Renshaw cell activity in man

The H-reflex elicited in triceps surae by percutaneous stimulation of the posterior tibial nerve was conditioned by stimuli applied through the same electrode. The differential sensitivity of motor and sensory fibres to duration of the stimulus pulse made it possible to condition the H-reflex with either a motor or a sensory stimulus. With both types of conditioning, the H-reflex was inhibited at conditioning-test intervals of 2-3 msec and was then facilitated, the peak of facilitation occurring at 5-8 msec with motor conditioning and 6-10 msec with sensory conditioning. The phase of facilitation was followed by further inhibition. We have concluded (1) that the effects of motor conditioning on the H-reflex result from the discharge of Renshaw cells activated by the antidromic volley in the motor axons, and (2) that the effects of sensory conditioning (at the times used in these experiments) are largely due to the activation of Renshaw cells secondary to the discharge of alpha motoneurones by the conditioning volley.     

Facilitation of motor evoked potentials by somatosensory afferent stimulation.

The effect of an electrically induced peripheral afferent volley upon electrical and magnetic motor evoked potentials (MEPs) from muscles of the upper and lower extremities was studied in 16 healthy volunteers. A standard conditioning-test (C-T) paradigm was employed whereby the test stimulus (transcranial electric or magnetic) was applied at random time intervals, from 10 msec prior to 90 msec after the conditioning stimulus (peripheral nerve stimulus). MEP amplitude facilitation was observed for the majority of the upper extremity muscles tested at two distinct periods, one occurring at short, and the other at long C-T intervals. This bimodal trend of MEP facilitation was found to be equally as prominent in the lower extremity muscles tested. The period of short C-T interval facilitation is consistent with modifications in the spinal excitability of the segmental motoneuron pool. On the other hand, the period of long C-T interval facilitation is suggested to be due to alterations in excitability of the motor cortex as a result of the arrival of the orthodromic sensory volley. Although most pronounced in muscles innervated by the nerve to which the conditioning stimulus was applied, this bimodal facilitatory effect was also observed in adjacent muscles not innervated by the stimulated nerve. Qualitatively, the conditioned MEPs from the upper and lower extremities responded similarly to both electrical and magnetic trans-cranial stimulation. In addition, our study demonstrates that the C-T paradigm has potential for use in the assessment of spinal and cortical sensorimotor integration by providing quantitative information which cannot be obtained through isolated assessment of sensory and/or motor pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Afferent excitation of human motor cortex as revealed by enhancement of direct cortico-spinal actions on motoneurones

Changes in motor cortex excitability induced by somatosensory afferences were evaluated in 5 subjects by testing how the short-latency cortico-spinal effects evoked by transcranial magnetic stimulation in flexor carpi radialis (FCR) motoneurones were influenced by volleys in median nerve afferent fibres. Transcranial magnetic stimulation induced two facilitatory peaks on FCR H reflex, the first at a conditioning-test interval of about −3 msec and the second at 0 msec, separated by a phase of inhibition. If an electric shock to the median nerve at the wrist, 0.8-1 × motor threshold (MT) for thenar muscles, preceded the cortical stimulus by 18–25 msec, an increase in size of both facilitatory peaks was observed. The increase was partly due to a direct action of the median nerve volley on motoneurones. When this contribution was subtracted, two peaks of additional facilitation resulted as the effect of combined conditioning. Additional facilitation was present even during the short-lasting phase ascribed to monosynaptic cortico-spinal excitation of motoneurones, i.e., the first millisecond of the earliest facilitatory peak. This result indicates that cortical responsiveness to magnetic stimulation had been enhanced by the peripheral stimulus. The time course of the excitability changes in motor cortex was compared with the cortical somatosensory evoked potentials (SEPs) induced by the same peripheral stimulus. Additional facilitation was present immediately after the N20 peak of SEPs and lasted 8–10 msec. Additional facilitation had the same threshold as N20 (0.6 × MT) and grew in parallel with it when grading the afferent stimulus up to 1 MT.     

