Modulation of presynaptic inhibition of Ia afferents during voluntary wrist flexion and extension in man

Changes in presynaptic inhibition of Ia terminals directed to flexor carpi radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at rest and during voluntary wrist flexion and extension. To that end, two independent methods were used: (1) the radial-induced D1 inhibition of the FCR H reflex, which assesses the excitability of PAD (primary afferent depolarisation) interneurones controlling presynaptic inhibition of Ia terminals mediating the afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals. With respect to results at rest, it was found that at the onset of (and during tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous monosynaptic Ia facilitation was increased. This suggests that, as in the lower limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs involved in the voluntary contraction. In contrast with results observed in the lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to be reduced at the onset of a voluntary contraction involving the antagonistic wrist extensors, suggesting that presynaptic inhibition of Ia terminals projecting to wrist flexors and extensors might be mediated through the same subsets of PAD interneurones. This is in keeping with other features showing that the organisation of reflex pathways between wrist flexors and extensors differs from that observed at other (elbow, ankle) joints.     

Pattern of monosynaptic heteronymous Ia connections in the human lower limb

Changes in the firing probability of single motor units in response to electrical stimulation of muscle nerves were used to derive the projections of muscle spindle Ia afferents to the motoneurones of various leg and thigh muscles. Discharges of units in soleus, gastrocnemius medialis, peroneus brevis, tibialis anterior, quadriceps, biceps femoris and semitendinosus were investigated after stimulation of inferior soleus, gastrocnemius medialis, superficial peroneal, deep peroneal and femoral nerves. Homonymous facilitation, occurring at the same latency as the H reflex and therefore attributed to monosynaptic Ia EPSPs, was found in virtually all the sampled units. In many motor nuclei an early facilitation was also evoked by heteronymous low-threshold afferents. The heteronymous facilitation was considered to be mediated through a monosynaptic pathway when the difference between the central latencies of heteronymous and homonymous peaks was not more than 0.2 ms. The heteronymous Ia connections were widely distributed. In particular, monosynaptic coupling between muscles operating at different joints appears to be the rule in humans, though it is rare between ankle and knee muscles in the cat and the baboon.     

Amplitude modulation of the human quadriceps tendon jerk reflex during gait

Summary Amplitude modulation of the quadriceps tendon jerk reflex was investigated during the step cycle in normal human subjects. Reflex amplitude was compared with that obtained during a control stance condition, with equivalent levels of EMG activity and limb position. During gait there was a progressive decrease in the reflex amplitude early in the stance phase, i.e. during yielding of the knee, and it remained reduced throughout the step cycle. This pattern of changes in reflex amplitude correlated with neither the quadriceps EMG activity nor with the knee joint movements. The behavior of the tendon reflex was similar to that described for the modulation of the quadriceps H-reflex during the early stages of the stance phase of gait. In the latter study it was argued that changes in presynaptic inhibition of quadriceps la terminals could account for the amplitude modulation. We conclude that there is no dramatic change in the gamma drive to quadriceps muscle spindles: tendon reflexes are modulated during the step cycle in much the same way as H-reflexes, in spite of the peripheral and central differences between them. Similar behavior has been described for the soleus H-reflex and Achilles tendon reflex during gait although the modulation of these reflexes followed a different pattern than that seen in the quadriceps.     

Cortical control of presynaptic inhibition of Ia afferents in humans

The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus. Received: 18 July 1997 / Accepted: 10 November 1997     

Changes in presynaptic inhibition of Ia fibres to soleus motoneurones during voluntary dorsiflexion of the foot

Summary Variations of presynaptic inhibition in heteronymous Ia fibres projecting to soleus motoneurones were studied during the first 250 ms of phasic voluntary isometric contractions of the antagonist tibialis anterior muscle in human subjects. During the first 60–80 ms of TA e.m.g activity, presynaptic inhibition was often more marked than at rest, but not in all experimental sessions. After 60–80 ms, presynaptic inhibition was always increased compared to rest and to the onset of TA e.m.g. activity. A rebound in femoral nerve induced Ia facilitation was often observed between 90–150 ms. The early increase in presynaptic inhibition was widespread and non specific since it was observed at the onset of extensor carpi radialis contractions of maximal strength. The rebound in heteronymous Ia facilitation was interpreted as a relative decrease in presynaptic inhibition to which nonspecific suprasegmental and cutaneous effects contributed. The late increase in presynaptic inhibition in Ia fibers to soleus motoneurones was considered as reciprocally inhibiting the Sol H-reflex, thus counteracting the phasic stretch of the antagonist muscle during TA contraction.     

