Evaluation of neck muscle size: long-term reliability and comparison of methods

Although it is important for prospective studies, the reliability of quantitative measures of cervical muscle size on magnetic resonance imaging is not well established. The aim of the current work was to assess the long-term reliability of measurements of cervical muscle size. In addition, we examined the utility of selecting specific sub-regions of muscles at each vertebral level, averaging between sides of the body, and pooling muscles into larger groups. Axial scans from the base of skull to the third thoracic vertebra were performed in 20 healthy male subjects at baseline and 1.5 years later. We evaluated the semi-spinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, anterior scalenes and middle with posterior scalenes. Bland-Altman analysis showed all measurements to be repeatable between testing-days. Reliability was typically best when entire muscle volume was measured (co-efficients of variation (CVs): 3.3-8.1% depending on muscle). However, when the size of the muscle was assessed at specific vertebral levels, similar measurement precision was achieved (CVs: 2.7-7.6%). A median of 4-6 images were measured at the specific vertebral levels versus 18-37 images for entire muscle volume. This would represent considerable time saving. Based on the findings we also recommend measuring both sides of the body and calculating an average value. Pooling specific muscles into the deep neck flexors (CV: 3.5%) and neck extensors (CV: 2.7%) can serve to reduce variability further. The results of the current study help to establish outcome measures for interventional studies and for sample size estimation.

Neuromuscular mechanics and hopping training in elderly

Purpose: The present study examined the effects of repetitive hopping training on muscle activation profiles and fascicle–tendon interaction in the elderly. Methods: 20 physically active elderly men were randomly assigned for training (TG) and control groups (CG). TG performed supervised bilateral short contact hopping training with progressively increasing training volume. Measurements were performed before the training period (BEF) as well as after 2 weeks (2 W) and 11 weeks (11 W) of training. During measurements, the gastrocnemius medialis–muscle (GaM) fascicle and its outer Achilles tendon length changes during hopping were examined by ultrasonography together with electromyographic (EMG) activities of calf muscles, kinematics, and kinetics. Results: At 2 W, the ankle joint stiffness was increased by 21.0 ± 19.3 % and contact time decreased by 9.4 ± 7.8 % in TG. Thereafter, from 2–11 W the jumping height increased 56.2 ± 18.1 % in TG. Simultaneously, tendon forces increased 24.3 ± 19.0 % but tendon stiffness did not change. GaM fascicles shifted to shorter operating lengths after training without any changes in their length modifications during the contact phase of hopping. Normalized EMG amplitudes during hopping did not change with training. Conclusions: The present study shows that 11 W of hopping training improves the performance of physically active elderly men. This improvement is achieved with shorter GaM operating lengths and, therefore, increased fascicle stiffness and improved tendon utilization after training. Based on these results, hopping training could be recommended for healthy fit elderly to retain and improve rapid force production capacity.

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles.

Analysis of phasic and tonic electromyographic signal characteristics: electromyographic synthesis and comparison of novel morphological and linear-envelope approaches

The pattern of tonic and phasic components in an EMG signal reflects the underlying behaviour of the central nervous system (CNS) in controlling the musculature. One avenue for gaining a better understanding of this behaviour is to seek a quantitative characterisation of these phasic and tonic components. We propose that these signal characteristics can range between unvarying, tonic and intermittent, phasic activation through a continuum of EMG amplitude modulation. In this paper, we present two new algorithms for quantifying amplitude modulation: a linear-envelope approach, and a mathematical morphology approach. In addition we present an algorithm for synthesising EMG signals with known amplitude modulation. The efficacy of the synthesis algorithm is demonstrated using real EMG data. We present an evaluation and comparison of the two algorithms for quantifying amplitude modulation based on synthetic data generated by the proposed synthesis algorithm. The results demonstrate that the EMG synthesis parameters represent 91.9% and 96.2% of the variance of linear-envelopes extracted from lumbo-pelvic muscle EMG signals collected from subjects performing a repetitive-movement task. This depended, however, on the muscle and movement-speed considered (F=4.02, p<0.001). Coefficients of determination between input and output amplitude modulation variables were used to quantify the accuracy of the linear-envelope and morphological signal processing algorithms. The linear-envelope algorithm exhibited higher coefficients of determination than the most accurate morphological approach (and hence greater accuracy, T=8.16, p<0.001). Similarly, the standard deviation of the coefficients of determination was 1.691 times smaller (p<0.001). This signal processing algorithm represents a novel tool for the quantification of amplitude modulation in continuous EMG signals and can be used in the study of CNS motor control of the musculature in repetitive-movement tasks.