Trigeminal sensory input elicited by electric or magnetic stimulation interferes with the central motor drive to the intrinsic hand muscles.

In 6 normal subjects, unilateral supraorbital magnetic or electric stimulation resulted in a consistent symmetrical inhibition of the motor evoked potentials (MEPs) of the relaxed and preactivated first dorsal interosseus (FDI) muscle. A supraorbital stimulus caused a significant reduction in amplitude when the trigeminal CS was given 30 to 65 ms before transcranial magnetic stimulation (TMS). In addition, supraorbital magnetic stimulation induced a bilateral EMG suppression of the isometrically contracting FDI muscles, starting about 40 to 50 ms after the magnetic stimulus. In 4 subjects, MEPs evoked by transcranial electric stimulation or by TMS during slight muscle contraction showed a comparable trigeminomotor inhibition. These findings demonstrate that electromagnetic stimulation of trigeminal afferents interferes with the motor output to the intrinsic hand muscles inducing a bilateral inhibition which is probably mediated by a multisynaptic subcortical network. In all 6 subjects, TMS over the motor hand area or the cerebellum elicited a reproducible blink reflex. Since the blink reflex is a sensitive indicator of trigeminal excitation, one has to assume that TMS is associated with a significant excitation of trigeminal afferents. Therefore, trigeminomotor inhibition has to be considered in all TMS studies that use a conditioning-test design.     

Magnetic brain stimulation: the silent period after the motor evoked potential.

In 25 normal subjects, we studied the EMG silent period following the magnetic motor evoked potential (MEP) when the target muscle was tonically contracted (post-EMP silent period [PMSP]). In the first dorsal interosseous muscle (FDI), PMSP duration increased in linear proportion to stimulus intensity, but not to the size of the preceding MEP. The PMSP was longer in hand and forearm muscles than in upper arm muscles. In the FDI, PMSP was longer than the peripheral silent period (PSP) even when multiple peripheral stimuli were used to get M responses whose twitch force was equivalent to that of MEPs. Weak magnetic stimuli evoked silent periods preceded by no MEP in several subjects. Spinal alpha-motoneurons (alpha-MNs) were partially inhibited during the first PMSP portion, but later this effect recovered. MEPs due to weak electrical stimuli to motor cortex were only slightly inhibited during the late PMSP. Segmental inhibitory loops evoked by the muscle twitch and inhibitory projections descending to alpha-MNs from the cortex predominantly underlie earlier PMSP portions, but recurrent intracortical inhibition may also contribute. Later portions are predominantly due to other stimulus-related cerebral inhibitory or suppressing phenomena.     

Recovery functions of common peroneal, posterior tibial and sural nerve somatosensory evoked potentials.

We studied recovery functions of the somatosensory evoked potentials (SEPs) of common peroneal (CPN), posterior tibial (PTN) and sural nerves (SN) using a paired conditioning-test paradigm. The interstimulus interval (ISI) of paired stimuli ranged from 2 to 400 msec. In all SEPs with ISIs of 12-20 msec, the amplitude recovery was close to or beyond 100% of the control response, though their latencies and wave forms were not the same as the control. Further increases of the ISI resulted in significant depression of SEP (late phase suppression), most markedly in CPN, and less prominently in SN-SEP. With a longer than 50 msec ISI there was progressive recovery of SEP, but full recovery differed depending on the nerve stimulated; 400 msec ISI was required for CPN-, 250 msec for PTN- and 100 msec for SN-SEP. The peroneal nerve block by local anesthetic injected just distal to the stimulus electrodes abolished the late phase SEP suppression observed before the nerve block. These findings suggest that the late phase SEP suppression is attributable to the "secondary" afferents as a result of activation of peripheral receptors (muscle, joint and/or cutaneous) by the efferent volley initiated from the stimulus point. The greater and longer duration of peripheral receptor activation in CPN than in PTN or SN stimulation could explain the more pronounced and the longer duration of late phase suppression in CPN-SEP.     

