Skeletal muscle fiber type and TMS-induced muscle relaxation in unfatigued and fatigued knee-extensor muscles.

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

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.

Performance fatigability and recovery after dynamic multi-joint maximal exercise in elbow flexors versus knee extensors.

Elbow flexors (EFs) and knee extensors (KEs) have shown differences in performance fatigability and recovery of neuromuscular function after isometric and isotonic single-joint fatiguing contractions. However, dynamic multi-joint movements are more representative of real-world activities. The aim of the study was to assess central and peripheral mechanisms of fatigability after either arm-cranking or cycling. Ten physically active men performed maximal incremental arm-cranking and cycling until task failure. Maximal voluntary isometric contraction (MVIC) and electrically evoked forces of both EF and KE were assessed before (PRE) and 1 (POST) and 20 (POST20) min after exercise. At POST, MVIC decreased similarly to 76 ± 8% and 81 ± 7% (both P < 0.001) of PRE for EF and KE, respectively. MVIC force remained lower than PRE at POST20 for both EF and KE (85 ± 8% vs. 95 ± 3% of PRE, P ≤ 0.033), having recovered less in EF than in KE (P = 0.003). Electrically evoked forces decreased similarly from PRE to POST in EF and KE (all P > 0.05). At POST20, the ratio of low-to-high frequency doublets was lower in EF than in KE (75 ± 13% vs. 85 ± 10% of PRE; P ≤ 0.034). Dynamic maximal incremental exercise acutely induced similar magnitudes of MVIC and evoked force loss in EF and KE. However, at POST20, impaired MVIC recovery and lower ratio of low-to-high frequency doublets in EF than in KE suggest the recovery of neuromuscular function after dynamic maximal exercises is specific to and dependent on changes within the muscles investigated.

Reliability of relaxation properties of knee-extensor muscles induced by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS)-induced relaxation rate reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. To determine the appropriateness of knee-extensor muscle relaxation measurements induced by TMS, this study aimed to establish both the within- and between-session reliability before and after a fatiguing exercise bout. Eighteen participants (9 females, 9 males, age 25 ± 2 years, height 171 ± 9 cm, body mass 68.5 ± 13.5 kg) volunteered to participate in two identical sessions approximately 30 days apart. Maximal and submaximal neuromuscular evaluations were performed with TMS six times before (PRE) and at the end (POST) of a 2-min sustained maximal voluntary isometric contraction. Within- and between-session reliability of PRE values were assessed with intraclass correlation coefficient (ICC2,1, relative reliability), repeatability coefficient (absolute reliability), and coefficient of variation (variability). Test-retest reliability of post-exercise muscle relaxation rates was assessed with Bland-Altman plots. For both the absolute and normalized peak relaxation rates and time to peak relaxation, data demonstrated low variability (e.g. coefficient of variation ≤ 7.8%) and high reliability (e.g. ICC2,1 ≥ 0.963). Bland-Altman plots showed low systematic errors. These findings establish the reliability of TMS-induced muscle relaxation rates in unfatigued and fatigued knee-extensor muscles, showing that TMS is a useful technique that researchers can use when investigating changes in muscle relaxation rates both in unfatigued and fatigued knee-extensor muscles.

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.

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.

The Relationship between Fatigue and Actigraphy-Derived Sleep and Rest-Activity Patterns in Cancer Survivors.

