Common synaptic inputs and persistent inward currents of vastus lateralis motor units are reduced in older male adults.

Although muscle atrophy may partially account for age-related strength decline, it is further influenced by alterations of neural input to muscle. Persistent inward currents (PIC) and the level of common synaptic inputs to motoneurons influence neuromuscular function. However, these have not yet been described in the aged human quadriceps. High-density surface electromyography (HDsEMG) signals were collected from the vastus lateralis of 15 young (mean ± SD, 23 ± 5 y) and 15 older (67 ± 9 y) men during submaximal sustained and 20-s ramped contractions. HDsEMG signals were decomposed to identify individual motor unit discharges, from which PIC amplitude and intramuscular coherence were estimated. Older participants produced significantly lower knee extensor torque (p < 0.001) and poorer force tracking ability (p < 0.001) than young. Older participants also had lower PIC amplitude (p = 0.001) and coherence estimates in the alpha frequency band (p < 0.001) during ramp contractions when compared to young. Persistent inward currents and common synaptic inputs are lower in the vastus lateralis of older males when compared to young. These data highlight altered neural input to the clinically and functionally important quadriceps, further underpinning age-related loss of function which may occur independently of the loss of muscle mass.

Menstrual Cycle Associated Alteration of Vastus Lateralis Motor Unit Function.

BACKGROUND: Estrogen and progesterone are the primary female sex hormones and have net excitatory and inhibitory effects, respectively, on neuronal function. Fluctuating concentrations across the menstrual cycle has led to several lines of research in relation to neuromuscular function and performance; however evidence from animal and cell culture models has yet to be demonstrated in human motor units coupled with quantification of circulating hormones. Intramuscular electromyography was used to record motor unit potentials and corresponding motor unit potential trains from the vastus lateralis of nine eumenorrheic females during the early follicular, ovulation and mid luteal phases of the menstrual cycle, alongside assessments of neuromuscular performance. Multi-level regression models were applied to explore effects of time and of contraction level. Statistical significance was accepted as p < 0.05. RESULTS: Knee extensor maximum voluntary contraction, jump power, force steadiness, and balance did not differ across the menstrual phases (all p > 0.4). Firing rate of low threshold motor units (10% maximum voluntary contraction) was lower during the ovulation and mid luteal phases (ß = - 0.82 Hz, p < 0.001), with no difference in motor unit potentials analysed from 25% maximum voluntary contraction contractions. Motor unit potentials were more complex during ovulation and mid luteal phase (p < 0.03), with no change in neuromuscular junction transmission instability (p > 0.3). CONCLUSIONS: Assessments of neuromuscular performance did not differ across the menstrual cycle. The suppression of low threshold motor unit firing rate during periods of increased progesterone may suggest a potential inhibitory effect and an alteration of recruitment strategy; however this had no discernible effect on performance. These findings highlight contraction level-dependent modulation of vastus lateralis motor unit function over the eumenorrheic cycle, occurring independently of measures of performance.

Acute adaptation of central and peripheral motor unit features to exercise-induced fatigue differs with concentric and eccentric loading.

NEW FINDINGS: What is the central question of this study? Conflicting evidence exists on motor unit (MU) firing rate in response to exercise-induced fatigue, possibly due to the contraction modality used: Do MU properties adapt similarly following concentric and eccentric loading? What is the main finding and its importance? MU firing rate increased following eccentric loading only despite a decline in absolute force. Force steadiness deteriorated following both loading methods. Central and peripheral MU features are altered in a contraction type-dependant manner, which is an important consideration for training interventions. ABSTRACT: Force output of muscle is partly mediated by the adjustment of motor unit (MU) firing rate (FR). Disparities in MU features in response to fatigue may be influenced by contraction type, as concentric (CON) and eccentric (ECC) contractions demand variable amounts of neural input, which alters the response to fatigue. This study aimed to determine the effects of fatigue following CON and ECC loading on MU features of the vastus lateralis (VL). High-density surface (HD-sEMG) and intramuscular (iEMG) electromyography were used to record MU potentials (MUPs) from bilateral VLs of 12 young volunteers (six females) during sustained isometric contractions at 25% and 40% of the maximum voluntary contraction (MVC), before and after completing CON and ECC weighted stepping exercise. Multi-level mixed effects linear regression models were performed with significance assumed as P < 0.05. MVC decreased in both CON and ECC legs post-exercise (P < 0.0001), as did force steadiness at both 25% and 40% MVC (P < 0.004). MU FR increased in ECC at both contraction levels (P < 0.001) but did not change in CON. FR variability increased in both legs at 25% and 40% MVC following fatigue (P < 0.01). From iEMG measures at 25% MVC, MUP shape did not change (P > 0.1) but neuromuscular junction transmission instability increased in both legs (P < 0.04), and markers of fibre membrane excitability increased following CON only (P = 0.018). These data demonstrate that central and peripheral MU features are altered following exercise-induced fatigue and differ according to exercise modality. This is important when considering interventional strategies targeting MU function.

Contrast-enhanced ultrasound repeatability for the measurement of skeletal muscle microvascular blood flow.