Differential modulation of motor evoked potential and silent period by activation of intracortical inhibitory circuits.

OBJECTIVES: To investigate the effect of activation of intracortical inhibitory circuits, as tested by short interval (3 ms) paired-pulse transcranial magnetic stimulation (TMS) with a conditioning-test paradigm, on the electromyographic (EMG) pause (silent period, SP) following the motor evoked potential (MEP) in normal subjects. METHODS: SPs and MEPs were recorded from the right first dorsal interosseous (FDI) muscle during a tonic voluntary contraction (from 70 to 90% of the maximum). Using a focal coil, we compared the SP duration after single-pulse TMS, paired-pulse TMS and single-pulse TMS of reduced intensity such as to evoke MEPs matched in size to the conditioned ones after paired-pulse TMS. In addition, we compared in a control experiment the duration of the SP following matched size MEPs evoked, respectively, by focal TMS with preferential activation of indirect I1- or I3-waves. RESULTS: SP duration after paired-pulse TMS was significantly longer than after single-pulse TMS evoking MEPs of a similar size. In no case the SP duration was longer when focal TMS preferentially activated I1-waves. CONCLUSIONS: The conditioning sub-threshold stimulus is more powerful in reducing the MEP size than in cutting down the subsequent EMG silence, suggesting that the neural circuits underlying MEP and SP are, at least in part, different.     

Motor potentials evoked by paired cortical stimuli.

We recorded the motor evoked potentials (MEPs) from the abductor pollicis brevis muscle, after supramaximal electrical transcranial stimulation, and studied the effect of paired transcranial shocks with varying interstimulus time intervals, in 10 normal subjects, 4 patients with median nerve neuropathy and 2 patients with motoneurone disease. In relaxed muscles the amplitude of the MEP evoked by a single shock averaged 30% of the M wave. With intervals from 1 to 2.5 msec 2 shocks evoked one MEP far larger in size than the control MEP (70% of the M wave). With intervals of 10 msec and longer, the 2 shocks evoked 2 independent MEPs; the size of the MEP following the second shock (test) was inversely correlated with the size of the control MEP: the more the control MEP approached the size of the M wave, the smaller the test MEP. Single motor unit records showed that, in the normal subjects and patients with peripheral neuropathy, the same motor unit was activated either by the first or the second shock, whereas in the patients with motoneurone disease it fired twice. In active muscles, the control MEP averaged 70% of the M wave. With intervals of 10 msec and longer the test MEP was markedly suppressed; with 100 msec intervals it fully recovered. In relaxed muscles, by delivering a double shock at a 1.5 msec interval, thus evoking a large MEP, followed by a second double-shock, the test MEP was completely suppressed for a period of 20 msec; it began to recover at 50 msec intervals and fully recovered after 150 msec.(ABSTRACT TRUNCATED AT 250 WORDS)     

Silent period in upper limb muscles after noxious cutaneous stimulation in man

We studied the effect of electrical stimulation of the C5–C8 dermatomes on voluntary electromyographic activity (EMG) recorded from the ipsilateral first dorsal interosseus (FDI), abductor digiti minimi, flexor and extensor carpi, triceps brachii, biceps brachii, and orbicularis oculi muscles of healthy humans. Finger stimulation (C6–C8) produced an EMG inhibition (silent period, SP), which progressively decreased in duration from distal to proximal muscles; in the biceps it induced a slight facilitation and in the orbicularis oculi muscle, it had no effect. Stimulation of the C5 dermatome induced no response in either distal or proximal muscles. Only high-intensity stimuli evoked clear silent periods. The threshold for evoking and SP was almost double that required for sensory action potentials, 3.25 times the sensory threshold, and decidedly above the pain threshold. An indirect estimation of the conduction velocity of SP afferent fibres placed them in the A-delta group of myelinated fibres. In double-shock experiments, used to study the recovery cycle of the SP in the FDI muscle after finger stimulation, neither low- nor high-intensity conditioning stimuli delivered 100–500 ms before the test stimulus changed test SPs. Experiments designed to evaluate motoneuronal excitability showed that in relaxed FDI muscle, finger stimulation markedly reduced the F wave at the 50 ms time interval, the time when the SP normally occurs. Our findings demonstrate that the activation of A-delta afferents from the fingers inhibits the C7-T1 motoneurons postsynaptically, through an oligosynaptic spinal circuit. We propose that the strong inhibitory effect exerted by noxious cutaneous stimuli on all distal muscles may contribute to a defence action which is specific or the human upper limb.     

