: Running and cycling represent two of the most common forms of endurance exercise. However, a direct comparison of the neuromuscular consequences of these two modalities after prolonged exercise has never been made. The aim of this study was to compare the alterations in neuromuscular function induced by matched intensity and duration cycling and running exercises.

Methods: During separate visits, 17 endurance-trained male participants performed 3 h of cycling and running at 105% of the gas exchange threshold. Neuromuscular assessments were taken are pre-, mid- and post-exercise, including knee extensor maximal voluntary contractions (MVC), voluntary activation (VA), high- and low-frequency doublets (Db100 and Db10, respectively), potentiated twitches (Qtw,pot), motor evoked potentials (MEP) and thoracic motor evoked potentials (TMEPs).

Results: Following exercise, MVC was similarly reduced by ~25% following both running and cycling. However, reductions in VA were greater following running (-16 ± 10%) than cycling (-10 ± 5%; p < 0.05). Similarly, reductions in TMEP were greater following running (-78 ± 24%) than cycling (15 ± 60%; p = 0.01). In contrast, reductions in Db100 (running: -6 ± 21% vs. cycling: -13 ± 6%) and Db10:100 (running: -6 ± 16% vs. cycling: -19 ± 13%) were greater for cycling than running (p ≤ 0.04).

Conclusions: Despite similar decrements in the knee extensor MVC following running and cycling, the mechanisms responsible for force loss differed. Running-based endurance exercise is associated with greater impairments in nervous system function, particularly at the spinal level, while cycling-based exercise elicits greater impairments in contractile function. Differences in the mechanical and metabolic demands imposed on the quadriceps could explain the disparate mechanisms of neuromuscular impairment following these two exercise modalities.

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Effect of ground technicity on cardio-respiratory and biomechanical parameters in uphill trail running
Authors : François Nicot, Frederic Sabater-Pastor, Pierre Samozino, Guillaume Y Millet, Thomas Rupp.
Published: Oct 2021 – Eur J Sport Sci.


The goal of this study was to analyze the effects of ground technicity on cardio-respiratory and biomechanical responses during uphill running. Ten experienced male trail-runners ran ∼ 10.5 min at racing pace on two trails with different (high and low) a priori technicity levels. These two runs were replicated (same slope, velocity, and distance) indoor on a motor-driven treadmill. Oxygen uptake, minute ventilation (VE), heart rate as well as step frequency and medio-lateral feet accelerations (i.e. objective indices of uneven terrain running patterns adjustments) were continuously measured throughout all sessions. Rating of perceived exertion (RPE) and perceived technicity were assessed at the end of each bout. Oxygen cost of running (O2Cr) (+10.5%; p<0.001), VE (+21%; p<0.004) and the range and variability of feet medio-lateral accelerations (+116% and +134%, respectively; p<0.001), were significantly greater when running on trail compared to treadmill, regardless of the a priori technicity level. Despite perceived technicity being lower on treadmill (p<0.001), RPE was not different between trail and treadmill runs (p < 0.68). It is concluded that running uphill on a trail vs. a treadmill significantly elevates both O2Cr and magnitude/variability of feet medio-lateral accelerations but no difference could be identified between trails of different a priori technicities. These results strengthen the need for trainers and race organizers to consider terrain technicity per se as a challenging cardio-respiratory and biomechanical component in uphill trail running.

Keywords:  Biomechanics; Efficiency; Endurance; Skill; feet accelerometry; gradient locomotion; key words: energy cost of running; rating of perceived exertion; uneven terrain.

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The effects of exercise intensity and duration on the relationship between the slow component of V̇O 2 and peripheral fatigue
Authors : Rafael de Almeida Azevedo, Daniel A Keir, Jonas Forot, Danilo Iannetta , Guillaume Y Millet, Juan M Murias
Published: Feb 2022 – Acta Physiol (Oxf)


Aim: If the development of the oxygen uptake slow component (V̇O2SC ) and muscle fatigue are related, these variables should remain coupled in a time- and intensity-dependent manner.

