Voluntary Force Generation Research Articles

Estimation of contractile parameters of successive twitches in unfused tetanic contractions of single motor units – A proof-of-concept study using ultrafast ultrasound imaging in vivo

During a voluntary contraction, motor units (MUs) fire a train of action potentials, causing summation of the twitch forces, resulting in fused or unfused tetanus. Twitches have been important in studying whole-muscle contractile properties and differentiation between MU types. However, there are still knowledge gaps concerning the voluntary force generation mechanisms. Current methods rely on the spike-triggered averaging technique, which cannot track changes in successive twitches’ properties in response to individual neural firings. This study proposes a method that estimates successive twitches contractile parameters of single MUs during low force voluntary isometric contractions in human biceps brachii. We used a previously developed ultrafast ultrasound imaging method to estimate unfused tetanic activity signals of single MUs. A twitch decomposition model was used to decompose unfused tetanic activity signals into individual twitches. This study found that the contractile parameters varied within and across MUs. There was an association between the inter-spike interval and the contraction time (r = 0.49,p < 0.001) and the half-relaxation time (r = 0.58,p < 0.001), respectively. The method shows the proof-of-concept to study MU contractile properties of individual twitches in vivo, which can provide further insights into the force generation mechanisms of voluntary contractions and response to individual neural discharges.

Motor inhibition and its contribution to recovery of dexterous hand use after stroke.

Recovery of dexterous hand use is critical for functional outcome after stroke. Grip force recordings can inform on maximal motor output and modulatory and inhibitory cerebral functions, but how these actually contribute to recovery of dexterous hand use is unclear. This cohort study used serially assessed measures of hand kinetics to test the hypothesis that behavioural measures of motor modulation and inhibition explain dexterity recovery beyond that explained by measures of motor output alone. We also investigated the structural and functional connectivity correlates of grip force control recovery.Eighty-nine adults (median age = 54 years, 26% females) with first-ever ischaemic or haemorrhagic stroke and persistent arm and hand paresis were assessed longitudinally, at 3 weeks, and at 3 and 6 months after stroke. Kinetic measures included: maximal grip force, accuracy of precision and power grip force control, and ability to release force abruptly. Dexterous hand use was assessed clinically with the Box and Block Test and motor impairment with the upper extremity Fugl-Meyer Assessment. Structural and functional MRI was used to assess weighted corticospinal tract lesion load, voxel-based lesion symptom mapping and interhemispheric resting-state functional connectivity.Fifty-three per cent of patients had severe initial motor impairment and a majority still had residual force control impairments at 6 months. Force release at 3 weeks explained 11% additional variance of Box and Block Test outcome at 6 months, above that explained by initial scores (67%). Other kinetic measures did not explain additional variance of recovery. The predictive value of force release remained significant when controlling for corticospinal tract lesion load and clinical measures. Corticospinal tract lesion load correlated with recovery in grip force control measures. Lesions involving the parietal operculum, insular cortex, putamen and fronto-striatal tracts were also related to poorer force modulation and release. Lesions to fronto-striatal tracts explained an additional 5% of variance in force release beyond the 43% explained by corticospinal injury alone. Interhemispheric functional connectivity did not relate to force control recovery.We conclude that not only voluntary force generation but also force release (reflecting motor inhibition) are important for recovery of dexterous hand use after stroke. Although corticospinal injury is a main determinant of recovery, lesions to integrative somatosensory areas and fronto-parietal white matter (involved in motor inhibition) explain additional variance in post-stroke force release recovery. Our findings indicate that post-stroke upper limb motor impairment profiling, which is essential for targeted treatment, should consider both voluntary grasp generation and inhibition.

Beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne muscular dystrophy.

Neuromuscular electrical stimulation (NMES) allows activation of muscle fibers in the absence of voluntary force generation. NMES could have the potential to promote muscle homeostasis in the context of muscle disease, but the impacts of NMES on diseased muscle are not well understood. We used the zebrafish Duchenne muscular dystrophy (dmd) mutant and a longitudinal design to elucidate the consequences of NMES on muscle health. We designed four neuromuscular stimulation paradigms loosely based on weightlifting regimens. Each paradigm differentially affected neuromuscular structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES improves muscle and neuromuscular junction morphology, swimming, and survival. Heme oxygenase and integrin alpha7 are required for eNMES-mediated improvement. Our data indicate that neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.

A Roadmap to Reconstructing Muscle Architecture from CT Data.

