Stimulation Of Low-threshold Afferents Research Articles

Role of cutaneous and proprioceptive inputs in sensorimotor integration and plasticity occurring in the facial primary motor cortex

Previous studies investigating the effects of somatosensory afferent inputs on cortical excitability and neural plasticity often used transcranial magnetic stimulation (TMS) of hand motor cortex (M1) as a model, but in this model it is difficult to separate out the relative contribution of cutaneous and muscle afferent input to each effect. In the face, cutaneous and muscle afferents are segregated in the trigeminal and facial nerves, respectively. We studied their relative contribution to corticobulbar excitability and neural plasticity in the depressor anguli oris M1. Stimulation of trigeminal afferents induced short-latency (SAI) but not long-latency (LAI) afferent inhibition of face M1, while facial nerve stimulation evoked LAI but not SAI. Plasticity induction was observed only after a paired associative stimulation protocol using the facial nerve. Physiological differences in effects of cutaneous and muscle afferent inputs on face M1 excitability suggest they play separate functional roles in behaviour. The lack of conventional muscle spindles in face muscles raises the question of how sensory input from the face is used to control muscle activation. In 16 healthy volunteers, we probed sensorimotor interactions in face motor cortex (fM1) using short-afferent inhibition (SAI), long-afferent inhibition (LAI) and LTP-like plasticity following paired associative stimulation (PAS) in the depressor anguli oris muscle (DAO). Stimulation of low threshold afferents in the trigeminal nerve produced a clear SAI (P<0.05) when the interval between trigeminal stimulation and transcranial magnetic stimulation (TMS) of fM1 was 15-30ms. However, there was no evidence for LAI at longer intervals of 100-200ms, nor was there any effect of PAS. In contrast, facial nerve stimulation produced significant LAI (P<0.05) as well as significant facilitation 10-30 minutes after PAS (P<0.05). Given that the facial nerve is a pure motor nerve, we presume that the afferent fibres responsible were those activated by the evoked muscle twitch. The F-wave in DAO was unaffected during both LAI and SAI, consistent with their presumed cortical origin. We hypothesize that, in fM1, SAI is evoked by activity in low threshold, presumably cutaneous afferents, whereas LAI and PAS require activity in (higher threshold) afferents activated by the muscle twitch evoked by electrical stimulation of the facial nerve. Cutaneous inputs may exert a paucisynaptic inhibitory effect on fM1, while proprioceptive information is likely to target inhibitory and excitatory polysynaptic circuits involved in LAI and PAS. Such information may be relevant to the physiopathology of several disorders involving the cranio-facial system.

Facilitation between extensor carpi radialis and pronator teres in humans: A study using a post-stimulus time histogram method

Group I muscle afferents modulate the excitability of motor neurons through excitatory and inhibitory spinal reflexes. Spinal reflex relationships between various muscle pairs are well described in experimental animals but not in the human upper limb, which exhibits a fine control of movement. In the present study, spinal reflexes between the extensor carpi radialis (ECR) and pronator teres (PT) muscles were examined in healthy human subjects using a post-stimulus time histogram method. Electrical stimulation of low-threshold afferents of ECR nerves increased the motor neuron excitability in 31 of 76 PT motor units (MUs) in all eight subjects tested, while stimulation of low-threshold afferents of PT nerves increased the motor neuron excitability in 36 of 102 ECR MUs in all 10 subjects. The estimated central synaptic delay was almost equivalent to that of homonymous facilitation. Mechanical stimulation (MS) of ECR facilitated 16 of 30 PT MUs in all five subjects tested, while MS of PT facilitated 17 of 30 ECR MUs in all six subjects. These results suggest excitatory reflex (facilitation) between PT and ECR. Group I afferents should mediate the facilitation through a monosynaptic path.

