Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury

Spinal cord injury (SCI) can result in paralysis of trunk muscles, which can affect sitting balance. The objective of this study was to analyze trunk muscle coordination of individuals with thoracic SCI and compare it to able-body individuals. A total of 27 individuals were recruited and subdivided into: (a) high thoracic SCI; (b) low thoracic SCI; and (c) able-body groups. Participants were seated and asked to lean their trunk in eight directions while trunk muscle activity was recorded. Muscle coordination was assessed using the non-negative matrix factorization (NMF) method to extract muscle modules, which are the synergistic trunk muscle activations, and their directional activation patterns. Our results showed that individuals with SCI used less muscle modules, more co-contractions, and less directional tuning, compared to able-bodied people. These results suggest impaired and simplified muscle coordination due to the loss of supraspinal input after SCI. Observed variability in muscle coordination within SCI groups also suggests that other mechanisms such as spasticity and muscle stretch reflexes or individual factors such as experience and training contributed to the postural muscle synergies. Overall, muscle coordination deficits revealed impaired neuromuscular strategies which provide implications for rehabilitation of trunk muscles during sitting balance after SCI.     

An improved cost function for modeling of muscle activity during running

This paper tries to improve a recently developed mass-spring-damper model of the human body during running. The previous model took the muscle activity into account using a nonlinear controller that tuned the mechanical properties of the soft-tissue package based on two physiological hypotheses, namely "constant-force" and "constant-vibration". Three cost functions were used, out of which one was based on the constant-force hypothesis and two others were based on the constant-vibration hypothesis. The results of the study showed that the proposed cost functions are only partially successful in capturing the experimentally observed trends of the ground reaction force and vibration. The current paper proposes an improved cost function that combines both above-mentioned hypotheses. It is shown that the improved cost function can capture all the trends that were observed in the measurements of the ground reaction force and vibration level. It is therefore advised to use the new cost function in place of the previous ones.     

Changes in expiratory muscle function following spinal cord section.

Following spinal cord injury, muscles below the level of injury develop variable degrees of disuse atrophy. The present study assessed the physiological changes of the expiratory muscles in a cat model of spinal cord injury. Muscle fiber typing, cross-sectional area, muscle weight, and changes in pressure-generating capacity were assessed in five cats spinalized at the T(6) level. Airway pressure (P)-generating capacity was monitored during lower thoracic spinal cord stimulation before and 6 mo after spinalization. These parameters were also assessed in five acute animals, which served as controls. In spinalized animals, P fell from 41 +/- l to 28 +/- 3 cm H2O (means +/- SE; P < 0.001). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal muscles decreased significantly (P < 0.05 for each). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal, but not rectus abdominis (RA), correlated linearly with P (r > 0.7 for each; P < 0.05 for each). Mean muscle fiber cross-sectional area of these muscles was significantly smaller (P < 0.05 for each; except RA) and also correlated linearly with P (r > 0.55 for each; P < 0.05 for each, except RA). In spinalized animals, the expiratory muscles demonstrated a significant increase in the population of fast muscle fibers. These results indicate that, following spinalization, 1) the expiratory muscles undergo significant atrophy and fiber-type transformation and 2) the P-generating capacity of the expiratory muscles falls significantly secondary to reductions in muscle mass.     

Mechanism of expiratory muscle activation during lower thoracic spinal cord stimulation.

Lower thoracic spinal cord stimulation (SCS) may be a useful method to restore an effective cough mechanism. In dogs, two groups of studies were performed to evaluate the mechanism of the expiratory muscle activation during stimulation at the T(9)-T(10) level, which results in the greatest changes in airway pressure. In one group, expiratory muscle activation was monitored by evoked muscle compound action potentials (CAPs) from the internal intercostal muscles in the 10th, 11th, and 12th interspaces and from portions of the external oblique innervated by the L(1) and L(2) motor roots. SCS, applied with single shocks, resulted in short-latency CAPs at T(10) but not at more caudal levels. SCS resulted in long-latency CAPs at each of the more caudal caudal recording sites. Bilateral dorsal column sectioning, just below the T(11) spinal cord level, did not affect the short-latency CAPs but abolished the long-latency CAPs and also resulted in a fall in airway pressure generation. In the second group, sequential spinal root sectioning was performed to assess their individual mechanical contribution to pressure generation. Section of the ventral roots from T(8) through T(10) resulted in negligible changes, whereas section of more caudal roots resulted in a progressive reduction in pressure generation. We conclude that 1) SCS at the T(9)-T(10) level results in direct activation of spinal cord roots within two to three segments of the stimulating electrode and activation of more distal roots via spinal cord pathways, and 2) pathway activation of motor roots makes a substantial contribution to pressure generation.     