Resistive vibration exercise reduces lower limb muscle atrophy during 56-day bed-rest

OBJECTIVES: The current study aimed to examine the effectiveness of a resistive vibration exercise countermeasure during prolonged bed-rest in preventing lower-limb muscle atrophy. METHODS: 20 male subjects underwent 56-days of bed-rest and were assigned to either an inactive control, or a countermeasure group which performed high-load resistive exercises (including squats, heel raises and toe raises) with whole-body vibration. Magnetic resonance imaging of the lower-limbs was performed at two-weekly intervals. Volume of individual muscles was calculated. RESULTS: Countermeasure exercise reduced atrophy in the triceps surae and the vastii muscles (F>3.0, p<.025). Atrophy of the peroneals, tibialis posterior and toe flexors was less in the countermeasure-subjects, though statistical evidence for this was weak (F

Resistive simulated weightbearing exercise with whole body vibration reduces lumbar spine deconditioning in bed-rest

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: Determine the effectiveness a resistive exercise countermeasure with whole-body vibration in relation to lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight (bed-rest). SUMMARY OF BACKGROUND DATA: Spinal lengthening, flattening of the spinal curves, increases in disc size, and muscle atrophy are commonly seen in spaceflight simulation. This may represent a risk for low back injury. Consideration of exercise countermeasures against these changes is critical for success of long-term spaceflight missions. METHODS: Twenty healthy male subjects underwent 8-weeks of bed-rest with 6-months follow-up and were randomly allocated to an inactive control or countermeasure exercise group. Magnetic resonance imaging of the lumbo-pelvic region was conducted at regular time-points during and after bed-rest. Using uniplanar images at L4, cross-sectional areas of the multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral abdominal, and rectus abdominis muscles were measured. Sagittal scans were used to assess lumbar spine morphology (length, sagittal disc area and height, and intervertebral angles). RESULTS: The countermeasure group exhibited less multifidus muscle atrophy (P = 0.024) and its atrophy did not persist long-term as in the control group (up to 3-months; P < 0.006). Spinal lengthening (P = 0.03) and increases in disc area (P = 0.041) were also reduced. Significant partial correlations (P < 0.001) existed between spinal morphology and muscle cross-sectional area changes. CONCLUSION: The resistive vibration exercise countermeasure reduced, but did not entirely prevent, multifidus muscle atrophy and passive spinal tissue deconditioning during bed-rest. Atrophy of the multifidus muscles was persistent long-term in the inactive subjects. Future work could consider closer attention to spinal posture during exercise and optimizing exercise dose.

Countermeasures against lumbar spine deconditioning in prolonged bed rest: resistive exercise with and without whole body vibration

To evaluate the effect of short-duration, high-load resistive exercise, with and without whole body vibration on lumbar muscle size, intervertebral disk and spinal morphology changes, and low back pain (LBP) incidence during prolonged bed rest, 24 subjects underwent 60 days of head-down tilt bed rest and performed either resistive vibration exercise (n = 7), resistive exercise only (n = 8), or no exercise (n = 9; 2nd Berlin Bed-Rest Study). Discal and spinal shape was measured from sagittal plane magnetic resonance images. Cross-sectional areas (CSAs) of the multifidus, erector spinae, quadratus lumborum, and psoas were measured on para-axial magnetic resonance images. LBP incidence was assessed with questionnaires at regular intervals. The countermeasures reduced CSA loss in the multifidus, lumbar erector spinae and quadratus lumborum muscles, with greater increases in psoas muscle CSA seen in the countermeasure groups (P ≤ 0.004). There was little statistical evidence for an additional effect of whole body vibration above resistive exercise alone on these muscle changes. Exercise subjects reported LBP more frequently in the first week of bed rest, but this was only significant in resistive exercise only (P = 0.011 vs. control, resistive vibration exercise vs. control: P = 0.56). No effect of the countermeasures on changes in spinal morphology was seen (P ≥ 0.22). The results suggest that high-load resistive exercise, with or without whole body vibration, performed 3 days/wk can reduce lumbar muscle atrophy, but further countermeasure optimization is required.

