Modulation of vastus medialis motoneuronal excitability by sciatic nerve afferents

We activated the sciatic nerve afferents by either the discharge of a magnetic coil or a needle inserted near the nerve. Both types of stimulation induced facilitation of the vastus medialis (VM) H reflex, and of the VM response to transcranial magnetic stimulation, at the joint time of arrival of conditioning and test volleys, while a subsequent inhibition was induced only in the H reflex. We conclude that sciatic nerve afferents induce reciprocal inhibition of VM motoneurons presynaptically on the Ia afferent terminals. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:936–939, 1998.     

Impaired heteronymous somatosensory motor cortical inhibition in dystonia.

A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning-test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory-motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level.     

Synaptic effects from chemically activated fine muscle afferents upon α-motoneurones in decerebrate and spinal cats

In spinal and decerebrate cats fine muscle afferents (group III and IV) were selectively activated by intra-arterial injection of bradykinin and KCl into the gastrocnemius-soleus muscle. By this method the synaptic responses induced in lumbar α-motoneurones by fine muscle afferents could be examinedwithout interference of effect from large afferents. α-Motoneurones receiving EPSPs evoked by electrical stimulation of cutaneous and high threshold muscle afferents (mainly flexor motoneurones) responded to the activation of fine muscle afferents with a depolarization of their membrane and an increase in synaptic noise, while motoneurones in which IPSPs were evoked by electrical stimulation of cutaneous and high threshold muscle afferents (mainly extensor motoneurones), responded with hyperpolarization of their membrane. Cells with mixed excitatory-inhibitory electrically induced response characteristic responded with an increase in synaptic noise without substantial change in the level of their membrane potential to chemical stimulation of fine muscle afferents. The results indicate that one function of group IIIand IV muscle afferents is to participate in the complex reflex control performed by the flexor reflex system.     

Inhibition of motoneuron discharge by peripheral nerve stimulation: an F response analysis

F waves were recorded from the abductor pollicis brevis stimulating the median nerve at the wrist. These data were compared to responses obtained after preceding supramaximal stimulation of digital fibers of the second (II) finger or the median nerve at the wrist. The time between conditioning and test stimuli were 50 msec. Following conditioning stimuli, F wave latencies were significantly increased while F amplitudes, durations, and persistences were all decreased. Chronodispersion was not significantly affected. These changes were associated with increased repetition of individual F responses. The most prominent changes were found after stimulation of fibers of digit II but only at levels of stimulation supramaximal for the sensory nerve action potential. Some, but relatively limited, changes were present after stimulation of digital fibers of the fifth finger. The results are consistent with afferent fiber, probably A delta, inhibition of antidromic motoneuron activation with associated decrease in central motor neuron pool excitability. The study also demonstrates that, except for chronodispersion, changes in F waves found with peripheral nerve injury may also occur due to physiological changes in the central nervous system.     

Effect of levetiracetam on cortical excitability: a transcranial magnetic stimulation study

Background and purpose:  We studied the effect of levetiracetam (LEV), an anticonvulsant with a novel mechanism of action, on cortical excitability, measured using transcranial magnetic stimulation (TMS). For this purpose, 38 healthy volunteers were assessed in two TMS sessions, before and after an oral dose of 3000 mg LEV.
Methods:  Resting motor threshold (RMT), intracortical facilitation (ICF) and intracortical inhibition (ICI), cortical silent period (CSP) threshold and duration and motor-evoked potential (MEP) amplitude were calculated.
Results:  After treatment with LEV, RMT was increased (mean ± SD: 63 ± 14% of the maximum stimulator output) compared with baseline (58 ± 11%). CSP threshold was decreased after LEV (54 ± 10%; baseline, 57 ± 11%). CSP duration was increased after LEV (116 ± 37 ms; baseline: 102 ± 33 ms). LEV did not affect ICF or ICI or mean MEP amplitude significantly.
Conclusions:  Our results indicate that LEV modulates some aspects of cortical excitability. Whereas the increase in the RMT most probably reflects the effect of LEV on ion channel activity, effects on the CSP might represent a modulation of GABA receptors at cortical and spinal level.     