Progressive decrease in heteronymous monosynaptic la facilitation with human ageing

To evaluate functional change in the spinal reflex pathway with ageing, we studied heteronymous Ia facilitation from the quadriceps to soleus muscle in 30 normal volunteers (aged 24–68 years). The size of the test H-reflex of the soleus muscle was adjusted to 25% that of the maximal M-response. The conditioning stimulus was adjusted to 1.5-fold the motor threshold to stimulate all the Ia fibres in the femoral nerve. Facilitation was quantified as the slope of the very early part of facilitation, within 0.8 ms of onset. This procedure enabled us to evaluate the extent of monosynaptic Ia facilitation without contamination by other effects. The extent of facilitation decreased linearly with age. This decrease in facilitation could reflect a decrease in the number of Ia fibres and in their conduction velocities, and an increase in presynaptic inhibition on Ia terminals. The increase in presynaptic inhibition may be an adaptive phenomenon in the ageing of the neuromuscular system or, alternatively, a deteriorating process with decreasing flexible supraspinal modulation.     

Amplitude modulation of the quadriceps H-reflex in the human during the early stance phase of gait

Summary Amplitude modulation of the quadriceps H reflex was investigated during the early part of the stance phase of gait in normal human subjects. Stability of the M wave was used to ensure constancy of the effective stimulus strength. In all subjects there was a progressive decrease in the reflex amplitude throughout the early knee flexion (yield of the knee), whereas the quadriceps EMG activity remained constant or even increased. At an equal stimulus strength and EMG level, the reflex was often larger at the onset of the stance phase of gait than during voluntary contraction, whereas it was always smaller during the knee extension following the yield of the knee. It is argued that changes in presynaptic inhibition of quadriceps Ia terminals could account for this amplitude modulation of the monosynaptic reflex during gait. The possible role of changes in the gain of the quadriceps stretch reflex during bipedal gait is discussed.     

Effects of flexor reflex afferent stimulation on the soleus H reflex in patients with a complete spinal cord lesion: evidence for presynaptic inhibition of Ia transmission

Summary The effects of electrically stimulating the Flexor Reflex Afferent (FRA) on the soleus H reflexes were investigated in 34 paraplegic patients having a clinically complete spinal cord lesion. Conditioning stimuli (5–50 mA) were applied to the ipsilateral or contralateral sural nerve. The conditioning-test interval ranged from 20 to 1000 ms. A late ipsilateral flexor reflex (EMG) was found in all patients. A late contralateral extension reflex was sporadically observed in only 3 patients. The excitability curves usually showed two phases of ipsilateral H reflex inhibition and contralateral H reflex facilitation, one between 50 and 130 ms and the other after over 200 ms. These intervals correspond to early and late flexion reflexes. With high intensity stimulation the early and late ipsilateral inhibition fused. An early low threshold ipsilateral facilitation occured in 9 patients. The contralateral late facilitation was followed by prolonged inhibition in 10 patients. Changes in presynaptic inhibition were assessed by measuring the heteronymous monosynaptic Ia facilitation from quadriceps to soleus. For methodological reasons, it was only possible to investigate the effect of contralateral conditioning volleys which was performed in 5 patients. A significant and regular reduction of the heteronymous Ia facilitation was found in 4 patients. This reduction is taken to indicate that the FRA evokes presynaptic inhibition of Ia transmission to alpha motoneurones. Presynaptic inhibition was also indicated by the enhancement of a vibratory stimulus induced inhibition in 2 subjects. These results are consistent with the hypothesis that the reflex organization in patients with a spinal cord section is similar to that of the acute spinal cat injected with DOPA.     

Projections of group Ia afferents to motoneurons of thigh muscles in man

Summary Changes in the firing probability of single motor units in response to electrical stimulation of muscle nerves and to tendon taps were used to derive the projections of large muscle afferents to the motoneurons of various thigh muscles in man. Homonymous facilitation was demonstrated to virtually all of the sampled motor units of biceps (BI), semitendinosus (ST), vastus lateralis (VL) and vastus medialis (VM). Heteronymous facilitation was readily demonstrated between VM and VL but was never obtained from ST to BI and never unequivocally obtained from BI to ST. Reciprocal inhibition was demonstrated from femoral nerve afferents to all of the sampled units of BI, and ST but reciprocal inhibition of VM or VL was never obtained from BI afferents and infrequently from ST afferents. These projections of group I afferents in man show certain specific differences from those of the cat and baboon that may reflect the normal function of the limb.     

