Performance Fatigability Research Articles

Intermittent hypoxia enhances voluntary activation and reduces performance fatigability during repeated lower limb contractions.

Prior research has highlighted the therapeutic benefits of acute intermittent hypoxia (AIH) in enhancing motor performance after motor incomplete spinal cord injury and in able-bodied individuals. While studies in rodents and humans indicate that AIH may facilitate motor excitability, the relationship between excitability changes and functional performance remains unclear. Additionally, discrepancies in the effects of AIH on excitability in able-bodied individuals merit further investigation. Understanding the concurrent impact of repetitive AIH on voluntary activation and spinal reflex excitability may clarify the functional implications of AIH for muscle force production. High voluntary activation is vital for sustaining torque production during activities that require repeated muscle contractions. We hypothesized that repetitive AIH would attenuate declines in both voluntary activation and maximum torque production typically observed during fatiguing contractions. To test this hypothesis, we examined the effects of four consecutive days of AIH on voluntary activation and torque generation during repeated maximal plantar flexion contractions. We assessed changes in voluntary activation using the central activation ratio (CAR) by calculating the ratio of voluntary torque to the torque produced with supramaximal electrical stimulation. Consistent with our hypothesis, we show that repetitive AIH significantly increases both CAR and peak torque during fatiguing contractions. We did not observe any changes in resting spinal reflex excitability or antagonist muscle coactivation during the fatiguing contractions post-AIH. Together, these findings suggest that repetitive AIH reduces performance fatigability through enhanced descending neural drive. Optimizing voluntary activation is critical for facilitating the recovery of functional walking skills after neurological injury.

Increased fatigability and impaired skeletal muscle microvascular reactivity in adults with obstructive sleep apnea: a cross-sectional study

BackgroundSympathetic nervous system hyperactivity and chronic intermittent nocturnal hypoxia in individuals with obstructive sleep apnea (OSA) predispose them to microvascular impairment, which may contribute to increased daytime muscle fatigue. This study aimed to assess microvascular reactivity of the skeletal muscle, examine fatigability, and determine the relationship between fatigability and microvascular reactivity in adults with OSA.MethodsTwenty-six participants were allocated into two groups—those with OSA and those without i.e. non-OSA. Each group comprised of 13 individuals who underwent an arterial occlusion test on their non-dominant leg. The percentage change of maximal hyperemic response (MHR) and the time to achieve MHR (tM) of both the total myoglobin/hemoglobin (∆[Hbtot]) and the oxygenated myoglobin/hemoglobin (∆[HbO2]) signals from near-infrared spectroscopy were calculated to examine microvascular reactivity. In addition, a 10-min walk test was performed to assess performance and perceived fatigability.ResultsThe OSA group demonstrated a reduced in ∆[Hbtot]MHR (150.9 ± 16.2% vs. 235.8 ± 72.7%, p = 0.006), ∆[HbO2]MHR (131.4 ± 8% vs. 161.7 ± 10.6%, p = 0.001) and increased ∆[Hbtot]tM (80.5 ± 13.1 s vs. 47.7 ± 9.9 s, p < 0.001), ∆[HbO2]tM (85.2 ± 22.4 s vs. 52.1 ± 5.9 s, p = 0.001) compared to the non-OSA group. In addition, participants in the OSA group experienced greater perceived (6 ± 1 vs. 2.8 ± 0.1, p = 0.001) and performance fatigability (1.1 ± 0.1 vs. 0.9 ± 0.1, p = 0.001) compared to adults in the non-OSA group. Moreover, both performance and perceived fatigability were significantly associated with microvascular reactivity parameters (all p < 0.05).ConclusionMicrovascular dysfunction, as determined by an attenuated post-occlusive reactive hyperemia, is observed in individuals with OSA that may contribute to increased fatigability in these individuals.

Overnight changes in performance fatigability and their relationship to modulated deep sleep oscillations via auditory stimulation.