Large Involuntary Forces Consistent with Plateau-Like Behavior of Human Motoneurons

When electrical stimulation is applied over human muscle, the evoked force is generally considered to be of peripheral origin. However, in relaxed humans, stimulation (1 msec pulses, 100 Hz) over the muscles that plantarflex the ankle produced more than five times more force than could be accounted for by peripheral properties. This additional force was superimposed on the direct response to motor axon stimulation, produced up to 40% of the force generated during a maximal voluntary contraction, and was abolished during anesthesia of the tibial nerve proximal to the stimulation site. It therefore must have resulted from the activation of motoneurons within the spinal cord. The additional force could be initiated by stimulation of low-threshold afferents, distorted the classical relationship between force and stimulus frequency, and often outlasted the stimulation. The mean firing rate of 27 soleus motor units recorded during the sustained involuntary activity after the stimulation was 5.8 +/- 0.2 Hz. The additional force increments were not attributable to voluntary intervention because they were present in three sleeping subjects and in two subjects with lesions of the thoracic spinal cord. The phenomenon is consistent with activation of plateau potentials within motoneurons and, if so, the present findings imply that plateau potentials can make a large contribution to forces produced by the human nervous system.

Resetting from low threshold afferents of [formula omitted] locomotor rhythm in the isolated spinal cord-hindlimb preparation from newborn rats

In this study we have investigated the effects of low threshold afferent stimulation on the centrally generated locomotor rhythm in an isolated spinal cord-hindlimb preparation from newborn (0–3 days old) rats. Locomotor activity was induced by bath application of N- methyl- d-aspartate (NMDA). Stimulation of low threshold afferents (below 2 times threshold (× T) for the incoming volley) in L 2 and L 3, but not L 4 and L 5 dorsal roots resets the ongoing rhythm. This is due to an abrupt excitation of the L 2 and L 3 ventral root bursts and an inhibition of the L 5 ventral root burst on the ipsilateral side followed by reciprocal effects on the contralateral side. Similar effects were seen after stimulation of the quadriceps nerve with weak intensity (below 1.8 × T). We conclude that low threshold muscle afferents, possible group I afferents, have access to central pattern generators early in postnatal life and suggest that these findings may give an important opening in ontogentic studies of how neural networks are assembled.

Pattern of projections of group I afferents from elbow muscles to motoneurones supplying wrist muscles in man

The pattern of projections of low threshold afferents from triceps and biceps brachii muscles onto motoneurones innervating muscles acting at the wrist was assessed by a reflex and a poststimulus time histogram (psth) technique. Activation of low-threshold afferents originating from elbow flexors or extensors resulted in an early, short-lasting inhibition of wrist flexor motoneurones (flexor carpi radialis, flexor carpi ulnaris). An inhibition was also found in the extensor carpi radialis (ECR) motoneurones after stimulation of low-threshold afferents from triceps. Evidence is presented that Ia fibres contribute to these effects. The inhibitory effects were found in all subjects, but they were constant in only 57% of the reflex experimental sessions and in 25% of the explored motor units. Stimulation of biceps low-threshold afferents was always ineffective on ECR motoneurones. No early facilitation was ever seen in motor nuclei innervating wrist muscles following stimulation of low threshold afferents from biceps and triceps. The pattern of transjoint projections of group I afferents from proximal to distal muscles and from distal to proximal ones (Cavallari and Katz 1989) is discussed in relation to that described in the cat forelimb.

Reciprocal inhibition in cerebral palsy

We studied reciprocal inhibition by recording the changes in firing probability of single motor units of the tibialis anterior muscle following stimulation of low-threshold afferents in the posterior tibial nerve. In 15 patients with cerebral palsy, the inhibition was as great or greater than normal. We found no evidence that group I afferents produce "reciprocal facilitation" in cerebral palsy.

Modulation of short latency cutaneous excitation in flexor and extensor motoneurons during fictive locomotion in the cat.

