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.

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.

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.

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.

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.

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.

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.

The relationship between oxygen uptake kinetics and neuromuscular fatigue in high-intensity cycling exercise.

PURPOSE: In theory, a slow oxygen uptake ([Formula: see text]) kinetics leads to a greater accumulation of anaerobic by-products, which can, in turn, induce more neuromuscular fatigue. However, the existence of this relationship has never been tested. METHODS: After two sessions to measure peak [Formula: see text], peak power output (POpeak), and [Formula: see text] kinetics responses in the unfatigued state (τ [Formula: see text] MOD), 10 healthy young adults performed a 6-min cycling bout at 80% POpeak (INT6-min). [Formula: see text] kinetics responses were also measured during INT6-min. Neuromuscular fatigue was measured isometrically pre- and post-INT6-min (immediately post- and 15-s post-INT6-min) with an innovative cycle ergometer. RESULTS: Maximal voluntary contraction (MVC) force, high-frequency doublet amplitude, and the ratio of low- to high-frequency doublet amplitudes decreased by 34 ± 7, 43 ± 11, and 31 ± 13%, respectively (all P < 0.01). A significant Spearman's rank correlation was observed between the change in low-frequency doublet force (ΔDb10) immediately after INT6-min and both τ [Formula: see text] MOD and τ [Formula: see text] INT6-min (ρ = -0.68 and ρ = -0.67, both P < 0.05). When considering the largest responses from the two neuromuscular evaluations post-INT6-min, significant correlations were also found between τ [Formula: see text] MOD and ΔDb10 (ρ = -0.74; P < 0.05) and between τ[Formula: see text] INT6-min and both ΔDb10 and low-frequency fatigue (ρ = -0.70 and ρ = -0.66; both P < 0.05). CONCLUSION: The present results suggest that subjects with slow [Formula: see text] kinetics experience more peripheral fatigue, in particular more excitation-contraction coupling failure, likely due to a greater accumulation of protons and/or inorganic phosphates.

Achilles tendon vibration-induced changes in plantar flexor corticospinal excitability.

Daily Achilles tendon vibration has been shown to increase muscle force, likely via corticospinal neural adaptations. The aim of the present study was to determine the extent by which corticospinal excitability is influenced during direct Achilles tendon vibration. Motor-evoked potentials (MEPs) were elicited in the soleus (SOL), gastrocnemius medialis (GM) and tibialis anterior (TA) by transcranial magnetic stimulation of the motor cortical area of the leg with and without Achilles tendon vibration at various frequencies (50, 80 and 110 Hz). Contralateral homologues were also investigated. SOL and GM MEP amplitude significantly increased by 226 ± 188 and 66 ± 39%, respectively, during Achilles tendon vibration, without any difference between the tested frequencies. No MEP changes were reported for TA or contralateral homologues. Increased SOL and GM MEP amplitude suggests increased vibration-induced corticospinal excitability independent of vibration frequency.

Modulation of soleus corticospinal excitability during Achilles tendon vibration.

Soleus (SOL) corticospinal excitability has been reported to increase during Achilles tendon vibration. The aim of the present study was to further investigate SOL corticospinal excitability and elucidate the changes to intracortical mechanisms during Achilles tendon vibration. Motor-evoked potentials (MEPs) were elicited in the SOL by transcranial magnetic stimulation (TMS) of the corresponding motor cortical area of the leg with and without 50-Hz Achilles tendon vibration. SOL input-output curves were determined. Paired-pulse protocols were also performed to investigate short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) by conditioning test TMS pulses with sub-threshold TMS pulses at inter-stimulus intervals of 3 and 13 ms, respectively. During Achilles tendon vibration, motor threshold was lower than in the control condition (43 ± 13 vs. 49 ± 11 % of maximal stimulator output; p = 0.008). Input-output curves were also influenced by vibration, i.e. there was increased maximal MEP amplitude (0.694 ± 0.347 vs. 0.268 ± 0.167 mV; p < 0.001), decreased TMS intensity to elicit a MEP of half the maximal MEP amplitude (100 ± 13 vs. 109 ± 9 % motor threshold; p = 0.009) and a strong tendency for decreased slope constant (0.076 ± 0.04 vs. 0.117 ± 0.04; p = 0.068). Vibration reduced ICF (98 ± 61 vs. 170 ± 105 % of test MEP amplitude; p = 0.05), but had no effect on SICI (53 ± 26 vs. 48 ± 22 % of test MEP amplitude; p = 0.68). The present results further document the increased vibration-induced corticospinal excitability in the soleus muscle and suggest that this increase is not mediated by changes in SICI or ICF.

