Antagonist Motoneurons Research Articles

V1 interneurons regulate the pattern and frequency of locomotor-like activity in the neonatal mouse spinal cord.

In the mouse spinal cord, V1 interneurons are a heterogeneous population of inhibitory spinal interneurons that have been implicated in regulating the frequency of the locomotor rhythm and in organizing flexor and extensor alternation. By introducing archaerhodopsin into engrailed-1-positive neurons, we demonstrate that the function of V1 neurons in locomotor-like activity is more complex than previously thought. In the whole cord, V1 hyperpolarization increased the rhythmic synaptic drive to flexor and extensor motoneurons, increased the spiking in each cycle, and slowed the locomotor-like rhythm. In the hemicord, V1 hyperpolarization accelerated the rhythm after an initial period of tonic activity, implying that a subset of V1 neurons are active in the hemicord, which was confirmed by calcium imaging. Hyperpolarizing V1 neurons resulted in an equalization of the duty cycle in flexor and extensors from an asymmetrical pattern in control recordings in which the extensor bursts were longer than the flexor bursts. Our results suggest that V1 interneurons are composed of several subsets with different functional roles. Furthermore, during V1 hyperpolarization, the default state of the locomotor central pattern generator (CPG) is symmetrical, with antagonist motoneurons each firing with an approximately 50% duty cycle. We hypothesize that one function of the V1 population is to set the burst durations of muscles to be appropriate to their biomechanical function and to adapt to the environmental demands, such as changes in locomotor speed.

Modulation of reciprocal inhibition at the wrist as a neurophysiological correlate of tremor suppression: a pilot healthy subject study.

It has been shown that Ia afferents inhibit muscle activity of the ipsilateral antagonist, a mechanism known as reciprocal inhibition. Stimulation of these afferents may be explored for the therapeutic reduction of pathological tremor (Essential Tremor or due Parkinson's Disease, for example). However, only a few studies have investigated reciprocal inhibition of wrist flexor / extensor motor control. The main goal of this study was to characterize reciprocal inhibition of wrist flexors / extensors by applying surface electrical stimulation to the radial and median nerves, respectively. Firstly, the direct (M) and monosynaptic (H) reflex responses to increasing median and radial nerve stimulation were recorded to characterize the recruitment curve of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, respectively. Based on the recruitment curve data, we then stimulated the median and radial nerves below (<; MT) and above (> MT) motor threshold (MT) during a submaximal isometric task to assess the amount of inhibition on ECR and FCR antagonist muscles, respectively. The stimulation of both nerves produced a long-duration inhibition of the antagonist motoneuron pool activity. On average, maximum peak of inhibition was 27 ± 6% for ECR and 32 ± 9% for FCR with stimulation <; MT; maximum peak of inhibition was 45 ± 7% for ECR and 44 ± 13% for FCR when using stimulation > MT. These results validate this neurophysiological technique that demonstrates a mechanism similar to classical reciprocal Ia inhibition reported for other limb joints and that can be used to benchmark strategies to suppress pathological tremor.

Impaired Ability to Suppress Excitability of Antagonist Motoneurons at Onset of Dorsiflexion in Adults with Cerebral Palsy.

We recently showed that impaired gait function in adults with cerebral palsy (CP) is associated with reduced rate of force development in ankle dorsiflexors. Here, we explore potential mechanisms. We investigated the suppression of antagonist excitability, calculated as the amount of soleus H-reflex depression at the onset of ankle dorsiflexion compared to rest, in 24 adults with CP (34.3 years, range 18–57; GMFCS 1.95, range 1–3) and 15 healthy, age-matched controls. Furthermore, the central common drive to dorsiflexor motoneurons during a static contraction in the two groups was examined by coherence analyses. The H-reflex was significantly reduced by 37% at the onset of dorsiflexion compared to rest in healthy adults (P < 0.001) but unchanged in adults with CP (P = 0.91). Also, the adults with CP had significantly less coherence. These findings suggest that the ability to suppress antagonist motoneuronal excitability at movement onset is impaired and that the central common drive during static contractions is reduced in adults with CP.

Measurement of voluntary activation based on transcranial magnetic stimulation over the motor cortex.

This article reviews the use of transcranial magnetic stimulation (TMS) over the motor cortex to make estimates of the level of voluntary drive to muscles. The method, described in 2003 (Todd et al. J Physiol 551: 661-671, 2003), uses a TMS pulse to produce descending corticospinal volleys that synaptically activate motoneurons, resulting in a muscle twitch. Linear regression of the superimposed twitch amplitude and voluntary force (or torque) can generate an "estimated" resting twitch for muscles involved in a task. This procedure has most commonly been applied to elbow flexors but also to knee extensors and other muscle groups. Data from 44 papers using the method were tabulated. We identify and discuss five major technical challenges, and the frequency with which they are addressed. The technical challenges include inadvertent activation of the cortical representation of antagonist muscles, the role of antagonist torques at the studied joint, uncertainty about the effectiveness of the TMS pulse in activating the motoneuron pool, the linearity of the voluntary force (or torque) and superimposed twitch relationship, and variability in the TMS-evoked EMG and force/torque responses. The ideal situation in which the descending corticospinal volleys recruit all of the agonist motoneurons and none of the antagonist motoneurons is unlikely to ever occur, and hence results must be carefully examined to assess the authenticity of the voluntary activation estimates in the context of the experimental design. A partial compromise lies in the choice of stimulus intensity. We also identify aspects of the procedure that require further investigation.

A Neural Control Model for Horizontal Visual, Auditory and Auditory-Visual Bisensory Stimuli Elicited Saccades

To provide a comprehensive investigation of goal-oriented saccades, experiments are designed to trigger fast eye movements by different types of targets, including visual, auditory, and auditory-visual bisensory stimuli. Human saccades are recorded using a high speed eye tracking system. Data is analyzed to produce parameter estimates using system identification technique for a 3rd-order linear horizontal saccadic eye movement model. Saccade characteristics are explored and compared. The auditory-visual stimuli provide the greatest saccade accuracy. Auditory saccades show lower peak velocity and longer duration. Saccade latent period is relatively independent of saccade amplitude, but there is a significant reduction in the bisensory saccades. Neural inputs of saccades are estimated and analyzed as well. Auditory saccades exhibit lower agonist pulse magnitude and longer agonist pulse duration. Antagonist onset delay is longer in auditory saccades. Post saccade phenomena are caused by the post-inhibitory rebound burst of the antagonist motoneurons. There is a higher incidence of dynamic overshoot in auditory saccades than visual saccades, with more in the abducting direction than the adducting direction.

The phase difference between neural drives to antagonist muscles in essential tremor is associated with the relative strength of supraspinal and afferent input.

The pathophysiology of essential tremor (ET), the most common movement disorder, is not fully understood. We investigated which factors determine the variability in the phase difference between neural drives to antagonist muscles, a long-standing observation yet unexplained. We used a computational model to simulate the effects of different levels of voluntary and tremulous synaptic input to antagonistic motoneuron pools on the tremor. We compared these simulations to data from 11 human ET patients. In both analyses, the neural drive to muscle was represented as the pooled spike trains of several motor units, which provides an accurate representation of the common synaptic input to motoneurons. The simulations showed that, for each voluntary input level, the phase difference between neural drives to antagonist muscles is determined by the relative strength of the supraspinal tremor input to the motoneuron pools. In addition, when the supraspinal tremor input to one muscle was weak or absent, Ia afferents provided significant common tremor input due to passive stretch. The simulations predicted that without a voluntary drive (rest tremor) the neural drives would be more likely in phase, while a concurrent voluntary input (postural tremor) would lead more frequently to an out-of-phase pattern. The experimental results matched these predictions, showing a significant change in phase difference between postural and rest tremor. They also indicated that the common tremor input is always shared by the antagonistic motoneuron pools, in agreement with the simulations. Our results highlight that the interplay between supraspinal input and spinal afferents is relevant for tremor generation.

A neuromechanical computational model of spinal control of locomotion

We developed a neuromechanical computational model of cat locomotion that simulated the locomotor movements of cat hindlimbs controlled by spinal locomotor central pattern generators (CPGs, one per limb). In the closed-loop model, CPG operation was adjusted by afferent feedback from the hindlimbs. The CPG model was based on the previous two-level model [4] and included a half-center rhythm generator (RG), producing alternating flexor and extensor activities, and a pattern formation (PF) network operating under control of RG and controlling the synergetic activities of different hindlimb motoneuron pools. This basic model [4] was extended by incorporating additional neural circuits at the PF level allowing the CPG to generate the complex activity patterns of motoneurons controlling two-joint muscles. The model included reflex circuits, mediating reciprocal inhibition between antagonistic motoneurons, recurrent inhibition of motoneurons via Renshaw cells, and di-synaptic excitation of extensors by extensor afferents during stance phase of locomotion. The hindlimbs with the pelvis and trunk were modeled as a 10 degree-of-freedom sagittal plane system of rigid segments interconnected by frictionless revolute joints. The hindlimb interactions with the ground and other body segments were modeled as linear springs and dampers [1,2]. The two hindlimbs were driven by 18 muscle actuators representing major hindlimb muscles in the cat. The dynamics of each muscle-tendon unit was described by a Hill-type model extended to account for muscle mass, pennation angle, and force-length-velocity properties of muscle and tendon [1,2]. All muscles generated motion-dependent afferent signals which were calculated as functions of muscle length, velocity and force using modified regression equations from [3]. Parameters of the musculoskeletal model were identified by minimizing a mismatch between the computed (based on the recorded hindlimb muscle activity) and experimentally recorded changes in the joint angles, joint moments and ground reaction forces using the simulated annealing optimization algorithm [1,2]. The developed neuromechanical model demonstrated stable locomotion and exhibited realistic patterns of muscle activation, limb kinematics, and ground reaction force dynamics. The model was used for investigation of the role of afferent feedback and the CPG in control of locomotion under different conditions.

Subthreshold corticospinal control of anticipatory actions in humans

Previous findings suggest that, by influencing the subthreshold state of motoneurons, the corticospinal pathways can set and reset the threshold position at which wrist muscle recruitment begins. Here we assumed that the corticospinal system can change the threshold position in a similar way before anticipated perturbation to pre-determine an appropriate emerging response to it. We first analyzed motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) applied to the wrist area of motor cortex before unloading of preloaded wrist flexors, i.e. before the subsequent involuntary wrist motion to another position (natural unloading). Subjects then learned to diminish the post-unloading movement extent without activating antagonist (extensor) muscles before unloading or making intentional movement corrections after unloading (adjusted unloading). Although activity levels of wrist muscles before unloading were similar, MEPs of extensor but not pre-loaded flexor muscles were higher before adjusted unloading. We also applied TMS in combination with a torque pulse that shortened extensor muscles such that the MEP occurred when the motoneuronal excitability was minimized. Although diminished following muscle shortening, MEPs before adjusted unloading were still higher than before natural unloading. Results suggest that the corticospinal system, possibly together with other descending systems participated in the tonic subthreshold facilitation of antagonist motoneurons before adjusted unloading, which appears sufficient in modifying motor commands and motion leading to adjusted unloading. This study reinforces previous findings that descending systems, in particular, the corticospinal system can employ threshold position control during and after learning a novel action.

A mathematical modeling study of inter-segmental coordination during stick insect walking

The biomechanical conditions for walking in the stick insect require a modeling approach that is based on the control of pairs of antagonistic motoneuron (MN) pools for each leg joint by independent central pattern generators (CPGs). Each CPG controls a pair of antagonistic MN pools. Furthermore, specific sensory feedback signals play an important role in the control of single leg movement and in the generation of inter-leg coordination or the interplay between both tasks. Currently, however, no mathematical model exists that provides a theoretical approach to understanding the generation of coordinated locomotion in such a multi-legged locomotor system. In the present study, I created such a theoretical model for the stick insect walking system, which describes the MN activity of a single forward stepping middle leg and helps to explain the neuronal mechanisms underlying coordinating information transfer between ipsilateral legs. In this model, CPGs that belong to the same leg, as well as those belonging to different legs, are connected by specific sensory feedback pathways that convey information about movements and forces generated during locomotion. The model emphasizes the importance of sensory feedback, which is used by the central nervous system to enhance weak excitatory and inhibitory synaptic connections from front to rear between the three thorax-coxa-joint CPGs. Thereby the sensory feedback activates caudal pattern generation networks and helps to coordinate leg movements by generating in-phase and out-of-phase thoracic MN activity.

Modeling the mammalian locomotor CPG: insights from mistakes and perturbations

A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-center rhythm generator (RG) and pattern formation (PF) networks is reviewed. The model consists of interacting populations of interneurons and motoneurons described in the Hodgkin-Huxley style. Locomotor rhythm generation is based on a combination of intrinsic (persistent sodium current dependent) properties of excitatory RG neurons and reciprocal inhibition between the two half-centers comprising the RG. The two-level architecture of the CPG was suggested from an analysis of deletions (spontaneous omissions of activity) and the effects of afferent stimulation on the locomotor pattern and rhythm observed during fictive locomotion in the cat. The RG controls the activity of the PF network that in turn defines the rhythmic pattern of motoneuron activity. The model produces realistic firing patterns of two antagonist motoneuron populations and generates locomotor oscillations encompassing the range of cycle periods and phase durations observed during cat locomotion. A number of features of the real CPG operation can be reproduced with separate RG and PF networks, which would be difficult if not impossible to demonstrate with a classical single-level CPG. The two-level architecture allows the CPG to maintain the phase of locomotor oscillations and cycle timing during deletions and during sensory stimulation. The model provides a basis for functional identification of spinal interneurons involved in generation and control of the locomotor pattern.

Intersegmental transfer of sensory signals in the stick insect leg muscle control system

Intersegmental coordination during locomotion in legged animals arises from mechanical couplings and the exchange of neuronal information between legs. Here, the information flow from a single leg sense organ of the stick insect Cuniculina impigra onto motoneurons and interneurons of other legs was investigated. The femoral chordotonal organ (fCO) of the right middle leg, which measures posture and movement of the femur-tibia joint, was stimulated, and the responses of the tibial motoneuron pools of the other legs were recorded. In resting animals, fCO signals did not affect motoneuronal activity in neighboring legs. When the locomotor system was activated and antagonistic motoneurons were bursting in alternation, fCO stimuli facilitated transitions from flexor to extensor activity and vice versa in the contralateral leg. Following pharmacological treatment with picrotoxin, a blocker of GABA-ergic inhibition, the tibial motoneurons of all legs showed specific responses to signals from the middle leg fCO. For the contralateral middle leg we show that fCO signals encoding velocity and position of the tibia were processed by those identified local premotor nonspiking interneurons known to contribute to posture and movement control during standing and voluntary leg movements. Interneurons received both excitatory and inhibitory inputs, so that the response of some interneurons supported the motoneuronal output, while others opposed it. Our results demonstrate that sensory information from the fCO specifically affects the motoneuronal activity of other legs and that the layer of premotor nonspiking interneurons is a site of interaction between local proprioceptive sensory signals and proprioceptive signals from other legs.

Similar response of agonist and antagonist muscles after eccentric exercise revealed by electromyography and mechanomyography

The purpose of this study was to investigate the influence of eccentric contractions (ECC) on the biceps (BB) and triceps brachii (TB) muscles during maximal voluntary contraction (MVC) of elbow flexors using electrical (EMG) and mechanomyographical activities (MMG). Each of 18 male students performed 25 submaximal contractions (50% MVC) of the elbow flexors. Root mean square amplitude (RMS) and median frequency (MDF) were calculated for the EMG and MMG signals recorded during MVC. All measurements were taken before, immediately after, 24, 48, 72, and 120h post-ECC from the BB and TB muscles. MVC was reduced by 34% immediately after exercise and did not return to the resting value within 120h (P⩽0.05). The EMG MDF decreased significantly (P⩽0.05) in both muscles after ECC. The MMG RMS at 24h, 48, 72 and 120h post-ECC was significantly lower compared to that recorded immediately after ECC in both muscles (P⩽0.05). The present research showed that (i) there were similar changes in electrical and mechanical activities during MVC after submaximal ECC in agonist and antagonist muscles suggesting a common drive controlling the agonist and antagonist motoneuron pool, (ii) the ECC induced different changes in EMG than in MMG immediately after ECC and during 120h of recovery that suggested an increased tremor and contractile impairments, i.e., reduced rate of calcium release from the sarcoplasmic reticulum (acute effect), and changes in motor control mechanisms of agonist and antagonist muscles, and increased muscle stiffness (chronic effect).

Neural Mechanisms Underlying Co-Activation of Functionally Antagonistic Motoneurons During aClioneFeeding Behavior

The ability of some neural networks to produce multiple motor patterns required during different behaviors is a well-documented phenomenon. We describe here a dramatic transition from coordinated inhibition between two functionally antagonistic groups of motoneurons to their co-activation in the feeding neural network of the predatory mollusk Clione limacina. To seize its prey, Clione uses specialized oral appendages, called buccal cones, which are controlled by two groups of motoneurons: cerebral A (Cr-A) neurons controlling buccal cone protraction and cerebral B (Cr-B) neurons controlling buccal cone retraction. When Cr-A neurons are active, Cr-B neurons usually receive strong inhibitory inputs that terminate their firing, which leads to the full protraction and elongation of the buccal cones. We have found, however, that the Cr-A and Cr-B motoneurons sometimes burst simultaneously without any traces of inhibition in the Cr-B motoneurons. This transformation of the neural network activity from inhibitory interactions to co-activation presumably occurs during the late "extraction" period of the feeding behavior when buccal cones become partially retracted and rhythmically active. The transition from the inhibitory interaction to co-activation is controlled by the activity of a single pair of cerebral interneurons (Cr-Aint interneurons), which are electrically coupled to the Cr-A neurons and monosynaptically inhibit Cr-B neurons. Normally, the Cr-Aint interneurons are active along with Cr-A motoneurons and inhibit Cr-B motoneurons. During a period of co-activation, however, these interneurons do not produce spikes, thus allowing Cr-A motoneuron activation without inhibition of the Cr-B motoneurons.

Deletions of Rhythmic Motoneuron Activity During Fictive Locomotion and Scratch Provide Clues to the Organization of the Mammalian Central Pattern Generator

We examined the features of spontaneous deletions of bursts of motoneuron activity that can occur within otherwise rhythmic alternating flexor and extensor activity during fictive locomotion and scratch in adult decerebrate cats. Deletions of activity were observed both in hindlimb flexor and extensor motoneuron pools during brain stem-stimulation-evoked fictive locomotion but only in extensors during fictive scratch. Paired intracellular motoneuron recordings showed that deletions reduced the depolarization of homonymous motoneurons in qualitatively similar ways. Differences occurred in the extent to which activity in synergist motoneuron pools operating at other joints within the limb was reduced during deletions. The timing of the rhythmic activity that followed a deletion was often at an integer multiple of the preexisting locomotor or scratch cycle period. This maintenance of cycle period was also seen during deletions in which there was a complete failure of motoneuron depolarization. The activity of antagonist motoneurons was usually sustained during deletions with some rhythmic modulation at intervals of the preexisting cycle period. We discuss an organization of the central pattern generator for locomotion and scratch that functions as a single rhythm generator with separate and multiple pattern formation modules for controlling the hyper- and depolarization of subsets of motoneurons within the limb.

