Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.

Eccentric Exercise-Induced Muscle Damage Reduces Gross Efficiency.

INTRODUCTION: The effect of eccentric exercise-induced muscle damage (EIMD) on cycling efficiency is unknown. The aim of the present study was to assess the effect of EIMD on gross and delta efficiency and the cardiopulmonary responses to cycle ergometry. METHODS: Twenty-one recreational athletes performed cycling at 70%, 90% and 110% of the gas exchange threshold (GET) under control conditions (Control) and 24 h following an eccentric damaging protocol (Damage). Knee extensor isometric maximal voluntary contraction (MVC), potentiated twitch (Qtw,pot) and voluntary activation (VA) were assessed before Control and Damage. Gross and delta efficiency were assessed using indirect calorimetry, and cardiopulmonary responses were measured at each power output. Electromyography root-mean-square (EMGRMS) during cycling was also determined. RESULTS: MVC was 25 ± 18% lower for Damage than Control (p < 0.001). Gross efficiency was lower for Damage than Control (p < 0.001) by 0.55 ± 0.79%, 0.59 ± 0.73% and 0.60 ± 0.87% for 70%, 90% and 110% GET, respectively. Delta efficiency was unchanged between conditions (p = 0.513). Concurrently, cycling EMGRMS was higher for Damage than Control (p = 0.004). An intensity-dependent increase in breath frequency and V̇E/V̇CO2 was found, which were higher for Damage only at 110% GET (p ≤ 0.019). CONCLUSIONS: Thus, gross efficiency is reduced following EIMD. The concurrently higher EMGRMS suggests that increases in muscle activation in the presence of EIMD might have contributed to reduced gross efficiency. The lack of change in delta efficiency might relate to its poor reliability hindering the ability to detect change. The findings also show that EIMD-associated hyperventilation is dependent on exercise intensity, which might relate to increases in central command with EIMD.

Reliability of Corticospinal and Motoneuronal Excitability Evaluation During Unfatiguing and Fatiguing Cycling Exercise.

INTRODUCTION: Central nervous system excitability depends on the task performed, muscle group solicited, and contraction type. However, little is known on corticospinal and motoneuronal excitability measured during locomotor exercise. This study aimed at determining the reliability of motor-evoked potentials (MEP) and thoracic motor-evoked potentials (TMEP) in dynamic mode during unfatiguing and fatiguing cycling exercise. METHODS: Twenty-two participants completed four visits. Visit 1 comprised familiarization and a maximal incremental test to determine maximal power output (Wmax). The remaining visits encompassed unfatiguing evaluations, which included 8 brief bouts of moderate (50% Wmax) and high intensity cycling (80% Wmax). In each bout, a set of two TMEPs, five MEPs and one M-max were obtained. Subsequently, a fatiguing exercise to exhaustion at 80% Wmax was performed, with four sets of measurements 3 min through the exercise and 4 additional sets at exhaustion, both measured at 50% Wmax. RESULTS: Intraclass correlation coefficients (ICCs) for 5, 10, 15 and 20 MEP·Mmax-1 revealed excellent reliability at both intensities and during fatiguing exercise (ICC ≥ 0.92). TMEP·Mmax-1 showed ICCs ≥0.82 for moderate and high intensity, and it was not affected by fatigability. Overall standard error of measurement was 0.090 [0.083, 0.097] for MEP·Mmax-1 and 0.114 [0.105, 0.125] for TMEP·Mmax-1. A systematic bias associated to the number of stimulations, especially at high intensity, suggested the evaluation itself may be influenced by fatigability. A mean reduction of 8% was detected in TMEP·Mmax-1 at exhaustion. CONCLUSIONS: Motoneuronal and corticospinal excitability measured in dynamic mode presented good to excellent reliability in unfatiguing and fatiguing exercise. Further studies inducing greater fatigability must be conducted to assess the sensitivity of central nervous system excitability during cycling.

Motor unit discharge rate modulation during isometric contractions to failure is intensity- and modality-dependent.