Methods: 16 participants (7 females) visited the laboratory on 7 separate occasions: (1) three 6-minutes moderate-intensity cycling exercise bouts proceeded by a ramp incremental test; (2-3) 30-minutes constant power output (PO) exercise bout to determine the maximal lactate steady state (MLSS); (4-7) constant-PO exercise bouts to task failure (TTF), pseudorandomized order, at (i) 15% below the PO at MLSS; (ii) 10 W below MLSS; (iii) MLSS; (iv) 10 W above MLSS (first intensity and randomized order thereafter). Neuromuscular fatigue was characterized by isometric maximal voluntary contractions and femoral nerve electrical stimulation of knee extensors to measure peripheral fatigue at baseline, at min 5, 10, 20, 30 and TTF. Pulmonary oxygen uptake (V̇O2 ) was continuously recorded during the constant-PO bouts and V̇O2SC was characterized based on each individual V̇O2 kinetics during moderate transitions.

Results: The development of V̇O2SC and peripheral fatigue were correlated across time (r2 adj range of 0.64-0.80) and amongst each exercise intensity (r2 adj range of 0.26-0.30) (all P < .001). Also, TTF was correlated with V̇O2SC and neuromuscular fatigue parameters (r2 adj range of 0.52-0.82, all P < .001).

Conclusion: The V̇O2SC and peripheral fatigue development are correlated throughout the exercise in a time- and intensity-dependent manner, suggesting that the V̇O2SC may depend on muscle fatigue even if the mechanisms of reduced contractile function are different amongst intensities.

Keywords: MLSS; cycling; exercise tolerance; fatigue; neuromuscular fatigue.

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Physiological and psychosocial correlates of cancer-related fatigue
Authors : Callum G Brownstein, Rosemary Twomey, John Temesi, James G Wrightson, Tristan Martin, Mary E Medysky, S Nicole Culos-Reed, Guillaume Y Millet.
Published: 05 October 2021 – J Cancer Surviv.


Purpose: Cancer-related fatigue (CRF) is a common and distressing symptom of cancer that may persist for years following treatment completion. However, little is known about the pathophysiology of CRF. Using a comprehensive group of gold-standard physiological and psychosocial assessments, this study aimed to identify correlates of CRF in a heterogenous group of cancer survivors.

Methods: Using a cross-sectional design to determine the physiological and psychosocial correlates of CRF, ninety-three cancer survivors (51 fatigued, 42 non-fatigued) completed assessments of performance fatigability (i.e. the decline in muscle strength during cycling), cardiopulmonary exercise testing, venous blood samples for whole blood cell count and inflammatory markers and body composition. Participants also completed questionnaires measuring demographic, treatment-related, and psychosocial variables.

Results: Performance fatigability, time-to-task-failure, peak oxygen uptake (V̇O2peak), tumor necrosis factor-α (TNF-α), body fat percentage, and lean mass index were associated with CRF severity. Performance fatigability, V̇O2peak, TNF-α, and age explained 35% of the variance in CRF severity. Those with clinically-relevant CRF reported more pain, more depressive symptoms, less perceived social support, and were less physically active than non-fatigued cancer survivors.

Conclusions: The present study utilised a comprehensive group of gold-standard physiological and psychosocial assessments and the results give potential insight into the mechanisms underpinning the association between physical inactivity, physical deconditioning and CRF.

Implications for cancer survivors: Given the associations between CRF and both physiological and psychosocial measures, this study identifies targets that can be measured by rehabilitation professionals and used to guide tailored interventions to reduce fatigue.

Keywords: Anthropometry; Cancer-related fatigue; Exercise; Fatigability; Inflammation.

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Fatigue Measured in Dynamic Versus Isometric Modes After Trail Running Races of Various Distances
Authors: Jerome Koral, Marie Fanget, Laurianne Imbert, Thibault Besson, Djahid Kennouche, Audrey Parent, Clément Foschia, Jérémy Rossi, Guillaume Y Millet
Published: 05 August 2021 – Int J Sports Physiol Perform.


Purpose: Fatigue has previously been investigated in trail running by comparing maximal isometric force before and after the race. Isometric contractions may not entirely reflect fatigue-induced changes, and therefore dynamic evaluation is warranted. The aim of the present study was to compare the magnitude of the decrement of maximal isometric force versus maximal power, force, and velocity after trail running races ranging from 40 to 170 km.

Methods: Nineteen trail runners completed races shorter than 60 km, and 21 runners completed races longer than 100 km. Isometric maximal voluntary contractions (IMVCs) of knee extensors and plantar flexors and maximal 7-second sprints on a cycle ergometer were performed before and after the event.