Skeletal muscle is responsible for voluntary force generation across animals, and muscle architecture largely determines the parameters of mechanical output. The ability to analyze muscle performance through muscle architecture is thus a key step towards better understanding the ecology and evolution of movements and morphologies. In pennate skeletal muscle, volume, fiber lengths, and attachment angles to force transmitting structures comprise the most relevant parameters of muscle architecture. Measuring these features through tomographic techniques offers an alternative to tedious and destructive dissections, particularly as the availability of tomographic data is rapidly increasing. However, there is a need for streamlined computational methods to access this information efficiently. Here, we establish and compare workflows using partially automated image analysis for fast and accurate estimation of animal muscle architecture. After isolating a target muscle through segmentation, we evaluate freely available and proprietary fiber tracing algorithms to reconstruct muscle fibers. We then present a script using the Blender Python API to estimate attachment angles, fiber lengths, muscle volume, and physiological cross-sectional area. We apply these methods to insect and vertebrate muscle and provide guided workflows. Results from fiber tracing are consistent compared to manual measurements but much less time-consuming. Lastly, we emphasize the capabilities of the open-source three-dimensional software Blender as both a tool for visualization and a scriptable analytic tool to process digitized anatomical data. Across organisms, it is feasible to extract, analyze, and visualize muscle architecture from tomography data by exploiting the spatial features of scans and the geometric properties of muscle fibers. As digital libraries of anatomies continue to grow, the workflows and approach presented here can be part of the open-source future of digital comparative analysis.

Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography

Objective. The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Approach. Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Main results. Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Significance. Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

Validation of an adjustment equation for the burst superimposition technique in subjects post‐stroke

Deficits in voluntary force generation may be due to incomplete activation or decreased maximum force-generating ability (MFGA) of the targeted muscle. The validity of techniques used to measure MFGA in individuals post-stroke has not been assessed. The objective of this study was to determine the reliability of the MFGA predicted using an adjusted burst superimposition method within a post-stroke population. Differences in paretic-side plantar flexor muscle MFGA between 2 trials was calculated using the standard and adjusted burst superimposition technique for 17 individuals post-stroke (15 men, 58.7 ± 10 years of age, ≥6 months post-stroke) to assess reliability of the techniques. The adjusted measurement was shown to be more reliable (P = 0.03), especially when volitional effort differed by >40 N. Reliable measurement of the MFGA in individuals who have sustained a stroke is of clinical importance. These results suggest that the adjusted burst superimposition method may be useful when performing multiple measurements of muscle performance.

The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function

Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg(-1) body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60h. Significantly greater (p< 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36h (p = 0.003) and 60h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p< 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol's effect on the magnitude of EIMD-related decrements in voluntary force generation.

Quadriceps femoris muscle function prior and after total knee arthroplasty in women with knee osteoarthritis

The aim of the present study was to evaluate an isometric voluntary force generation and relaxation capacity of the quadriceps femoris (QF) muscle prior and after total knee arthroplasty (TKA). Isometric maximal voluntary contraction force, rate of force development, voluntary activation, half-relaxation time, and latency of contraction of the QF muscle were recorded in 12 female patients (aged 49-68 years) with knee osteoarthritis one day before, 3 and 6 months following TKA in the operated and nonoperated leg. Knee pain intensity was assessed by visual analog scale, and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire was used to assess knee problems during daily living. A significant decrease in knee pain and significant increase in KOOS were established after TKA. Maximal voluntary isometric force in the operated leg was lower (P < 0.05) before, 3 and 6 months after TKA as compared to the nonoperated leg. Rate of force development of the QF muscle in the operated leg compared to the nonoperated leg was significantly lower (P < 0.05) 3 and 6 months after TKA. Voluntary activation, latency of contraction, and half-relaxation time of the QF muscle did not differ significantly before, 3 and 6 months after TKA. The present study indicated reduced maximal and explosive strength of quadriceps femoris muscle in the operated leg 3 and 6 months after TKA with no significant changes in voluntary activation, and capacity for rapid contraction and relaxation. Prospective comparative study, Level II.

Does central fatigue exist under low-frequency stimulation of a low fatigue-resistant muscle?

