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INTRODUCTION: This two-part study explored the safety, feasibility, and efficacy of a mild-moderate resistance isometric leg exercise program in ambulatory boys with Duchenne Muscular Dystrophy (DMD). METHODS: First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12-week in-home, remotely-supervised, mild-moderate intensity strengthening program in 8 boys. Safety measures included T(2) MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend 4 stairs) were also measured. RESULTS: Dose-escalation revealed no signs of muscle damage. Seven of the 8 boys completed the 12-week in-home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors p < 0.01; knee flexors p < 0.05) and function (descending steps p < 0.05). DISCUSSION: An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

Introduction: Neuromuscular electrical stimulation (NMES) is used to prevent muscle atrophy. However, the effect of pulse duration modulation for reducing muscle fatigue and pain is unknown. Methods: Two 2-minute stimulation protocols were applied to the knee extensors of 10 healthy individuals. In one session, a long pulse duration (1,000 μs) and a low current amplitude (LL) set to evoke 25% maximal voluntary contraction at 30 Hz were applied. The other session was identical except that a short pulse duration (200 μs) and a high current amplitude (SH) were used. Results: Muscle fatigue was lower for LL than for SH (p ˂ 0.01). Force recovery rate was higher for LL than for SH (p ˂ 0.05). Pain scores were also lower for LL than for SH (p ˂ 0.05). Discussion: The use of 1ms pulse durations reduces fatigue and pain during NMES for moderate-level contractions compared to 200 µs durations. This article is protected by copyright. All rights reserved.

Introduction Although it has been shown that voluntary activation (%VA) of the knee extensors during isometric contractions can be reliably assessed with the interpolated twitch technique, little is known about the reliability of %VA during concentric and eccentric muscle actions. Therefore, relative and absolute intersession reliability of quadriceps muscle's %VA during different contraction modes was determined. Methods After a familiarization session, 21 participants (17 males, 25 ± 2 yrs) completed two testing sessions. Paired supramaximal electrical stimuli were administered to the femoral nerve during isometric, concentric, eccentric MVCs, and at rest to assess %VA (stimuli were applied at 70° knee flexion). Results and discussion Data indicate that %VA of the knee extensors can be reliably measured during isometric [intraclass correlation coefficient (ICC) = 0.89, coefficient of variation (CV) = 4.1%], concentric (ICC = 0.87, CV = 6.6%), and eccentric muscle actions (ICC = 0.86, CV = 7.0%). Muscle Nerve 56: 324-327, 2017.

Introduction The aim of this study was to investigate the effects of high intensity resistance circuit (HIRC) and traditional strength training (TST) on neuromuscular fatigue and metabolic responses. Methods Twelve trained young subjects performed HIRC and TST in a counterbalanced order with 1 week rest in-between. The amount of workload and the inter-set time for each local muscle group were matched (180 s), however, the time between successive exercises differed. The twitch interpolation technique was used to test neuromuscular function of the knee extensor muscles. Blood lactate concentration was used to evaluate metabolic responses. Results Maximum voluntary contraction and resting potentiated twitch amplitude (Qtw) were significantly reduced after HIRC, but there were not changes after TST, while reductions in voluntary activation were similar. Lactate concentration increased significantly more after HIRC. Conclusions The higher lactate concentration after HIRC probably impaired excitation-contraction coupling, indicating larger peripheral fatigue than after TST. Muscle Nerve 56: 152–159, 2017.

Introduction Dynamometry is increasingly used as an objective measurement of muscle strength in neurological diseases. No study has applied dynamometry in untreated newly diagnosed patients with myasthenia gravis (MG). Methods Isometric muscle strength at the shoulder, knee, and ankle was determined in 21 MG patients before and after initial anti-myasthenic treatment. Isometric strength was compared with MG evaluation scales. Results Muscle strength was reduced for knee extensors and shoulder abductors but normal for ankle extensors. Isometric muscle strength did not correlate significantly with manual muscle testing (MG Composite). Dynamometry revealed improved muscle strength of up to 50% (median 17%; range -1.8-49.8) despite no change in the MG Composite score. Conclusions Dynamometry appears to be a more sensitive method of identifying changes in limb strength than MG evaluation scales. This supports the use of dynamometry in MG patients, especially for evaluation of the effect of anti-myasthenic treatment. Muscle Nerve 54: 709-714, 2016.

