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The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements.

Purpose: This study aimed at investigating the mechanisms involved in the force reduction induced by two electrical stimulation (ES) protocols that were designed to activate motor units differently., Methods: The triceps surae of 11 healthy subjects (8 men; age, ~28 yr) was activated using ES applied over the tibial nerve. Two ES protocols (conventional [CONV]: 20 Hz, 0.05 ms vs wide-pulse high-frequency [WPHF]: 80 Hz, 1 ms) were performed and involved 40 trains (6 s on-6 s off) delivered at an intensity (IES) evoking 20% of maximal voluntary contraction. To analyze the mechanical properties of the motor units activated at IES, force-frequency relation was evoked before and after each protocol. H-reflex and M-wave responses evoked by the last stimulation pulse were also assessed during each ES protocol. Electromyographic responses (∑EMG) were recorded after each train to analyze the behavior of the motor units activated at IES. Metabolic variables, including relative concentrations of phosphocreatine and inorganic phosphate as well as intracellular pH, were assessed using P-MR spectroscopy during each protocol., Results: Larger H-reflex amplitudes were observed during WPHF as compared with CONV, whereas opposite findings were observed for M-wave amplitudes. Despite this difference, both the force reduction (-26%) and metabolic changes were similar between the two protocols. The CONV protocol induced a rightward shift of the force-frequency relation, whereas a significant reduction of the ∑EMG evoked at IES was observed only for the WPHF., Conclusions: These results suggest that a decreased number of active motor units mainly contributed to WPHF-induced force decrease, whereas intracellular processes were most likely involved in the force reduction occurring during CONV stimulation.

Background & Aims: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage., Methods: (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage., Results: No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4)., Conclusions: The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In the present study, we proposed an original and robust methodology which combines the spatial normalization of skeletal muscle images, the statistical parametric mapping (SPM) analysis and the use of a specific parcellation in order to accurately localize and quantify the extent of skeletal muscle damage within the four heads of the quadriceps femoris. T2 maps of thigh muscles were characterized before, two (D2) and four (D4) days after 40 maximal isometric electrically-evoked contractions in 25 healthy young males. On the basis of SPM analysis of coregistrated T2 maps, the alterations were similarly detected at D2 and D4 in the superficial and distal regions of the vastus medialis (VM) whereas the proportion of altered muscle was higher in deep muscle regions of the vastus lateralis at D4 (deep: 35 ± 25%, superficial: 23 ± 15%) as compared to D2 (deep: 18 ± 13%, superficial: 17 ± 13%). The present methodology used for the first time on skeletal muscle would be of utmost interest to detect subtle intramuscular alterations not only for the diagnosis of muscular diseases but also for assessing the efficacy of potential therapeutic interventions and clinical treatment strategies.

Objective: In contrast to conventional (CONV) neuromuscular electrical stimulation (NMES), the use of "wide-pulse, high-frequencies" (WPHF) can generate higher forces than expected by the direct activation of motor axons alone. We aimed at investigating the occurrence, magnitude, variability and underlying neuromuscular mechanisms of these "Extra Forces" (EF)., Methods: Electrically-evoked isometric plantar flexion force was recorded in 42 healthy subjects. Additionally, twitch potentiation, H-reflex and M-wave responses were assessed in 13 participants. CONV (25Hz, 0.05ms) and WPHF (100Hz, 1ms) NMES consisted of five stimulation trains (20s on-90s off)., Results: K-means clustering analysis disclosed a responder rate of almost 60%. Within this group of responders, force significantly increased from 4% to 16% of the maximal voluntary contraction force and H-reflexes were depressed after WPHF NMES. In contrast, non-responders showed neither EF nor H-reflex depression. Twitch potentiation and resting EMG data were similar between groups. Interestingly, a large inter- and intrasubject variability of EF was observed., Conclusion: The responder percentage was overestimated in previous studies., Significance: This study proposes a novel methodological framework for unraveling the neurophysiological mechanisms involved in EF and provides further evidence for a central contribution to EF in responders., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remain to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise, but the magnitude of muscle energetics alterations for NMES EIMD has never been documented., Methods: ³¹P magnetic resonance spectroscopy measurements were performed in 13 young healthy males during a standardized rest-exercise-recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec)., Results: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly owing to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%)., Conclusion: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of noncontractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.

Background: Histological anomalies associated with malignant hyperthermia (MH) have been scarcely reported. In some patients susceptible to MH (MHS), central cores have been identified and a genetic association has been proposed, but multiminicore lesions have not been systematically reported., Objective: To analyze the association between multiminicores and MHS in a large family with MH with an approach combining histology, in vitro contracture tests, and genetic analysis., Patients and Methods: Twenty-nine members of an MH family (147 members) were investigated., Main Outcome Measures: Muscle biopsy specimens were analyzed histologically and with in vitro contracture tests. Genetic analyses were performed to determine the presence of mutations in the ryanodine receptor (RYR1) gene., Results: According to the gold standard in vitro contracture tests, 17 patients were diagnosed as having MHS and 10 as not being susceptible. Multiminicores were found in 16 of the 17 MHS patients and in a single nonsusceptible participant. A linkage between the MH trait and the RYR1 locus in chromosome 19 was demonstrated, whereas no already known mutations were found. Two missense heterozygous mutations (R2676W and T2787S) were identified from sequencing of the entire coding complementary DNA. Overall, we found a significant association between MHS and the presence of multiminicores (chi(2) = 26.5, P<.001) on the one hand and the presence of new mutations in the RYR1 gene (chi(2) = 19.0, P<.001) on the other hand. This remarkably high occurrence of multiminicores in an MHS family is uncommon, and genetic analyses indicate that the association between multiminicores and MHS is linked to a novel R2656W and T2787S substitution present on the same allele of the RYR1 gene., Conclusions: These results indicate that multiminicore lesions are observed in MHS patients with neither clinical signs related to multiminicore disease nor histological features of congenital myopathies. These multiminicore lesions may be secondary to mutations in the RYR1 gene. As a consequence, these patients must be distinguished from patients with multiminicore disease and from other MHS patients for whom multiminicores are not observed.

Interindividual variations in skeletal muscle metabolism make comparative analyses difficult. In this study, we have addressed the issue of capturing the variability of metabolic performance observed during muscle exercise in humans by using an original method of normalization.Metabolic changes induced by various kinds of exercise were investigated using 31P magnetic resonance spectroscopy (MRS) at 4.7 T in 65 normal subjects (23 women and 42 men) and 12 patients with biopsy-proven muscular disorders. Large variations in the extent of PCr breakdown and intracellular acidosis were recorded among subjects and exercise protocols. For all the data pooled, the amplitude of mechanical performance accounts for 50% of these variations. When scaled to the work output, variations of PCr consumption account for 65% of pH changes through a linear relationship. This linear relationship was substantially improved (90%) when both variables were scaled to the square of work output performed (P1 and P2). By capturing most of the initial interindividual variability (90%), P1 vs. P2 relationship represents an ideal standardization procedure, independent of any anthropometric measurements. This relationship also discloses a significant link between the extent of PCr breakdown and intracellular acidosis regardless of exercise protocol. Moreover, changes in the slope of the P1 vs. P2 regression curve, as measured in old subjects and in selected patients, directly reflect alterations of energy production in muscle.