Crossed spinal soleus muscle communication demonstrated by H-reflex conditioning

Introduction: A conditioning volley to the ipsilateral tibial nerve (iTN) inhibits contralateral soleus (cSOL) electromyographic activity at latencies of 37–41 ms. This is evidence for spinal muscular communication in opposing limbs. The aim of our study was to determine whether the cSOL H‐reflex would be inhibited in a similar manner. Methods: Thirteen subjects participated in two experiments: (1) stimuli delivered to the iTN at 85% of the maximal peak‐to‐peak M‐wave (85% M‐max) with a pre‐contracted cSOL; (2) 510 stimuli delivered at 85% M‐max to the iTN with a test volley delivered to the contralateral tibial nerve at interstimulus intervals of ?6 to 100 ms. Results: Significant inhibition was observed in the cSOL H‐reflex when conditioning stimuli were delivered 3–33 ms before the test H‐reflex. Conclusions: The activity of this spinal pathway can be quantified using H‐reflex conditioning to provide a controlled model for further studies of this response. Muscle Nerve, 2011     

Abnormalities of cortical excitability and cortical inhibition in cervical dystonia

Cortical excitability and cortico-cortical inhibition were examined in twenty-one patients suffering from idiopathic rotational cervical dystonia. Polymyography of cervical muscles, somatosensory evoked potential recordings, and paired transcranial magnetic stimulation were used to assess the dystonic disorder. The results were compared with those obtained in a group of sixteen healthy age-matched volunteers. Statistically significant differences between the patient group and the control group were found when the amplitude values of the mean P22/N30 component measured at F [3, 4] and C[3, 4]' electrode positions were compared. The mean amplitude of P22/N30 in both of these electrode positions contralaterally to the direction of head deviation was significantly higher in the patient group (p ≤ 0.05). The mean side-to-side P22/N30 amplitude ratio was calculated in both groups in the F[3, 4] and C[3, 4]' electrode positions: there was a significant difference between the two groups. The mean ratio (calculated contralaterally/ipsilaterally in the patient group and left/right side in the control group) was significantly higher in the patient group (p ≤ 0.05). There were statistically significant differences between the two groups when the mean values of MEP amplitudes following paired stimuli at short and medium interstimulus intervals (ISI)) were compared. The percentage of amplitude reduction registered at short ISI was significantly lower in the patient group when both 3 ms ISI and 5 ms ISI were considered, and when the hemisphere contralateral to the direction of head deviation was stimulated. There was also a difference (with the short ISI) when the hemisphere ipsilateral to the direction of head deviation was stimulated, but this difference was not significant (p < 0.5). Almost all of the amplitude changes following the paired stimulus at the longer ISI, i. e. 10, 15, and 20 ms were significantly different when the patient group was compared with control group: when the ipsilateral hemisphere was stimulated, the amplitude of conditioned responses was significantly higher following all three paired stimuli (with 10, 15, and 20 ms ISI) at the p ≤ 0.05 significance level; when the contralateral hemisphere was stimulated, they were significantly higher following the 10 and 20 ms ISI paired stimuli (significance level p ≤ 0.05). The interhemispheric difference in the patient group was significant only for the paired stimuli using 3 and 5 ms (short) ISI and 15 and 20 ms (medium) ISI. There was a significantly decreased inhibition at 3 and 5 ms ISI when the hemisphere contralateral to the direction of head deviation was stimulated, as compared with the hemisphere ipsilateral (p ≤ 0.05). Similarly, there was a significantly increased facilitation at 15 and 20 ms when the hemisphere contralateral to the direction of head deviation was stimulated, as compared with the hemisphere ipsilateral (p ≤ 0.05). The results indicate that a disorder of both cortical excitability and intracortical inhibition exists in patients with cervical dystonia, and that this disorder is lateralized, i. e. it is located within the hemisphere contralateral to the direction of head deviation. Received: 5 March 2002, Received in revised form: 1 August 2002, Accepted: 2 August 2002 Correspondence to Doc. MUDr Petr Kaňovsky, CSc.     

Evaluation of the motor cortical excitability changes after ischemic stroke

Background:

We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).