Excitability of human motoneurones after discharge in a conditioning reflex.

A new method of exploring the H reflex excitability cycle is proposed which permits the exploration of motoneurones that discharged in response to the conditioning shock. This is made possible by using a test stimulus supramaximal for the alpha motor fibres of the nerve, which causes a collision in the alpha fibres between the orthodromic conditioning reflex volley and the antidromic motor volley. As a result of this collision, a test reflex contraction appears in the EMG, due to motoneurones that have already discharged in the conditioning response. This method permits studies in human subjects of the poststimulus refractory period of motoneurones as well as the early inhibitory phenomena related to the conditioning stimulus and response. It is shown that during the initial period of the classical H reflex excitability cycle, the test shock explores only alpha motoneurones corresponding to a fringe of cells subliminally excited by the conditioning stimulus. The difference between the populations of motoneurones tested by the two methods explains the differences between the features of the cycles obtained.     

Short latency afferent inhibition and facilitation in patients with writer's cramp.

Patients with writer's cramp (WC) show abnormalities of sensorimotor integration possibly contributing to their motor deficit. We studied sensorimotor integration by determining short-latency afferent inhibition (SAI) in 12 WC patients and 10 age-matched healthy controls. A conditioning electrical median nerve stimulus was followed 14 to 36 msec later by transcranial magnetic stimulation of the contralateral primary motor cortex, and motor evoked potentials (MEP) were recorded from the relaxed or contracting abductor pollicis brevis muscle (APB). SAI was normal in WC but during APB relaxation SAI was followed by abnormal MEP facilitation, which was absent during APB contraction and in the controls. These findings suggest that somatosensory short-latency inhibitory input into the primary motor cortex is normal in WC, whereas a later excitatory input, which very likely reflects the long-latency reflex II, is exaggerated.     

Silent period induced by cutaneous stimulation.

An electrical stimulus applied to a cutaneous nerve during isometric muscle contraction causes a suppression of EMG activity (silent period) followed by a rebound. The extent of inhibition is related to the stimulus intensity as the silent period is more evident when stimulation is perceived as painful. The silent period is present in different limb and cranial muscles after stimulation of the same cutaneous nerve and in the same muscle after stimulation of distant cutaneous nerves. It also occurs synchronously in antagonist muscles. Within the silent period induced after cutaneous stimulation the maximal inhibition on the opponens pollicis motor neuron pool, as tested by the motor response evoked after transcranial cortical stimulation, occurs between 50 and 70 msec. Using the double stimulus technique to study the recovery cycle, the silent period is present at interstimulus intervals as low as 100 msec, and does not habituate with trains of stimuli at frequencies up to 5 Hz. Our results suggest that motor neuron inhibition from nociceptive stimulation may be mediated by Renshaw cells directly activated by high threshold cutaneous afferents.     