The aim of the present study was to determine whether central fatigue occurs when fatigue is electrically induced in the abductor pollicis brevis muscle. Three series of 17 trains (30 Hz, 450 μs, 4 s on/6 s off, at the maximal tolerated intensity) were used to fatigue the muscle. Neuromuscular tests consisting of electrically evoked and voluntary contractions were performed before and after every 17-train series. Both the force induced by the stimulation trains and maximal voluntary force generation capacity significantly decreased throughout the protocol (-27 and -20%, respectively, at the end of the protocol, P < 0.001). These decreases were accompanied by failure in muscle excitability (P < 0.01), as assessed by the muscle compound action potential (M-wave or Mmax), leading to significant impairment in the muscle contractile properties (P < 0.05), as assessed by the muscle mechanical response (Pt). Central fatigue indices (level of activation, RMS/Mmax and H reflex) were not significantly changed at any point in the protocol. This gives evidence of preserved motor command reaching the motor neurons and preserved spinal excitability. The results indicate that this low-frequency stimulation protocol entails purely peripheral fatigue development when applied to a low fatigue-resistant muscle.

Soleus muscle of Down syndrome (DS) mice exhibits elevated markers of oxidative and nitrosative stress

Individuals with DS have a reduced capacity for voluntary force generation compared to individuals with and without other forms of intellectual disability. Oxidative stress (OS) is thought to be a key factor in DS pathologies that may be the result of triplication and over‐expression of copper‐zinc superoxide dismutase (CuZnSod). Our aim was to assess markers of OS and nitrosative stress (NS) in soleus muscle of a well established mouse model of DS, the Ts65Dn mouse, which is segmental trisomic for CuZnSod. We hypothesized that soleus muscle of Ts65Dn mice would exhibit elevated markers of OS and NS compared to soleus from wild‐type (WT) controls. Eighteen (n=9 per group) 4–7 month old male Ts65Dn and WT mice were used in these experiments. Western blot analysis was performed to quantify the relative expression of markers of OS (4‐hydroxy‐nonenal (4‐HNE)) and NS (3‐nitrotryosine (3‐NT)). Levels of soleus muscle 4‐HNE and 3‐NT were 476% and 276% higher in Ts65Dn mice (p&lt;0.05), respectively. These findings suggest that soleus muscle from Ts65Dn mice exhibits elevated markers of OS and NS, which is consistent with the human phenotype of DS. Additionally, preliminary microarray analysis identified 43 up‐regulated and 66 down‐regulated genes in soleus of Ts65Dn compared to WT mice (p&lt;0.001, ± 1.5‐fold). We are currently categorizing these differentially expressed genes.Supported by Syracuse University SOE

Multijoint dynamics and postural stability of the human arm.

The goal of this study was to examine how the mechanical properties of the human arm are modulated during isometric force regulation tasks. Specifically, we examined whether the dynamic stability of the limb remained nearly invariant across a range of voluntarily generated endpoint forces and limb postures. Previous single joint studies have demonstrated that dynamic joint stability, as quantified via estimates of the joint damping ratio, is nearly invariant during isometric torque regulation tasks. However, the relevance of these findings to the control of multijoint posture has not been investigated previously. A similar degree of invariance at the multijoint level could suggest a fundamental property of the motor system that could be incorporated into the planning and execution of multijoint tasks. In this work, limb mechanics were quantified using estimates of dynamic endpoint stiffness, which characterizes the relationship between imposed displacements of limb posture and the forces opposing those displacements. Endpoint stiffness was estimated using a two-link robot operating in the horizontal plane at the height of each subject's glenohumeral joint. The robot was used to apply stochastic position perturbations to the arm and to measure the resulting forces. Endpoint stiffness dynamics were estimated nonparametrically and subsequently summarized using inertial, viscous and elastic parameters. We found that in the tasks studied, there was a differential modulation of endpoint elasticity and endpoint viscosity. Elasticity increased nearly linearly with increases in voluntary force generation while viscosity increased nonlinearly. This differential regulation resulted in limb dynamics that had a remarkably consistent damping ratio across all subjects and all tested conditions. These results emphasize the importance of considering the full dynamic response of a limb when investigating multijoint stability, and suggest that a minimal degree of limb stability is maintained over a wide range of force regulation tasks.

Effects of voluntary force generation on the elastic components of endpoint stiffness.

The goal of this work was to determine how force loads applied at the hand change the elastic mechanical properties of the arm. Endpoint stiffness, which characterizes the relationship between hand displacements and the forces required to effect those displacements, was estimated during the application of planar, stochastic displacement perturbations to the human arm. A nonparametric system identification algorithm was used to estimate endpoint stiffness from the measured force and displacement data. We found that changes in the elastic component of arm stiffness during isometric force regulation tasks were due primarily to the actions of the single-joint muscles spanning the shoulder and elbow. This was shown to result in a nearly posture-independent regulation of joint torque-stiffness relationships, suggesting a simplified strategy that is used to regulate arm mechanics during these tasks.