The physiological mechanisms determining the progressive decline in the maximal muscle torque production capacity during isometric contractions to task failure are known to depend on task demands. Task-specificity of the associated adjustments in motor unit discharge rate (MUDR), however, remains unclear. This study examined MUDR adjustments during different submaximal isometric knee extension tasks to failure. Participants performed a sustained and an intermittent task at 20% and 50% of maximal voluntary torque (MVT), respectively (Experiment 1). High-density surface EMG signals were recorded from vastus lateralis (VL) and medialis (VM) and decomposed into individual MU discharge timings, with the identified MUs tracked from recruitment to task failure. MUDR was quantified and normalised to intervals of 10% of contraction time (CT). MUDR of both muscles exhibited distinct modulation patterns in each task. During the 20% MVT sustained task, MUDR decreased until ∼50% CT, after which it gradually returned to baseline. Conversely, during the 50% MVT intermittent task, MUDR remained stable until ∼40-50% CT, after which it started to continually increase until task failure. To explore the effect of contraction intensity on the observed patterns, VL and VM MUDR was quantified during sustained contractions at 30% and 50% MVT (Experiment 2). During the 30% MVT sustained task, MUDR remained stable until ∼80-90% CT in both muscles, after which it continually increased until task failure. During the 50% MVT sustained task the increase in MUDR occurred earlier, after ∼70-80% CT. Our results suggest that adjustments in MUDR during submaximal isometric contractions to failure are contraction modality- and intensity-dependent. KEY POINTS: During prolonged muscle contractions a constant motor output can be maintained by recruitment of additional motor units and adjustments in their discharge rate. Whilst contraction-induced decrements in neuromuscular function are known to depend on task demands, task-specificity of motor unit discharge behaviour adjustments is still unclear. In this study, we tracked and compared discharge activity of several concurrently active motor units in the vastii muscles during different submaximal isometric knee extension tasks to failure, including intermittent vs. sustained contraction modalities performed in the same intensity domain (Experiment 1), and two sustained contractions performed at different intensities (Experiment 2). During each task, motor units modulated their discharge rate in a distinct, biphasic manner, with the modulation pattern depending on contraction intensity and modality. These results provide insight into motoneuronal adjustments during contraction tasks posing different demands on the neuromuscular system.

Exacerbated impairments in neuromuscular function when two bouts of team sport match simulations are separated by 48 h.

Intermittent team sports, involving high metabolic and mechanical demands, elicit prolonged impairments in neuromuscular function which persist for ∼48-72 h. Whether impairments in neuromuscular function are exacerbated when such exercise is repeated with incomplete recovery is unknown. This study assessed the neuromuscular, heart rate and metabolic responses to two bouts of ∼90 min modified team sport match simulations separated by 48 h in 12 competitive football players. Before and 2 min after both bouts, knee extensor isometric maximal voluntary contraction (MVC), contractile function (Qtw,pot ) and voluntary activation (VA) were measured. Heart rate (HR), sprint time, blood lactate and glucose were measured throughout both bouts. MVC was reduced relative to baseline at post-bout 1 (21 ± 12%; P = 0.003) and pre-bout 2 (14 ± 11%; P = 0.009), and was lower post-bout 2 (33 ± 14%; P < 0.001) relative to post-bout 1 (P = 0.036). Qtw,pot was reduced post-bout 1 (30 ± 11%; P < 0.001) and pre-bout 2 (9 ± 6%; P = 0.004), and was not different post-bout 2 (28 ± 8%; P < 0.001) relative to post-bout 1 (P = 0.872). VA was reduced post-bout 1 (8 ± 7%; P = 0.023), recovered pre-bout 2 (P = 0.133) and was lower post-bout 2 (16 ± 7%; P < 0.001) relative to post-bout 1 (P = 0.029). Total sprint time was longer, and HR, blood lactate and glucose were lower during bout 2 than bout 1 (P ≤ 0.021). Thus, impairments in neuromuscular function are exacerbated when high-intensity intermittent exercise is performed with incomplete recovery concurrent with accentuated reductions in VA. The lower blood lactate and glucose during the second bout might be due, at least in part, to reduced glycogen availability upon commencing exercise and consequently a greater reliance on glucose extraction. NEW FINDINGS: What is the central question of this study? There is limited evidence on whether impairments in neuromuscular function are exacerbated when prolonged high-intensity intermittent exercise is repeated with incomplete recovery: what are the neuromuscular consequences of performing two bouts of a modified team sport match simulations separated by 48 h? What is the main finding and its importance? Impairments in knee extensor force generating capacity are exacerbated concurrent with accentuated reductions in nervous system activation of muscle when prolonged high-intensity intermittent exercise is repeated with 48 h recovery.