Deep sleep oscillations are proposed to be central in restoring brain function and to affect different aspects of motor performance such as facilitating the consolidation of motor sequences resulting in faster and more accurate sequence tapping. Yet, whether deep sleep modulates performance fatigability during fatiguing tasks remains unexplored. We investigated overnight changes in tapping speed and resistance against performance fatigability via a finger tapping task. During fast tapping, fatigability manifests as a reduction in speed (or "motor slowing") which affects all tapping tasks, including motor sequences used to study motor memory formation. We further tested whether overnight changes in performance fatigability are influenced by enhancing deep sleep oscillations using auditory stimulation. We found an overnight increase in tapping speed alongside a reduction in performance fatigability and perceived workload. Auditory stimulation led to a global enhancement of slow waves and both slow and fast spindles during the stimulation window and a local increase in slow spindles in motor areas across the night. However, overnight performance improvements were not significantly modulated by auditory stimulation and changes in tapping speed or performance fatigability were not predicted by individual changes in deep sleep oscillations. Our findings demonstrate overnight changes in fatigability but revealed no evidence suggesting that this effect is causally linked to temporary augmentation of slow waves or sleep spindles. Our results are important for future studies using tapping tasks to test the relationship between sleep and motor memory consolidation, as overnight changes in objectively measured and subjectively perceived fatigue likely impact behavioural outcomes.

Are females getting more fatigable as they age?

The aim of this study was to compare performance fatigability between young (n = 13; 18-35 yr.; 23.5 ± 3.3 yr.), old (n = 13; 60-79 yr.; 68.2 ± 4.3 yr.), and very old (n = 11; ≥ 80 yr.; 85.6 ± 1.8 yr.) females during single-limb isometric (ISO) vs. isokinetic concentric (CON) vs. cycling (BIKE) fatiguing tasks. Participants randomly performed three incremental fatiguing tasks where increments were set as percentage of body weight to better reflect the daily life: (1) ISO and (2) CON consisted of stages of 75 contractions (120 s, 0.8 s on/0.8 s off) on an isokinetic dynamometer and (3) BIKE consisted of stages of 120 s at 37.5 rpm with similar duty cycle. Knee extensors maximal force, voluntary activation and potentiated twitch amplitude were measured at baseline, after each stage and at exhaustion. Compared to young, exercise performance was 20% and 53% lower in old and very old females in ISO, 46% and 76% lower in CON and 32% and 62% lower in BIKE (all p < 0.01). For a given workload (i.e. common stages), performance fatigability (i.e. force loss) was greater for very old compared to young females in CON only (p = 0.018). At exhaustion, performance fatigability was similar across groups and conditions (~ 30%; all p > 0.05), with similar impairments in both voluntary activation and twitch amplitude. These results emphasize the importance of the kind of fatiguing task and modalities of evaluation when investigating the effects of aging on performance fatigability.

Neural and Muscular Determinants of Performance Fatigability Are Independent of Work and Recovery Durations During High-Intensity Interval Exercise in Males

ABSTRACT The present study aimed to investigate the effect of two protocols of high-intensity interval exercise (HIIE) on performance fatigability and its neural and muscular determinants. On different days, 14 healthy males performed two HIIE protocols with different work and recovery durations (matched for total duration, work and recovery intensities, and density): 1) 4 × 4 min at 90% HRpeak,180-s recovery at 70% HRpeak; and 2) 16 × 1 min at 90% HRpeak, 45-s recovery at 70% HRpeak. Pre- to post-HIIE reduction in maximal voluntary isometric contraction (MVIC) was used as marker of performance fatigability, while voluntary activation (VA) and potentiated quadriceps twitch force (Qtw) as markers of the neural (i.e. central fatigue) and muscular (i.e. peripheral fatigue) determinants, respectively. In addition, pre- to post-HIIE reduction in twitch force stimulated at 100 Hz (Qtw100) and 10:100 Hz ratio (Qtw10:Qtw100) were used as markers of high- and low-frequency performance fatigability, respectively. The MVIC, VA, Tw, Qtw100, and Qtw10:Qtw100 ratio decreased similarly from pre- to post-HIIE in both HIIE protocols (p < .05). The rating of perceived effort, blood pH, and plasma lactate responses were similar between HIIE protocols (p > .05), but the heart rate was higher in the longer HIIE protocol (p < .05). In conclusion, performance fatigability and its neural and muscular determinants seemed to be independent of the work and recovery durations of the HIIE, at least when HIIE protocols were matched for total work duration, work and recovery intensities, and density. Further, HIIE with long work and recovery might be preferable when the intention is to stress the chronotropic response.

Performance fatigability in adults with spinal muscular atrophy treated long-term with nusinersen.