We examined modulation of transmission in short-latency, distal hindlimb cutaneous reflex pathways during fictive locomotion in 19 decerebrate cats. Fictive stepping was produced either by electrical stimulation of the mesencephalic locomotor region (MLR) or by administration of Nialamide and 1-DOPA to acutely spinalized animals. Postsynaptic potentials (PSPs) produced by electrical stimulation of low threshold afferents (less than 2.5 times threshold) in the superficial peroneal (SP), sural, saphenous or medial plantar nerves were recorded intracellularly from various extensor (n = 28) and flexor (n = 24) motoneurons and averaged throughout the step cycle, together with voltage responses to intrasomatic constant current pulses (in order to monitor relative cell input resistance). Each motoneuron studied displayed rhythmic background oscillations in membrane potential and correlated variations in input resistance. The average input resistance of extensor motoneurons was lowest during mid-flexion, when the cells were relatively hyperpolarized and silent. Conversely, average input resistance of flexor motoneurons was highest during mid-flexion, when they were depolarized and active. The amplitude of the minimum-latency excitatory components of PSPs produced by cutaneous nerve stimulation were measured from computer averaged records representing six subdivisions of the fictive step cycle. Oligosynaptic EPSP components were consistently modulated only in the superficial peroneal responses in flexor motoneurons, which exhibited enhanced amplitude during the flexion phase. With the other skin nerves tested (sural, saphenous, and plantar), no consistent patterns of modulation were observed during fictive locomotion. We conclude that transmission through some, but not all, oligosynaptic excitatory cutaneous pathways is enhanced by premotoneuronal mechanisms during the flexion phase of fictive stepping in several cat hindlimb motor nuclei. The present results suggest that the patterns of interaction between the locomotor central pattern generator and excitatory cutaneous reflex pathways depend on the source of afferent input and on the identity of the target motoneuron population.

Inhibition of neurones transmitting non-monosynaptic Ia excitation to human wrist flexor motoneurones.

1. The possibility was investigated that the transmission of the interneuronally mediated Ia excitation to wrist flexor motoneurones described in the companion paper is inhibited by stimulation of afferent fibres. Two techniques were used: (i) the post-stimulus time histogram (PSTH) method for studying changes in firing probability of individual voluntarily activated wrist flexor motor units following various peripheral stimulations; and (ii) the indirect technique of spatial facilitation of the H reflex. 2. In those individual units where stimulation of the median and/or the ulnar nerve evoked a non-monosynaptic excitation, this excitation was reduced when the afferent input was increased. This reduction of the non-monosynaptic Ia excitation was found in 80% of the motor unit recordings, whether the afferent input was increased by increasing the stimulus intensity to one nerve or by using combined stimulation of two nerves. 3. Both group I muscle and low-threshold cutaneous afferents were shown to be able to reduce the non-monosynaptic Ia excitation. 4. The onset of the depression of the excitation was always found within the same 1 ms bin as that of the excitation. 5. Whatever the amount of afferent input (stimulus intensity increased up to motor threshold, spatial and temporal summation, summation of inhibitory effects from different origins), the depression could at the very most suppress the non-monosynaptic Ia excitation: i.e. a trough in the PSTH, reflecting an inhibition at the motoneuronal level, never appeared. In those units in which there was not non-monosynaptic excitation, peripheral stimulation did not evoke any inhibition appearing as a trough in the PSTH either. Hence, inhibition only appeared when there was a non-monosynaptic excitation, and then as a depression of it. 6. On the basis of these findings it is argued that the inhibition is not exerted directly onto motoneurones but acts at a pre-motoneuronal level on the interneurones mediating the non-monosynaptic Ia excitation to motoneurones. 7. Similarly, the homonymous non-monosynaptic Ia facilitation of the flexor carpi radialis H reflex was shown to be reduced by a preceding stimulation applied to the ulnar nerve. It is argued that this result is also compatible with an inhibition of transmission in interneuronal excitatory pathways to motoneurones. 8. It is suggested that the non-monosynaptic excitation of wrist flexor motoneurones in man and the inhibition of this excitation, both evoked by stimulation of low-threshold afferents, could be mediated through a system of cervical propriospinal neurones. Some aspects of the possible role of this system during movement are discussed.