NEW FINDINGS: What is the central question of this study? Contrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion but its day-to-day repeatability over time has not yet been validated: is CEUS a repeatable method for the measurement of skeletal muscle microvascular blood flow (MBF) at rest and in response to exercise, across independent assessment sessions? What is the main finding and its importance? A strong agreement between CEUS MBF measures across sessions suggests it is a repeatable method for assessing skeletal muscle perfusion over time. This validation provides confidence for incorporating these measures into longitudinal studies such as a chronic intervention or disease progression to gain further knowledge of skeletal muscle microvascular function. ABSTRACT: Contrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion. However, its repeatability over time has not yet been validated and therefore its use in longitudinal measures (i.e., exploring the impact of a chronic intervention or disease progression) is limited. This study aimed to determine the repeatability of CEUS for the measurement of skeletal muscle microvascular blood flow (MBF) at baseline and in response to exercise, across independent assessment sessions. Ten healthy volunteers (five female; 30 ± 6 years) had CEUS of the right vastus lateralis recorded in two separate sessions, 14 days apart. Measurements were taken at baseline, during an isometric leg extension and during recovery. Acoustic intensity data from a region of interest were plotted as a replenishment curve to obtain blood volume (A) and flow velocity (ß) values from a one-phase association non-linear regression of mean tissue echogenicity. Linear regression and Bland-Altman analyses of A and ß values were performed, with significance assumed as P < 0.05. Strong positive correlations were observed across sessions for all A and ß values (both P < 0.0001). Bland-Altman analysis showed a bias (SD) of -0.013 ± 1.24 for A and -0.014 ± 0.31 for ß. A bias of 0.201 ± 0.770 at baseline, 0.527 ± 1.29 during contraction and -0.203 ± 1.29 at recovery was observed for A, and -0.0328 ± 0.0853 (baseline), -0.0446 ± 0.206 (contraction) and 0.0382 ± 0.233 (recovery) for ß. A strong agreement between CEUS MBF measures across independent sessions suggests it to be a repeatable method for assessing skeletal muscle perfusion over time, and therefore facilitates wider use in longitudinal studies.

Training-induced improvements in knee extensor force accuracy are associated with reduced vastus lateralis motor unit firing variability.

NEW FINDINGS: What is the central question of this study? Can bilateral knee extensor force accuracy be improved following 4 weeks of unilateral force accuracy training and are there any subsequent alterations to central and/or peripheral motor unit features? What is the main finding and its importance? In the trained limb only, knee extensor force tracking accuracy improved with reduced motor unit firing rate variability in the vastus lateralis, and there was no change to neuromuscular junction transmission instability. Interventional strategies to improve force accuracy may be directed to older/clinical populations where such improvements may aid performance of daily living activities. ABSTRACT: Muscle force output during sustained submaximal isometric contractions fluctuates around an average value and is partly influenced by variation in motor unit (MU) firing rates. MU firing rate (FR) variability seemingly reduces following exercise training interventions; however, much less is known with respect to peripheral MU properties. We therefore investigated whether targeted force accuracy training could lead to improved muscle functional capacity and control, in addition to determining any alterations of individual MU features. Ten healthy participants (seven females, three males, 27 ± 6 years, 170 ± 8 cm, 69 ± 16 kg) underwent a 4-week supervised, unilateral knee extensor force accuracy training intervention. The coefficient of variation for force (FORCECoV ) and sinusoidal wave force tracking accuracy (FORCESinu ) were determined at 25% maximal voluntary contraction (MVC) pre- and post-training. Intramuscular electromyography was utilised to record individual MU potentials from the vastus lateralis (VL) muscles at 25% MVC during sustained contractions, pre- and post-training. Knee extensor muscle strength remained unchanged following training, with no improvements in unilateral leg-balance. FORCECoV and FORCESinu significantly improved in only the trained knee extensors by ∼13% (P = 0.01) and ∼30% (P < 0.0001), respectively. MU FR variability significantly reduced in the trained VL by ∼16% (n = 8; P = 0.001), with no further alterations to MU FR or neuromuscular junction transmission instability. Our results suggest muscle force control and tracking accuracy is a trainable characteristic in the knee extensors, which is likely explained by the reduction in MU FR variability which was apparent in the trained limb only.

Ageing and exercise-induced motor unit remodelling.

A motor unit (MU) comprises the neuron cell body, its corresponding axon and each of the muscle fibres it innervates. Many studies highlight age-related reductions in the number of MUs, yet the ability of a MU to undergo remodelling and to expand to rescue denervated muscle fibres is also a defining feature of MU plasticity. Remodelling of MUs involves two coordinated processes: (i) axonal sprouting and new branching growth from adjacent surviving neurons, and (ii) the formation of key structures around the neuromuscular junction to resume muscle-nerve communication. These processes rely on neurotrophins and coordinated signalling in muscle-nerve interactions. To date, several neurotrophins have attracted focus in animal models, including brain-derived neurotrophic factor and insulin-like growth factors I and II. Exercise in older age has demonstrated benefits in multiple physiological systems including skeletal muscle, yet evidence suggests this may also extend to peripheral MU remodelling. There is, however, a lack of research in humans due to methodological limitations which are easily surmountable in animal models. To improve mechanistic insight of the effects of exercise on MU remodelling with advancing age, future research should focus on combining methodological approaches to explore the in vivo physiological function of the MU alongside alterations of the localised molecular environment.