Persons with spinal muscular atrophy (pwSMA) report progressive muscle weakness but also reduced endurance when performing repetitive tasks in daily life, referred to as "performance fatigability" (PF). Data regarding the effects of the new disease-modifying drugs on PF are scarce. Thus, our main objective was to examine PF in adult ambulatory pwSMA treated long-term with nusinersen. Six-minute walk test (6MWT) data from 14 adult pwSMA treated with nusinersen for up to 70 months were retrospectively analyzed to determine PF. Performance fatigability was defined as the percentage change in the distance covered between the last and first minute of the 6MWT. In addition, relationships between PF and other clinical features were assessed. Performance fatigability was found in 12/14 pwSMA (85.7%) prior to treatment. The mean distance walked in the sixth minute (71.1 m) was shorter than the distance covered in the first minute (81.8 m), corresponding to a mean PF of 13.1% (95% confidence interval (CI): 6.5-19.6, p = .0007). During treatment with nusinersen, there was a mean reduction in PF of 5.6% (95% CI: -10.0 to -1.3, p = .0148). We found no relationship between PF and fatigue as measured by the Fatigue Severity Scale. This study demonstrates the presence of PF as an independent component of motor impairment and as a potential therapeutic target in our cohort of adult ambulatory pwSMA. Furthermore, the observations in our cohort suggest that nusinersen may have a beneficial effect on PF.

The effects of sex and contraction intensity on fatigability and muscle oxygenation in trained individuals.

Fatigability varies depending on sex and contraction intensity during sustained exercise. This study examined the responses of time to task failure (TTF), performance fatigability (PF), and muscle oxygenation (SmO2) in males and females during isometric handgrip holds to failure (HTF) at 30% and 60% maximum voluntary isometric contraction (MVIC). Males (n=12) and females (n=12) performed a pre-MVIC, handgrip HTF at randomly ordered percentages of MVIC (either 30% or 60%), followed by a post-MVIC on the dominant arm. During the HTF testing, the TTF and SmO2 responses were recorded, and PF was determined from the pre- to post-MVICs. TTF for 30% MVIC HTF was greater than 60% MVIC HTF (p<0.001), but was not different between males and females (p=0.117). PF exhibited an inverse relationship with intensity for each sex, while males demonstrated greater PF than females for both 30% and 60% MVIC HTF. For the 60% MVIC HTF, males demonstrated greater desaturation than females (CI95% = [-28.1, -2.6%], p=0.021, d=0.621), but not for the 30% MVIC HTF (CI95% = [-12.2, 7.9%], p=0.315, d=0.621). Sex differences in PF and SmO2 may be attributed to the differences in muscle mass, absolute strength, contractile properties, and muscle metabolism between males and females. However, these proposed differences between males and females may not fully inform exercise performance (e.g., TTF). Sex-specific fatigue responses may be affected by complex physio-psychological mechanisms, and therefore, additional investigations under diverse exercise conditions are required to better prescribe exercise for both males and females.

The effects of low vs. high rating of perceived exertion clamp exercise on performance, neuromuscular, and muscle oxygen saturation responses in females.

This study examined the time course of changes in force, relative to critical force (CF), electromyographic amplitude (EMG AMP), neuromuscular efficiency (NE), and muscle oxygen saturation (SmO2), as well as time to task failure (TTF) and performance fatigability (PF) during isometric handgrip holds to failure (HTF) anchored to the rating of perceived exertion (RPE) at 3 and 7. Ten females completed pre-test maximal voluntary isometric contractions (MVICs), submaximal HTF at four percentages of MVIC, an HTF at RPE = 3 and 7, and post-test MVICs. Analyses included paired samples t-tests, repeated measures ANOVAs and planned comparisons. TTF was not different between RPE 3 (540.4 ± 262.1s) and 7 (592.2 ± 299.6s), but PF for RPE 7 (42.1 ± 19.1%) was greater than RPE 3 (33.5 ± 15.4%) (p < 0.05). There were RPE-dependent decreases in force, EMG AMP, and NE across three discernable phases during the HTF (p < 0.01), but there were no significant changes in SmO2 across time. Although there were overall similar patterns across time for force, neuromuscular, and muscle metabolic responses between the RPE holds, the greater PF at RPE 7 than RPE 3 may be explained by the longer sustained time above CF at RPE 7, resulting in greater accumulation of intramuscular metabolites and afferent feedback. Throughout each trial, it is possible that force was adjusted to avoid the sensory tolerance limit, and the task was ended when force could no longer be reduced to maintain the assigned RPE, resulting in a similar TTF for RPE 7 and RPE 3.