Transcranial magnetic double stimulation: influence of the intensity of the conditioning stimulus

The influence of stimulus parameters on compound muscle potentials evoked by transcranial magnetic double stimulation was systematically investigated. Two magnetic stimulators were discharged via a figure-of-eight-shaped magnetic coil (outer diameter of each circular coil, 7 cm) over the left hemisphere, 6 cm lateral to Cz, using a Bistim interface. Recordings were made from the right first dorsal interosseus muscle. In experiment I, in 12 healthy volunteers the intensity of the conditioning subthreshold stimulus was varied from 0 to 100% of the relaxed motor threshold at an interstimulus interval of 1 ms. In experiment II, interstimulus intervals of 1, 3 and 5 ms were used to investigate the effect of conditioning stimuli of 3 fixed intensities. Maximal reduction of the amplitude of motor evoked potentials was found at a conditioning stimulus intensity of 65% of the relaxed motor threshold (and at an interstimulus interval of 1 ms). Because intensities of the conditioning stimulus higher than 65% reduced amplitudes of motor evoked potentials less effectively than at this intensity, refractoriness of pyramidal neurons can be ruled out as the main mechanism contributing to the observed inhibition. Activation of inhibitory interneurons by intensities lower than is necessary to activate pyramidal neurons is discussed as a possible mechanism for the inhibitory effects evoked by transcranial magnetic stimulation.     

Late facilitations of motor evoked potentials by contralateral mixed nerve stimulation

The effect on motor evoked potentials (MEPs) of a peripheral afferent volley (a single square pulse delivered to the contralateral median nerve at the wrist) was studied in abductor digiti minimi muscle of 9 normal patients following magnetic stimulation of the motor cortex. Long intervals were used (200–700 cosec) between the electrical conditioning stimulus and magnetic test stimulation. An MEP amplitude increase, with no change in latency, was observed when the C-T interval was about 500 cosec, and the motor threshold was decreased by the conditioning stimulation. The observed long latency and duration of the facilitation effect would seem consistent with activation of suprasegmental areas.     

Motor potentials evoked by magnetic stimulation of the motor cortex in normal subjects and patients with motor disorders.

Motor evoked potentials (MEPs) elicited by magnetic coil stimulation of motor cortex were studied at rest and during maximum voluntary muscle contraction in 20 normal subjects and 42 patients with motor disorders. MEP parameters employed in this study included: onset latency, amplitude, MEP/M wave amplitude ratio and background EMG/MEP area ratio. Maximum voluntary contraction increased the amplitude of MEPs compared to the size of M waves elicited by peripheral nerve stimulation. A reduced MEP/M wave amplitude ratio had a higher correlation with pyramidal tract involvement than did a prolonged MEP onset latency. Analysis of MEP parameters may help in the differential diagnosis of cerebral infarction, ALS and cervical spondylotic radiculomyelopathy. The inhibitory period which follows MEPs during voluntary contraction was observed in all subjects; the mean duration in normal subjects was 126.6 +/- 29.5 msec. The mean duration of the inhibitory period in patients with cerebral infarction, ALS and cervical spondylotic radiculomyelopathy was 73.9 +/- 41.7 msec, 79.5 +/- 54.5 msec and 85.1 +/- 36.5 msec, respectively. These values were significantly shorter than in normal subjects.     

Intracortical inhibition and facilitation in paired-pulse transcranial magnetic stimulation: effect of conditioning stimulus intensity on sizes and latencies of motor evoked potentials.

The influence of the intensity of the conditioning stimulus on intracortical inhibition (ICI) and intracortical facilitation (ICF) was assessed in a study using paired-pulse transcranial magnetic stimulation. Interstimulus intervals (ISIs) between conditioning and test stimuli were 3 msec and 13 msec. Latencies and areas of motor evoked potentials in response to the test stimulus were measured in the right extensor carpi radialis muscle. Motor evoked potential areas with ISIs of 3 msec and 13 msec showed a different dependence on the intensity of the conditioning stimulus. In contrast, the changes of motor evoked potential latencies were fairly similar with both ISIs. The findings point to a parallel action of ICI and ICF. Furthermore, the latencies seem to be a more sensitive indicator for ICF action than the size parameters of motor evoked potentials.     

