Quadriceps arthrogenic muscle inhibition: the effects of experimental knee joint effusion on motor cortex excitability

Introduction

Marked weakness of the quadriceps muscles is typically observed following injury, surgery or pathology affecting the knee joint. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhibition (AMI). This study aimed to further investigate the mechanisms underlying AMI by exploring the effects of experimental knee joint effusion on quadriceps corticomotor and intracortical excitability.

Methods

Seventeen healthy volunteers participated in this study. Transcranial magnetic stimulation was used to measure quadriceps motor evoked potential area, short-interval intracortical inhibition, intracortical facilitation and cortical silent period duration before and after experimental knee joint effusion. Joint effusion was induced by the intraarticular infusion of dextrose saline into the knee.

Results

There was a significant increase in quadriceps motor evoked potential area following joint infusion, both at rest (P = 0.01) and during voluntary muscle contraction (P = 0.02). Cortical silent period duration was significantly reduced following joint infusion (P = 0.02). There were no changes in short interval intracortical inhibition or intracortical facilitation over time (all P > 0.05).

Conclusions

The results of this study provide no evidence for a supraspinal contribution to quadriceps AMI. Paradoxically, but consistent with previous observations in patients with chronic knee joint pathology, quadriceps corticomotor excitability increased after experimental knee joint effusion. The increase in quadriceps corticomotor excitability may be at least partly mediated by a decrease in gamma-aminobutyric acid (GABA)-ergic inhibition within the motor cortex.     

Proprioceptive proximo-distal relationships between the quadriceps and soleus muscles in man

Electrical stimulation of femoral nerve modulates voluntary tonic activity o of ipsilateral soleus muscle. Stimulus time-locked inhibitory and facilitatory phases can be distinguished. EMG temporal analysis suggests that early perturbations are correlated with spinal effects of centripetal electrical activity. The inhibitory effects which momentarily abolish voluntary soleus activity are thought to result from quadriceps Ib fibres recruitment. While no heteronymous activity is induced at rest, femoral nerve Ia fibres activation can produce soleus muscle reflex when soleus motor nucleus excitability is increased by voluntary command. Recurrent discharge resulting from soleus reflex response enhances inhibition initially due to quadriceps Ib volley. Secondary effects of isometric quadriceps contraction (and soleus contraction when the femoral stimulus elicits a reflex in this muscle) have their own effects later. These findings suggest that proprioceptive relationships of the two muscular groups are efficient during tonic isometric voluntary command.     

Computational analysis of knee joint stability following total knee arthroplasty

The overall objective of this study was to introduce knee joint power as a potential measure to investigate knee joint stability following total knee arthroplasty (TKA). Specific aims were to investigate whether weakened knee joint stabilizers cause abnormal kinematics and how it influences the knee joint kinetic (i.e., power) in response to perturbation.Patient-specific musculoskeletal models were simulated with experimental gait data from six TKA patients (baseline models). Muscle strength and ligament force parameter were reduced by up to 30% to simulate weak knee joint stabilizers (weak models). Two different muscle recruitment criteria were tested to examine whether altered muscle recruitment pattern can mask the influence of weakened stabilizers on the knee joint kinematics and kinetics. Level-walking knee joint kinematics and kinetics were calculated though force-dependent kinematic and inverse dynamic analyses. Bode analysis was then recruited to estimate the knee joint power in response to a simulated perturbation.Weak models resulted in larger anterior-posterior (A-P) displacement and internal-external (I-E) rotation compared to baseline (I-E: 18.4 ± 8.5 vs. 11.6 ± 5.7 (deg), A-P: 9.7 ± 5.6 vs. 5.5 ± 4.1 (mm)). Changes in muscle recruitment criterion however altered the results such that A-P and I-E were not notably different from baseline models. In response to the simulated perturbation, weak models versus baseline models generated a delayed power response with unbounded magnitudes. Perturbed power behavior of the knee remained unaltered regardless of the muscle recruitment criteria.In conclusion, impairment at the knee joint stabilizers may or may not lead to excessive joint motions but it notably affects the knee joint power in response to a perturbation. Whether perturbed knee joint power is associated with the patient-reported outcome requires further investigation.     