Higher striatal dopamine is related with lower physical performance fatigability in community-dwelling older adults.

Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.

Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles.

Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.

Acute performance fatigability following continuous versus intermittent cycling protocols is not proportional to total work done.

Classical training theory postulates that performance fatigability following a training session should be proportional to the total work done (TWD); however, this notion has been questioned. This study investigated indices of performance and perceived fatigability after primary sessions of high-intensity interval training (HIIT) and constant work rate (CWR) cycling, each followed by a cycling time-to-task failure (TTF) bout. On separate days, 16 participants completed an incremental cycling test, and, in a randomized order, (i) a TTF trial at 80% of peak power output (PPO), (ii) an HIIT session, and (iii) a CWR session, both of which were immediately followed by a TTF trial at 80% PPO. Central and peripheral aspects of performance fatigability were measured using interpolated twitch technique, and perceptual measures were assessed prior to and following the HIIT and CWR trials, and again following the TTF trial. Despite TWD being less following HIIT (P=0.029), subsequent TTF trial was an average of 125s shorter following HIIT versus CWR (P<0.001), and this was accompanied by greater impairments in voluntary and electrically evoked forces (P<0.001), as well as exacerbated perceptual measures (P<0.001); however, there were no differences in any fatigue measure following the TTF trial (P≥0.149). There were strong correlations between the decline in TTF and indices of peripheral (r=0.70) and perceived fatigability (r≥0.80) measured at the end of HIIT and CWR. These results underscore the dissociation between TWD and performance fatigability and highlight the importance of peripheral components of fatigability in limiting endurance performance during high-intensity cycling exercise.

Comparison of Force, Neuromuscular, and Metabolic Responses During Sustained, Isometric Handgrip Holds to Failure Anchored to Low and High Perceptual Intensities in Men: An Exploratory Study.

Kwak, M, Succi, PJ, Benitez, B, Mitchinson, C, Samaan, MA, Abel, MG, and Bergstrom, HC. Comparison of force, neuromuscular, and metabolic responses during sustained, isometric handgrip holds to failure anchored to low and high perceptual intensities in men: An exploratory study. J Strength Cond Res 38(8): e405-e416, 2024-This study examined the responses of force alterations, relative to critical force (CF), neuromuscular parameters, and muscle oxygenation (SmO2) for isometric handgrip holds to failure (HTF) anchored to ratings of perceived exertion (RPE) of 3 and 7. Twelve men completed pre-maximal voluntary isometric contractions (pre-MVIC), submaximal HTF at 4 percentages of pre-MVIC, HTF at RPE = 3 and 7, and post-MVIC. Mechanomyograpic (MMG) signals and SmO2 were recorded during the RPE HTF. Analyses included paired-samples t-tests and repeated-measures ANOVAs at an alpha level of p ≤ 0.05. Time to task failure was not different between RPE 3 (478.7 ± 196.6 s) and RPE 7 (495.8 ± 173.8 s). Performance fatigability (PF) and MMG amplitude (AMP) were greater for RPE 7 (PF: 37.9 ± 12.9%; MMG AMP: 15.7 ± 7.4% MVIC) than RPE 3 (PF: 30.0 ± 14.5%; MMG AMP: 10.2 ± 6.5% MVIC), but MMG mean power frequency (MPF) was greater for RPE 3 (146.2 ± 31.1% MVIC) than RPE 7 (128.8 ± 23.0% MVIC). There were RPE-dependent decreases in force (p ≤ 0.01) across 3 discernable phases during the HTF. There were decreases in MMG AMP across time for both RPEs, but there were no significant changes in MMG MPF or SmO2. There were overall similar motor unit control strategies and local metabolic demand between RPEs. The majority of the HTF performed below CF at RPE 3 and 7 indicated CF did not reflect the highest sustainable force. When prescribing isometric exercise anchored to RPE, practitioners should be aware of the magnitude of force loss and relative intensity of the task to be sure desired training loads are met.

Are performance and perceived fatigability dependent on the anchor scheme of fatiguing isometric tasks in men?

