An analog computer study of fast,isolated movements

The peripheral part of the motor control system is modelled on an analog computer. The model consists of an inertial load connected to an antagonistic muscle pair with their muscle spindles and neural connexions. It has inputs as well as inputs. The model is used for studying the hypothesis that simple on-off activities control fast isolated movements. It is found that the model responses on activation of the input alone are not realistic ones. A fair simulation may be obtained if the input and the input are activated simultaneously. Results suggest a diminished muscle spindle sensitivity during the movement.     

Lumped and population stochastic models of skeletal muscle: Implications and predictions

Lumped models of skeletal muscle have been assumed a) in the design of experiments and the interpretation of experimental findings, b) in theoretical studies. In this paper, a population model that takes into account the differing properties and separate (independent) activation of motor units is presented as the most appropriate for muscle. A realistic (for muscle) transformation, populationlumped model, resulting in the lumping of motor unit neural signals or system responses, is proposed. On this basis, the possibility of modelling muscle as a single system is examined; and the consequences of treating muscle as a lumped system, in experiments or theoretical studies, are discussed. Also, the advantages of lumping, in models of muscle, are reviewed. Predictions of a computer population model, together with actual recordings from a hand muscle, are used to confirm the results of the analysis.     

Ruthenium-red staining of skeletal and cardiac muscles

Summary The effects of ruthenium red (RR) on amphibian and mammalian skeletal muscles and mammalian myocardium were examined. In skeletal muscle cells, a discrete pattern of staining can be brought about within the lumina of the terminal cisternae (junctional sarcoplasmic reticulum [SR]) by sequential exposure to RR and OsO₄. After prolonged immersion in RR solution, formation of pentalaminar segments (zippering) occurs at various points along the longitudinal (network) SR tubules. Zippering can be elicited in skeletal SR at any stage of preparation prior to postfixation with OsO₄. By means of dispersive X-ray analysis, both ruthenium and osmium were seen to be deposited in skeletal muscle junctional SR, and ruthenium was detected in the myoplasm as well. In skeletal muscles whose T tubules were ruptured by exposure to glycerol, the pattern of SR staining and zippering resulting from ruthenium-osmium treatment was not affected. These findings indicate that RR is capable of passage across the sarcolemma of skeletal muscle and that this passage does not occur solely under conditions in which the plasma membrane is damaged. In contrast, RR does not opacify or modify any region of the SR of cardiac muscle. However, after this treatment, randomly distributed opaque bodies, composed of parallel lamellar structures, appear throughout the myocardial cells. A few of these bodies are associated with lipid droplets, but the rest are of unknown origin. The failure of the SR of cardiac muscle to stain after exposure to ruthenium dye (even though this material enters these cells) suggests that the chemical composition of cardiac SR is significantly different from that of skeletal muscle SR.Supported in part by PHS grant HL-11155 (to N.S.) and American Heart Grant-in-Aid 78-753 (to M.S.F.). The authors are grateful to Drs. David Harder and Lawrence Sellin for their assistance with the preparation of frog skeletal muscle, to Dr. S.K. Jirge for his helpful suggestions and discussions, and particularly to Dr. Kenneth R. Lawless and Ms. Ann Marshall of the Department of Materials Sciences, University of Virginia School of Engineering, and Col. John M. Brady of the United States Army Institute of Dental Research, Walter Reed Army Medical Center, for their help with, and for the use of, the X-ray analysis equipment     

A linear stochastic model of the single motor unit

The production of force and of the electrical signal by an active motor unit is theoretically described. Neural spikes are modelled using the Dirac delta function. Mechanisms for the generation of random impulse trains and the properties of the corresponding stochastic processes are discussed; the renewal model is proposed as the most appropriate. The possibility of using a linear model for the systems that produce force and electrical signal in the unit is examined. It is concluded that the linear assumption is justifiable during steady, constant-strength contractions of muscle. This linear stochastic model of the motor unit is used in two subsequent papers to study the muscle force and the electromyogram.     