A Comprehensive Evaluation of Multiple Sclerosis-Related Fatigue with a Special Focus on Fatigability.

INTRODUCTION: Fatigue is the most common and disabling symptom in multiple sclerosis (MS), being reported by 55% to 78% of patients with MS (PwMS). Etiology of MS-related fatigue remains poorly understood, but an increased neuromuscular fatigability (i.e., greater loss of torque during exercise) could contribute to this phenomenon. This study aimed to characterize the correlates of MS-related fatigue in PwMS using a comprehensive group of physiological and psychosocial measures, with a particular focus on fatigability. METHODS: Forty-two relapsing-remitting PwMS and 20 healthy subjects were recruited. PwMS were assigned in two groups (high (HF) and low (LF) fatigue) based on two fatigue questionnaires (Fatigue Severity Scale and Modified Fatigue Impact Scale). The main outcomes of this study are derived from incremental cycling completed to task failure (i.e., inability to pedal around 60 rpm). Maximal voluntary contraction (MVC), rating of perceived exertion, and central and peripheral parameters measured using transcranial magnetic and peripheral nerve stimulation were assessed in the knee extensor muscles before, during, and after the fatiguing task. Other potential correlates of fatigue were also tested. RESULTS: MVC torque decreased to a greater extent for the HF group than LF group after the third common stage of the incremental fatiguing exercise (-15.7% ± 6.6% vs -5.9% ± 13.0%, P < 0.05), and this occurred concurrently with a higher rating of perceived exertion for HF (11.8 ± 2.5 vs 9.3 ± 2.6, P < 0.05). Subjective parameters (depression, quality of life) were worse for HF compared with LF and healthy subjects ( P < 0.001). Moreover, MVC torque loss at the final common stage and maximal heart rate explained 29% of the variance of the Modified Fatigue Impact Scale. CONCLUSIONS: These results provide novel insight into the relationship between MS-related fatigue and fatigability among PwMS. The HF group exhibited greater performance fatigability, likely contributing to a higher perceived exertion than the LF group when measured during a dynamic task.

Acute effects of conventional versus wide-pulse neuromuscular electrical stimulation on quadriceps evoked torque and neuromuscular function.

PURPOSE: The effectiveness of a neuromuscular electrical stimulation (NMES) program is proportional to the level of evoked torque, which can be achieved with either conventional or wide-pulse stimulations. The aim of this study was to compare evoked torque, objective fatigability, and related peripheral and central alterations, as well as changes in central nervous system (CNS) excitability induced by an acute session of conventional versus wide-pulse NMES. METHODS: Seventeen young men underwent three 20-min NMES sessions: conventional (0.2 ms/50 Hz), wide-pulse at 50 Hz (1 ms/50 Hz), and wide-pulse at 100 Hz (1 ms/100 Hz). Neuromuscular measurements (i.e., maximal voluntary contraction, voluntary activation, evoked responses to femoral nerve stimulation, and CNS excitability) were performed on the right quadriceps femoris muscle before and after each NMES session. CNS excitability was measured using transcranial magnetic, thoracic, and transcutaneous spinal cord stimulations. RESULTS: The level of evoked torque was not significantly different between conventional and wide-pulse protocols applied at the maximal tolerable current intensity. All NMES protocols induced objective fatigability (~14% decrease in maximal voluntary contraction torque, p < 0.001) associated with peripheral (decrease in doublet torque and potentiated M-wave amplitude, p = 0.002 and p < 0.001, respectively) but not central (unchanged voluntary activation, p = 0.79) alterations. However, these acute changes did not differ between NMES protocols and none of the NMES protocols modified markers of CNS excitability. CONCLUSION: These results may allow to conjecture that chronic effects and treatment effectiveness could be comparable between conventional and wide-pulse NMES.

Changes in Cost of Locomotion Are Higher after Endurance Cycling Than Running When Matched for Intensity and Duration.