Ratings of perceived exertion (RPE) can be used to regulate exercise intensity. This study examined the effect of anchor scheme on performance fatigability and neuromuscular responses following fatiguing forearm flexion tasks. Twelve men (age 20.9±2.2 years; height 179.8±5.3 cm; body mass 80.2±9.9 kg) performed sustained, isometric forearm flexion tasks to failure anchored to RPE=6 (RPEFT) and the torque (TRQFT) that corresponded to RPE=6. Pre-test and post-test maximal voluntary isometric contractions (MVIC) were performed to quantify changes in the amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) and mechanomyographic (MMG) signals. Neuromuscular efficiency (NME) was calculated by dividing normalized torque by normalized EMG AMP. A dependent t-test was used to assess the mean difference for time to task failure (TTF). Repeated measures ANOVAs were used to compare mean differences for performance fatigability and normalized neuromuscular parameters. The RPEFT had a greater TTF than the TRQFT (P<0.001). MVIC and NME decreased from pre-test to post-test following the RPEFT and TRQFT (P<0.05) with no differences between anchor schemes. Following the TRQFT, normalized EMG MPF decreased from pre-test to post-test (P=0.004). Following the RPEFT, normalized MMG MPF increased from pre-test to post-test (P=0.021). There were no changes in normalized EMG AMP or MMG AMP (P>0.05). These findings indicated anchor scheme-specific neuromuscular responses and TTF, despite no difference in performance fatigability. Furthermore, performance fatigability was likely due to peripheral fatigue (based on normalized EMG MPF and NME) following the TRQFT, but peripheral and central fatigue (based on normalized MMG MPF and NME) following the RPEFT.

Greater intramuscular metabolic perturbations contribute to faster muscle fatigue development in males than females during intermittent isometric exercise

INTRODUCTION: Previous studies reported faster performance fatigability in males than females during isometric exercise, ultimately prolonging time to task failure in the latter at the same relative intensity. Several authors suggested anatomical and physiological factors as primary determinants, but it remains unknown whether exercise-related accumulation of metabolites within skeletal muscle differentially affects fatigue development in female and males. PURPOSE: This study aimed to investigate intramuscular metabolic perturbations during fatiguing intermittent isometric knee-extensor exercise in males and females. Herein, we tested the hypothesis that greater metabolic perturbation during intermittent isometric exercise results in greater fatigue development in males compared to females. Methods: Fifteen males (M)(26±2y) and fifteen eumenorrheic females (F)(24±3y) visited the laboratory twice. During visit 1, isometric knee-extensors critical torque (CT) was estimated by a 5-min all-out test. In visit 2, participants performed intermittent isometric knee-extensor exercises to task failure at 110% of CT. To determine knee-extensors magnitude and etiology of fatigue maximal voluntary isometric contraction (MVIC), voluntary activation (VA) and potentiated twitches (St) amplitudes were evaluated before (PRE), at 9min (MID), and at task failure (POST). At the same time points, intramuscular pH and concentrations of ATP, PCr, Cr and La were determined in vastus lateralis muscle biopsies. Results: Time to task failure was shorter in M than F (1017±498 vs 1511±506s; P&lt;.01). At PRE, MVIC torque was higher in M than F (259±70 vs 152±24Nm; P&lt;.001). Relative decline in MVIC torque from PRE to MID was greater in M than F (-43±9 vs -34±8% from PRE; P&lt;.05) but reached similar decline at POST (-55±7 vs -53±6% from PRE). VA decreased throughout the test similarly in both sexes (P&lt;.001). St loss from PRE was higher in M than F (-45±13 vs -37±15%; P&lt;.05) at MID whereas no sex differences were observed at POST. Muscle pH decreased at a similar rate in M and F during the test (P&lt;.03). Muscle [ATP] did not change from PRE to MID or POST. Muscle [Cr] increased at a similar rate in M and F during the test (P&lt;.01). Muscle [PCr] was lower in M than F at any time point (P&lt;.03). At MID, [La] increased to a greater extent in M than F (P&lt;.01) with no between-sex differences at POST. CONCLUSION: Males showed greater fatigue development than females associated with greater metabolic perturbation during intermittent isometric exercise performed at same relative intensity. Higher PCr depletion and higher La accumulation suggest females were less fatigable than males due to higher glycolytic rate and less intramuscular inorganic phosphate concentration. The present work was funded by a Travelling Fellowship grant JEBTF2210859 to MC from The Company Of Biologists Limited. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Factors Associated with Fatigue in COVID-19 ICU Survivors.