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient''s pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.Download video file.^{(50M, mov)}     

Swimming muscle helps warm the brain of lamnid sharks

Summary Lamnid sharks are known to have warm red muscle and warm brains. We describe a large vein in lamnid sharks that provides a route for transfer of warm blood from the red muscle to the central nervous system. This red muscle vein runs longitudinally in the red muscle and is valved to direct blood flow anteriorly. It joins the myelonal vein in the neural canal, thus providing a route for blood flow from the red muscle to the brain. Temperature profiles along the neural canal of freshly caught mako sharks show that warm blood enters the myelonal vein from the red muscle vein. Experiments with heat generation by model brains indicate that the metabolic heat produced by the brain is probably not sufficient to cause the temperature elevations observed. Metabolic heat imported from the red swimming muscle may be a valuable addition to the heat budget of the head.     

The control of multi-muscle systems: human jaw and hyoid movements

A model is presented of sagittal plane jaw and hyoid motion based on the model of motor control. The model, which is implemented as a computer simulation, includes central neural control signals, position- and velocity-dependent reflexes, reflex delays, and muscle properties such as the dependence of force on muscle length and velocity. The model has seven muscles (or muscle groups) attached to the jaw and hyoid as well as separate jaw and hyoid bone dynamics. According to the model, movements result from changes in neurophysiological control variables which shift the equilibrium state of the motor system. One such control variable is an independent change in the membrane potential of -motoneurons (MNs); this variable establishes a threshold muscle length () at which MN recruitment begins. Motor functions may be specified by various combinations of s. One combination of s is associated with the level of coactivation of muscles. Others are associated with motions in specific degrees of freedom. Using the model, we study the mapping between control variables specified at the level of degrees of freedom and control variables corresponding to individual muscles. We demonstrate that commands can be defined involving linear combinations of change which produce essentially independent movements in each of the four kinematic degrees of freedom represented in the model (jaw orientation, jaw position, vertical and horizontal hyoid position). These linear combinations are represented by vectors in space which may be scaled in magnitude. The vector directions are constant over the jaw/hyoid workspace and result in essentially the same motion from any workspace position. The demonstration that it is not necessary to adjust control signals to produce the same movements in different parts of the workspace supports the idea that the nervous system need not take explicit account of musculo-skeletal geometry in planning movements.This article was processed by the author using the LAT_EX style file pljour2 from Springer-Verlag.     

A model of the feline medial gastrocnemius motoneuron-muscle system subjected to recurrent inhibition

Recurrent inhibition in the mammalian spinal cord is complex, and its functions are not yet well understood. Skeletomotoneurons (-MNs) excite, via recurrent axon collaterals, inhibitory Renshaw cells (RCs), which in turn inhibit -MNs and other neurons. The anatomical and functional structure of the recurrent inhibitory network is nonhomogeneous, and the gain and filtering characteristics of RCs are modulated by inputs circumventing -MNs. This complex organization is likely to play important roles for the discharge and recruitment properties of -MNs. Modeling this system is a way of investigating hypothesized roles for normal functioning including muscle fatigue and different forms of physiological pathological tremor. In this paper, a detailed model including -MNs, RCs, and the muscle fibers innervated by the -MNs is presented. Outlines of the experimental data underlying the model and the modeling philosophy and procedure are presented. Then the behavior of a RC model is compared with experimental data reported in the literature. Model and experimental data agree well for burst responses elicited by synchronous single-pulse activation of different numbers of motor axons. In addition, the static relation between motor-axon activation rate and RC firing rate agree fairly well in model and experiment, and the same applies to the dynamic responses to step changes in motor-axon rate. The ultimate objective is to use this model in probing the role of recurrent inhibition in the control and stability of (isometric) muscular force under normal and altered conditions occurring during fatigue and muscle pain.     