On the cause of hyporeflexia in the Holmes-Adie syndrome.

Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.

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

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 presynaptic inhibition of Ia afferents occurs in man.

Location of, and peripheral convergence on, the interneuron in the disynaptic path from the coronal gyrus of the cerebral cortex to the trigeminal motoneurons in the cat.

Primary afferent and descending cortico-bulbar convergence on 186 interneurons located in the intertrigeminal area was investigated. The experiments were performed on cats anaesthetized with chloralose. Nerves from the three trigeminal dermatomes were stimulated electrically at intensities below and above twice the threshold level. Nerves from oral, perioral and periorbital structures, and afferents from the masseteric and digastric muscles were included. The surface of the cerebral cortex was stimulated electrically in systematically selected, maximally receptive points within the trigeminal primary projection fields. The intertrigeminal neurons generally responded to stimulation of low-threshold afferents from periodontal, lingual or perioral cutaneous receptors with a polysynaptic latency. Inputs from 3-5 nerves were common but one afferent input was usually most effective. The neurons were generally discharged from two or more cortical points, as a rule those of the oral and perioral projection fields in areas 3a and 3b of the coronal gyrus. The fastest path from the cerebral cortex to the intertrigeminal area was monosynaptic. However, the median latency was 4-5 ms which indicates an oligosynaptic path. The path went through the pyramid at the pontine level. The discharge pattern of the intertrigeminal neurons was 1-4 spikes in 54% of the neurons and a high frequency train of spikes in 46%. Cortical excitation followed by inhibition of the neurons was observed. The neurons were not discharged by electrical stimulation in the defence-attack area of the hypothalamus. Transsynaptic responses evoked from the mesencephalon were seen in 1/3 of the tested neurons.

Locomotor limb synergism through short latency afferent links

Reports of facilitation of lower limb synergists through afferent stimulation in resting humans lead to study of short latency reflex responses during activity of the legs. Four synergistic muscles of the right leg were examined following electrical stimulation of low threshold afferents of the posterior tibial (PTN) and femoral (FN) nerves. Four males cycled on an ergometer with pedals modified to measure the force applied. Movement frequency was 0.8 Hz with 15 N ergometer resistance for two 6 min trials, one involving PTN and the other FN. Collection of EMGs of soleus, lateral gastrocnemius, vastus medialis and rectus femoris lasted for 200 msec after stimulation, which was triggered when the pedal was 56 degrees beyond top-dead-center. Control EMGs were similarly collected during intervening, non-stimulated, pedal cycles within the same work bout. Collection of force on pedals occurred over the same 200 msec period as well as the following two complete pedal revolutions. From PTN stimulation short latency increase occurred not only in homonymous EMGs but also in heteronymous as distant as rectus femoris. FN stimulation similarly resulted in short latency changes in quadriceps and also in triceps surae. Pedal force changes accompanied the EMGs. M response confounding in many cases resulted in only tentative identification of the reflex force evoked. Little change with stimulation was seen in the force in subsequent cycles. The responses represent a net of pathways which could affect within-limb coordination of muscles during human locomotion and extend previous investigations of Ia projections in spinal cats and resting humans.

Effect of haloperidol on reflex activation of rat alpha-motoneurones. A possible explanation for akinesia and catalepsy?

Effects of haloperidol on rat flexor and extensor alpha-motoneurones were studied in ventral roots of laminectomized rats under halothane anesthesia. The alpha-motoneurones were activated by tetanic stimulation of low-threshold afferents (group I and II), either of the ipsilateral peroneal nerve ("flexor alpha-motoneurones") or gastrocnemius-soleus nerve ("extensor alpha-motoneurones"). Haloperidol, given in the doses of 0.075, 0.15 and 0.30 mg/kg i.p. inhibited the reflex activation of flexor alpha-motoneurones; higher doses seemed to be more effective than lower ones. Apomorphine (2 mg/kg s.c.) partially antagonized the inhibitory action of haloperidol with some latency. Higher doses of haloperidol (0.15-0.60 mg/kg i.p.) also inhibited the reflex activation of extensor alpha-motoneurones; this inhibitory effect was, at least for a short time, antagonized by apomorphine (2 mg/kg s.c.). The threshold for reflex activation both of flexor and extensor alpha-motoneurones was raised by haloperidol and lowered by a subsequent administration of apomorphine. Our results suggest that akinesia and catalepsy, induced in rats by haloperidol might be, at least in part, due to a decrease in sensitivity of alpha-motoneurones to proprioceptive stimuli.