Pattern of expiratory muscle activation during lower thoracic spinal cord stimulation.

Large positive airway pressures (Paws) can be generated by lower thoracic spinal cord stimulation (SCS), which may be a useful method of restoring cough in spinal cord-injured patients. Optimal electrode placement, however, requires an assessment of the pattern of current spread during SCS. Studies were performed in anesthetized dogs to assess the pattern of expiratory muscle recruitment during SCS applied at different spinal cord levels. A multicontact stimulating electrode was positioned over the surface of the lower thoracic and upper lumbar spinal cord. Recording electromyographic electrodes were placed at several locations in the abdominal and internal intercostal muscles. SCS was applied at each lead, in separate trials, with single shocks of 0.2-ms duration. The intensity of stimulation was adjusted to determine the threshold for development of the compound action potential at each electrode lead. The values of current threshold for activation of each muscle formed parabolas with minimum values at specific spinal root levels. The slopes of the parabolas were relatively steep, indicating that the threshold for muscle activation increases rapidly at more cephalad and caudal sites. These results were compared with the effectiveness of SCS (50 Hz; train duration, 1-2 s) at different spinal cord levels to produce changes in Paw. Stimulation at the T9 and T10 spinal cord level resulted in the largest positive Paws with a single lead. At these sites, threshold values for activation of the internal intercostal (7-11th interspaces) upper portions of external oblique, rectus abdominis, and transversus abdominis were near their minimum. Threshold values for activation of the caudal portions of the abdominal muscles were high (>50 mA). Our results indicate that 1) activation of the more cephalad portions of the abdominal muscles is more important than activation of caudal regions in the generation of positive Paws and 2) it is not possible to achieve complete activation of the expiratory muscles with a single electrode lead by using modest current levels. In support of this latter conclusion, a two-electrode lead system results in more uniform expiratory muscle activation and significantly greater changes in Paw.     

Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The depression in size of the TST response, but no attenuation of the conventional motor-evoked potential, suggested increased probability of repetitive spinal MN activation during exercise, even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST [quadruple stimulation (QuadS) and quintuple stimulation (QuintS)] to examine the influence of fatiguing exercise on second and third MN discharges after a single TMS in healthy subjects. This method allows an estimation of the percentage of double and triple discharging MNs. Following a sustained contraction of the abductor digiti minimi muscle at 50% maximal force maintained to exhaustion, the size of QuadS and QuintS responses increased markedly, reflecting that a greater proportion of spinal MNs was activated two or three times by the transcranial stimulus. The size of QuadS responses did not return to precontraction levels during 10-min observation time, indicating long-lasting increase in excitatory input to spinal MNs. In addition, the postexercise behavior of QuadS responses was related to the duration of the contraction, pointing to a correlation between repeated activation of MNs and the subject's ability to maintain force. In conclusion, the study confirmed that an increased fraction of spinal MNs fire more than once in response to TMS when the muscle is fatigued. Repetitive MN firing may provide an adaptive mechanism to maintain motor unit activation and task performance during sustained voluntary activity.     

Rectus femoris and vastus intermedius fiber excursions predicted by three-dimensional muscle models

Computer models of the musculoskeletal system frequently represent the force-length behavior of muscle with a lumped-parameter model. Lumped-parameter models use simple geometric shapes to characterize the arrangement of muscle fibers and tendon; this may inaccurately represent changes in fiber length and the resulting force-length behavior, especially for muscles with complex architecture. The purpose of this study was to determine the extent to which the complex features of the rectus femoris and vastus intermedius architectures affect the fiber changes in length ("fiber excursions"). We created three-dimensional finite-element models of the rectus femoris and vastus intermedius muscles based on magnetic resonance (MR) images, and compared the fiber excursions predicted by the finite-element models with fiber excursions predicted by lumped-parameter models of these muscles. The finite-element models predicted rectus femoris fiber excursions (over a 100 degrees range of knee flexion) that varied from 55% to 70% of the excursion of the muscle-tendon unit and vastus intermedius fiber excursions that varied from 55% to 98% of the excursion muscle-tendon unit. In contrast, the lumped-parameter model of the rectus femoris predicted fiber excursions that were 86% of the excursion of the muscle-tendon unit and vastus intermedius fiber excursions that were 97% of the excursion of the muscle-tendon unit. These results suggest that fiber excursions of many fibers are overestimated in lumped-parameter models of these muscles. These new representations of muscle architecture can improve the accuracy of computer simulations of movement and provide insight into muscle design.     

Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/- 0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.     