Modulation of the biceps femoris tendon jerk reflex during human locomotion

 During gait it is generally accepted that there is a reduction in amplitude of H-reflexes as compared to standing. For short-latency stretch reflexes, however, it is less clear whether a similar reduction in reflex gain is present during locomotion. Stretches of constant amplitude are hard to produce under these circumstances and for this reason some previous studies on the biceps femoris (BF) have used ”reduced gait” in which the stimulated leg is stepping on the spot while the contralateral leg is walking on a treadmill. With this method it was possible to show that BF tendon jerk reflexes are larger at end swing and therefore are likely to contribute to the EMG burst normally occurring in that part of the step cycle when the BF is rapidly stretched. In the present study two questions were addressed: first, whether the reflex is different in size during gait compared to standing and, second, whether it is modulated in size during the gait cycle not only during reduced but also during normal gait. It was found that during both types of gait there was a general reflex depression with regard to the respective control values obtained during standing at similar EMG activity levels. In previous studies on soleus and quadriceps, discrepancies between EMG activity and reflex amplitude have been ascribed to changes in presynaptic inhibition of Ia terminals mediating the afferent volley of the reflex. Based on the data presented, this may also be true for the BF. In both normal and reduced gait the reflex was similarly modulated in size, showing a maximum at the end of swing. This similarity implies that reduced gait may be useful as an acceptable alternative for normal gait in studies on phase-dependent reflex modulation during locomotion. Received: 9 March 1998 / Accepted: 14 August 1998     

Evidence for mutual inhibition of opposite Ia interneurones in the human upper limb

Summary The H-reflex technique was used to collect indirect evidence for changes in excitability of the interneurones mediating reciprocal Ia inhibition between wrist extensors and flexors. Stimulating the radial nerve results in an inhibition of the flexor carpi radialis (FCR) H-reflex and evidence has previously been presented that the early phase of inhibition is mediated by extensor-coupled Ia interneurones (Ext Ia INs), i.e. by inhibitory interneurones fed by muscle spindle Ia afferents from wrist extensors. Variations in the level of this inhibition were used to assess changes in excitability of Ext Ia INs. Stimulation of group I fibres from flexors was shown to depress the reference Ia inhibition, i.e. to inhibit the Ext Ia INs. The central latency of this interneuronal inhibition was compatible with a disynaptic linkage between flexor Ia afferents and Ext Ia INs. Its threshold and time course profile could almost exactly be superimposed on those of reciprocal Ia inhibition from flexors to extensor carpi radialis (ECR) motoneurones (MNs). This suggests that the Ia inhibitions to extensor MNs and extensor Ia INs are collateral effects mediated by the same flexor-coupled Ia interneurones. In two subjects, in whom it was possible to elicit an H-reflex in the ECR, inhibition of flexor-coupled Ia interneurones by activation of extensor Ia interneurones could similarly be demonstrated.     

Differential effects of (−)-baclofen on Ia and descending monosynaptic EPSPs

Summary 1. In cats anesthetized with alpha-chloralose, population synaptic responses of motoneurons produced by stimulation of group I afferents were recorded from ventral roots with a sucrose gap or extracellularly from the motor pool. These responses were depressed, and often abolished, following the intravenous injection of 1–3 mg/kg of (–)-baclofen, a presumed GABA_b agonist. 2. The monosynaptic population responses of motoneurons produced by stimulation of the ipsilateral ventromedial funiculus (VMF), the bulbar reticular formation or the vestibular nucleus, were also depressed following the administration of (–)-baclofen, but to a lesser degree than responses produced by stimulation of group I fibers. 3. Depression of the synaptic actions of Ia and of descending fibers following the administration of (–)-baclofen occurred without significant changes in the presynaptic volley recorded from the cord dorsum. However, in 3/4 experiments the intraspinally recorded Ia terminal potential was reduced following the injection of (–)-baclofen. The VMF terminal potentials were also depressed, but to a lesser degree. 4. Intracellular recordings from spinal motoneurons indicate that the (–)-baclofen-induced depression of the monosynaptic Ia- and VMF-EPSPs occurred without important changes in the time course of EPSP decay. This suggests that with the amounts used, postsynaptic changes were not contributing significantly to the EPSP depression. 5. It is suggested that (–)-baclofen depresses synaptic transmission probably by activation of GABA_b receptors located at the intraspinal terminations of Ia and descending fibers. The lower sensitivity of VMF actions to (–)-baclofen would be accounted for by a relatively low density of baclofen receptors in descending fiber terminals.     