Introduction: We studied the time course of neuro- muscular fatigue during maximal intensity intermittent-sprint cycling. Methods: Eight participants completed 10, 10-s sprints interspersed with 180 s of recovery. The power outputs were recorded for each sprint. Knee extensor maximum voluntary contraction (MVC) force, voluntary activation, and evoked con- tractile properties were recorded presprint, postsprint 5, and postsprint 10. Results: Total work over the 10 sprints decreased significantly (P

Introduction: We examined the extent to which fatiguing cycling exercise in the heat influences contractile function in modulating the force–frequency relationship. Methods: Before (∽37.0°C) and after (∽38.5°C) exercise (ExH) and passive (PaH) hyperthermia, an 8-s train of stimulation at 10, 20, 50, and 100 Hz (2 s per frequency) and a potentiated twitch were evoked on the relaxed knee extensors using percutaneous stimulation. Results: ExH and PaH produced a decrease in the 20:50 Hz force ratio, indicative of low-frequency fatigue (P

Introduction: Susceptibility to muscle fatigue during aging could depend on muscle activation patterns. Methods: Young (mean age, 22 years) and older (mean age 70 years) men and women completed two fatigue tests of knee extensor muscles using voluntary and electrically stimulated contractions. Results: Older subjects displayed a shift to the left of the torque-frequency relationship and held a sustained voluntary isometric contraction at 50% maximal strength for significantly longer than young (P < 0.001). Young and old showed similar fatigue during electrically induced, intermittent isometric contractions (1-s on, 1-s off for 2 min), but women fatigued less than men (P = 0.001). Stronger muscles fatigued more quickly, and slower contractile properties were associated with longer sustained contractions. Conclusions: The slowing and weakness of older muscle was associated with superior fatigue resistance during sustained isometric contractions. Young and old showed similar fatigue following a series of brief, intermittent contractions, but women fatigued less than men.

Introduction: Changes in muscle architecture induced by eccentric knee extensor training remain unclear, as well the adaptive responses of synergistic knee extensor muscles with different geometrical designs. Methods: Ultrasonography images were taken from rectus femoris (RF) and vastus lateralis (VL) of 20 male volunteers before and after a non-training control period of 4 weeks, and additional evaluations were performed after 4, 8, and 12 weeks of isokinetic eccentric training. Results: RF and VL had significant changes in muscle architecture within the first 4 training weeks, and the adaptive response throughout the intervention was similar. Muscle thickness increased by around 7–10%, fascicle length increased 17–19%, and pennation angle was unchanged. Conclusions: Increased muscle thickness due to eccentric training was related to increased fascicle length and not to pennation angle changes. Although RF and VL have a different fascicular geometry, they had similar morphological adaptations to eccentric training. Muscle Nerve 48: 498–506, 2013

Introduction: This study determined the between-session reliability of neuromuscular measurements during explosive isometric contractions, with special consideration of electromyography (EMG) normalization. Methods: Following familiarization, 13 men participated in 3 identical measurement sessions involving maximal and explosive voluntary contractions of the knee extensors, while force and surface EMG were recorded. Root mean square EMG amplitude was normalized to different reference measures: (evoked maximal M-wave peak-to-peak amplitude and area, maximum and sub-maximum voluntary contractions). Results: Explosive voluntary force measurements were reliable on a group level, whereas within-subject reliability was low over the initial 50 ms and good from 100 ms onward. Normalization of EMG during explosive voluntary contractions, irrespective of the reference method, did not reduce the within-subject variability, but it did reduce substantially the variability between-subject. Conclusions: The high intra-individual variability of EMG and early phase explosive voluntary force production may limit their use to measuring group as opposed to individual responses to an intervention. Muscle Nerve 46: 566–576, 2012