Results: Maximal power output (Pmax; -14% [11%], P < .001), theoretical maximum force (F0; -11% [14%], P < .001), and theoretical maximum velocity (-3% [8%], P = .037) decreased significantly after both races. All dynamic parameters but theoretical maximum velocity decreased more after races longer than 100 km than races shorter than 60 km (P < .05). Although the changes in IMVCs were significantly correlated (P < .05) with the changes in F0 and Pmax, reductions in IMVCs for knee extensors (-29% [16%], P < .001) and plantar flexors (-26% [13%], P < .001) were larger (P < .001) than the reduction in Pmax and F0.

Conclusions: After a trail running race, reductions in isometric versus dynamic forces were correlated, yet they are not interchangeable because the losses in isometric force were 2 to 3 times greater than the reductions in Pmax and F0. This study also shows that the effect of race distance on fatigue measured in isometric mode is true when measured in dynamic mode.

Keywords: dynamic exercise; isometric maximal voluntary contraction; neuromuscular fatigue assessment; power-force-velocity profile.

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Effect of race distance on performance fatigability in male trail and ultra-trail runners
Authors: John Temesi, Thibault Besson, Audrey Parent, Benjamin Singh, Vincent Martin, Callum G Brownstein, Loïc Espeit, Nicolas Royer, Diana Rimaud, Thomas Lapole, Léonard Féasson, Guillaume Y Millet.
Published: 25 June 2021 – Scand J Med Sci Sports.


The etiology of changes in lower-limb neuromuscular function, especially to the central nervous system, may be affected by exercise duration. Direct evidence is lacking as few studies have directly compared different race distances. This study aimed to investigate the etiology of deficits in neuromuscular function following short versus long trail-running races. Thirty-two male trail runners completed one of five trail-running races as LONG (>100 km) or SHORT (<60 km). Pre- and post-race, maximal voluntary contraction (MVC) torque and evoked responses to electrical nerve stimulation during MVCs and at rest were used to assess voluntary activation and muscle contractile properties of knee-extensor (KE) and plantar-flexor (PF) muscles. Transcranial magnetic stimulation (TMS) was used to assess evoked responses and corticospinal excitability in maximal and submaximal KE contractions. Race distance correlated with KE MVC (ρ = -0.556) and twitch (ρ = -0.521) torque decreases (P ≤ 0.003). KE twitch torque decreased more in LONG (-28 ± 14%) than SHORT (-14 ± 10%, P = 0.005); however, KE MVC time × distance interaction was not significant (P = 0.073). No differences between LONG and SHORT for PF MVC or twitch torque were observed. Maximal voluntary activation decreased similarly in LONG and SHORT in both muscle groups (P ≥ 0.637). TMS-elicited silent period decreased in LONG (P = 0.021) but not SHORT (P = 0.912). Greater muscle-contractile property impairment in longer races, not central perturbations, contributed to the correlation between KE MVC loss and race distance. Conversely, PF fatigability was unaffected by race distance.

Keywords: fatigue; knee extensors; plantar flexors.

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Dépasser ses limites physiques et mentales : la performance en ultra endurance à l’épreuve de la science
Journées d’Études de la Société Française de Psychologie du Sport
Date: 09 June 2021

Webconférence grand public avec l’intervention de : 

>>  Roberta Antonini Philippe, Université de Lausanne 

>> Guillaume Millet , Professeur de Physiologie de l’Exercice – Directeur du Laboratoire Interuniversitaire de Biologie de la Motricité – Coordinateur de la chaire ActiFS – Membre Senior de l’Institut Universitaire de France

Enhancing Adaptations to Neuromuscular Electrical Stimulation Training Interventions
Authors: Anthony J Blazevich, David F Collins, Guillaume Y Millet, Marco A Vaz, Nicola A Maffiuletti
Published: 8 June 2021 – Exerc Sport Sci Rev.


Neuromuscular electrical stimulation (NMES) applied to skeletal muscles is an effective rehabilitation and exercise training modality. However, the relatively low muscle force and rapid muscle fatigue induced by NMES limits the stimulus provided to the neuromuscular system, and subsequent adaptations. We hypothesise that adaptations to NMES will be enhanced by the use of specific stimulation protocols and adjuvant interventions.