Role of afferent input in muscle atrophy.

It is well known that soleus muscle of rat atrophies following spaceflight or hindlimb suspension (Ohira et al., 1992). It is, further, reported that the electromyogram (EMG) of soleus muscle disappears immediately in response to unloading by exposure to actual micro-g environment (Kawano et al., 2002; Leterme and Falempin, 1998) and by hindlimb suspension of rats (Alford et al., 1987; Ohira et al., 2000). However, the EMG level is increased gradually to the control level following 7-10 days of continuous hindlimb suspension (Alford et al., 1987; Ohira, 2000), while muscle atrophy is progressing (Winiarski et al., 1987). We previously reported that reduction of the EMG level of rat soleus in response to actual micro-g environment, created by a parabolic flight of a jet airplane, was closely associated with a decrease of the afferent input recorded at the L5 segmental level of spinal cord (Kawano et al., 2002). However, it is still unclear how the EMG level of soleus muscle adapts to unloading condition. The current study was performed to investigate the responses of soleus EMG and both afferent and efferent neurogram at the L5 segmental level of spinal cord to acute (20 seconds) and chronic (14 days) unloading.     

Enhanced stretch reflex excitability in the soleus muscle during passive standing posture in humans

The purpose of this study was to test whether the spinal reflex excitability of the soleus muscle is modulated as posture changes from a supine to a passive upright position. Eight healthy subjects (29.6 ± 5.4 yrs) participated in this study. Stretch and H-reflex responses were elicited while the subjects maintained passive standing (ST) and supine (SP) postures. The passive standing posture was accomplished by using a gait orthosis to which a custom-made device was mounted to elicit stretch reflex in the soleus muscle. This orthosis makes it possible to elicit stretch and H-reflexes without background muscle activity in the soleus muscle. The results revealed that the H-reflex amplitude in the ST was smaller than that in the SP condition, which is in good agreement with previous reports. On the other hand, the stretch reflex was significantly larger in the ST than in the SP condition. Since the experimental conditions of both the stretch and H-reflex measurements were exactly the same, the results were attributed to differences in the underlying neural mechanisms of the two reflex systems: different sensitivity of the presynaptic inhibition onto the spinal motoneuron pool and/or a change in the muscle spindle sensitivity.     

Coincident increases in oxytocin receptor expression and EMG responsiveness to oxytocin in the ovine cervix at oestrus

This study has localised oxytocin receptor (OTR) mRNA expression within the cervix of non-pregnant ewes and related this to changes in the sensitivity of the cervical musculature to administered oxytocin (OT) during the oestrous cycle by recording electromyographic (EMG) activity. Cervices were collected from 34 ewes at specified time points throughout the cycle. OTR mRNA expression was localised by in situ hybridisation and results were expressed as optical density measurements from autoradiographs in each of four different cervical regions. EMG recordings were made for up to 8 h per day from four non-pregnant ewes undergoing seasonal oestrous cycles between Days −3 and +3 relative to oestrus (Day 0). The highest concentrations of OTR mRNA were detectable within the luminal epithelium (LE) of the cervix, with values increasing from Day 15 of the cycle, peaking during the follicular phase (P<0.001, compared to the mid-luteal phase) and returning to basal by Day 2. There was a small but significant increase in OTR mRNA hybridisation (above basal/luteal phase values) within the stromal cells (STR) adjacent to the lumen (P<0.05) during the same time period, but no differences from basal values were detectable in the dense collagenous annular ring or in tissue superficial to this. Analysis of pooled EMG activity recorded daily from the cervix indicated that endogenous contractile activity was higher on Day 0 than on the Days +1 (P<0.05), −2, +2 and +3 (P<0.001). The response to bolus intravenous (i.v.) injections of 25 mU OT (25 mU) varied with day of the cycle. This dose produced a measurable and significant response on Days 0 (P<0.001) and +1 (P<0.001), but not on any of the other days, indicating that the sensitivity of the cervical musculature to OT peaked on these days. These data show that the cervix is highly responsive to OT at oestrus. This coincides with an increase in OTR mRNA expression in the luminal epithelial cells, suggesting the likely production of an intermediary messenger between the epithelial and smooth muscle cells.     

Knee joint laxity affects muscle activation patterns in the healthy knee.

This study investigated the effects of anterior knee joint laxity on muscle activation patterns prior to and following a lower extremity perturbation. Participants were subjected to a forward and either internal (IR) or external (ER) rotation perturbation of the trunk and thigh on the weight-bearing shank. Pre-activity (%MVIC) before the perturbation, and reflex time (ms) and mean reflex amplitude (%MVIC) following the perturbation were recorded via surface electromyography (sEMG) in the medial and lateral gastrocnemius, hamstring and quadriceps muscles. Twenty-one NCAA DI intercollegiate female athletes with below average anterior knee laxity (3-5 mm) were compared to 21 with above average anterior knee laxity (7-14 mm) as measured by a standard knee arthrometer. Groups differed in reflex timing by muscle (P = 0.013), with females with above average knee laxity (KT((>7 mm))) demonstrating a 16 ms greater delay in biceps femoris reflex timing compared to females with below average knee laxity (KT((<5 mm))). Groups also differed in muscle activation amplitude by response, muscle and direction of rotation (i.e. a 4-way interaction; P = 0.027). The magnitude of change from pre to post perturbation was significantly less in KT((>7 mm)) vs. KT((<5 mm)) for the medial (MG) and lateral (LG) gastrocnemius muscles, primarily due to higher levels of muscle preactivity while awaiting the perturbation (MG = 20% vs. 12% MVIC, P = 0.05; LG = 33% vs. 21% MVIC, P = 0.11). Further, KT((>7 mm)) demonstrated higher activation levels in the biceps femoris than KT((<5 mm)) (47% vs. 27% MVIC; P = 0.025) regardless of response (pre vs. post perturbation) or direction of rotation. These findings suggest females with increased knee laxity may be less sensitive to joint displacement or loading (delayed reflex), and are more reliant on active control of the gastrocnemius and biceps femoris muscles to potentially compensate for reduced passive joint stability.     

Role of reflex dynamics in spinal stability: intrinsic muscle stiffness alone is insufficient for stability

Spinal stability is related to both the intrinsic stiffness of active muscle as well as neuromuscular reflex response. However, existing analyses of spinal stability ignore the role of the reflex response, focusing solely on the intrinsic muscle stiffness associated with voluntary activation patterns in the torso musculature. The goal of this study was to empirically characterize the role of reflex components of spinal stability during voluntary trunk extension exertions. Pseudorandom position perturbations of the torso and associated driving forces were recorded in 11 healthy adults. Nonlinear systems-identification analyses of the measured data provided an estimate of total systems dynamics that explained 81% of the movement variability. Proportional intrinsic response was less than zero in more than 60% of the trials, e.g. mean value of P(INT) during the 20% maximum voluntary exertion trunk extension exertions -415+/-354N/m. The negative value indicated that the intrinsic muscle stiffness was not sufficient to stabilize the spine without reflex response. Reflexes accounted for 42% of the total stabilizing trunk stiffness. Both intrinsic and reflex components of stiffness increased significantly with trunk extension effort. Results reveal that reflex dynamics are a necessary component in the stabilizing control of spinal stability.     

Assessment of soleus motoneuronal excitability using the joint angle dependent H reflex in humans.

As variations in the amplitude of H reflex potentials can be influenced by changes in muscle length, motoneuronal excitability in terms of H reflex during free movement has long been argued. With the maximal M response controlled, the present study compared several H reflex parameters in order to assess motoneuronal excitability of the resting soleus for different ankle angles (plantarflexion 20 degrees, neutral, and dorsiflexion 20 degrees ). All H-related parameters were dependent on joint angle, suggesting that soleus motoneuronal excitability in the dorsiflexed position was significantly suppressed. By contrast, soleus motoneuronal excitability in the plantarflexed position was not effectively modulated since H-related parameters did not differ from their neutral-position analogs. Methodologically, assessment of joint angle-dependent modulation of motoneuronal excitability requires meticulous control of M responses and selection of appropriate parameters that are insensitive to possible physical modulation and spatial shift of the M recruitment curve confounded by geometrical factors.     

Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects

Introduction  

A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether γ-loop dysfunction contributes to AMI in people with knee joint OA.     

Joint kinetic response during unexpectedly reduced plantar flexor torque provided by a robotic ankle exoskeleton during walking

During human walking, plantar flexor activation in late stance helps to generate a stable and economical gait pattern. Because plantar flexor activation is highly mediated by proprioceptive feedback, the nervous system must modulate reflex pathways to meet the mechanical requirements of gait. The purpose of this study was to quantify ankle joint mechanical output of the plantar flexor stretch reflex response during a novel unexpected gait perturbation. We used a robotic ankle exoskeleton to mechanically amplify the ankle torque output resulting from soleus muscle activation. We recorded lower-body kinematics, ground reaction forces, and electromyography during steady-state walking and during randomly perturbed steps when the exoskeleton assistance was unexpectedly turned off. We also measured soleus Hoffmann- (H-) reflexes at late stance during the two conditions. Subjects reacted to the unexpectedly decreased exoskeleton assistance by greatly increasing soleus muscle activity about 60 ms after ankle angle deviated from the control condition (p<0.001). There were large differences in ankle kinematic and electromyography patterns for the perturbed and control steps, but the total ankle moment was almost identical for the two conditions (p=0.13). The ratio of soleus H-reflex amplitude to background electromyography was not significantly different between the two conditions (p=0.4). This is the first study to show that the nervous system chooses reflex responses during human walking such that invariant ankle joint moment patterns are maintained during perturbations. Our findings are particularly useful for the development of neuromusculoskeletal computer simulations of human walking that need to adjust reflex gains appropriately for biomechanical analyses.     

The role of reflex mechanisms in postinhibitory rebound studied by analysis of human single motor unit activity

The mechanism of onset of rebound after inhibition induced by electrical stimulation of a nerve of maximal and submaximal strength for M-response was studied in single motor units of normal human soleus, rectus femoris, and hand muscles. Poststimulus histograms and changes in the duration of interspike intervals were compared with mechanical recordings of muscle contractions. In all muscles tested, during strong isotonic contraction, the increase in motor unit activity after a silent period was partly due to synchronization of their emergence from inhibition. However, it also contained a component of true facilitation of motoneurons, which was evidently a reflex response to lengthening of the muscle in the relaxation phase after evoked contraction. The latent period of this facilitation in the soleus and rectus femoris muscles coincided in value with the latent period of the monosynaptic spinal reflex, whereas in the hand muscles, in which a monosynaptic response to electrical nerve stimulation could not be evoked, the latent period of facilitation as a result of spindle activation during muscle relaxation was significantly longer than the latent period of the monosynaptic reflex. These findings support the hypothesis of presynaptic suppression of monosynaptic connections of Ia afferents with the motoneurons of some human muscles by descending tonic influences and of the use of information coming from spindles by supraspinal levels of the CNS.     