Dynamic and kinematic strategies for head movement control.

This paper describes our analysis of the complex head-neck system using a combination of experimental and modeling approaches. Dynamical analysis of head movements and EMG activation elicited by perturbation of trunk position has examined functional contributions of biomechanically and neurally generated forces in lumped systems with greatly simplified kinematics. This has revealed that visual and voluntary control of neck muscles and the dynamic and static vestibulocollic and cervicocollic reflexes preferentially govern head-neck system state in different frequency domains. It also documents redundant control, which allows the system to compensate for lesions and creates a potential for substantial variability within and between subjects. Kinematic studies have indicated the existence of reciprocal and co-contraction strategies for voluntary force generation, of a vestibulocollic strategy for stabilizing the head during body perturbations and of at least two strategies for voluntary head tracking. Each strategy appears to be executed by a specific muscle synergy that is presumably optimized to efficiently meet the demands of the task.

A Simplified Model for Head-Neck Segment Fast Movements in the Frontal Plane

The objective of the current work is to develop a simplified model representing the physiological systems acting during fast head movements in frontal plane. All the contributions mechanically concurring to the head movement have been considered: voluntary force generation, viscosity, stiffness, physiological limit to movement range, gravitational field contribution and gamma reflex, depending on spindle activity. Model parameters have been partly derived form literature, when possible, whereas undetermined blocks parameters have been determined by optimising model output correspondence to real data acquired by ELITETM system in specific designed experimental set-ups. The optimisation have been performed by genetic algorithms. Results show that the model studied is very well representing fast head movements in the whole range of inclination in the frontal plane. Such model is, thus, proposed as a tool for transforming kinematics data on head movements in "neural equivalent data", especially for the assessing head control deasease and planning properly the rehabilitation process.

Characteristics of motor unit discharge in subjects with hemiparesis.

We studied the discharge rates and recruitment characteristics of single motor units in paretic and contralateral arm muscles of 6 hemiparetic subjects. Motor unit activity in biceps brachii was recorded at different elbow torques, and the activity related both to the mean level of surface electromyographic activity, and to the degree of weakness. In 3 of the 6 subjects, there were significant reductions in mean discharge rate of motor units in the paretic muscle. All 6 subjects showed compression of the range of motoneuron recruitment forces, and a failure to increase motor unit discharge rate during voluntary force increases in paretic muscles. These rate reductions could potentially alter the precise match of motoneuron properties to the mechanical properties of the innervated muscle fibers, and reduce the efficiency of muscle contraction. This reduction could lead, in turn to increased effort, to fatigue, and ultimately to a sense of weakness for voluntary force generation.

Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.

Mechanical influences on long‐lasting human muscle fatigue and delayed‐onset pain.

1. The influence of three mechanical factors, force, muscle length and passive lengthening, on long-lasting changes in voluntary force generation, the force:frequency relationship and the development of tenderness has been studied in healthy human skeletal muscle. The elbow flexors were used in all studies. The effect of muscle length was also investigated in the quadriceps and adductor pollicis muscles. Eighty maximal voluntary contractions (MVCs) were performed: one contraction, lasting approximately 2 s, every 15 s. The MVC and force:frequency relationships were measured before and immediately after the exercise and, together with an assessment of tenderness, at 24 h intervals thereafter. 2. In a series of experiments designed to investigate the effects of force, eccentric (lengthening) contractions were found to cause greater fatique and delayed-onset muscle pain than either isometric or concentric (shortening) contractions. There were, however, no substantial differences between the effects of isometric and concentric contractions. Changes in MVC took 24-48 h to return to normal while the low-frequency fatigue required 3-4 days to recover. 3. Passive lengthening with a comparable number of movements over the full range had no effect on the force generation of the muscle, nor did it cause any muscle pain. 4. In the series of experiments designed to investigate the effects of length, isometric MVCs were performed at either short or long length and the muscles subsequently tested at an intermediate length. The contractions at long length resulted in greater low-frequency fatigue and pain, despite the fact that they generated less force than those at the short length. 5. The results demonstrate that there is no simple relationship between the force generated during exercise and the development of long-lasting muscle fatigue and pain. Furthermore, there is a length-dependent component in the generation of low-frequency fatigue and muscle pain.