Modulation of synaptic effectiveness of Ia and descending fibers in cat spinal cord.

1. In the unanesthetized spinal cord, conditioning stimulation of low-threshold afferents (below 1.3 times threshold strength) in the biceps semitendinosus (BST) nerve often reduced the peak amplitude of the monosynaptic Ia EPSPs evoked in gastrocnemius motoneurons without affecting the monosynaptic component of the EPSPs evoked by stimulation of the ipsilateral ventral funiculus (VF) in the thoracic cord. 2. Volleys to the BST nerve comprising higher threshold afferents (usually above 1.4 times threshold strength) reduced the peak amplitude of the monosynaptic Ia and VF EPSPs and shortened their falling phase. 3. Conditioning volleys to low-threshold cutaneous afferents often increased the Ia-EPSP peak amplitude, sometimes without affecting the monosynaptic component of the VF EPSP. 4. In most cases the Ia nd VF monosynaptic EPSPs elicited in a given motoneuron summated nonlinearly. The amount of nonlinear summation between Ia and VF monosynaptic EPSPs was often reduced by low-threshold BST conditioning volleys. These observations suggest that in many instances, both species of fibers end in "electrotonically close" synaptic loci over the motoneuron surface. Therefore, amplitude changes of monosynaptic Ia EPSPs produced by conditioning afferent volleys without concomitant changes of monosynaptic VF EPSPs do not appear to result from postsynaptic remote conductance changes and may be attributed to a presynaptic mechanism. 5. At the time of occurrence of the Ia and VF monosynaptic EPSP the variance of the motoneuron membrane potential may be increased above base-line levels with a time course approximately matching the EPSP itself. Conditioning stimulation of BST afferents usually reduced Ia EPSP variance, often without affecting or even increasing the variance of the monosynaptic VF EPSPs. These observations provide additional evidence that Ia EPSP variability is introduced, at least in part, through the segmental pathways mediating primary afferent depolarization. 6. The possibility of a differential control of the information flow transmitted through two independent channels converging on a given cell ensemble is discussed.

Inhibition of hypoglossal motoneurons by stimulation of the jaw-opening muscle afferents.

The synaptic linkage of jaw-opening muscle afferents with the retractive and the protrusive motoneurons (R-Mns and P-Mns) in the hypoglossal motor nucleus was explored in anesthetized cats. It was found that stimulation of low-threshold afferents arising in the jaw-opening muscles (m. mylohyoideus and m. digastricus) evoked IPSPs in both R-Mns and P-Mns with about 10 to 15 msec latencies. By injecting Cl ions into R-Mns or P-Mns, the hyperpolarizing postsynaptic potentials evoked by jaw-opening muscle afferent impulses were reversed to depolarizing potentials. The lingual-IPSPs of hypoglossal motoneurons were concluded to be dependent on increase of Cl conductance. Stimulation of low threshold lingual afferents evoked a reflex discharge in the retractive nerve fibers with a 6.0 msec latency and in the protrusive nerve fibers with a 5.5 msec latency. Inhibition of the linguohypoglossal reflex by stimulation of the jaw-opening muscle afferents was completely removed by an intravenous injection of strychnine (0.1 mg/kg) or picrotoxin (6 mg/kg). It is concluded that the low threshold afferents arising in the jaw-opening muscles are connected to both R-Mns and P-Mns and P-Mns through inhibitory synapses via a polysynaptic pathway.