INTRODUCTION: Cost of locomotion (C L ) has been shown to increase after endurance running and cycling bouts. The main purpose of this study was to compare, in the same participants, the effect of both modalities on C L when matched for relative intensity and duration. METHODS: Seventeen recreational athletes performed two incremental tests in running and cycling to determine the first ventilatory threshold then two 3-h bouts of exercise at 105% of threshold, with gas exchange measurements taken for 10 min at the start, middle and end of the 3 h to calculate C L . Neuromuscular fatigue during isometric knee extensor contractions and force-velocity profile on a cycle ergometer were assessed before and immediately after the 3-h trials. RESULTS: C L significantly increased at mid (+3.7%, P = 0.006) and end (+7.4%, P < 0.001) of exercise for cycling compared with start, whereas it did not change with time for running. Cardio-respiratory and metabolic variables changed similarly for cycling and running, therefore not explaining the time-course differences in C L between modalities. Changes in C L during cycling correlated significantly with loss of maximal force extrapolated from the force-velocity profile ( r = 0.637, P = 0.006) and changes in cadence ( r = 0.784, P < 0.001). CONCLUSIONS: The type of locomotion influences the effects of exercise on energy cost because 3 h of exercise at the same relative intensity caused a significant increase of cycling C L , and no changes in running C L . The changes in C L in cycling are likely due, at least in part, to fatigue in the locomotor muscles.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Power Output Manipulation from Below to Above the Gas Exchange Threshold Results in Exacerbated Performance Fatigability.

INTRODUCTION: Performance fatigability is substantially greater when exercising in the severe- versus heavy-intensity domain. However, the relevance of the boundary between moderate- and heavy-intensity exercise, the gas exchange threshold (GET), to performance fatigability is unclear. This study compared alterations in neuromuscular function during work-matched exercise above and below the GET. METHODS: Seventeen male participants completed work-matched cycling for 90, 110, and 140 min at 110%, 90%, and 70% of the GET, respectively. Knee extensor isometric maximal voluntary contraction (MVC), high-frequency doublets (Db100), low- to high-frequency doublet ratio (Db10:100), and voluntary activation were measured at baseline, 25%, 50%, 75%, and 100% of task completion. During the initial baseline visit and after each constant work rate bout, ramp-incremental exercise was performed, and peak power output and oxygen uptake (V̇O 2peak ) were determined. RESULTS: After the 70% and 90% GET trials, similar reductions in MVC (-14% ± 6% and -14% ± 8%, respectively, P = 0.175) and Db100 (-7% ± 9% and -6% ± 9%, respectively, P = 0.431) were observed. However, for a given amount of work completed, reductions in MVC (-25% ± 15%, P = 0.008) and Db100 (-12% ± 8%, P = 0.029) were up to 2.6-fold greater during the 110% than the 90% GET trial. Peak power output and V̇O 2peak during ramp-incremental exercise were reduced by 7.0% ± 11.3% and 6.5% ± 9.3%, respectively, after the 110% GET trial relative to the baseline ramp ( P ≤ 0.015), with no changes after the moderate-intensity trials ( P ≥ 0.078). CONCLUSIONS: The lack of difference in fatigability between the trials at 70% and 90% GET, coupled with the greater fatigability at 110% relative to 90% GET, shows that exceeding the moderate- to heavy-intensity boundary has implications for performance fatigability, while also impairing maximal exercise performance capacity.

Mechanisms of Neuromuscular Fatigability in People with Cancer-Related Fatigue.

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 posttreatment CRF have greater neuromuscular fatigability. The aim of this secondary analysis was to examine the etiology of neuromuscular fatigability in people with posttreatment CRF. METHODS: Ninety-six people who had completed cancer treatment were dichotomized into two groups (fatigued and nonfatigued) based on a clinical cut point for fatigue. Alterations in neuromuscular function (maximal voluntary contraction peak force, voluntary activation, potentiated twitch force, and 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 maximal voluntary contraction peak force and potentiated twitch force 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). EMG 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 neuromuscular fatigability in people with CRF were primarily due to disturbances at the level of the muscle rather than the central nervous system. This could affect the ability to tolerate daily physical activities.