An EMG-level muscle model for a fast arm movement to target

A model of human muscle action is presented for a maximally fast, large-amplitude forearm movement to target. the inputs to the model are approximately the biceps and triceps EMG envelopes over a single movement. The model's output gives the corresponding displacement angle of the forearm about a fixed elbow position as a function of time. The idea of the model is to conceive of both EMG input drives as successions of millisecond input pulses, with each pulse resulting in a muscle tension twitch. Every twitch is amplitude-scaled, parametrically-shaped, and duration-limited as a function of the muscle's contractile history thus far in the movement. The muscle tension at any time t is the sum of the residual tension levels of all twitches begun before t. The model was developed and tested with special reference to two subjects: one, according to the model dynamics, was a comparatively slow-twitch type, and the other modelled as a fast-twitch type. Good agreement was found between model output and subject response data whenever the subject's EMG's were synchronous. The model can be used to characterize each subject's responses by a suite of twitch characteristics. This will enable us to check the accepted but now suspect correlation between muscle biopsy-and performance-determined muscle twitch type.This study was supported by contract DAMD 17-80-C-0101 from the U.S. Army Medical Research and Development Command. The views, opinions and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision, unless so designated by other documentation     

A model of a human neuromuscular system for small isometric tensions

A model is constructed of the motor units in the human first dorsal interosseus (FDI) muscle. Each motorneuron is simulated using a pseudo-steady-state model that omits the membrane capacity and the events underlying the action potential. Properties of individual twitches in the corresponding muscle units are based on the data of Milner-Brown et al. for the FDI, while the transduction between steady firing rate and percentage of maximum tension in a muscle unit is based on the work of Rack and Westbury on the cat soleus muscle. Since we are concerned only with small isometric tensions, we ignore effects due to muscle spindles and to recurrent inhibition. The model allows one to to determine, by simulation, the tension-time functions produced by different programs of input to an entire pool of 120 motorneurons. Thus, for example, in order to produce tension rising linearly with time, it suffices to deliver to each neuron in the pool a non-linearly rising conductance; the conductance can be the same for all neurons in the pool, but can NOT be scaled in proportion to the surface area of the respective neurons. The input may be delivered to any part of the neuron's dendritic tree, as long as the electrotonic distribution of input is the same for all the neurons. For a linearly rising force produced in this way, most of the motorneurons yield similar slopes for their frequency-force curves, as observed by Milner-Brown et al. To produce tensions greater than about 1 kg, mechanisms not included in this model must come into play, i.e. perhaps introduction of phasic motorneurons. The most important data needed to improve this model are sets of isometric frequency-force curves for muscle units of different twitch tensions.     