Influence of prolonged bed-rest on spectral and temporal electromyographic motor control characteristics of the superficial lumbo-pelvic musculature

Little is known about the motor control of the lumbo-pelvic musculature in microgravity and its simulation (bed-rest). Analysis of spectral and temporal electromyographic variables can provide information on motor control relevant for normal function. This study examined the effect of 56-days of bed-rest with 1-year follow-up in 10 male subjects on the median frequency and the activation timing in surface electromyographic recordings from five superficial lumbo-pelvic muscles during a repetitive knee movement task. Trunk fat mass (from whole body-composition measurements) and movement accuracy as possible explanatory factors were included. Increased median frequency was observed in the lumbar erector spinae starting late in bed-rest, but this was not seen in its synergist, the thoracic erector spinae (p<.0001). These changes persisted up to 1-year after bed-rest and were independent of changes in body-composition or movement accuracy. Analysis suggested decreases of median frequency (p<.0001) in the abdominal and gluteal muscles to result from increased (p<.01) trunk fat levels during and after bed-rest. No changes in lumbo-pelvic muscle activation timing were seen. The results suggest that bed-rest particularly affects the shorter lumbar erector spinae and that the temporal sequencing of superficial lumbo-pelvic muscle activation is relatively robust.

Differential atrophy of the postero-lateral hip musculature during prolonged bedrest and the influence of exercise countermeasures

As part of the 2nd Berlin BedRest Study (BBR2-2), we investigated the pattern of muscle atrophy of the postero-lateral hip and hamstring musculature during prolonged inactivity and the effectiveness of two exercise countermeasures. Twenty-four male subjects underwent 60 days of head-down tilt bedrest and were assigned to an inactive control (CTR), resistive vibration exercise (RVE), or resistive exercise alone (RE) group. Magnetic resonance imaging (MRI) of the hip and thigh was taken before, during, and at end of bedrest. Volume of posterolateral hip and hamstring musculature was calculated, and the rate of muscle atrophy and the effect of countermeasure exercises were examined. After 60 days of bedrest, the CTR group showed differential rates of muscle volume loss (F = 21.44; P ≤ 0.0001) with fastest losses seen in the semi-membranosus, quadratus femoris and biceps femoris long head followed by the gluteal and remaining hamstring musculature. Whole body vibration did not appear to have an additional effect above resistive exercise in preserving muscle volume. RE and RVE prevented and/or reduced muscle atrophy of the gluteal, semi-membranosus, and biceps femoris long head muscles. Some muscle volumes in the countermeasure groups displayed faster recovery times than the CTR group. Differential atrophy occurred in the postero-lateral hip musculature following a prolonged period of unloading. Short-duration high-load resistive exercise during bedrest reduced muscle atrophy in the mono-articular hip extensors and selected hamstring muscles. Future countermeasure design should consider including isolated resistive hamstring curls to target this muscle group and reduce the potential for development of muscle imbalances.

Muscle atrophy and changes in spinal morphology: is the lumbar spine vulnerable after prolonged bed-rest?

STUDY DESIGN: prospective longitudinal study. OBJECTIVE: to evaluate the effect of bed-rest on the lumbar musculature and soft-tissues. SUMMARY OF BACKGROUND DATA: earlier work has suggested that the risk of low back injury is higher after overnight bed-rest or spaceflight. Changes in spinal morphology and atrophy in musculature important in stabilizing the spine could be responsible for this, but there are limited data on how the lumbar musculature and vertebral structures are affected during bed-rest. METHODS: nine male subjects underwent 60-days head-down tilt bed-rest as part of the second Berlin Bed-Rest Study. Disc volume, intervertebral spinal length, intervertebral lordosis angle, and disc height were measured on sagittal plane magnetic resonance images. Axial magnetic resonance images were used to measure cross-sectional areas (CSAs) of the multifidus (MF), erector spinae, quadratus lumborum, and psoas from L1 to L5. Subjects completed low back pain (LBP) questionnaires for the first 7-days after bed-rest. RESULTS: increases in disc volume, spinal length (greatest at lower lumbar spine), loss of the lower lumbar lordosis, and move to a more lordotic position at the upper lumbar spine (P < 0.0097) were seen. The CSAs of all muscles changed (P < 0.002), with the rate of atrophy greatest at L4 and L5 in MF (P < 0.002) and at L1 and L2 in the erector spinae (P = 0.0006). Atrophy of the quadratus lumborum was consistent throughout the muscle (P = 0.15), but CSA of psoas muscle increased (P < 0.0001). Subjects who reported LBP after bed-rest showed, before reambulation, greater increases in posterior disc height, and greater losses of MF CSA at L4 and L5 than subjects who did not report pain (all P < 0.085). CONCLUSION: these results provide evidence that changes in the lumbar discs during bed-rest and selective atrophy of the MF muscle may be important factors in the occurrence of LBP after prolonged bed-rest.