Disparate Mechanisms of Fatigability in Response to Prolonged Running versus Cycling of Matched Intensity and Duration.

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 exercise. 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 preexercise, midexercise, and postexercise, 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 (TMEP). RESULTS: After exercise, MVC was similarly reduced by ~25% after both running and cycling. However, reductions in VA were greater after running (-16% ± 10%) than cycling (-10% ± 5%; P < 0.05). Similarly, reductions in TMEP were greater after running (-78% ± 24%) than cycling (-15% ± 60%; P = 0.01). In contrast, reductions in Db100 (running vs cycling, -6% ± 21% vs -13% ± 6%) and Db10:100 (running vs cycling, -6% ± 16% vs -19% ± 13%) were greater for cycling than running (P ≤ 0.04). CONCLUSIONS: Despite similar decrements in the knee extensor MVC after 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, whereas 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 after these two exercise modalities.

Physiological and psychosocial correlates of cancer-related fatigue.

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.

Effect of race distance on performance fatigability in male trail and ultra-trail runners.

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 ≤ .003). KE twitch torque decreased more in LONG (-28 ± 14%) than SHORT (-14 ± 10%, p = .005); however, KE MVC time × distance interaction was not significant (p = .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 ≥ .637). TMS-elicited silent period decreased in LONG (p = .021) but not SHORT (p = .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.

Sex Differences in Neuromuscular Fatigue and Changes in Cost of Running after Mountain Trail Races of Various Distances.

INTRODUCTION: Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). METHODS: Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (<60 and >100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. RESULTS: Compared with men, women displayed a smaller decrease in maximal strength in KE (-36% vs -27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: -10% vs -24%, respectively, P < 0.05). Cr increased similarly in men and women. CONCLUSIONS: Women experience less neuromuscular fatigue than men after both "classic" and "extreme" prolonged running exercises but this does not impact the degradation of the energy Cr.

French Translation and Validation of the Rating-of-Fatigue Scale.

BACKGROUND: The Rating of Fatigue (ROF) scale can measure changes in perceived fatigue in a variety of contexts. OBJECTIVE: The aim of the present study was to translate and subsequently validate the ROF scale in the French language. METHODS: The study was composed of three phases. Phase 1 involved a comprehensive translation, back-translation, and consolidation process in order to produce the French ROF scale. During phase 2, the face validity of the French ROF scale was assessed. A cohort of 60 native French speaking participants responded to a range of Likert scale items which probed the purposes of the ROF scale and what it is intended to measure. During phase 3, the convergent and divergent validity of the ROF scale was assessed during ramped cycling to exhaustion and 10 min of resting recovery. RESULTS: The results from phase 1 demonstrated comparability and interpretability between the original and back-translated ROF scale. In phase 2, participants reported a high face validity, with a score of 3.48 ± 0.70 out of 4 when given the item probing whether the scale "measures fatigue". This score further improved (3.67 ± 0.57, P = 0.01) after participants read the accompanying instructions. Participants were able to distinguish the purposes of the scale for measuring fatigue rather than exertion. In phase 3, strong correlations were found between ROF and heart rate (HR) both during exercise (r = 0.91, P < 0.01) and recovery (r = 0.92, P < 0.01), while discriminant validity between ROF and rating of perceived exertion (RPE) was found during recovery. CONCLUSION: The present study permits the applications of the ROF scale in the French language.

Reductions in motoneuron excitability during sustained isometric contractions are dependent on stimulus and contraction intensity.