Synaptic activation of thoracic spinal interneurons by reticulospinal pathways

Synaptic processes of 119 thoracic spinal interneurons (T10–11) were investigated in anesthetized cats in response to stimulation of the medial and central zones of the gigantocellular nucleus in the medulla and the ventral columns of the spinal cord. Fast (90–130 m/sec) reticulospinal fibers running in the ventral column were found to produce monosynaptic or disynaptic excitation of interneurons of Rexed's layers VII–VIII, which are connected monosynaptically with group I muscle afferents, and interneurons excited both by group I muscle afferents and low-threshold cutaneous afferents. In most neurons of layer IV, connected monosynaptically with low-threshold cutaneous afferents, and in neurons of layers VII–VIII excited by afferents of the flexor reflex no marked postsynaptic processes were observed during stimulation of the reticular formation. Excitatory, inhibitory, and mixed PS Ps during activation of reticulospinal fibers were found in 14 neurons, high-threshold afferents in which evoked predominantly polysynaptic IPSPs. Seventeen neurons activated monosynaptically by reticulospinal fibers and not responding to stimulation of segmental afferents were found in the medial part of the ventral horn (layers VII–VIII).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 566–578, November–December, 1972.     

Muscle synergies during shifts of the center of pressure by standing persons: identification of muscle modes

When a standing person performs a movement such that the center of gravity shifts, the activity of postural muscles adjusts to keep the balance. We assume that such adjustments are controlled using a small set of central variables, while each variable induces changes in the activity of a subgroup of postural muscles. The purpose of this study has been to identify such muscle groups (muscle modes or M-modes) and compare them across tasks and subjects. Four tasks required the subjects to release a load from extended arms leading to a center of pressure (COP) shift prior to the load release. The fifth task required an explicit COP shift by voluntary sway. Electromyographic activity of 11 postural muscles on one side of the body was integrated over a 100-ms interval corresponding to the early stage of the COP shift, and this integrated EMG activity was subjected to a principal component (PC) analysis across multiple repetitions of each task. Three PCs were identified and associated with a push-back M-mode, a push-forward M-mode, and a mixed M-mode. Cluster analysis of the PC vectors across tasks and across subjects confirmed the existence of distinctive push-forward and push-back muscle groups. PC vectors were also compared across tasks and across subjects using cosines as a measure of colinearity between pairs of vectors. In general, M-modes were similar across both tasks and subjects. We conclude that shifts of the COP, whether implicit or explicit, are controlled using a small set of central variables associated with changes in the activity of robust subsets of postural muscles. These results can be used for future analysis of muscle synergies associated with postural tasks.     

Using a cost function based on kinematics and electromyographic data to quantify muscle forces

A reliable evaluation of muscle forces in the human body is highly desirable for several applications in both clinical and research contexts. Several models of muscle force distribution based on non-invasive measurements have been proposed since 1836 (Weber and Weber, 1836), amongst which Crowninshield’s model (Crowninshield and Brand, 1981), which maximizes a cost-function representing the muscle fiber endurance, is the most popular. It is worth noting that Crowninshield’s model is the most widely adopted notwithstanding its major limitations of physiological coherence. Forster et al. (2004) pointed out that “these (conventional) criteria however do not predict co-contraction adequately”. Besides, electromyographic (EMG)-driven models have been proposed to assess individual muscle forces, which have not been broadly adopted due to their complexity and the need for a calibration before each test. In this context, a cost function based on kinematic and electromyographic data could provide the advantage of being physiologically more coherent with muscle activations compared to conventional cost-functions based on kinematics solely, and easier to use than the EMG-driven models. The objective of this study is to propose the first cost-function based on kinematics and electromyographic data to quantify muscle forces. When applying this new cost-function on a database of upper limb motions data of 17 subjects, healthy or with cerebral palsy, the muscle force prediction of the proposed model was 17.74% more coherent with the EMG pattern than the prediction of Crowninshield’s model. And on average, these results were more consistent whether the subjects were healthy or with cerebral palsy. In conclusion, we propose this cost-function for the quantification of muscle forces.     

Calcium-independent activation of skinned cardiac muscle by secophalloidin

Thin filament regulation of muscle contraction is believed to be mediated by both Ca2+ and strongly bound myosin cross-bridges. We found that secophalloidin (SPH, 5-8 mM) activates cross-bridge cycling without Ca2+ causing isometric force comparable to that induced by Ca2+. At saturated [SPH], Ca2+ further increased force by 20%. SPH-induced force was reversible upon washing with a relaxing solution. However, there was more than 30% irreversible loss in subsequent Ca2+-activated force. We hypothesize that SPH activates muscle via strongly bound cross-bridges. SPH-activated contraction provides a new model for studying the role of Ca2+ and cross-bridges in muscle regulation.     

Adenosine 5''-triphosphate consumption by smooth muscle as predicted by the coupled four-state crossbridge model.