Changes in intervertebral disc morphology persist 5 mo after 21-day bed rest

As part of the nutrition-countermeasures (NUC) study in Cologne, Germany in 2010, seven healthy male subjects underwent 21 days of head-down tilt bed rest and returned 153 days later to undergo a second bout of 21-day bed rest. As part of this model, we aimed to examine the recovery of the lumbar intervertebral discs and muscle cross-sectional area (CSA) after bed rest using magnetic resonance imaging and conduct a pilot study on the effects of bed rest in lumbar muscle activation, as measured by signal intensity changes in T(2)-weighted images after a standardized isometric spinal extension loading task. The changes in intervertebral disc volume, anterior and posterior disc height, and intervertebral length seen after bed rest did not return to prebed-rest values 153 days later. While recovery of muscle CSA occurred after bed rest, increases (P ≤ 0.016) in multifidus, psoas, and quadratus lumborum muscle CSA were seen 153 days after bed rest. A trend was seen for greater activation of the erector spinae and multifidus muscles in the standardized loading task after bed rest. Greater reductions of multifidus and psoas CSA muscle and greater increases in multifidus signal intensity with loading were associated with incidence of low back pain in the first 28 days after bed rest (P ≤ 0.044). The current study contributes to our understanding of the recovery of the lumbar spine after 21-day bed rest, and the main finding was that a decrease in spinal extensor muscle CSA recovers within 5 mo after bed rest but that changes in the intervertebral discs persist.

Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise

Protein calcium sensors of the Homer family have been proposed to modulate the activity of various ion channels and nuclear factor of activated T cells (NFAT), the transcription factor modulating skeletal muscle differentiation. We monitored Homer expression and subcellular localization in human skeletal muscle biopsies following 60 d of bedrest [Second Berlin Bedrest Study (BBR2-2)]. Soleus (SOL) and vastus lateralis (VL) biopsies were taken at start (pre) and at end (end) of bedrest from healthy male volunteers of a control group without exercise (CTR; n=9), a resistive-only exercise group (RE; n=7), and a combined resistive/vibration exercise group (RVE; n=7). Confocal analysis showed Homer immunoreactivity at the postsynaptic microdomain of the neuromuscular junction (NMJ) at bedrest start. After bedrest, Homer immunoreactivity decreased (CTR), remained unchanged (RE), or increased (RVE) at the NMJ. Homer2 mRNA and protein were differently regulated in a muscle-specific way. Activated NFATc1 translocates from cytoplasm to nucleus; increased amounts of NFATc1-immunopositive slow-type myonuclei were found in RVE myofibers of both muscles. Pulldown assays identified NFATc1 and Homer as molecular partners in skeletal muscle. A direct motor nerve control of Homer2 was confirmed in rat NMJs by in vivo denervation. Homer2 is localized at the NMJ and is part of the calcineurin-NFATc1 signaling pathway. RVE has additional benefit over RE as countermeasure preventing disuse-induced neuromuscular maladaptation during bedrest.

Resistive vibration exercise during bed-rest reduces motor control changes in the lumbo-pelvic musculature

To understand the effects of a resistive vibration exercise (RVE) countermeasure on changes in lumbo-pelvic muscle motor control during prolonged bed-rest, 20 male subjects took part in the Berlin Bed-Rest Study (in 2003-2005) and were randomised to a RVE group or an inactive control group. Surface electromyographic signals recorded from five superficial lumbo-pelvic muscles during a repetitive knee movement task. The task, which required stabilisation of the lumbo-pelvic region, was performed at multiple movement speeds and at multiple time points during and after bed-rest. After excluding effects that could be attributed to increases in subcutaneous fat changes and improvements in movement skill, we found that the RVE intervention ameliorated the generalised increases in activity ratios between movement speeds (p⩽0.012), reductions in lumbo-pelvic extensor and flexor co-contraction (p=0.058) and increases in root-mean-square electromyographic amplitude (p=0.001) of the lumbar erector spinae muscles. Effects of RVE on preventing increases in amplitude-modulation (p=0.23) of the lumbar erector spinae muscles were not significant. Few significant changes in activation-timing were seen. The RVE intervention during bed-rest, with indirect loading of the spine during exercise, was capable of reducing some, but not all, motor control changes in the lumbo-pelvic musculature during and after bed-rest.

Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy

Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting.