Julien Gondin

Time‐of‐Day Effect on the Torque and Neuromuscular Properties of Dominant and Non‐Dominant Quadriceps Femoris

The study was conducted first, to determine the possibility of a dichotomy between circadian rhythm of maximal torque production of the knee extensors of the dominant and non‐dominant legs, and second, to determine whether the possible dichotomy could be linked to a change in the downward drive of the central nervous system and/or to phenomena prevailing at the muscular level. The dominant leg was defined as the one with which subjects spontaneously kick a football. Tests were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. To distinguish the neural and muscular mechanisms that influence muscle strength, the electromyographic and mechanical muscle responses associated with electrically evoked and/or voluntary contractions of the human quadriceps and semi‐tendinosus muscles for each leg were recorded and compared. The main finding was an absence of interaction between time‐of‐day and dominance effects on the torque associated with maximal voluntary contraction (MVC) of both quadriceps. A significant time‐of‐day effect on MVC torque of the knee extensors was observed for the dominant and non‐dominant legs when the data were collapsed, with highest values occurring at 18:00 h (p<0.01). From cosinor analysis, a circadian rhythm was documented (p<0.001) with the peak (acrophase) estimated at 18:18±00:12 h and amplitude (one‐half the peak‐to‐trough variation) of 3.3±1.1%. Independent of the leg tested, peripheral mechanisms demonstrated a significant time‐of‐day effect (p<0.05) on the peak‐torque of the single and doublet stimulations, with maximal levels attained at 18:00 h. The central activation of the quadriceps muscle of each leg remained unchanged during the day. The present results confirmed previous observations that muscle torque changes in a predictable manner during the 24 h period, and that the changes are linked to modifications prevailing at the muscular, rather than the neural, level. The similar rhythmicity observed in this study between the dominant and non‐dominant legs provides evidence that it is not essential to test both legs when simple motor tasks are investigated as a function of the time of day.

Differences in twitch potentiation between voluntary and stimulated quadriceps contractions of equal intensity

This study compared the extent of twitch and M‐wave potentiation (POT) between voluntary and stimulated quadriceps contractions performed at the same intensity. Sixteen healthy men completed 10‐s isometric knee extensions at 40% of the maximal voluntary contraction torque under electrical stimulation and voluntary conditions. Single stimuli were delivered to the femoral nerve to evoke twitches before (PRE) and from 3 to 600 s after the end of each conditioning contraction. Changes in twitch contractile properties and M‐wave characteristics were compared between the conditions. The extent of twitch peak torque POT was smaller for the stimulated (122±20% of PRE) than for the voluntary condition (133±20% of PRE). The magnitude of POT for the maximal rate of twitch torque development was also smaller for the stimulated trial. Rectus femoris M‐wave amplitude was potentiated by the voluntary but not by the stimulated contraction. It was concluded that stimulated contractions resulted in smaller twitch and M‐wave POT than voluntary contractions, despite equivalent torque output and duration. The spatially and temporally fixed recruitment of motor units with electrical stimulation and therefore the lower number of activated motor units compared with voluntary actions of equal intensity could explain the present findings.

Neural drive preservation after detraining following neuromuscular electrical stimulation training

The purpose of the study was to investigate the behaviour of the central nervous system when 5 weeks of neuromuscular electrical stimulation (NMES) training was followed by 5 weeks of detraining. Nineteen males were divided into the neuromuscular electrostimulated group (EG, n=12) and the control group (CG, n=7). The training program consisted of 15 sessions of isometric NMES over a 5-week period. The EG subjects were tested before training (PRE), after 5 weeks of NMES training (POST) and after 5 weeks of detraining (DE) while CG subjects were only tested at PRE and at POST. Soleus (SOL) and gastrocnemii (GAS) maximal H-reflex and M-wave potentials were evoked at rest (i.e., H(max) and M(max), respectively) and during maximal voluntary contraction (MVC) (i.e., H(sup) and M(sup), respectively). SOL and GAS V-wave were recorded by supramaximal stimulation delivered during MVC. SOL and GAS electromyographic (EMG) activity as well as muscle activation were also assessed during MVC. After training, plantar flexor MVC increased significantly by 22% (P<0.001). Torque gains were associated with an increase in muscle activation (P<0.05), SOL and GAS normalized EMG activity (P<0.01 and P<0.05, respectively) and V/M(sup) ratios (P<0.01 and P<0.05, respectively). No significant changes occurred in any of these parameters between POST and DE. H(max)/M(max) and H(sup)/M(sup) ratios for both muscles were unchanged after both the training and detraining periods. In conclusion, the NMES training-induced neural adaptations were maintained after detraining, suggesting that neural changes are long-lasting and did not affect the elements of H-reflex pathways.

Wide-pulse-high-frequency neuromuscular stimulation of triceps surae induces greater muscle fatigue compared with conventional stimulation

We compared the extent and origin of muscle fatigue induced by short-pulse-low-frequency [conventional (CONV)] and wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation. We expected CONV contractions to mainly originate from depolarization of axonal terminal branches (spatially determined muscle fiber recruitment) and WPHF contractions to be partly produced via a central pathway (motor unit recruitment according to size principle). Greater neuromuscular fatigue was, therefore, expected following CONV compared with WPHF. Fourteen healthy subjects underwent 20 WPHF (1 ms-100 Hz) and CONV (50 μs-25 Hz) evoked isometric triceps surae contractions (work/rest periods 20:40 s) at an initial target of 10% of maximal voluntary contraction (MVC) force. Force-time integral of the 20 evoked contractions (FTI) was used as main index of muscle fatigue; MVC force loss was also quantified. Central and peripheral fatigue were assessed by voluntary activation level and paired stimulation amplitudes, respectively. FTI in WPHF was significantly lower than in CONV (21,717 ± 11,541 vs. 37,958 ± 9,898 N·s P<0,001). The reductions in MVC force (WPHF: -7.0 ± 2.7%; CONV: -6.2 ± 2.5%; P < 0.01) and paired stimulation amplitude (WPHF: -8.0 ± 4.0%; CONV: -7.4 ± 6.1%; P < 0.001) were similar between conditions, whereas no change was observed for voluntary activation level (P > 0.05). Overall, our results showed a different motor unit recruitment pattern between the two neuromuscular electrical stimulation modalities with a lower FTI indicating greater muscle fatigue for WPHF, possibly limiting the presumed benefits for rehabilitation programs.

EFFECTS OF STIMULATION FREQUENCY AND PULSE DURATION ON FATIGUE AND METABOLIC COST DURING A SINGLE BOUT OF NEUROMUSCULAR ELECTRICAL STIMULATION

We have investigated the effects of stimulation frequency and pulse duration on fatigue and energy metabolism in rat gastrocnemius muscle during a single bout of neuromuscular electrical stimulation (NMES). Electrical pulses were delivered at 100 Hz (1‐ms pulse duration) and 20 Hz (5‐ms pulse duration) for the high (HF) and low (LF) frequency protocols, respectively. As a standardization procedure, the averaged stimulation intensity, the averaged total charge, the initial peak torque, the duty cycle, the contraction duration and the torque‐time integral were similar in both protocols. Fatigue was assessed using two testing trains delivered at a frequency of 100 Hz and 20 Hz before and after each protocol. Metabolic changes were investigated in vivo using 31P‐magnetic resonance spectroscopy (31P‐MRS) and in vitro in freeze‐clamped muscles. Both LF and HF NMES protocols induced the same decrease in testing trains and metabolic changes. We conclude that, under carefully controlled and comparable conditions, the use of low stimulation frequency and long pulse duration do not minimize the occurrence of muscle fatigue or affect the corresponding stimulation‐induced metabolic changes so that this combination of stimulation parameters would not be adequate in the context of rehabilitation. Muscle Nerve, 2010

Effect of electrostimulation training–detraining on neuromuscular fatigue mechanisms

The aim of this study was to evaluate the effects of neuromuscular electrical stimulation (NMES) training and subsequent detraining on neuromuscular fatigue mechanisms. Ten young healthy men completed one NMES fatigue protocol before and after a NMES training program of 4 weeks and again after 4 weeks of detraining. Muscle fatigue (maximal voluntary torque loss), central fatigue (activation failure), and peripheral fatigue (transmission failure and contractile failure) of the plantar flexor muscles were assessed by using a series of electrically evoked and voluntary contractions with concomitant electromyographic and torque recordings. At baseline, maximal voluntary torque decreased significantly with fatigue (P<0.001), due to both activation and transmission failure. After detraining, maximal voluntary torque loss was significantly reduced (P<0.05). In the same way, the relative decrease in muscle activation after training and detraining was significantly lower compared to baseline values (P<0.05). Short-term NMES training-detraining of the plantar flexor muscles significantly reduced the muscle fatigue associated to one single NMES exercise session. This was mainly attributable to a reduction in activation failure, i.e., lower central fatigue, probably as a result of subjects accommodation to pain and discomfort during NMES.