Changes in polysynaptic Ia excitation to quadriceps motoneurones during voluntary contraction in man

Summary Homonymous Ia facilitation of quadriceps (Q) motoneurones (MNs) was significantly larger during (and at the onset of) a very weak Q voluntary contraction than at rest. This increase in Ia facilitation only appeared with a conditioning-test interval within the narrow range of 5–9 ms, which fits the time course of the recently described polysynaptic Ia excitation to Q MNs. This suggests that interneurones mediating polysynaptic Ia excitatory effects to Q MNs receive a strong descending excitation during such a contraction. It is therefore argued that these interneurones might mediate part of the descending command to Q MNs during voluntary contraction.     

Further observations on the depression of group Ia facilitation of motoneurons by vibration in man

Summary Stimulation of low threshold afferents in the peroneal nerve causes a short latency facilitation of individual tibialis anterior motor units considered to be due to the composite Ia EPSP. This facilitation is depressed by vibration 20 to 128 Hz applied over the tibialis anterior. The depression occurs without any change in the firing rate of the motor unit or in the facilitation from cutaneous afferents and so is unlikely to be due to postsynaptic inhibition. The depression can occur with vibration frequencies as low as 40 Hz and is therefore unlikely to be due to occlusion in Ia afferents. There is no evidence that vibration alters the electrical threshold of large afferents. A similar facilitation of soleus motor units resulting from stimulation of low threshold afferents in the tibial nerve is depressed for up to 75 ms following a 40 ms burst of 50 Hz vibration applied to the tendon of the tibialis anterior. The burst of vibration itself did not facilitate soleus motor units so there is no evidence to suggest that the vibration spread to soleus spindles. Homosynaptic depression is, therefore, unlikely. These findings provide further evidence that pesynaptic inhibition of Ia afferents occurs in man.     

Effects of cortical stimulation on reciprocal inhibition in humans

We attempted to demonstrate convergence onto human spinal Ia inhibitory interneurons from Ia afferents and from fast conducting corticospinal axons. Stimulation of the common peroneal nerve at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H-reflex, attributed to reciprocal inhibition. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the soleus H-reflex, including a short latency-inhibition. To test for convergence, the two stimuli were given together so that the two inhibitions coincided.When each stimulus alone produced clear inhibition, the inhibition produced by both stimuli was less than expected, implying an interaction between the two volleys, for example, occlusion occurring in interneurons or motoneurons.When the H-reflex was relatively unaffected by one or other conditioning volley, the inhibition produced by the combined stimulation was greater than expected, as might be expected with convergence onto a common pool of interneurons.     

Effects of stimulation of group I afferents from flexor muscles on heterosynaptic facilitation of monosynaptic reflexes produced by Ia and descending inputs: a test for presynaptic inhibition

Summary 1. In the chloralose anesthetized cat, conditioning stimulation of group I flexor afferents depresses the monosynaptic potentials generated by Ia afferents in single spinal motoneurons or in populations of motoneurons without affecting the monosynaptic potentials produced by stimulation of descending fibers in the ipsilateral ventromedial fasciculus (VMF). 2. Heterosynaptic facilitation of monosynaptic reflexes was used to test changes in the presynaptic effectiveness of excitatory inputs with direct connections with motoneurons. We found that the heterosynaptic facilitation of Ia origin was reduced by conditioning stimulation of group I afferents from flexors, without affecting the heterosynaptic facilitation produced by stimulation of the VMF. 3. These results confirm and expand previous observations showing that the synaptic effectiveness of descending fibers synapsing with motoneurons is not subjected to a presynaptic control mechanism of the type acting on Ia fiber terminals, and provide further basis for the use of changes in heterosynaptic facilitation of monosynaptic reflexes of Ia origin as an estimate of changes in presynaptic inhibition of Ia fibers (Hultborn et al. 1987a).     