Recruitment gain of antagonistic motoneurons is higher during lengthening contraction than during shortening contraction in man

The purpose of this study was to investigate how the recruitment gain, as derived from the Hoffmann (H)-reflex measurement, of antagonistic motoneurons is modulated during voluntary lengthening (LEN) and shortening (SHO) contractions in the human tibialis anterior (TA) muscle. To this end, the parameters of the ratios of the slope in each ascending part of the H and M recruitment curves (Hslp/Mslp) in the antagonist muscle were compared between LEN and SHO contractions in nine young, healthy subjects. Although there were no differences in the levels of background activity (BGA) between LEN and SHO contractions in the agonist (TA) and antagonist (soleus) muscles, the Hslp/Mslp of the antagonist muscle was significantly higher during LEN contractions than during SHO contractions ( P<0.01). It was therefore demonstrated that the recruitment gain of the antagonistic motoneurons to the la afferent inputs was higher during LEN contractions than during SHO contractions despite similar BGA levels. This result might reflect differences in the extent of the reciprocal inhibition from the agonist to the antagonist muscles and/or in the neural mechanism underlying the length-changing manners of the antagonist muscle itself.

Appearance of reciprocal facilitation of ankle extensors from ankle flexors in patients with stroke or spinal cord injury.

The purpose of the present study was to investigate the pathophysiological role of reciprocal facilitation between antagonistic motoneuron pools in spasticity. The soleus H-reflex was conditioned by prior stimulation of the peroneal nerve in 15 healthy subjects, six hemiplegic patients and 11 spinal cord injured (SCI) patients. The hemiplegic patients were tested from soon after the onset of hemiplegia and up to 2 years later. Whereas stimulation of the peroneal nerve produced short-latency inhibition of the soleus H-reflex in healthy subjects, it produced facilitation in spastic SCI and hemiplegic patients. This facilitation was demonstrated to have a low threshold compatible with activation of group I afferents and was most likely mediated by an oligosynaptic (reciprocal) excitatory pathway. The facilitation appeared in parallel with the development of hyperactive Achilles tendon reflexes, which was the only clinical finding that could be correlated positively with the facilitation. It is suggested that the appearance of reciprocal excitation plays a role in the pathophysiology of spasticity.

Inhibitory component of the resistance reflex in the locomotor network of the crayfish.

The aim of this study was to investigate the inhibitory components of a resistance reflex in the walking system of the crayfish. This study was performed using an in vitro preparation of several thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo-basipodite chordotonal organ-CBCO). Sinusoidal movements were imposed on the CBCO, and intracellular responses were recorded from levator (Lev) and depressor (Dep) motoneurons (MNs). We found that in MNs that oppose the imposed movements (e.g., the Lev MNs during the imposed downward movement), the response consists in a depolarization resulting from the summation of excitatory postsynaptic potentials (EPSPs). A movement in the opposite direction resulted in hyperpolarization during which inhibitory postsynaptic potentials (IPSPs) summated. The inhibitory pathway to each MN is oligosynaptic (i.e., composed of a small number of neurons in series) and involves spiking interneurons because it was blocked in the presence of a high-divalent cation solution. The IPSPs were mediated by a chloride conductance because their amplitude was sensitive to the chloride concentration of the bathing solution and because they were blocked by the chloride channel blocker, picrotoxin. Resistance reflex IPSPs related to single CBCO neurons could be identified. These unitary IPSPs were blocked in the presence of 3-mercapto-propionic acid, an inhibitor of gamma-amino-butyric acid (GABA) synthesis, indicating that they are mediated by GABA. In addition to this GABAergic pathway, electrical stimulation of the CBCO sensory nerve induced compound IPSPs that were blocked by glutamate pyruvate transaminase (GPT), indicating the presence of glutamatergic inhibitory pathways. These glutamatergic interneurons do not appear to be involved in the resistance reflex, however, as GPT did not block the unitary IPSPs. Functionally, the resistance reflex is mainly supported by movement-coding CBCO sensory neurons. We demonstrate that such movement-coding CBCO neurons produce both monosynaptic EPSPs in the MNs opposing imposed movements and oligosynaptic IPSPs in the antagonistic motoneurons. These results highlight the similarities between the inhibitory pathways in resistance reflex of the crayfish and in the stretch reflex of vertebrates mediated by Ia inhibitory interneurons.

Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short-latency inhibition of the soleus H-reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross-correlation analysis revealed normal short-term synchronization of TA motor units accompanied by coherence in the 8-12 Hz and 18-35 Hz frequency bands in the 10 patients. As in healthy subjects, 8-12 Hz coherence accompanied by decreased tendency to discharge synchronously (de-synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de-synchronization of antagonistic motor units, but that other GABAergic-inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

Coupling of antagonistic ankle muscles during co-contraction in humans.

In 35 healthy human subjects coupling of EMGs recorded from the tibialis anterior (TA) and soleus (Sol) muscles during voluntary co-contraction was analysed in the time and frequency domains. Two patterns were observed in different subjects or in the same subject on different occasions. One pattern consisted of central peaks in the cumulant density function of the two signals, which was often accompanied by coherence in the 15-35 Hz frequency band. The other pattern consisted of a central trough in the cumulant density function, which was mostly accompanied by coherence around 10 Hz. When this was the case oscillations were usually observed in the cumulant density function with time lags of 100 ms. Both patterns could be observed in the same subject, but usually not at the same time. Coherence around 10 Hz associated with a central trough in the cumulant density function was less common during weak than during strong co-contraction. The central peak with coherence in the 15-35 Hz frequency band in contrast tended to be most common during weak contraction. There was a tendency for the 10-Hz coherence with central trough to occur when the contractions had been maintained for some time. Both patterns could be observed when sensory feedback in large diameter afferents was blocked by ischaemia. When a central peak with coherence in the 15-35 Hz frequency band was observed for paired TA and Sol EMG recordings (10 out of 19 subjects), a coupling in the same frequency band was also observed between the EMG activities from the two muscles and the EEG activity recorded from the leg area of the motor cortex. When the central trough and the coherence around 10 Hz was observed for the EMG recordings (8 out of 19 subjects), no significant coherence was observed between EEG and EMG in 7 of the 8 subjects. In the last subject coherence around 10 Hz was observed. It is suggested that these findings signify the existence of two different central input systems to antagonistic ankle motoneurones: one input activates one muscle while depressing the antagonist and the other coactivates antagonistic motoneurones. The data suggest that at least the latter input depends on motor cortical activity.

Central nervous system lesions and segmental activity.

Study of activity in segmental pathways can help in understanding the pathophysiology of clinical disorders due to basal ganglia damage. Disynaptic Ia reciprocal inhibition (DI) acts by actively inhibiting antagonistic motoneurones and reducing the inhibition of agonist ones. During movement, activity of interneurones mediating DI is significantly modulated by descending inputs. In Parkinsonian patients, this descending modulation almost completely vanished. Lack of modulation was not dependent on L-DOPA as it occurred in treated patients and was not modified when patients were off medication. A potent heteronymous group II excitation of quadriceps MNs has been recently demonstrated in normal subjects after stimulation of the common peroneal nerve. This group II excitation was significantly enhanced in the rigid lower limb of Parkinsonian patients. We propose that enhanced group II excitation could contribute to rigidity in PD and result from a change in a tonic noradrenergic descending inhibitory control from locus coeruleus.