Materials and Methods:

Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2^nd), 4^th, and 6^th week of stroke.

Results: Affected hemisphere:

MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.

Unaffected hemisphere:

MEP was recordable in all patients at baseline, and reduced significantly over time (2^nd week 43.52 ± 9.60, 4^th week 38.84 ± 7.83, and 6^th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.

Conclusion:

The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.     

After-effects of pedaling exercise on spinal excitability and spinal reciprocal inhibition in patients with chronic stroke

Purpose of the study: To evaluate the after-effects of pedaling on spinal excitability and spinal reciprocal inhibition in patients with post-stroke spastic hemiparesis. Materials and methods: Twenty stroke patients with severe hemiparesis participated in this study and were instructed to perform 7 min of active pedaling and 7 min of passive pedaling with a recumbent ergometer at a comfortable speed. H reflexes and M waves of paretic soleus muscles were recorded at rest before, immediately after and 30 min after active and passive pedaling. The Hmax/Mmax ratio and H recruitment curve were measured. Reciprocal inhibition was assessed using the soleus H reflex conditioning test paradigm. Results: The Hmax/Mmax ratio was significantly decreased after active and passive pedaling exercise. The decreased Hmax/Mmax ratio after active pedaling lasted at least for 30 min. The H recruitment curve and reciprocal inhibition did not change significantly after active or passive pedaling exercise. Conclusions: Pedaling exercise decreased spinal excitability in patients with severe hemiparesis. Pedaling may be effective in rehabilitation following stroke.     

The acute effects of capsaicin on rat primary afferents and spinal neurons

Capsaicin applied to the soma of fast and slow conducting primary afferent fibers had a depolarizing action associated with an increase in membrane conductance. The depolarizing effect desensitized rapidly and was only partially reversible in slow conducting fibers.Capsaicin application to the entry zone of the appropriate dorsal rootlets led to strong excitation of dorsal horn neurons receiving multimodal input. After acute capsaicin treatment the response to noxious heat was attenuated or totally absent, while other noxious stimuli were still effective. The present data suggest that capsaicin exerts its specific degenerative action by a long-lasting depolarizing action on small-calibre fibers.     

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes. Received: 28 December 2001, Received in revised form: 19 March 2002, Accepted: 21 March 2002     

Comparative effects of ischemia and acute hypoxemia on muscle afferents from tibialis anterior in cats

Comparative effects of ischemia and acute hypoxemia (PaO₂ = 24 mm Hg) were studied in anesthetized cats on afferents from the tibialis anterior limb muscle. Metaboreceptors (groups III and IV fibers) and mechanoreceptors were identified by their activation by an intraarterial injection of lactic acid (LA) or high-frequency vibrations (HFV) applied to the extremity of the muscle tendon, respectively. Ischemia and hypoxemia exerted opposite influences on the two categories of muscle afferents: they depressed the response of mechanoreceptors to HFV, but markedly enhanced the spontaneous tonic activity of metaboreceptors. The effects of hypoxamia were delayed but slightly greater and lasted longer during the recovery period than those exerted by ischemia. The inhibitory action on mechanoreceptors exerted by a reduced oxyden supply to muscle is interpreted as a result from local acidosis. Indeed, under normoxic conditions, a LA bolus injection during the HFV test also reduced the firing rate of these receptors. © 1993 John Wiley & Sons, Inc.     

Responses of human motoneurons to high‐frequency stimulation of Ia afferents

This study was designed to extend to humans the findings of classical studies on anesthetized cats, which have examined the discharge of spinal motoneurons in response to high‐frequency stimulus trains delivered to Ia afferents. Experiments were conducted on the monosynaptic pathway in the flexor carpi radialis (FCR) and soleus muscles. Subjects maintained a rhythmic discharge of a single motor unit (SMU) in either the FCR or soleus while homonymous Ia afferents were stimulated with either a single‐ or multipulse train. An n@IPI stimulus train had n pulses (n = 2–4) and an interpulse interval (IPI) of 1–8 ms. For each condition and motor unit, surface electromyographic (EMG) activity was averaged, and peristimulus–time histograms (PSTHs) were constructed for the SMU. The magnitude of the EMG was high for IPI = 1 ms, low for IPI = 2–3 ms, and high for IPI = 4–8 ms. SMU responses showed a similar pattern, which indicated that the increased EMG response was due to the presence of multiple peaks in a PSTH. The key results indicate that: (1) a short, high‐frequency stimulus train enhances the discharge probability of a motoneuron above that observed with a single pulse; and (2) the increased motoneuron responses are significantly greater for the FCR than for the soleus muscle. © 2008 Wiley Periodicals, Inc. Muscle Nerve 38: 1604–1615, 2008     