An exteroceptive reflex in the sternocleidomastoid muscle produced by electrical stimulation of the supraorbital nerve in normal subjects and patients with spasmodic torticollis

We examined suppression of EMG activity in the contracting sternocleidomastoid muscles, produced by electrical stimulation of the supraorbital nerve in 10 normal subjects and 9 patients with spasmodic torticollis. This exteroceptive reflex in the sternocleidomastoid muscle consisted of 2 or 3 phases: (1) an early, small, and unstable phase of facilitation, followed by (2) a period of suppression beginning 35 msec after the stimulus, lasting for 35 msec with a reduction in EMG activity to approximately 40% of the prestimulus level, and (3) a further phase of facilitation at a latency of 70 msec, with duration 35 msec and an increase in EMG activity to approximately 35% above prestimulus levels. The latency and duration of the suppressive phase of this reflex were similar to the exteroceptive suppression of EMG activity in the masseter muscle after supraorbital nerve stimulation (masseter silent period). In patients with spasmodic torticollis, the depth of this exteroceptive suppression in the sternocleidomastoid muscles was less than that observed in an age-matched cohort of normal subjects, although the latency and duration were normal. In contrast, exteroceptive suppression in the masseter muscle was normal. These findings suggest abnormal function of inhibitory interneuronal networks between the 5th cranial nerve and the motor neurons of the spinal accessory and upper cervical nerves which mediate exteroceptive suppression in the sternocleidomastoid muscle in patients with spasmodic torticollis.     

Somatosensory evoked potentials in the evaluation of patients with stocking/glove paresthesias

We studied 10 patients referred for suspicion of peripheral neuropathy. They all complained of paresthesias with a stocking distribution. As EMG, motor and sensory nerve conduction studies failed to confirm the clinical diagnosis, we studied somatosensory evoked potentials (SEP) following median and tibial nerve stimulation. The SEP findings were compared with controls and 10 spastic paraplegias. The evoked potential study revealed prolonged latencies of cortical potentials after tibial nerve stimulation in all the patients with paresthesias and were considered evidence of myelopathy.     

Pathophysiology of fasciculations in ALS as studied by electromyography of single motor units

Electromyographic potentials of fasciculations were studied in ten patients with amyotrophic lateral sclerosis (ALS). The EMG recordings were made from the extensor digitorum brevis muscle. The EMG recording was so selective that only one motor unit potential appeared on maximal voluntary effort and on supramaximal electrical stimulation of the peroneal nerve. In a series of fasciculations, the shapes of the EMG potentials varied, while in a series of voluntary twitch activations of electrical nerve stimulations the EMG potentials were mainly constant. Fasciculations were followed by antidromic impulses in the test unit axon as judged from collision tests, and they persisted after lidocaine blockades of the nerve to the muscle. The findings are compatible with a conclusion of distal multifocal triggering of fasciculation. Fasciculating motor units had voluntary firing properties close to those of normal low-threshold motor units. Widespread fasciculations were abolished by a nonparalytic dose of a synthetic curare derivative (Pavulon) and augmented by administration of neostigmine in two cases. The fasciculations in ALS thus have the same characteristics as experimental fasciculations evoked by cholinesterase inhibitors, and there is reason to believe that the underlying pathophysiological mechanism is similar in the two cases.     

Interfering cutaneous stimulation and the muscle afferent contribution to cortical potentials

Cerebral potentials were recorded in response to selective stimulation using microelectrodes of muscle afferents in motor fascicles innervating the intrinsic muscles of the foot or at the motor point of abductor hallucis. The early components of these potentials (P40, N50 and P60) were consistently attenuated by continuous tactile stimulation of related skin areas and by electrical stimulation of digital nerves, timed so that the digital volley reached cortex approximately 5 msec before the muscle afferent volley. The same conditioning cutaneous inputs also attenuated the cerebral potentials evoked by selective stimulation of cutaneous afferents. These findings confirm that there are intermodality and intramodality interactions between low-threshold cutaneous and muscle afferents and between cutaneous afferents, respectively. The findings indicate that 'interference phenomena' (Kakigi and Jones 1986) can occur between different afferent modalities, and within any one modality, and cannot be used to determine the afferent species responsible for the test evoked potential.