Multimodal MRI and 31P-MRS Investigations of the ACTA1(Asp286Gly) Mouse Model of Nemaline Myopathy Provide Evidence of Impaired In Vivo Muscle Function, Altered Muscle Structure and Disturbed Energy Metabolism

Nemaline myopathy (NM), the most common non-dystrophic congenital disease of skeletal muscle, can be caused by mutations in the skeletal muscle α-actin gene (ACTA1) (~25% of all NM cases and up to 50% of severe forms of NM). Muscle function of the recently generated transgenic mouse model carrying the human Asp286Gly mutation in the ACTA1 gene (Tg(ACTA1)Asp286Gly) has been mainly investigated in vitro. Therefore, we aimed at providing a comprehensive picture of the in vivo hindlimb muscle function of Tg(ACTA1)Asp286Gly mice by combining strictly noninvasive investigations. Skeletal muscle anatomy (hindlimb muscles, intramuscular fat volumes) and microstructure were studied using multimodal magnetic resonance imaging (Dixon, T2, Diffusion Tensor Imaging [DTI]). Energy metabolism was studied using 31-phosphorus Magnetic Resonance Spectroscopy (31P-MRS). Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (1–150 Hz) and a fatigue protocol (6 min–1.7 Hz). Tg(ACTA1)Asp286Gly mice showed a mild muscle weakness as illustrated by the reduction of both absolute (30%) and specific (15%) maximal force production. Dixon MRI did not show discernable fatty infiltration in Tg(ACTA1)Asp286Gly mice indicating that this mouse model does not reproduce human MRI findings. Increased T2 values were observed in Tg(ACTA1)Asp286Gly mice and might reflect the occurrence of muscle degeneration/regeneration process. Interestingly, T2 values were linearly related to muscle weakness. DTI experiments indicated lower λ2 and λ3 values in Tg(ACTA1)Asp286Gly mice, which might be associated to muscle atrophy and/or the presence of histological anomalies. Finally 31P-MRS investigations illustrated an increased anaerobic energy cost of contraction in Tg(ACTA1)Asp286Gly mice, which might be ascribed to contractile and non-contractile processes. Overall, we provide a unique set of information about the anatomic, metabolic and functional consequences of the Asp286Gly mutation that might be considered as relevant biomarkers for monitoring the severity and/or the progression of NM and for assessing the efficacy of potential therapeutic interventions.

In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype

Nemaline myopathy is the most common congenital skeletal muscle disease, and mutations in the nebulin gene account for 50% of all cases. Recent studies suggest that the disease severity might be related to the nebulin expression levels. Considering that mutations in the nebulin gene are typically recessive, one would expect that a single functional nebulin allele would maintain nebulin protein expression which would result in preserved skeletal muscle function. We investigated skeletal muscle function of heterozygous nebulin knock-out (i.e., nebulin(+/-)) mice using a multidisciplinary approach including protein and gene expression analysis and combined in vivo and in vitro force measurements. Skeletal muscle anatomy and energy metabolism were studied strictly non-invasively using magnetic resonance imaging and 31P-magnetic resonance spectroscopy. Maximal force production was reduced by around 16% in isolated muscle of nebulin(+/-) mice while in vivo force generating capacity was preserved. Muscle weakness was associated with a shift toward a slower proteomic phenotype, but was not related to nebulin protein deficiency or to an impaired energy metabolism. Further studies would be warranted in order to determine the mechanisms leading to a mild skeletal muscle phenotype resulting from the expression of a single nebulin allele.

Combined MRI and 31P-MRS Investigations of the ACTA1(H40Y) Mouse Model of Nemaline Myopathy Show Impaired Muscle Function and Altered Energy Metabolism

Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1) account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and 31Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1–150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (−40%) and specific (−25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.

Effect of Playing Surface Properties on Neuromuscular Fatigue in Tennis

PURPOSE The aim of this study was to evaluate the effect of the playing surface properties on the development of neuromuscular fatigue in tennis. METHODS Ten subjects played randomly two tennis matches on hard court (HARD) and clay court (CLAY) for an effective playing duration of 45 min (i.e., corresponding approximately to a 3-h game). Before and after each match, the maximal voluntary contraction (MVC) force of the plantar flexors, the maximal voluntary activation level, the maximal compound muscle action characteristic, and the EMG activity were determined on the soleus (SOL) and lateralis gastrocnemius (LG) muscles. Tetanic and single stimulations were also delivered to evaluate the presence of low-frequency fatigue and contractile impairment. Finally, reflex responses were evoked on the relaxed muscle (H-reflex) and during MVC (H-reflex and V-wave). RESULTS Statistical analysis did not reveal any significant difference between playing surfaces. MVC was similarly reduced after the game (HARD, -9.1% ± 8.7%; CLAY, -4.3% ± 19.9%) and was associated with alterations of the contractile properties of the plantar flexor muscles. The implication of central factors was less clear, as evidenced by the significant reduction (P < 0.05) of the H-reflex on the relaxed LG (HARD, -16.2% ± 33.3%; CLAY, -23.9% ± 54.0%) and SOL (HARD, -16.1% ± 48.9%; CLAY, -34.9% ± 35.9%) and the nonsignificant reduction of the activation level. In addition, the reflex responses evoked during MVC were not significantly modified by the exercise. CONCLUSION These results suggest that the ground surface properties influence neither the extent nor the origin of neuromuscular fatigue in tennis. The moderate force decrement observed in the current study was mainly associated with peripheral fatigue.