Cancer-related fatigue can continue long after curative cancer treatment. The aim of this study was to investigate sleep and rest-activity cycles in fatigued and non-fatigued cancer survivors. We hypothesized that sleep and rest-activity cycles would be more disturbed in people experiencing clinically-relevant fatigue, and that objective measures of sleep would be associated with the severity of fatigue in cancer survivors. Cancer survivors (n = 87) completed a 14-day wrist actigraphy measurement to estimate their sleep and rest-activity cycles. Fatigue was measured using the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F). Participants were dichotomised into two groups using a previously validated score (fatigued n = 51 and non-fatigued n = 36). The participant's perception of sleep was measured using the Insomnia Severity Index (ISI). FACIT-F score was correlated with wake after sleep onset (r = -0.28; p = 0.010), sleep efficiency (r = 0.26; p = 0.016), sleep onset latency (r = -0.31; p = 0.044) and Insomnia Severity Index (ISI) score (r = -0.56; p < 0.001). The relative amplitude of the rest-activity cycles was lower in the fatigued vs. the non-fatigued group (p = 0.017; d = 0.58). After treatment for cancer, the severity of cancer-related fatigue is correlated with specific objective measures of sleep, and there is evidence of rest-activity cycle disruption in people experiencing clinically-relevant fatigue.

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 allows assessment of muscle relaxation rates in unfatigued and fatigued knee extensors (KE). We assessed the ability of this technique to measure time course of fatigue-induced changes in muscle relaxation rate and compared relaxation rate from resting twitches evoked by femoral nerve stimulation. Twelve healthy men performed maximal voluntary isometric contractions (MVC) twice before (PRE) and once at the end of a 2-min KE MVC and five more times within 8 min during recovery. Relative (intraclass correlation coefficient; ICC2,1) and absolute (repeatability coefficient) reliability and variability (coefficient of variation) were assessed. Time course of fatigue-induced changes in muscle relaxation rate was tested with generalized estimating equations. In unfatigued KE, peak relaxation rate coefficient of variation and repeatability coefficient were similar for both techniques. Mean (95% CI) ICC2,1 for peak relaxation rates were 0.933 (0.724-0.982) and 0.889 (0.603-0.968) for TMS and femoral nerve stimulation, respectively. TMS-induced normalized muscle relaxation rate was - 11.5 ± 2.5 s-1 at PRE, decreased to - 6.9 ± 1.2 s-1 (- 37 ± 17%, P < 0.001), and recovered by 2 min post-exercise. Normalized peak relaxation rate for resting twitch did not show a fatigue-induced change. During fatiguing KE exercise, the change in muscle relaxation rate as determined by the two techniques was different. TMS provides reliable values of muscle relaxation rates. Furthermore, it is sufficiently sensitive and more appropriate than the resting twitch evoked by femoral nerve stimulation to reveal fatigue-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 (PRE) 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 ≥ 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.NEW & NOTEWORTHY By comparing the changes in motoneuron excitability in elbow-flexor and knee-extensor muscles after sustained fatiguing maximal voluntary contractions, this study shows that motoneuron recovery behavior depends on the muscle performing the exercise. A different recovery pattern in motoneuron excitability occurs in elbow flexors as it recovered by 60 s whereas knee extensors were unaffected by fatigue. This finding can help to increase understanding of the effect of a fatigue and subsequent recovery on neural processes.

Sustained Maximal Voluntary Contractions Elicit Different Neurophysiological Responses in Upper- and Lower-Limb Muscles in Men.

This study compared the effects of fatigue on corticospinal responsiveness in the upper- and lower-limb muscles of the same participants. Seven healthy males performed a 2-min maximal voluntary isometric contraction of the elbow flexors or knee extensors on four separate days. Electromyographic responses were elicited by nerve stimulation (maximal M-wave) in all sessions and by transcranial magnetic stimulation (motor-evoked potential; silent period) and spinal tract stimulation (cervicomedullary or thoracic motor-evoked potentials; silent period) in one session each per limb. During sustained maximal voluntary contractions, motor-evoked potential area normalised to M-waves increased from baseline in biceps brachii (155 ±â€¯55%) and rectus femoris (151 ±â€¯44%) (both p ≤ 0.045). At the end of maximal voluntary contractions, spinal tract motor-evoked potential area normalised to M-waves was smaller than baseline in biceps brachii (74 ±â€¯23%; p = 0.012) but not rectus femoris (108 ±â€¯40%; p = 0.999). The ratio of motor-evoked potential to spinal tract-evoked potential areas increased dramatically from 90 to 115 s in biceps brachii (p = 0.001) but not in rectus femoris (p = 0.999). Silent period durations increased similarly in both muscles (p ≤ 0.008) after transcranial and spinal stimulation. Sustained maximal contractions elicit different neurophysiological adjustments in upper- and lower-limb muscles. Specifically, motoneuronal excitability was reduced in biceps brachii, but not in rectus femoris, and this reduction required greater compensatory adjustments from the motor cortex. Therefore, changes in cortical and spinal excitability during sustained maximal exercise are likely specific to the muscle performing the task.