Mouse Model of Muscle Crush Injury of the Legs

Because crush injury to skeletal muscle is an important cause of morbidity in natural disaster and battlefield settings, a reproducible and refined animal model of muscle crush injury is needed. Both open and closed small-animal models of skeletal muscle crush injury are available but are limited by their need for surgical isolation of the muscle or by the adverse effect of fibular fracture, respectively. In the current study, we developed and validated a novel, noninvasive mouse model of lower-extremity muscle crush injury. Despite the closed nature of our model, gross evidence of muscle damage was evident in all mice and was verified microscopically through hematoxylin and eosin staining. The injury elicited both neutrophil and macrophage infiltration at 24 and 48 h after injury. The area percentage and mean antigen area of F4/80-positive macrophages were higher at 48 h than at 24 h after injury, and CD68-positive macrophage area percentage and mean antigen area differed significantly between injured and uninjured muscle. In addition, the incidence of fibular fracture was one third lower than that reported for an alternative noninvasive model. In conclusion, our model is a reproducible method for muscle crush injury in the mouse pelvic limb and is a refinement of previous models because of its decreased bone fractures and reduction of animal numbers.Abbreviations: AOI, area of interestSkeletal muscle crush injury is an important cause of morbidity in both civilian and military populations. During earthquakes, tornados, and other natural disasters, collapsed structures result in crush injuries in approximately 40% of victims entrapped in the rubble,¹⁴ and crush injuries sustained during these events primarily affect skeletal muscle tissue.¹³ Crush injuries to skeletal muscle received during military conflict can occur when a limb is compressed for an extended time period, and combat-related crush injuries of the extremities frequently are present in wounded troops who are transported via aeromedical evacuation.²²A muscle-crush injury is induced when pressure is applied to skeletal muscle, interrupting blood flow and damaging the cell membranes of the muscle fibers. Several animal models of skeletal muscle-crush injury are used to study the pathophysiology of acute muscle inflammation and to investigate potential therapies.^{1,2,3,5,8,9,12,17,18,21} The most common model is the application of force to a surgically isolated pelvic limb muscle by using a clamp.¹⁶ Although closed models have been investigated, these studies typically involve dropping weights onto rodents’ pelvic limbs, thereby increasing the adverse event of fractures. Although not often reported in the literature, the incidence of fibular fractures in rats as a result of the dropped weight was 27% in one study.³ An additional drawback to the dropped-weight model is that it simulates a high-force contusion injury and does not provide the ischemic effect of the continuous pressure applied by the open clamp model. The ideal crush-injury model would mimic a force-induced injury, because 40% of survivors trapped in building rubble develop ischemia-induced crush syndrome.¹⁴We chose to investigate a novel model of closed crush injury for several reasons. An animal model of skeletal muscle injury should mimic the human clinical presentation, and a closed model more closely simulates a real-world crush injury. Second, because the incision created in the open model can activate the inflammatory response, a group of sham-operated animals is needed to control for the variable of the incision-induced inflammation. By using a closed model, the contralateral limb can serve as the uninjured control, thereby reducing the number of animals needed to perform the study. Last, the closed model represents a refinement of the crush injury procedure by removing the additional tissue damage and inflammation that result from the incision and tissue dissection of the surgical procedure and by reducing the incidence of fractures.Because this model has not been described in the literature, the objective of the current study was to develop a closed, sustained-force model of lower-extremity crush injury that induces a measurable leukocyte response and minimizes damage to nearby bones. In addition, we used monoclonal antibodies to characterize the leukocyte populations associated with this skeletal muscle crush injury model.     

Optimal control of antagonistic muscle stiffness during voluntary movements

This paper presents a study on the control of antagonist muscle stiffness during single-joint arm movements by optimal control theory with a minimal effort criterion. A hierarchical model is developed based on the physiology of the neuromuscular control system and the equilibrium point hypothesis. For point-to-point movements, the model provides predictions on (1) movement trajectory, (2) equilibrium trajectory, (3) muscle control inputs, and (4) antagonist muscle stiffness, as well as other variables. We compared these model predictions to the behavior observed in normal human subjects. The optimal movements capture the major invariant characteristics of voluntary movements, such as a sigmoidal movement trajectory with a bell-shaped velocity profile, an N-shaped equilibrium trajectory, a triphasic burst pattern of muscle control inputs, and a dynamically modulated joint stiffness. The joint stiffness is found to increase in the middle of the movement as a consequence of the triphasic muscle activities. We have also investigated the effects of changes in model parameters on movement control. We found that the movement kinematics and muscle control inputs are strongly influenced by the upper bound of the descending excitation signal that activates motoneuron pools in the spinal cord. Furthermore, a class of movements with scaled velocity profiles can be achieved by tuning the amplitude and duration of this excitation signal. These model predictions agree with a wide body of experimental data obtained from normal human subjects. The results suggest that the control of fast arm movements involves explicit planning for both the equilibrium trajectory and joint stiffness, and that the minimal effort criterion best characterizes the objective of movement planning and control.     

Tissue specific expression of an α-skeletal actin-lacZ fusion gene during development in transgenic mice

Transgenic mice carrying a chimaeric transgene containing 730 bp of the 5-flanking sequences and the entire first intron of the rat -skeletal actin gene fused to thelacZ reporter gene have been produced by microinjection. ThelacZ reporter gene was used to verify the suitability of using the rat -actin promoter elements to target expression of genes of agricultural and therapeutic value exclusively to skeletal and heart muscle cells and fibres of transgenic mice. Expression of the transgene indicates a tightly regulated developmental and muscle specific control of the rat -skeletal actin gene, making it a useful promoter for gene targeting to muscle tissues. The cells destined to form muscle tissues in these transgenic mice are readily visualized in intact embryos by staining for -galactosidase activity, making them a suitable animal model for studying the origin and development of skeletal and cardiac muscle tissues.     