We have proposed a four-state crossbridge model to explain contraction and the latch state in arterial smooth muscle. Ca(2+)-dependent crossbridge phosphorylation was the only postulated regulatory mechanism and the latchbridge (a dephosphorylated, attached crossbridge) was the only novel element in the model. In this study, we used the model to predict rates of ATP consumption by crossbridge phosphorylation (JPhos) and cycling (JCycle) during isometric and isotonic contractions in arterial smooth muscle; then we compared model predictions with experimental data. The model predicted that JPhos and JCycle were similar in magnitude in isometric contractions, and both increased almost linearly with myosin phosphorylation. The predicted relationship between isometric stress and ATP consumption was quasihyperbolic, but approximately linear when myosin phosphorylation was below 35%, in agreement with most of the available data. Muscle shortening increased the predicted values of JCycle up to 3.7-fold depending on shortening velocity and the level of myosin phosphorylation. The predicted maximum work output per ATP was 7.4-7.8 kJ/mol ATP and was relatively insensitive to changes in myosin phosphorylation. The predicted increase in JCycle with shortening was in agreement with available data, but the model prediction that work output per ATP was insensitive to changes in myosin phosphorylation was unexpected and remains to be tested in future experiments.     

Development of coordinated movement in chicks: II. Temporal analysis of hindlimb muscle synergies at embryonic day 10 in embryos with spinal gap transections

Spinal neural circuits can recruit muscles to produce organized patterns of activity early in embryonic development. In a previous study, using multichannel electromyographic (EMG) recordings, we characterized burst parameters for these patterns in the legs of chick embryos during spontaneous motility in ovo at embryonic days (E) 9 and E10 (Bradley and Bekoff, 1990). Results of the study suggested both neural and biomechanical factors play an important role in the development of coordinated limb movements. In this study, to explore the contribution of descending neural inputs to the control of leg movements during motility, we applied similar methods to characterize motor patterns produced by the spinal cord in the absence of descending inputs. Thoracic spinal gap transections were performed at E2 and EMG patterns were recorded at E10. Several EMG features for chronic spinal embryos were similar to those for normal embryos and demonstrate that lumbar spinal circuits can be correctly assembled to control limb movements in the absence of connectivity with more rostral neural structures during early differentiation processes. However, certain aspects of the EMG patterns in chronic spinal embryos were different from patterns in normal embryos and provide support for conclusions drawn earlier by Oppenheim (1975). Specifically, our data support the view that propriospinal and/or supraspinal inputs function to regulate the timing of cyclic limb movements controlled by spinal neural circuits. Finally, we consider the possible long-term effects of chronic spinal gap transections as compared to acute spinal transections on the development of motility. © 1992 John Wiley & Sons, Inc.     

Development of coordinated movement in chicks: II. Temporal analysis of hindlimb muscle synergies at embryonic day 10 in embryos with spinal gap transections.

Spinal neural circuits can recruit muscles to produce organized patterns of activity early in embryonic development. In a previous study, using multichannel electromyographic (EMG) recordings, we characterized burst parameters for these patterns in the legs of chick embryos during spontaneous motility in ovo at embryonic days (E) 9 and E10 (Bradley and Bekoff, 1990). Results of the study suggested both neural and biomechanical factors play an important role in the development of coordinated limb movements. In this study, to explore the contribution of descending neural inputs to the control of leg movements during motility, we applied similar methods to characterize motor patterns produced by the spinal cord in the absence of descending inputs. Thoracic spinal gap transections were performed at E2 and EMG patterns were recorded at E10. Several EMG features for chronic spinal embryos were similar to those for normal embryos and demonstrate that lumbar spinal circuits can be correctly assembled to control limb movements in the absence of connectivity with more rostral neural structures during early differentiation processes. However, certain aspects of the EMG patterns in chronic spinal embryos were different from patterns in normal embryos and provide support for conclusions drawn earlier by Oppenheim (1975). Specifically, our data support the view that propriospinal and/or supraspinal inputs function to regulate the timing of cyclic limb movements controlled by spinal neural circuits. Finally, we consider the possible long-term effects of chronic spinal gap transections as compared to acute spinal transections on the development of motility.     

PPARs调控巨噬细胞的活化与功能

巨噬细胞是先天性防御病原体的关键组分,它参与炎症的发生和消退,同时也参与了组织的修复。巨噬细胞的多种功能通过不同的活化状态完成,即从经典活化状态到替代性活化状态,再到失活状态。巨噬细胞活化的失调与代谢、炎症和免疫病变有关,调节蛋白控制巨噬细胞的活化可作为新的治疗靶点。主要综述过氧化物酶体增殖物激活受体（PPARs）调控巨噬细胞活化的作用。