Neurophysiological responses and adaptation following repeated bouts of maximal lengthening contractions in young and older adults.

A bout of maximal lengthening contractions is known to produce muscle damage, but confers protection against subsequent damaging bouts, with both tending to be lower in older adults. Neural factors contribute to this adaptation, but the role of the corticospinal pathway remains unclear. Twelve young (27 ± 5 yr) and 11 older adults (66 ± 4 yr) performed two bouts of 60 maximal lengthening dorsiflexions 2 weeks apart. Neuromuscular responses were measured preexercise, immediately postexercise, and at 24 and 72 h following both bouts. The initial bout resulted in prolonged reductions in maximal voluntary torque (MVC; immediately postexercise onward, P < 0.001) and increased creatine kinase (from 24 h onward, P = 0.001), with both responses being attenuated following the second bout (P < 0.015), demonstrating adaptation. Smaller reductions in MVC following both bouts occurred in older adults (P = 0.005). Intracortical facilitation showed no changes (P ≥ 0.245). Motor-evoked potentials increased 24 and 72 h postexercise in young (P ≤ 0.038). Torque variability (P ≤ 0.041) and H-reflex size (P = 0.024) increased, while short-interval intracortical inhibition (SICI; P = 0.019) and the silent period duration (SP) decreased (P = 0.001) in both groups immediately postexercise. The SP decrease was smaller following the second bout (P = 0.021), and there was an association between the change in SICI and reduction in MVC 24 h postexercise in young adults (R = -0.47, P = 0.036). Changes in neurophysiological responses were mostly limited to immediately postexercise, suggesting a modest role in adaptation. In young adults, neural inhibitory changes are linked to the extent of MVC reduction, possibly mediated by the muscle damage-related afferent feedback. Older adults incurred less muscle damage, which has implications for exercise prescription.NEW & NOTEWORTHY This is the first study to have collectively assessed the role of corticospinal, spinal, and intracortical activity in muscle damage attenuation following repeated bouts of exercise in young and older adults. Lower levels of muscle damage in older adults are not related to their neurophysiological responses. Neural inhibition transiently changed, which might be related to the extent of muscle damage; however, the role of processes along the corticospinal pathway in the adaptive response is limited.

Do aerobic characteristics explain isometric exercise-induced neuromuscular fatigue and recovery in upper and lower limbs?

This study investigated the relationships between aerobic characteristics and (i) neuromuscular fatigue induced by 2-min sustained isometric maximal voluntary contractions (MVC) and (ii) subsequent recovery, in the upper and lower limbs. In a pseudo-randomized order, eleven healthy males completed four sessions on different days: maximal incremental cycling test (100 W + 40 W every 2 min); maximal arm-cranking test (50 W + 20 W every 2 min); and 2-min sustained isometric MVCs of the knee extensors (KE) and elbow flexors (EF). Neuromuscular assessment was performed with transcranial magnetic and peripheral nerve stimulation to evaluate central and peripheral neuromuscular factors of fatigue and the subsequent recovery. Peak oxygen uptake, gas exchange threshold and the corresponding power outputs were correlated with recovery of voluntary force after the 2-min KE MVC. Regression analysis showed that power output at the gas exchange threshold alone explained 72% of the variability in ∆recovery of KE voluntary force. No relationships with fatigue or recovery in EF were observed. These results suggest that participants with greater aerobic capacities experience the same amount of fatigue and faster recovery of voluntary force in KE but not EF. The potential reasons behind the relationship in KE but not EF are discussed.

Tailored exercise interventions to reduce fatigue in cancer survivors: study protocol of a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a common and distressing symptom of cancer and/or cancer treatment that persists for years after treatment completion in approximately one third of cancer survivors. Exercise is beneficial for the management of CRF, and general exercise guidelines for cancer survivors are available. There are multiple potential pathways by which exercise improves CRF, and cancer survivors with CRF are diverse with respect to cancer type, treatments and experienced side effects. While the general exercise guidelines are likely sufficient for most cancer survivors, tailoring of exercise interventions may be more effective in those with persistent fatigue. The primary aim of this research is to investigate the effect of a traditional vs. tailored exercise intervention on CRF severity in cancer survivors with persistent CRF. METHODS/DESIGN: Cancer survivors (≥ 3 months and ≤ 5 years since primary treatment) who score ≤ 34 on the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) will be randomly allocated to one of two parallel treatment arms: traditional (active control) and tailored exercise. Participants in the traditional exercise group will engage in aerobic and resistance exercise that is consistent with exercise guidelines for cancer survivors. The tailored exercise group will be prescribed an intervention designed to address individual deficits identified at baseline, such as loss of muscular strength, cardiorespiratory deconditioning or sleep disturbance. Participants will be assessed before and after the intervention for CRF severity and other patient-reported outcomes, neuromuscular function and fatigue in response to whole-body exercise, sleep quantity and quality, physical activity levels, cardiorespiratory fitness and blood biomarkers. DISCUSSION: To our knowledge, this will be the first study to compare the effects of a traditional vs. tailored exercise intervention on CRF severity in cancer survivors with persistent CRF. Using physiological, behavioural and patient-reported outcomes, this study will add to the current knowledge about both the factors contributing to CRF, and the potential reduction in CRF severity with an exercise intervention. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov ( NCT03049384 ), February, 2017.

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 2 decades, particularly ultramarathons run on trails. The present paper reviews the role of the central nervous system 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 central nervous system, 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 owing 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.

An Innovative Ergometer to Measure Neuromuscular Fatigue Immediately after Cycling.

PURPOSE: When assessing neuromuscular fatigue (NMF) from dynamic exercise using large muscle mass (e.g., cycling), most studies have delayed measurement for 1 to 3 min after task failure. This study aimed to determine the reliability of an innovative cycling ergometer permitting the start of fatigue measurement within 1 s after cycling. METHODS: Twelve subjects participated in two experimental sessions. Knee-extensor NMF was assessed by electrical nerve and transcranial magnetic stimulation with both a traditional chair setup (PRE- and POST-Chair, 2 min postexercise) and the new cycling ergometer (PRE, every 3 min during incremental exercise and POST-Bike, at task failure). RESULTS: The reduction in maximal voluntary contraction force POST-Bike (63% ± 12% PRE; P < 0.001) was not different between sessions and there was excellent reliability at PRE-Bike (intraclass correlation coefficient [ICC], 0.97; coefficients of variation [CV], 3.2%) and POST-Bike. Twitch (Tw) and high-frequency paired-pulse (Db100) forces decreased to 53% ± 14% and 62% ± 9% PRE, respectively (P < 0.001). Both were reliable at PRE-Bike (Tw: ICC, 0.97; CV, 5.2%; Db100: ICC, 0.90; CV, 7.3%) and POST-Bike (Tw: ICC, 0.88; CV, 11.9; Db100: ICC, 0.62; CV, 9.0%). Voluntary activation did not change during the cycling protocol (P > 0.05). Vastus lateralis and rectus femoris M-wave and motor-evoked potential areas showed fair to excellent reliability (ICC, 0.45-0.88). The reduction in maximal voluntary contraction and Db100 was greater on the cycling ergometer than the isometric chair. CONCLUSIONS: The innovative cycling ergometer is a reliable tool to assess NMF during and immediately postexercise. This will allow fatigue etiology during dynamic exercise with large muscle mass to be revisited in various populations and environmental conditions.