Postural maintenance during movement: Simulations of a two joint model

Voluntary movements of the upper body are accompanied by anticipatory postural adjustments to the lower body in a standing subject. The long-standing hypothesis is that these anticipatory adjustments serve to counteract the perturbation to the body's center of gravity caused by the voluntary arm movement. This paper presents model simulations investigating the possible roles of anticipatory postural activity that accompanies a rapid, upward arm swing. The model encorporates two (idealized) antagonistic muscle pairs controlling the movements of a double-joint system, with a shoulder joint between the arm and stiff body links, and an ankle joint between the stiff body-leg segment and the ground. Each muscle is represented by a nonlinear viscoelastic element and also includes proprioceptive feedback. Four inputs to the model define the motor control signals for muscle force generation in both the arm and the postural muscle pairs. The neurological component of the model describes consequences of alternate strategies for cocontractions, stretch reflex activity, and anticipatory and synchronous postural activities (or combinations thereof). Simulations with this model show that: (1) none of the postural maintenance schemes considered in these simulations (including varying anticipation) could suppress the initial backward thrust on the body link; (2) the more important destabilizing perturbation is a subsequent forward sway that, left uncountered by postural activity, would eventually leave the body to fall flat on its face; and (3) anticipatory silencing of the postural extensor followed by a brief period of extensor activation (descending control) and synchronous reflex activity (feedback control) appears to be the most likely postural stabilizing strategy that inhibits the continuous forward sway and is consistent with the experimental evidence.     

The Influence of the Way the Muscle Force is Modeled on the Predicted Results Obtained by Solving Indeterminate Problems for a Fast Elbow Flexion

A critical point in models of the human limbs when the aim is to investigate the motor control is the muscle model. More often the mechanical output of a muscle is considered as one musculotendon force that is a design variable in optimization tasks solved predominantly by static optimization. For dynamic conditions, the relationship between the developed force, the length and the contraction velocity of a muscle becomes important and rheological muscle models can be incorporated in the optimization tasks. Here the muscle activation can be a design variable as well. Recently a new muscle model was proposed [22] Raikova R.T. Aladjov H.Ts. 2002 Hierarchical genetic algorithm versus static optimization–investigation of elbow flexion and extension movements Journal of Biomechanics 35 1123 1135  [Google Scholar]. A muscle is considered as a mixture of motor units (MUs) with different peculiarities and the muscle force is calculated as a sum of the MUs twitches. The aim of the paper is to compare these three ways for presenting the muscle force. Fast elbow flexion is investigated using a planar model with five muscles. It is concluded that the rheological models are suitable for calculation of the current maximal muscle forces that can be used as weight factors in the objective functions. The model based on MUs has many advantages for precise investigations of motor control. Such muscle presentation can explain the muscle co-contraction and the role of the fast and the slow MUs. The relationship between the MUs activation and the mechanical output is more clear and closer to the reality.     

Structural diversity in muscle fibres of chicken breast

Summary Chicken breast muscle is usually considered to be a relatively homogeneous white muscle and has therefore been widely used for studies of muscle proteins. In a previous study, however, we have found different M-region structures in different fibres from this muscle. Because of this result, we have now carried out a combined histochemical and ultrastructural survey of this muscle. In particular, we have made use of large transverse cryo-sections that include most of the muscle cross-section.Although the white region is fairly homogeneous in fibre content according to normal histochemical criteria (mAT-Pase), we have found that there is a gradation of fibre structure across the muscle. The bulk of the muscle stains conventionally for Type-II fibres according to mATPase tests (the white part) but, in the small red part of the muscle, there are also Type-I fibres together with the Type-II fibres. Superimposed on this division into Type-I and Type-II fibres are variations in fibre size, oxidative and glycolytic staining properties, and variations of Z-band width and M-band structure; there is no strict correlation among any of these parameters. The apparently uniform staining across most of the muscle when tested for myofibrillar ATPase may be a misleading indicator of fibre properties.     