Reflex muscle contractions can be elicited by valgus positional perturbations of the human knee

Experimental evidence on the reflex responses of thigh muscles to valgus mechanical perturbations at the human knee are presented. Random step positional deflections, ranging from 5 degrees to 12 degrees at 60 degrees /s, were applied to the fully extended knees of seven healthy subjects. Subjects were instructed to maintain a constant background co-activation ( approximately 2-11% MVC) of the quadriceps and hamstring muscles prior to and during the mechanical stimulus. We found that the reflex response to sustained valgus joint deflection in the vasti muscles had longer onset latencies (range: 83-92ms) than did the stretch reflex in the same muscles (latencies: 29-31ms). This reflex EMG response consisted typically of a peak followed by sustained muscle activity throughout the step perturbation. The sustained EMG activity was dependent on the amplitude of the perturbing stimulus, but in a nonlinear manner. The long latency of the valgus response suggests that the reflex originates in nonmuscular sensory pathways, potentially from mechanoreceptors lying in periarticular tissues such as joint ligaments and capsule. Analysis of the spatial distribution of reflex responses showed an asymmetrical pattern with preferential activation of medial vs. lateral muscles of the knee. We assess whether these asymmetric reflex contractions could promote joint stability, either by inducing generalized joint stiffening, or by preferential activation of those muscles that are best suited to resist induced ligament strain.     

Neurophysiological characteristics of human leg muscle action potentials evoked by transcutaneous magnetic stimulation of the spine

The objectives of this study were to establish the neurophysiological properties of the compound muscle action potentials (CMAPs) evoked by transcutaneous magnetic stimulation of the spine (tsMSS) and the effects of tsMSS on the soleus H‐reflex. In semi‐prone seated subjects with trunk semi‐flexed, the epicenter of a figure‐of‐eight magnetic coil was placed at Thoracic 10 with the handle on the midline of the vertebral column. The magnetic stimulator was triggered by monophasic single pulses of 1 ms, and the intensity ranged from 90% to 100% of the stimulator output across subjects. CMAPs were recorded bilaterally from ankle and knee muscles at the interstimulus intervals of 1, 3, 5, 8, and 10 s. The CMAPs evoked were also conditioned by posterior tibial and common peroneal nerve stimulation at a conditioning‐test (C‐T) interval of 50 ms. The soleus H‐reflex was conditioned by tsMSS at the C‐T intervals of 50, 20, ?20, and ?50 ms. The amplitude of the CMAPs was not decreased when evoked at low stimulation frequencies, excitation of group I afferents from mixed peripheral nerves in the leg affected the CMAPs in a non‐somatotopical neural organization pattern, and tsMSS depressed soleus H‐reflex excitability. These CMAPs are likely due to orthodromic excitation of nerve motor fibers and antidromic depolarization of different types of afferents. The latency of these CMAPs may be utilized to establish the spine‐to‐muscle conduction time in central and peripheral nervous system disorders in humans. tsMSS may constitute a non‐invasive modality to decrease spinal reflex hyperexcitability and treat hypertonia in neurological disorders. Bioelectromagnetics 34:200–210, 2013. © 2012 Wiley Periodicals, Inc.     

Afferent feedback in the control of human gait.

Sensory activity contributes to motor control in two fundamentally different ways. It may mediate 'error signals' following sudden external perturbations and it may contribute to the pre-programmed motoneuronal drive. Here we review data, which illustrate these two functions of sensory feedback in relation to human walking. When ankle plantarflexors are unloaded in the stance phase there is a sudden decrease in the sensory activity in muscle and tendon afferents from the active muscles. This decrease in sensory activity results in a drop in EMG activity recorded from the soleus muscle, which demonstrates that the sensory activity contributes importantly to the activation of the muscles. Data suggests that a spinal pathway from gr. II muscle afferents is responsible for this positive feedback contribution to the motoneuronal drive during walking.When cutaneous nerves from the foot are stimulated in the early swing phase of walking a late reflex response may be observed in the tibialis anterior muscle. This reflex may help to ensure that the foot is lifted effectively over an obstacle. Data suggest that this reflex response is at least partly mediated by a transcortical reflex pathway. It seems to be important that reactions to external perturbations are integrated at a supraspinal level during human walking.     