Topographical organization of group II afferent input in the rat spinal cord

The organization of neurons in the lumbar enlargement of the rat spinal cord processing information conveyed by group II afferents of hind-limb muscle nerves has been investigated by using cord dorsum and intraspinal field potential recording. Group II afferents of different muscle nerves were found to evoke their strongest synaptic actions in specific segments of the lumbar cord. Group II afferents of quadriceps and deep peroneal nerves evoked potentials mainly at the rostral end of the lumbar enlargement (L1-rostral L3), whereas group II afferents of gastrocnemius-soleus and hamstring nerves evoked their main synaptic actions at the caudal end of the lumbar enlargement (L5). In the central lumbar segments (caudal L3–L4), the largest group II potentials were produced by afferents of tibialis posterior and, to a lesser degree, flexor digitorum longus. Field potentials evoked by group II afferents of quadriceps, tibialis posterior, and flexor digitorum longus were largest in the dorsal horn (up to 600 μV), but also occurred in the ventral horn where they were sometimes preceded by group I field potentials. In contrast, field potentials evoked by group II afferents of gastrocnemius-soleus and hamstring nerves were restricted to the dorsal horn. These results indicate that neurons in different segments of the rat lumbar spinal cord process information from group II afferents of different hind-limb muscles. Furthermore, the topographical organization of group II neuronal systems in the rat is similar in several respects to that in the cat and may therefore represent a general organizational feature of the mammalian spinal cord. J. Comp. Neurol. 394:357–373, 1998. © 1998 Wiley-Liss, Inc.     

Activation of lumbar spinoreticular neurons by stimulation of muscle, cutaneous and sympathetic afferents

Forty-four spinal neurons located mainly in laminae IV–VII of the L7 and S1 segments projected primarily contralaterally and to the lateral reticular nucleus. Muscle and cutaneous input was via group II and III afferents, whereas sympathetic input was via group III or IV afferents. Close-arterial injection of bradykinin and/or caosaicin excited most of the neurons so tested. These responses make these neurons likely candidates for the ascending pathway of the exercise pressor reflex.     

Vesicular glutamate transporter immunoreactivity in the central and peripheral endings of muscle-spindle afferents

Expression of vesicular glutamate transporters (VGLUTs: VGLUT1, VGLUT2 and VGLUT3) in muscle spindle afferents was examined in rats. VGLUT1 immunoreactivity was detected in the sensory endings on the equatorial and juxta-equatarial regions of intrafusal fibers as well as in many axon terminals within lamina IX of the spinal cord. VGLUT1 might be expressed not only in the central axon terminals but also in the peripheral sensory endings of muscle-spindle afferents.     

Cortical stimulation and reflex excitability of spinal cord neurones in man

Summary The H reflex technique was used to evaluate the influence exerted by cortical conditioning on the excitability of the alpha-motoneurone pool and on IA interneuronal activity (reciprocal inhibition). In ten subjects at absolute rest electrical and magnetic stimulation of the motor cortex was transcranially applied during flexor carpi radialis H reflex eliciting and in conditions of reciprocal inhibition induced by radial nerve stimulation. The time courses showed that at intensities below motor threshold, electrical brain conditioning induced an increase in the amplitude of the test reflex when the cortical shock was given 4 ms after the test H reflex. On the contrary, reciprocal inhibition was reduced by electrical cortical conditioning when the scalp stimulation was applied 2–3 ms after the test stimulus. Magnetic transcranial stimulation induced an increase of H reflex amplitude when the test shock was administered 5 and 2 ms prior to the scalp shock; it did not modify the degree of reciprocal inhibition. The experimental findings could be considered the electrophysiological manifestation of a differential cortico-spinal control on the pathway alpha-motoneurone/IA interneurone. Considerations on the delay allow the hypothesis of a further synapse between the cortico-spinal ending and the IA interneurone.Discrepancies with magnetic conditioning might be ascribed to a preferential transynaptic action of magnetic mode of neural activation.This work was supported by grants from the Consiglio Nazionale delle Ricerche and the Ministero dell'Università e delia Ricerca Scientifica e Tecnologica, Roma, Italy     

Movement-related cortical potentials before jaw excursions in oromandibular dystonia.