Ultrastructure of a muscle spindle-analogous receptor organ in the mandible of Oncopeltus fasciatus (Insecta,Heteroptera) with remarks on the homology of the mandibular muscles

Summary A non-ciliary muscle receptor organ in the first mandibular retractor muscle of Oncopeltus fasciatus is described. The organ consists of two specialized muscle fibres of the first retractor, which are embedded in a thickened layer of connective tissue. The sensory innervation is supplied by three multiterminal sense cells sending several dendrites to the receptor muscle fibres. Naked dendritic terminals are attached to the muscle surface or connective tissue fibrils. The far-reaching analogy of the receptor to the intrafusal chain-fibres of vertebrate muscle spindles is remarkable. The existence of a muscle receptor organ in the first mandibular retractor may serve as an argument in favor of the homology of this muscle with the musculus tentorio-mandibularis of orthopteroid insects.Supported by a grant from the Deutsche Forschungsgemeinschaft     

Histochemical fiber types characteristics in the normal and the persistent levator ani muscle of the rat

Summary Morphological features of the persistent levator ani (LA) muscle of the female rat normally undergoing involution but maintained by application of testosterone propionate to newborn animals were compared with that of the normal LA muscle of untreated male rat. The two muscles differ in number and size of muscle fibers.Using histochemical methods for myofibrillar adenosine triphosphatase (ATPase), mitochondrial -glycerophosphate dehydrogenase (-GPDH) and succinic dehydrogenase (SDH) the distribution of these enzymes in individual muscle fiber types was studied.ATPase and -GPDH activities show a homogenously positive reaction in the muscle fibers of the male rat, whereas a small portion of fibers with low activity is found in the persistent muscle of female rat.The most pronounced difference concerns SDH activity, i.e. two kinds of fibre types are barely discernible with prolonged incubation in LA muscle of male rat, but three basic fibre types (white, intermediate and red) are clearly distinguished in LA muscle of the female rat.The results are discussed in relation to neural and hormonal influences on histochemical features in cross-striated muscle.This work was supported by a grant from the Muscular Dystrophy Association of America to the Institute of General Pathology, University of Padua, Italy.     

Silencing TNFα activity by using Remicade or Enbrel blocks inflammation in whole muscle grafts: an in vivo bioassay to assess the efficacy of anti-cytokine drugs in mice

Dramatic clinical success in the treatment of chronic inflammatory diseases has resulted from the use of anti-cytokine therapies including specific blocking antibodies, soluble receptors and traps to silence the actions of inflammatory cytokines such as tumour necrosis factor alpha (TNF) and interleukin-1 (IL-1). Two agents used clinically to block the functional activity of TNF protein are Remicade (an antibody) and Enbrel (a soluble TNF receptor). These tools are now being extended to many other clinical disorders. We have a specific interest in the treatment of muscle diseases. In order to study the effects of novel anti-cytokine drugs on mouse models of human disease, such drugs must be investigated to determine whether they are indeed effective in blocking the inflammatory response in mouse. This has been carried out by means of a simple in vivo bioassay. Histological examination of transverse sections from whole muscle autografts in C57BL/10ScSn mice sampled at 5 days after transplantation provides an excellent assay model and clearly shows that Remicade and Enbrel block the acute inflammatory cell response in vivo. This graft model has also been used to show that a single intraperitoneal injection of Remicade (10 g/g) is long-lived and effective when administered at 1 week and even 4 weeks prior to the assay. Enbrel is highly effective when injected twice at –3 days and –1 day (2×100 g) before muscle grafting but shows no inhibition of the inflammatory response after a single injection (100 g) 1 week prior to grafting. This striking ablation of inflammation by pharmacological blockage of TNF is in marked contrast to the lack of any effect in TNF null mice. This simple reproducible in vivo assay model in mice can be used to evaluate the efficacy of many novel anti-cytokine interventions designed to block inflammation.