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. Fifty-nine patients (38-78 yr) hospitalized in ICU for COVID-19 infection for 32 (6-80) d, including 23 (3-57) d of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 d after discharge and was dedicated to questionnaires, blood sampling, and cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 d later. 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 1 s, 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). COVID-19 survivors showed altered respiratory function 4 to 8 wk after discharge, which 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.

Performance and perceived fatigability across the intensity spectrum: role of muscle mass during cycling.

The role of muscle mass in modulating performance and perceived fatigability across the entire intensity spectrum during cycling remains unexplored. We hypothesized that at task failure (Tlim), muscle contractile function would decline more following single- (SL) versus double-leg (DL) cycling within severe and extreme intensities, but not moderate and heavy intensities. After DL and SL ramp-incremental tests, on separate days, 11 recreationally active males (V̇o2max: 49.5 ± 7.7 mL·kg-1·min-1) completed SL and DL cycling until Tlim within each intensity domain. Power output for SL trials was set at 60% of the corresponding DL trial. Before and immediately after Tlim, participants performed an isometric maximal voluntary contraction (MVC) coupled with one superimposed and three resting femoral nerve stimulations [100 Hz; 10 Hz; single twitch (Qtw)] to measure performance fatigability. Perceived fatigue, leg pain, dyspnea, and effort were collected during trials. Tlim within each intensity domain was not different between SL and DL (all P > 0.05). MVC declined more for SL versus DL following heavy- (-42 ± 16% vs. -30 ± 18%; P = 0.011) and severe-intensity cycling (-41 ± 12% vs. -31 ± 15%; P = 0.036). Similarly, peak Qtw force declined more for SL following heavy- (-31 ± 12% vs. -22 ± 10%; P = 0.007) and severe-intensity cycling (-49 ± 13% vs. -40 ± 7%; P = 0.048). Except for heavy intensity, voluntary activation reductions were similar between modes. Similarly, except for dyspnea, which was lower for SL versus DL across all domains, ratings of fatigue, pain, and effort were similar at Tlim between exercise modes. Thus, the amount of muscle mass modulates the extent of contractile function impairment in an intensity-dependent manner.NEW & NOTEWORTHY We investigated the modulatory role of muscle mass on performance and perceived fatigability across the entire intensity spectrum. Despite similar time-to-task failure, single-leg cycling resulted in greater impairments in muscle contractile function within the heavy- and severe-intensity domains, but not the moderate- and extreme-intensity domains. Perceived fatigue, pain, and effort were similar between cycling modes. This indicates that the modulatory role of muscle mass on the extent of performance fatigability is intensity domain-dependent.

The measurement of fatigability severity in individuals with multiple sclerosis and healthy controls

BackgroundMultiple Sclerosis (MS) is a chronic disease that substantially diminishes one's ability to undertake daily living activities. Fatigue has been reported by at least 80 % of persons with MS (PwMS). Yet, little is known concerning the quantification of fatigability using prolonged walking tests. ObjectivesTo compare fatigability severity measures using the 10-minute walk test for PwMS against age- and gender-matched healthy controls (HCs). MethodsParticipants included 53 ambulatory PwMS and 49 HCs. Perceived fatigability was measured by dividing a participant's change in self-reported tiredness by the number of meters walked. Performance fatigability was calculated by dividing the change in walking speed (at 2.5 and 10 min) by the total distance walked in meters. ResultsThere was a significant difference in perceived fatigability between PwMS and HCs (mean difference: 2.73 ± 0.83; p = 0.001) and in performance fatigability (mean difference: 0.24 ± 0.11; p = 0.01). Moreover, there were significant differences in speed and distance at all time points (p ≤ 0.05) between PwMS and HCs. ConclusionsPwMS have significant walking deficits as reflected by greater fatigability in both perceived and performance measures. These methods can enhance therapeutic strategies that improve the walking performances of PwMS.

Edward F. Adolph Distinguished Lecture. Age and sex differences in the limits of human performance: fatigability and real-world data.