Introduction: The effect of recovery time on neuromuscular function after a fatiguing task was compared in both the upper and lower limbs between patients with Charcot–Marie–Tooth type 1A (CMT1A) and healthy individuals. Methods: Torque of elbow flexors and knee extensors and surface electromyography (sEMG) data of biceps brachii and vastus lateralis were recorded from 8 CMT1A patients and 8 matched, healthy individuals during maximal voluntary contraction (MVC) before (pre-fatigue MVC), 10 s after (10-s post-fatigue MVC), and 10 min after (10-min post-fatigue MVC) a fatiguing task at 80% MVC until exhaustion. Results: Only in the lower limb, torque and root mean square of sEMG (RMS) during pre-fatigue MVC were lower (P < 0.05) in patients (91.93 ± 45.95 Nm, 0.11 ± 0.07 mV) than in controls (161.06 ± 75.5 Nm, 0.24 ± 0.16 mV). In the 10-min post-fatigue MVC, muscle-fiber conduction velocity (MFCV) and RMS, expressed as a percentage of pre-fatigue MVC, were lower (P < 0.05) in patients (MFCV 90.3 ± 6.91%, RMS 84.50 ± 9.89%) than in controls (MFCV 100.87 ± 5.1%, RMS 92.71 ± 11.84%). Conclusions: CMT1A patients are not only weaker than healthy individuals in the knee extensors, but they also have impaired neuromuscular recovery after fatigue. Muscle Nerve 46: 434–439, 2012

Introduction: Muscle fatigue could have a greater impact on position sense when antagonists of the movement are fatigued. Hence, this study aimed to compare the effects of antagonist and agonist exercise-induced muscle fatigue on knee joint position sense. Methods: This within-subjects repeated-measures study included 40 subjects. Knee position sense and muscle strength were measured before and after two exercise protocols consisting of 30 consecutive maximal concentric/eccentric contractions of the knee extensors or flexors on the isokinetic dynamometer at an angular velocity of 180°/s (3.14 rad/s). Results: Both exercise protocols increased the absolute angular error (F1.78 = 39.89, P < 0.001; knee extensors protocol from 2.0 ± 1.3° to 3.5 ± 2.0°, knee flexors protocol from 2.1 ± 1.2° to 3.7 ± 2.2°), and no differences were detected between protocols (F1.78 = 0.034, P = 0.855). No changes were observed in the relative angular error. Conclusions: Muscle fatigue affects knee position sense, and the deleterious effect is not different depending upon the muscle group fatigued. Muscle Nerve, 2011.

The purpose of this study was to compare the extent of twitch potentiation (TP) after stimulated or voluntary contractions at identical intensities for the human knee extensor muscles. Isometric knee extensions of 10 s were performed at 20%, 40%, and 60% of maximal voluntary contraction (MVC) torque level, through percutaneous electrical stimulation of the quadriceps at 80 Hz or voluntary contraction. Twitch responses were evoked by stimulating the femoral nerve percutaneously with supramaximal intensity. The extent of TP after the stimulated contraction was greater than that after the voluntary contraction at the 20% MVC torque level, whereas a stimulated contraction induced a smaller extent of TP than did a voluntary contraction at contraction intensities higher than 40% MVC. We suggest that this contraction intensity dependence of differences in TP after stimulated and voluntary isometric conditioning contractions is responsible for differences in the recruitment pattern of motor units during the conditioning contractions.

In this study we investigate the effects of unilateral voluntary contraction (VC) and electromyostimulation superimposed on VC (EV) training on maximal voluntary (MVC) force and cross-sectional area (CSA), as assessed by magnetic resonance imaging of knee extensors. Thirty young men were randomly assigned to either a control group (CG), VC group (VG), or EV group (EVG). The VG and EVG trained the right leg isometrically three sessions per week for 6 weeks. After training, MVC increased in the right leg in the VG and in both legs in the EVG, and EVG was significantly different from CG (all P < 0.01). Increased CSA was found only in the right leg in the VG and EVG (P < 0.01), and correlated with improvements of MVC (r = 0.49, P = 0.01). It appeared that the EV training was equally effective as VC at increasing MVC and CSA, while having a greater cross-education effect. Increased strength without muscle hypertrophy in the unexercised leg of the EVG indicated that neural adaptation was responsible for the cross-education effect.

Performance in high-intensity exercise is dependent on the ability to activate motor units. The main aim of this study was to test the hypothesis that adult men and women (age 19-27 years) are able to maintain higher levels of voluntary activation (VA) in knee extensor muscles than boys and girls (age 12-14 years). The volunteers (n = 7 in each group) performed three 5-s maximal voluntary contractions (MVCs) and a continuous 2-min MVC. The VA and fatigue of the muscles was assessed by applying 250-ms 100-HZ test tetani (TT100HZ). During brief MVCs girls showed lower VA than women, but the difference between boys and men was not significant. During the 2-min MVC, VA in boys and girls was more depressed than in adults. The end-exercise values of the relative TT100HZ torque correlated with the average VA during the exercise. Thus, the results of the study support the hypothesis that children are more susceptible to central fatigue than adults. This should be taken into account when evaluating results of fitness tests that require high levels of motor unit activation.