Neuromuscular recruitment strategies of the vastus lateralis according to sex.

AIM: Despite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex-based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalized forces and during progressive increases in force. METHODS: The study includes 29 healthy male and 31 healthy female participants (18-35 years). Intramuscular electromyography (iEMG) was used to record individual motor unit potentials (MUPs) and near-fibre MUPs from the vastus lateralis (VL) during 10% and 25% maximum isometric voluntary contractions (MVC), and spike-triggered averaging was used to obtain motor unit number estimates (MUNE) of the VL. RESULTS: Males exhibited greater muscle strength (P < .001) and size (P < .001) than females, with no difference in force steadiness at 10% or 25% MVC. Females had 8.4% and 6.5% higher FR at 10% and 25% MVC, respectively (both P < .03), while the MUP area was 33% smaller in females at 10% MVC (P < .02) and 26% smaller at 25% MVC (P = .062). However, both sexes showed similar increases in MU size and FR when moving from low- to mid-level contractions. There were no sex differences in any near-fibre MUP parameters or in MUNE. CONCLUSION: In the vastus lateralis, females produce muscle force via different neuromuscular recruitment strategies to males which is characterized by smaller MUs discharging at higher rates. However, similar strategies are employed to increase force production from low- to mid-level contractions. These findings of similar proportional increases between sexes support the use of mixed sex cohorts in studies of this nature.

Lifelong exercise is associated with more homogeneous motor unit potential features across deep and superficial areas of vastus lateralis.

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Seasonal weight changes in laboratory ferrets.

Ferrets (Mustela putorius furo) are a valuable animal model used in biomedical research. Like many animals, ferrets undergo significant variation in body weight seasonally, affected by photoperiod, and these variations complicate the use weight as an indicator of health status. To overcome this requires a better understanding of these seasonal weight changes. We provide a normative weight data set for the female ferret accounting for seasonal changes, and also investigate the effect of fluid regulation on weight change. Female ferrets (n = 39) underwent behavioural testing from May 2017 to August 2019 and were weighed daily, while housed in an animal care facility with controlled light exposure. In the winter (October to March), animals experienced 10 hours of light and 14 hours of dark, while in summer (March to October), this contingency was reversed. Individual animals varied in their body weight from approximately 700 to 1200 g. However, weights fluctuated with light cycle, with animals losing weight in summer, and gaining weight in winter such that they fluctuated between approximately 80% and 120% of their long-term average. Ferrets were weighed as part of their health assessment while experiencing water regulation for behavioural training. Water regulation superimposed additional weight changes on these seasonal fluctuations, with weight loss during the 5-day water regulation period being greater in summer than winter. Analysing the data with a Generalised Linear Model confirmed that the percentage decrease in weight per week was relatively constant throughout the summer months, while the percentage increase in body weight per week in winter decreased through the season. Finally, we noted that the timing of oestrus was reliably triggered by the increase in day length in spring. These data establish a normative benchmark for seasonal weight variation in female ferrets that can be incorporated into the health assessment of an animal's condition.

Sit-to-walk and sit-to-stand-and-walk task dynamics are maintained during rising at an elevated seat-height independent of lead-limb in healthy individuals.

INTRODUCTION: Sit-to-walk (STW) is a common transitional motor task not usually included in rehabilitation. Typically, sit-to-stand (STS), pause, then gait initiation (GI) before walking is used, which we term sit-to-stand-and-walk (STSW). Separation between centre-of-pressure (COP) and whole-body centre-of-mass (BCOM) during GI is associated with dynamic postural stability. Rising from seats higher than knee-height (KH) is more achievable for patients, but whether this and/or lead-limb significantly affects task dynamics is unclear. This study tested whether rising from seat-heights and lead-limb affects STW and STSW task dynamics in young healthy individuals. METHODS: Ten (5F) young (29±7.7 years) participants performed STW and STSW from a standardised position. Five trials of each task were completed at 100 and 120%KH leading with dominant and non-dominant legs. Four force-plates and optical motion capture delineated key movement events and phases with effect of seat-height and lead-limb determined by 2-way ANOVA within tasks. RESULTS: At 120%KH, lower peak vertical ground-reaction-forces (vGRFs) and vertical BCOM velocities were observed during rising irrespective of lead-limb. No other parameters differed between seat-heights or lead-limbs. During GI in STSW there was more lateral, and less posterior, COP excursion than expected. CONCLUSION: Reduction in vGRFs and velocity during rising at 120%KH is consistent with reduced effort in young healthy individuals and is likely therefore to be an appropriate seat-height for patients. Lead-limb had no effect upon STSW or STW parameters suggesting that normative data independent of lead-limb can be utilised to monitor motor rehabilitation should differences be observed in patients. STSW should be considered an independent movement transition.