High-level athletic performances may be a proxy for the trajectory of optimal function of human biology with advanced aging and the differences between males and females. Males are faster, stronger, and more powerful than females and these physical attributes decline dramatically with advanced aging for both sexes. Experimental mechanistic studies determine the physiological mechanisms for these sex and age differences in human physical performance. The assumption however, that real-world performances solely reflect the biological and physiological differences between the sexes and with advanced aging, even among elite athletes, is not complete. This review presents evidence that an integrated approach encompassing analysis of real-world data and experimental mechanistic studies is necessary to determine the biological and sociocultural factors attributed to the limits of performance with aging and between males and females. First, experimental studies are presented that focus on the sex and age differences in performance fatigability that determine the physiological mechanisms of absolute and relative exercise performance. Second, analysis of current and historical real-world data including world records, and performances of elite, collegiate, and competitive age-group athletes are highlighted. These data illustrate that the upper limits of physical performance that have changed historically, and other factors such as sociocultural influences, explain the widening of the sex and age gaps in human performance observed in real-world data even in present-day performances. These approaches have broader significance when applied to understanding the impact of the historically low representation of females and minority groups in biomedical research on health outcomes.

The effects of sustained, low- and high-intensity isometric tasks on performance fatigability and the perceived responses that contributed to task termination.

The present study examined the effects of sustained, isometric low- versus high-intensity tasks on time to task failure (TTF), performance fatigability (PF), ratings of perceived exertion (RPE), and the perceived causes of task termination from a post-test questionnaire (PTQ). Ten men (mean ± SD: age = 21.1 ± 2.3 years; height = 180.2 ± 5.7 cm; body mass = 79.5 ± 8.8 kg) performed maximal voluntary isometric contractions (MVICs) before and after fatiguing, isometric forearm flexion tasks anchored to the torque corresponding to RPE values of 2 (TRQ2FT = 23.8 ± 7.1 N·m) and 8 (TRQ8FT = 60.9 ± 11.4 N·m). In addition, the subjects completed a PTQ which surveyed whether the perceived sensations of fatigue or pain, and/or the psychological factors of loss of focus and motivation contributed to the decision to terminate the task. Repeated measures ANOVAs, Wilcoxon-Signed Rank tests, and Spearman's Rank-Order Correlations were used to analyze the data. Across the fatiguing tasks, there were similar decreases in MVIC torque (95.2 ± 20.3 vs. 68.9 ± 15.6 N·m; p < 0.001) and RPE values (p = 0.122) at task failure for TRQ2FT (7.4 ± 2.7) and TRQ8FT (8.9 ± 1.0), but a longer (p = 0.005) TTF for the TRQ2FT (245.0 ± 177.0 s) than TRQ8FT (36.8 ± 11.1 s). Despite reaching task failure, the subjects were able to perform MVICs that were 100-300% greater than the target torque values within seconds of terminating the tasks. Thus, we hypothesized that task failure was not caused by an inability to produce sufficient torque to sustain the tasks, but rather an unwillingness to continue the task.

SKELETAL MUSCLE ENERGETICS ARE ASSOCIATED WITH PERFORMANCE FATIGABILITY

Abstract Performance fatigability manifests as insufficient energy to complete daily physical tasks and worsens with aging, exacerbating vulnerability to disability. Skeletal muscle energetics also declines with aging. Thus, we hypothesized muscle energetics may be an important contributor to performance fatigability. In the Study of Muscle, Mobility and Aging (SOMMA), participants completed a usual-paced 400m walk while wearing a wrist-worn ActiGraph, from which raw data were used to derive the Pittsburgh Performance Fatigability Index (PPFI, higher=more severe fatigability) that quantifies percent decline in the entire individual cadence-versus-time trajectory. Maximal oxidative phosphorylation (maxOXPHOS) in skeletal muscle mitochondria was quantified in vitro using high-resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATPmax) was assessed in vivo by 31P magnetic resonance spectroscopy. We conducted separate tobit regressions to examine associations of maxOXPHOS and ATPmax with PPFI, adjusting for technician/site, age, sex, race, height, weight, and mins/day moderate-to-vigorous physical activity measured by ActiGraph in free-living, in N=795 participants with complete PPFI scores and &amp;gt;1 energetics measure (70-94 yrs, 58% women). Median PPFI scores were 1.4% [IQR: 0-2.9%]. After adjustment, each SD (18.4 pmol/(s*mg)) lower maxOXPHOS was associated with 0.55% (95% CI: 0.26, 0.85) higher PPFI scores, while each SD (0.2 mM/sec) lower ATPmax was associated with 0.54% (95% CI: 0.27, 0.81) higher PPFI scores. Our results indicate that lower skeletal muscle energetics were associated with more severe performance fatigability. This suggests that therapeutics targeting muscle energetics may thereby potentially mitigate fatigability and lessen susceptibility to disability among older adults.