Differential control during maximal concentric and eccentric loading revealed by characteristics of the electromyogram

Maximal eccentric loading has been associated with higher levels of spindle afferent activity but lower levels of integrated EMG as compared to maximal concentric loading. Elbow flexor EMG was recorded from 17 subjects during concentric (CONC) and eccentric (ECC) elbow flexion at 70° s⁻¹ using a Kin-Com dynamometer. We hypothesized that peak EMG amplitude would be more sensitive to fluctuations in facilitation by the spindle primary afferents via the segmental stretch reflex pathway, and that the mean EMG would be more reflective of the ongoing level of muscle activation. A ratio of peak to mean EMG (P/M EMG ratio) was predicted to be larger during maximal eccentric loading than maximal concentric loading. The peak EMG (P<0.013) and the P/M EMG ratio (P<0.001) were significantly greater during the ECC condition than the CONC condition. In a subgroup of three subjects who underwent 3 weeks of eccentrically biased weight training, EMG, peak torque and torque variability were assessed before and after training. P/M EMG ratio decreased, while peak torque and torque variability increased following the training. Differences in the P/M EMG ratio appear to reflect differences in the way eccentric and concentric muscle actions are controlled and do not simply represent less control during the eccentric task.     

A numeric study of the noise-induced tremor in a mathematical model of the stretch reflex

A mathematical model of the stretch reflex for the cat soleus muscle is presented. The time-delay differential equations of the model are solved using the fourth-order Runge-Kutta algorithm, introducing a Gaussian-noise term to simulate the environmental noise. The muscle response dynamics are then studied under various levels of average muscle activation. Finally, the feasibility of explaining the so-called physiological tremor from the properties of the stretch reflex mechanisms is discussed by comparing our results with reported experimental evidence.     

Effects of different vibration frequencies on spinal cord reflex circuits and thermoalgesic perception

Objectives:We studied the effect of different vibration frequencies on spinal cord excitability and heat pain perception. We hypothesized that the effects of vibration on spinal cord reflexes, and, also those on heat pain perception, depend on vibration frequency.Methods:In 9 healthy subjects, we applied vibration over the tibialis anterior muscle at three different frequencies (50, 150, or 250 Hz) on spinal cord reflex excitably, tested with the H reflex and the T wave in the soleus muscle, as well as on sensory and pain perception, tested by measuring warm perception (WT) and heat pain perception thresholds, (HPT) in sites rostral and caudal to vibration. Exams were carried out before, during, and after vibration.Results:The amplitude of the H reflex and T wave significantly decreased during vibration in comparison to baseline. Low frequencies (50 and 150Hz) induced greater reflex suppression than high frequency (250Hz). No significant changes were observed on WT and HPT.Conclusions:The effects of vibratory stimulation can be summarized as frequency-related suppression of the spinal cord excitability without an effect on warm and heat pain perception. The present results may help to design vibration-related interventions intended to diminish spinal cord reflex excitability in spastic patients.     

Spinal and supraspinal effects of activity in ligament afferents.

In this paper available knowledge on effects from joint and ligament afferents on spinal neurones and pathways are briefly reviewed, and possible functional implications discussed. Ligament afferents may contribute to joint stability, muscle coordination and proprioception through direct polysynaptic reflex effects onto ascending pathways and skeletomotoneurones, and/or indirectly via reflex actions on the gamma-muscle spindle system. Theoretical and experimental evidence indicate that ligament afferents, together with afferents from other joint structures, muscles and the skin, provide the CNS with information on movements and posture through ensemble coding mechanisms, rather than via modality specific private pathways. The existence and functional relevance of ligamentomuscular protective reflexes, that are triggered when the ligament is threatened by potentially harmful loads, has been seriously questioned. It seems more likely that peripheral sensory inputs from ligament afferents participate in a continuous control of the muscle activity through feedforward, or preprogramming, mechanisms. In line with these ideas it has been suggested that ligament mechanoreceptors have an important role in muscle coordination and in the reflex regulation of the functional joint stability, by contributing to the preprogramming of the muscle stiffness through reflex modulation of the gamma-muscle spindle system.