Comparison of electrical nerve stimulation, electrical muscle stimulation and magnetic nerve stimulation to assess the neuromuscular function of the plantar flexor muscles.

INTRODUCTION: As it might lead to less discomfort, magnetic nerve stimulation (MNS) is increasingly used as an alternative to electrical stimulation methods. Yet, MNS and electrical nerve stimulation (ENS) and electrical muscle stimulation (EMS) have not been formally compared for the evaluation of plantar flexor neuromuscular function. METHODS: We quantified plantar flexor neuromuscular function with ENS, EMS and MNS in 10 volunteers in fresh and fatigued muscles. Central alterations were assessed through changes in voluntary activation level (VAL) and peripheral function through changes in M-wave, twitch and doublet (PS100) amplitudes. Discomfort associated with 100-Hz paired stimuli delivered with each method was evaluated on a 10-cm visual analog scale. RESULTS: VAL, agonist and antagonist M-wave amplitudes and PS100 were similar between the different methods in both fresh and fatigued states. Potentiated peak twitch was lower in EMS compared to ENS, whereas no difference was found between ENS and MNS for any parameter. Discomfort associated with MNS (1.5 ± 1.4 cm) was significantly less compared to ENS (5.5 ± 1.9 cm) and EMS (4.2 ± 2.6 cm) (p < 0.05). CONCLUSION: When PS100 is used to evaluate neuromuscular properties, MNS, EMS and ENS can be used interchangeably for plantar flexor neuromuscular function assessment as they provide similar evaluation of central and peripheral factors in unfatigued and fatigued states. Importantly, electrical current spread to antagonist muscles was similar between the three methods while discomfort from MNS was much less compared to ENS and EMS. MNS may be potentially employed to assess neuromuscular function of plantar flexor muscles in fragile populations.

Dynamics of corticospinal changes during and after high-intensity quadriceps exercise.

This study tested the hypothesis that during fatiguing quadriceps exercise, supraspinal fatigue develops late, is associated with both increased corticospinal excitability and inhibition and recovers quickly. Eight subjects performed 20 s contractions [15 s at 50% maximal voluntary contraction (MVC) followed by 5 s MVC] separated by a 10 s rest period until task failure. Transcranial magnetic stimulation (TMS) and electrical femoral nerve stimulation (PNS) were delivered ∼ 2 s apart during 50% MVC, during MVC and after MVC in relaxed muscle. Voluntary activation was assessed by TMS (VATMS) immediately before and after exercise and then three times over a 6 min recovery period. During exercise, MVC and twitch force evoked by PNS in relaxed muscle decreased progressively to 48 ± 8 and 36 ± 16% of control values, respectively (both P < 0.01). Significant changes in voluntary activation assessed by PNS and twitch evoked by TMS during MVC were observed during the last quarter of exercise only (from 96.4 ± 1.7 to 86 ± 13%, P = 0.03 and from 0.76 ± 0.8 to 4.9 ± 4.7% MVC, P = 0.02, from baseline to task failure, respectively). The TMS-induced silent period increased linearly during both MVC (by ∼ 79 ms) and 50% MVC (by ∼ 63 ms; both P < 0.01). Motor-evoked potential amplitude did not change during the protocol at any force levels. Both silent period and VATMS recovered within 2 min postexercise, whereas MVC and twitch force evoked by PNS in relaxed muscle recovered to only 84 ± 9 and 73 ± 17% of control values 6 min after exercise, respectively. In conclusion, high-intensity single-joint quadriceps exercise induces supraspinal fatigue near task failure, with increased intracortical inhibition and, in contrast to previous upper-limb results, unchanged corticospinal excitability. These changes recover rapidly after task failure, emphasizing the need to measure corticospinal adaptations immediately at task failure to avoid underestimation of exercise-induced corticospinal changes.