Surface electromyographic (EMG) crosstalk between vastus lateralis, vastus medialis, and rectus femoris muscles was evaluated by selective electrical stimulation of one muscle and recording from the stimulated and another muscle with linear surface arrays of eight electrodes. The ratio between the amplitude of the signals recorded over nonstimulated and stimulated muscles and their correlation coefficient were used as indices to quantify crosstalk. Single-differential and double-differential detection systems were used with interelectrode distances in the range 10-40 mm. The multichannel EMG signals clearly showed that crosstalk is largely due to nonpropagating potentials that correspond in time to the end of the propagation of the action potentials generated by the stimulated muscle. The crosstalk signal increased with increasing interelectrode distance and was statistically higher for single- than for double-differential recordings. The correlation-based indices of crosstalk were poorly correlated with the amplitude-based indices. Moreover, the characteristic spectral frequencies of the signals detected over the nonstimulated muscles were statistically higher than those from the stimulated muscles. A mathematical model of signal generation was used to explain the experimental findings. This study clarifies many controversial findings of past investigations and creates the basis for crosstalk interpretation, simulation, and reduction.

The purpose of this study was to investigate the relationship between the estimated muscle fiber type and tendon properties in human knee extensors and plantar flexors (n = 50). Measurements included time-to-peak twitch torque (TPT) and tendon properties. TPT did not correlate significantly with the maximal elongation and stiffness of tendon. In conclusion, we found that the muscle fiber type was not related to the properties of tendons.

Muscle strength, activation, and size were studied in 11 very elderly subjects (8 women and 3 men; age range, 85-97 years) who completed 12 weeks of strength training of the knee extensor muscles. Training increased the maximum amount of weight that could be lifted once (134%; P < 0.05) and maximum voluntary isometric strength, measured as both force recorded at the ankle with the knee flexed 90 degrees (17%, ns) and as torque with the knee flexed 60 degrees (37%; P < 0.05). Anatomical lean quadriceps cross-sectional area (LCSA) measured at midthigh using magnetic resonance imaging increased from 27.5 +/- 9.6 cm2 to 30.2 +/- 10.0 cm2 (9.8%; P < 0. 05) after training. Both before and after training, isometric strength was closely related to LCSA, but training resulted in no significant change in muscle force per unit area of quadriceps muscle. Using the twitch interpolation technique, muscle activation during a maximal voluntary isometric contraction was shown to be incomplete in all subjects before training (ranging from 69% to 93%) and was not significantly increased after training. An increase in skeletal muscle mass may have important functional and metabolic benefits for very elderly people.

The purpose of this study was to investigate the behavior of electromyographical (EMG) and vibromyographical (VMG) signals in the time and frequency domains during a fatigue protocol. EMG and VMG records were obtained from the rectus femoris (RF) and vastus lateralis (VL) muscles of 11 adult male subjects during sustained, isometric knee extensor contractions performed at 70% of maximal voluntary contraction (MVC). The average median frequencies of the power density spectra decreased during the fatigue protocol for the EMG (from 73 to 54 Hz for RF, and from 75 to 57 Hz for VL) and the VMG signals (from 40 to 19 Hz for RF, and from 25 to 12 Hz for VL). Raw EMG signals remained the same qualitatively throughout the fatigue protocol, whereas corresponding VMG records appeared to become "smoother." The results of this study indicate that the pronounced decrease in the high-frequency content of the VMG signal may be observed in the time domain as a "smoothing" of the signal, and thus, that the raw VMG records (which may be displayed readily online) can be used to assess qualitatively the onset and progression of muscular fatigue.

The series elastic component (SEC) of Hill's muscle model is sensitive to a modification in muscle functional demand. In this study, SEC stiffness was quantified from quick-released movements in knee extensors of Duchenne muscular dystrophy (DMD) boys to look for possible modifications with the stage of disease. A SEC stiffness index (SI) was defined and was found significantly lower for controls than for DMD. Moreover, a linear relationship was established between mean SI and knee extensors involvement. This suggests a role for this parameter, together with other functional tests, for following patients with DMD.