Faster V̇O2 kinetics after priming exercises of different duration but same fatigue.

This study compared the responses of two priming exercises of similar fatigue on the adjustment of the oxygen uptake time constant (τV̇O2) in cycling. Ten healthy young adults (25 ± 3 yr) performed: three step transitions from a 20-W baseline to the power output (PO) below the gas exchange threshold (MOD, MODPRE); a 3-min bout (P3MIN) at 90% of peak PO (POpeak), followed by MOD (MOD3MIN); and a 6-min bout (P6MIN) at 80% of POpeak, followed by MOD (MOD6MIN). The O2 supply-to-O2 demand ([HHb]/V̇O2) ratio was calculated for MODPRE, MOD3MIN, and MOD6MIN. Neuromuscular fatigue was measured isometrically pre- and post-priming exercise. Reductions in maximal voluntary contraction (-29 ± 6 vs -34 ± 7%) and high-frequency doublet amplitude (-48 ± 13 vs -43 ± 11%) were not significantly different between P3MIN vs P6MIN, suggesting similar fatigue. τV̇O2 for MOD3MIN and MOD6MIN were similar, being ~25% smaller than MODPRE. The [HHb]/V̇O2 ratio was significantly greater in MODPRE (1.13 ± 0.12) compared to MOD3MIN (1.02 ± 0.04) and MOD6MIN (1.02 ± 0.04). This study showed that priming exercise of shorter duration and higher intensity, was sufficient to accelerate V̇O2 kinetics similarly to that observed subsequent to P6MIN when the muscle fatigue was similar.

Mechanisms of Fatigue and Recovery in Upper versus Lower Limbs in Men.

PURPOSE: To compare the mechanisms of fatigue and recovery between upper and lower limbs in the same subjects. METHODS: Twelve healthy young men performed a 2-min sustained maximal voluntary isometric contraction (MVC) of the knee extensors (KE) and on another day a 2-min MVC of the elbow flexors (EF). Neuromuscular function evaluations were performed with both transcranial magnetic and peripheral stimulations before (PRE), at the end of the 2-min MVC, and five more times within 8 min of recovery. RESULTS: Decreases in MVC and cortical voluntary activation were approximately 12% (P < 0.001) and approximately 25% greater (P = 0.04) in KE than EF at end of the 2-min MVC. Conversely, twitch response decreased approximately 29% more (P = 0.02) in EF than KE. Changes in motor-evoked potential with fatigue were not different between upper and lower limbs (P > 0.05), whereas the increase in silent period duration was approximately 30% greater in EF than KE (P < 0.05). CONCLUSIONS: Upper and lower limbs presented different magnitudes of total, central and peripheral fatigue. Total neuromuscular fatigue and central fatigue were greater in KE than EF. Conversely, peripheral fatigue and corticospinal inhibition were greater in EF than KE.

Exercise, sleep and cancer-related fatigue: Are they related?

Cancer-related fatigue (CRF) is a commonly reported and debilitating side effect of cancer and/or cancer treatment. Sleep disorders are also highly reported in the cancer population; however it is unknown if sleep is associated with fatigue. In the general population, exercise has been shown to improve sleep, however in the cancer population this idea is under investigation. The primary purposes of this review were to: (i) review the prevalence and causes of sleep disorders in cancer patients and survivors, (ii) examine the relationship between sleep and CRF and (iii) review the impact of exercise interventions on sleep in cancer patients and survivors. A scoping review of the literature was conducted regarding exercise interventions in cancer patients and survivors with sleep as at least one outcome measure. A search of the literature revealed limited studies (n=21) assessing the effect of exercise on sleep disorders in the cancer population. Methodological issues are evident because assessing sleep is often not the main outcome of interest. The reviewed studies revealed that exercise positively impacts sleep quality and quantity. There seems to be possible relationship between sleep disorders, exercise and CRF. Further investigation of this relationship is necessary, specifically using objective measurement tools, in large, controlled studies, focusing on sleep as the primary outcome.