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

BACKGROUND: Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. Recently, there has been a surge in TMS studies evaluating lower-limb fatigue. TMS intensity of 120-130% resting motor threshold (RMT) and 120% active motor threshold (AMT) and TMS intensity determined using stimulus-response curves during muscular contraction have been used in these studies. With the expansion of fatigue research in locomotion, the quadriceps femoris is increasingly of interest. It is important to select a stimulus intensity appropriate to evaluate the variables, including voluntary activation, being measured in this functionally important muscle group. This study assessed whether selected quadriceps TMS stimulus intensity determined by frequently employed methods is similar between methods and muscles. METHODS: Stimulus intensity in vastus lateralis, rectus femoris and vastus medialis muscles was determined by RMT, AMT (i.e. during brief voluntary contractions at 10% maximal voluntary force, MVC) and maximal motor-evoked potential (MEP) amplitude from stimulus-response curves during brief voluntary contractions at 10, 20 and 50% MVC at different stimulus intensities. RESULTS: Stimulus intensity determined from a 10% MVC stimulus-response curve and at 120 and 130% RMT was higher than stimulus intensity at 120% AMT (lowest) and from a 50% MVC stimulus-response curve (p < 0.05). Stimulus intensity from a 20% MVC stimulus-response curve was similar to 120% RMT and 50% MVC stimulus-response curve. Mean stimulus intensity for stimulus-response curves at 10, 20 and 50% MVC corresponded to approximately 135, 115 and 100% RMT and 180, 155 and 130% AMT, respectively. Selected stimulus intensity was similar between muscles for all methods (p > 0.05). CONCLUSIONS: Similar optimal stimulus intensity and maximal MEP amplitudes at 20 and 50% MVC and the minimal risk of residual fatigue at 20% MVC suggest that a 20% MVC stimulus-response curve is appropriate for determining TMS stimulus intensity in the quadriceps femoris. The higher selected stimulus intensities at 120-130% RMT have the potential to cause increased coactivation and discomfort and the lower stimulus intensity at 120% AMT may underestimate evoked responses. One muscle may also act as a surrogate in determining optimal quadriceps femoris stimulation intensity.

Mechano-responses of quadriceps muscles evoked by transcranial magnetic stimulation.

Mechanomyography (MMG) may be used to quantify very small motor responses resulting from muscle activation, voluntary or involuntary. The purpose of this study was to investigate the MMG mean peak amplitude (MPA) and area under the curve (AUC) and the corresponding mechanical responses following delivery of transcranial magnetic stimulation (TMS) to the knee extensors. Fourteen adults (23 ± 1 years) received single TMS pulses at intensities from 30-80 % maximum stimulator output to elicit muscle responses in the relaxed knee extensors while seated. An accelerometer-based sensor was placed on the rectus femoris (RF) and vastus lateralis (VL) muscle bellies to measure the MMG signal. Pearson correlation revealed a positive linear relationship between MMG MPA and TMS intensity for RF (r=0.569; p<0.001) and VL (r=0.618; p<0.001). TMS intensity of ≥60 % maximum stimulator output produced significantly higher MPA than at 30 % TMS intensity and evoked measurable movement at the knee joint. MMG MPA was positively correlated to AUC (r=0.957 for RF and r=0.603 for VL; both p<0.001) and knee extension angle (r=0.596 for RF and r=0.675 for VL; both p<0.001). In conclusion, MMG captured knee extensor mechanical responses at all TMS intensities with the response increasing with increasing TMS intensity. These findings suggest that MMG can be an additional tool for assessing muscle activation.

Effect of different approaches to target force on transcranial magnetic stimulation responses.

INTRODUCTION: The aim of this study was to determine whether the manner in which a target force is approached can influence the electromyographic (EMG) and mechanical parameters evoked by transcranial magnetic stimulation (TMS) during brief muscle contractions. METHODS: The amplitude of motor-evoked potentials (MEP) and superimposed twitch and the duration of the silent period were recorded in 8 healthy participants in response to TMS delivered during brief isometric voluntary contractions of the quadriceps maintaining a target force (10% and 50% of maximal voluntary force) or gradually increasing or decreasing to reach this point. RESULTS: MEP and superimposed twitch, unlike the silent period, are influenced by the manner of reaching a low force. CONCLUSIONS: Clear instructions must be provided to research participants and patients. Rapidly increasing to a target force without exceeding it and maintaining the force before the delivery of TMS results in stable, representative MEP amplitudes.

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.

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.