Cervicomedullary stimulation provides a means of assessing motoneuron excitability. Previous studies demonstrated that during low-intensity sustained contractions, small cervicomedullary evoked potentials (CMEPs) conditioned using transcranial magnetic stimulation (TMS-CMEPs) are reduced, whereas large TMS-CMEPs are less affected. As small TMS-CMEPs recruit motoneurons most active during low-intensity contractions whereas large TMS-CMEPs recruit a high proportion of motoneurons inactive during the task, these results suggest that reductions in motoneuron excitability could be dependent on repetitive activation. To further test this hypothesis, this study assessed changes in small and large TMS-CMEPs across low- and high-intensity contractions. Twelve participants performed a sustained isometric contraction of the elbow flexor for 4.5 min at the electromyography (EMG) level associated with 20% maximal voluntary contraction force (MVC; low intensity) and 70% MVC (high intensity). Small and large TMS-CMEPs with amplitudes of ∼15% and ∼50% Mmax at baseline, respectively, were delivered every minute throughout the tasks. Recovery measures were taken at 1-, 2.5- and 4-min postexercise. During the low-intensity trial, small TMS-CMEPs were reduced at 2-4 min (P ≤ 0.049) by up to -10% Mmax, whereas large TMS-CMEPs remained unchanged (P ≥ 0.16). During the high-intensity trial, small and large TMS-CMEPs were reduced at all time points (P < 0.01) by up to -14% and -33% Mmax, respectively, and remained below baseline during all recovery measures (P ≤ 0.02). TMS-CMEPs were unchanged relative to baseline during recovery following the low-intensity trial (P ≥ 0.24). These results provide novel insight into motoneuron excitability during and following sustained contractions at different intensities and suggest that contraction-induced reductions in motoneuron excitability depend on repetitive activation.NEW & NOTEWORTHY This study measured motoneuron excitability using cervicomedullary evoked potentials conditioned using transcranial magnetic stimulation (TMS-CMEPs) of both small and large amplitudes during sustained low- and high-intensity contractions of the elbow flexors. During the low-intensity task, only the small TMS-CMEP was reduced. During the high-intensity task, both small and large TMS-CMEPs were substantially reduced. These results indicate that repetitively active motoneurons are specifically reduced in excitability compared with less active motoneurons in the same pool.

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.

Relationship between intensive care unit-acquired weakness, fatigability and fatigue: What role for the central nervous system?

PURPOSE: To provide a comprehensive review of studies that have investigated fatigue in intensive care unit (ICU) survivors and questions the potential link between intensive care unit-acquired weakness (ICUAW), fatigability and fatigue. We also question whether the central nervous system (CNS) may be the link between these entities. MATERIAL AND METHODS: A narrative review of the literature that investigated fatigue in ICU survivors and review of clinical trials enabling understanding of CNS alterations in response to ICU stays. RESULTS: Fatigue is a pervasive and debilitating symptom in ICU survivors that can interfere with rehabilitation. Due to the complex pathophysiology of fatigue, more work is required to understand the roles of ICUAW and/or fatigability in fatigue to provide a more holistic understanding of this symptom. While muscle alterations have been well documented in ICU survivors, we believe that CNS alterations developing early during the ICU stay may play a role in fatigue. CONCLUSIONS: Fatigue should be considered and treated in ICU survivors. The causes of fatigue are likely to be specific to the individual. Understanding the role that ICUAW and fatigability may have in fatigue would allow to tailor individual treatment to prevent this persistent symptom and improve quality of life.

The knowns and unknowns of neural adaptations to resistance training.

The initial increases in force production with resistance training are thought to be primarily underpinned by neural adaptations. This notion is firmly supported by evidence displaying motor unit adaptations following resistance training; however, the precise locus of neural adaptation remains elusive. The purpose of this review is to clarify and critically discuss the literature concerning the site(s) of putative neural adaptations to short-term resistance training. The proliferation of studies employing non-invasive stimulation techniques to investigate evoked responses have yielded variable results, but generally support the notion that resistance training alters intracortical inhibition. Nevertheless, methodological inconsistencies and the limitations of techniques, e.g. limited relation to behavioural outcomes and the inability to measure volitional muscle activity, preclude firm conclusions. Much of the literature has focused on the corticospinal tract; however, preliminary research in non-human primates suggests reticulospinal tract is a potential substrate for neural adaptations to resistance training, though human data is lacking due to methodological constraints. Recent advances in technology have provided substantial evidence of adaptations within a large motor unit population following resistance training. However, their activity represents the transformation of afferent and efferent inputs, making it challenging to establish the source of adaptation. Whilst much has been learned about the nature of neural adaptations to resistance training, the puzzle remains to be solved. Additional analyses of motoneuron firing during different training regimes or coupling with other methodologies (e.g., electroencephalography) may facilitate the estimation of the site(s) of neural adaptations to resistance training in the future.