Changes in reciprocal Ia inhibition from wrist extensors to wrist flexors during voluntary movement in man

Summary Transmission in the Ia inhibitory pathway from wrist extensor muscles onto flexor MNs was studied at various times after the onset of voluntary wrist extension or flexion. At the very onset of wrist movements Ia inhibition was not changed, as compared to at rest, whereas later it progressively increased during wrist extension and decreased during wrist flexion. These results are discussed in relation to the different inputs converging onto Ia interneurones and it is suggested that their inhibition by Renshaw cells might be responsible for the results found at the onset of contraction     

Synaptic connections from large muscle afferents to the motoneurons of various leg muscles in man

Summary Cross-correlations between stimuli delivered to peripheral nerves and the discharges of single, voluntarily activated, motor units can provide information about facilitatory and inhibitory projections to single spinal motoneurons in man. The projection frequency, under the given circumstances, of a facilitatory or inhibitory pathway can be obtained from the proportion of the sampled motor units of a given muscle showing the facilitatory or inhibitory effect. Deductions about the shape and relative amplitude of the underlying post-synaptic potentials can be made from the profile of the changes in firing probability. This technique has been used to explore the projections of low threshold muscle afferents to motoneurons of various leg muscles in man. Homonymous facilitation was demonstrated to all the sampled motor units of soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA) and vastus medialis (VM) and is presumed to represent the effects of the composite muscle spindle group Ia EPSP. Heteronymous facilitation was demonstrated between certain synergists. The projection frequency was less and the magnitude of the change in firing probability was smaller than for homonymous facilitation. SOL motoneurons, however, were not facilitated from low threshold afferents in the medial gastrocnemius nerve. Reciprocal inhibition was demonstrated between certain antagonists. The majority of the sampled motor units of SOL, however, were facilitated from low threshold afferents in the common peroneal nerve. The threshold for this facilitation was higher than for the homonymous facilitation elicited from this nerve and thus a different class of afferents and/or intercalated interneurons may be involved. There are projections across the knee joint in man. Motor units in vastus medialis (VM) were facilitated from low threshold afferents in the common peroneal nerve. It is likely that these reflex connections, which differ from those in other species, reflect the functional relationships between various lower limb muscles in man.     

Distribution of heteronymous Ia facilitation and recurrent inhibition in the human deltoid motor nucleus

Summary Distribution of heteronymous Ia facilitation and of heteronymous recurrent inhibition in motoneurones innervating the anterior part of the deltoid muscle were investigated in normal human subjects following electrical stimulation of the nerves innervating the main muscles of the upper limb. Activation of group I afferents originating from deltoid, biceps, triceps and extensor carpi radialis (ECR) muscles resulted in an early increase in firing probability of voluntarily activated motor units belonging to the anterior part of the deltoid muscle whereas activation of motor axons supplying deltoid, triceps, ECR and flexor carpi radialis (FCR) muscles resulted in an early and long-lasting decrease in firing probability. No effect was seen following activation of group I afferents and motor axons contained in the ulnar nerve. The characteristics of the early facilitation suggest that it is at least partly due to heteronymous Ia monosynaptic connections while these of the long-lasting inhibition suggest that it is at least partly due to heteronymous recurrent inhibition. Their patterns of distribution are discussed with regards to the functional role of the human deltoid.     

Ia afferents of the antagonist are inhibited presynaptically before the onset of a ballistic muscle contraction in man

Summary The aim of the present investigation was to study whether the pre-movement inhibition of the H reflex in the antagonist of a ballistic voluntary contraction was due to a reduced activity of the motoneuronal pool of the antagonist, or to a reduced excitatory effect of the afferent volley reaching these motoneurons. Human subjects performed visually conditioned ballistic dorsal flexions of the ankle. The inhibition of the H reflex in the antagonist (soleus muscle) was similar if the muscle was initially relaxed or if there was a preexisting level of motor discharge. Since the soleus muscle was inhibited before movement onset in parallel with the H reflex inhibition, the relation between the level of a background activity and the size of superimposed H reflexes was studied. The finding that H reflexes were only slightly reduced in size with decreasing steady EMG levels could not explain the pre-movement inhibition, and it was concluded than an increased presynaptic inhibition of Ia terminals was the source of the H reflex inhibition.