Oromandibular dystonia is a neurological disorder characterized by involuntary contraction of masticatory and/or tongue muscles. Cortical negative shifts preceding voluntary movements called "movement-related cortical potentials" (MRCPs) reflect a central motor control process. Reduced amplitude of MRCPs has been reported in other types of dystonia. To elucidate whether the abnormality is observed also in oromandibular dystonia, we compared MRCPs associated with mandibular movements in 6 patients with this condition and in 8 normal subjects. Electroencephalograms (EEGs) were recorded from 11 electrodes, and electromyograms (EMGs) were recorded from the masseter muscle and the suprahyoid muscles. The subjects were asked to repeat mouth opening, closing, and left and right lateral mandibular excursions. MRCPs were obtained by averaging the EEG using the EMG onset as the trigger signal. In the patient group, MRCP amplitudes over central and parietal areas for mouth opening and lateral movements were significantly reduced compared to normal subjects. In normal controls, the MRCPs at mouth opening and closing were symmetrically distributed, whereas those at lateral movements showed predominance over the hemisphere ipsilateral to the direction of the movement. This laterality was lost in the patient group. These results suggest impaired cortical preparatory process for jaw movements in oromandibular dystonia.     

Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord.

Subunits of glutamate receptors participate in the regulation of sensory transmission at primary afferent synapses in the superficial laminae of dorsal horn (DH). We report here on the distribution of kainate receptors (GluR5/6/7) in these laminae by using light microscope (LM) and electron microscope (EM) immunocytochemistry. Standard (4%) paraformaldehyde fixation resulted in immunostaining for GluR5/6/7 in perikarya and fine processes in lamina II, especially its inner part (IIi). Preembedding EM revealed immunostaining of dendrites, perikarya, and occasional terminals, presumed to be from primary afferent fibers, at the center of glomerular arrangements. In rats perfused with 0.5% paraformaldehyde, LM showed a more punctate staining, mainly in the ventral part of lamina IIi and lamina III, than in material fixed with 4% paraformaldehyde. Approximately two-thirds of GluR5/6/7 puncta were also immunostained with synaptophysin, suggesting that in material fixed with 0.5% paraformaldehyde, a large fraction of these are synaptic terminals. Double immunostained puncta disappear 4 days after dorsal rhizotomy, suggesting that most of GluR5/6/7-immunopositive terminals are from primary afferent fibers. EM material fixed with 0.5% paraformaldehyde confirmed the expression of GluR5/6/7 in numerous synaptic endings with morphology of primary afferents. To determine the type of primary afferent terminals that express GluR5/6/7, two neuroanatomic tracers were injected in the sciatic nerves. The lectin from Bandeiraea simplicifolia (IB4) is selectively taken up by unmyelinated primary afferent fibers that terminate in the outer part of lamina II (IIo) and dorsal part of lamina IIi, whereas the B subunit of the cholera toxin (CTB) is selectively taken up by a broader class of primary afferents which, in superficial DH, terminate mainly in laminae I, ventral part of IIi, and III. Approximately 20% of GluR5/6/7-immunoreactive puncta colocalized with IB4, whereas approximately 40% of GluR5/6/7-immunoreactive puncta colocalized with CTB. The present study shows that (1) GluR5/6/7 does not have a clear and consistent spatial relation with postsynaptic sites, (2) a large number of primary afferents express GluR5/6/7, and (3) these are not limited to one functional class. Thus, modulation by glutamate of primary afferent terminals by means of kainate receptors in the superficial laminae of DH may predominantly involve presynaptic mechanisms.