Peripheral Nerve Stimuli Research Articles

Changes in Excitability of the Cortical Projections to the Human Tibialis Anterior After Paired Associative Stimulation

Paired associative stimulation (PAS) based on Hebb's law of association can induce plastic changes in the intact human. The optimal interstimulus interval (ISI) between the peripheral nerve and transcranial magnetic stimulus is not known for muscles of the lower leg. The aims of this study were to investigate the effect of PAS for a variety of ISIs and to explore the efficacy of PAS when applied during dynamic activation of the target muscle. PAS was applied at 0.2 Hz for 30 min with the tibialis anterior (TA) at rest. The ISI was varied randomly in seven sessions (n = 5). Subsequently, PAS was applied (n = 14, ISI = 55 ms) with the TA relaxed or dorsi-flexing. Finally, an optimized ISI based on the subject somatosensory evoked potential (SEP) latency plus a central processing delay (6 ms) was used (n = 13). Motor-evoked potentials (MEPs) were elicited in the TA before and after the intervention, and the size of the TA MEP was extracted. ISIs of 45, 50, and 55 ms increased and 40 ms decreased TA MEP significantly (P = 0.01). PAS during dorsi-flexion increased TA MEP size by 92% (P = 0.001). PAS delivered at rest resulted in a nonsignificant increase; however, when the ISI was optimized from SEP latency recordings, all subjects showed significant increases (P = 0.002). No changes in MEP size occurred in the antagonist. Results confirm that the excitability of the corticospinal projections to the TA but not the antagonist can be increased after PAS. This is strongly dependent on the individualized ISI and on the activation state of the muscle.

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Vasoactive intestinal polypeptide produces depolarization and facilitation of C-fibre evoked synaptic responses in superficial dorsal horn neurones (laminae I–IV) of the rat lumbar spinal cord in vitro

The actions of vasoactive intestinal polypeptide (VIP) were investigated on superficial dorsal horn (LI–IV) neurones in longitudinal slices of the rat lumbar spinal cord in vitro. Bath application of VIP (1–2 mM) cause depolarizations which were accompanied by a lowering of the threshold for excitation of the neurone by current injection in the majority of cells studied. In some cases these depolarizations were very large and caused depolarization block and prolonged desensitization. An increase in spontaneous excitatory postsynaptic potential (EPSP) frequency and amplitude was also produced by VIP. Synaptic responses evoked by peripheral nerve stimuli at intensities which recruited C-fibres were also facilitated by VIP. The principle action was on the later components of these responses which are dependent on C-fibre activation. EPSP summation evoked by trains of peripheral nerve stimulation (wind-up) was also facilitated by VIP and the duration of these responses was clearly increased. These observations are discussed briefly in the context of the possible role of VIP in neuropathic pain.

Distribution of Ia effects onto human hand muscle motoneurones as revealed using an H reflex technique.

1. The possibility of eliciting H reflexes in relaxed hand muscles using a collision between the orthodromic impulses generated by magnetic cortical stimulation and the antidromic motor volley due to a supramaximal (SM) peripheral nerve stimulus was investigated in seven subjects. 2. Magnetic stimuli, applied through a circular coil (outer diameter, 13 cm) centred at the vertex, evoking EMG responses of 3-5 mV amplitude in the relaxed abductor digit minimi (ADM) muscle, and SM test stimuli to the ulnar nerve at the wrist producing a direct maximal motor response (Mmax) in the ADM muscle, were given either alone or combined. 3. In all subjects, combined cortical and SM ulnar stimulation produced a response after the Mmax with the latency of an H reflex evoked by the ulnar stimulus. This response occurred only within interstimulus intervals (1-20 ms) compatible with collision in the motor axons. The response behaved like an H reflex being time-locked to the SM ulnar stimulus, facilitated by voluntary activation of ADM muscle, depressed by vibration (4 s, 100 Hz) of ADM tendon and by a submotor-threshold ulnar nerve stimulus applied 50 and 80 ms before the combined stimulation, respectively. 4. In some subjects, it was also possible to distinguish an earlier response preceding the H reflex by 3 ms. Evidence is given that this response is probably of cortical origin. 5. Varying the intensity of magnetic stimulation resulted in a non-linear relationship between the H reflex size and the size of the cortical response. When the latter was between 5-25% of Mmax, H reflexes were small (2.5-7.5% of Mmax); with cortical responses between 25-50% of Mmax, there was a steep increase in H reflex amplitude (10-30% of Mmax). We suggest that this behaviour is due to an uneven distribution of Ia effects within the motoneurone pool.

Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input

In active muscle, a supramaximal conditioning stimulus to peripheral nerve produces a classic silent period in the EMG. The present experiments examined the effect of this type of conditioning stimulus on motoneurone excitability in relaxed muscle. EMG responses evoked by transcranial magnetic stimulation of the brain were recorded from the first dorsal interosseus muscle (FDI) in 10 healthy subjects and 5 patients with sensory neuropathy. These responses (motor evoked potentials) were conditioned by supramaximal peripheral nerve stimuli given 0–150 msec beforehand. In the normal subjects, the classic silent period in the FDI lasted about 100 msec. The same conditioning stimulus only abolished motor evoked potentials when the conditioning-test interval was so short that the antidromic peripheral nerve volley collided with the orthodromic volley set up by magnetic brain stimulation. At longer conditioning-test intervals, although remarkably inhibited (65% mean suppression between 10 and 40 msec), the test motor potential was never completely abolished and gradually recovered by 100 msec. Inhibition of cortically evoked motor potentials did not depend upon activity set up by the conditioning stimulus in peripheral nerve sensory fibres. The patients with complete peripheral sensory neuropathy had the same extent and time-course of inhibition as the normal subjects. We conclude that in relaxed subjects the inhibitory effect of peripheral conditioning results almost exclusively from the motoneuronal inhibitory mechanisms consequent to antidromic invasion.

A preliminary clinical evaluation of magnetic stimulation of the ulnar nerve for monitoring neuromuscular transmission

The evoked motor responses to magnetic and electrical peripheral nerve stimuli were quantitatively assessed after vecuronium in 15 women undergoing gynaecological surgery. Anaesthesia was induced with thiopentone and fentanyl and maintained with intermittent doses of fentanyl and 66% nitrous oxide in oxygen. After immobilisation of both forearms in splints, the ulnar nerves were stimulated supramaximally every 10 s with a magnetic stimulator (Magstim Model 200) and an electric stimulator (Myotest) on opposite sides. The adduction forces of both thumbs to magnetic and electric stimuli were measured simultaneously before and after 0.06 mg.kg-1 of vecuronium. After vecuronium administration the twitch responses to magnetic stimulation decreased more slowly than those to electric stimulation. The difference in the evoked responses between the two types of stimulation was approximately 20% overall and was significant 2 min after vecuronium administration (p < 0.05). The rate of recovery of the evoked twitch responses was more rapid with magnetic than electric stimulation. It is concluded that magnetic stimulation of peripheral nerve is a useful technique for evaluating residual neuromuscular blockade.

Orbicularis oculi responses to stimulation of nerve afferents from upper and lower limbs in normal humans

A brief mechanical or electrical stimulus to peripheral nerve afferents from the upper and lower limbs elicited a small and inconsistent EMG response of the orbicularis oculi muscles. This response was facilitated when the stimuli were delivered at fixed leading time intervals, of 45–300 ms, with respect to a supraorbital nerve electrical stimulus. Also, the peripheral nerve stimulus modified the conventional blink reflex responses, inducing facilitation of R1 and inhibition of R2. These results suggest a complex processing of sensory inputs from the face and the limbs at the brainstem, where they are probably integrated in a network of interneurons influencing the excitability of facial motoneurons.

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. This approach might be used for assessment of unconsciousness and/or comatose head injured patients.

Activation by high intensity peripheral nerve stimulation of adrenergic and opioidergic inhibition of a spinal reflex in the decerebrated rabbit

The short-latency sural to gastrocnemius reflex in the decerebrated rabbit was depressed for 20–30 min following high intensity conditioning stimulation of the common peroneal nerve. This effect was observed in animals with or without spinal section, but was greater in non-spinalized preparations. Graded conditioning stimuli showed that it was necessary to activate fine myelinated common peroneal axons to inhibit the reflex. In spinalized rabbits, maximal inhibition was achieved with conditioning stimulation of fine myelinated axons and was completely reversed by the opioid antagonist naloxone. In non-spinalized rabbits, maximal inhibition was only obtained with conditioning stimuli which activated non-myelinated axons. In these preparations the effects of common peroneal nerve stimuli were only blocked by co-administration of naloxone with the α 2-adrenoceptor antagonist idazoxan. Thus high intensity peripheral nerve stimuli activated a segmental opioidergic and a supraspinal adrenergic suppression of the sural-gastrocnemius withdrawal reflex. Such long-lasting suppression of reflex excitability may contribute to recovery from intensely noxious stimuli.

Observations on chloralose-induced myoclonus in guinea-pigs.

1 The physiological, biochemical and pharmacological features of alpha-chloralose-induced myoclonus in the guinea-pig have been studied. 2 EMG bursts in muscles jerking in chloralose-induced myoclonus are long, and are not time-locked to any cortical event recorded in the EEG, although they are evoked by auditory or peripheral nerve stimuli. 3 The efferent conduction velocity down the spinal cord of the signals generating the EMG bursts is fast but the afferent conduction velocity up the cord for stimulus-evoked jerks is slow, in distinction to the reverse characteristics of the spino-bulbo-spinal relfex arc. 4 alpha-Choralose did not cause any consistent change in 5-hydroxytryptamine (5-HT) or 5-hydroxyindoleacetic acid levels in any brain area, nor did it alter 5-HT turnover as judged by the depletion of 5-HT after p-chlorophenylalanine pretreatment. 5 Pretreatment of animals with drugs that increase brain 5-HT action (L-tryptophan with a monoamine oxidase inhibitor, or 5-hydroxytryptophan), or antagonize the action of 5-HT (cyproheptadine) did not abolish or obviously increase chloralose-induced myoclonus. 6 Chloralose-induced myoclonus is not similar to 5-HT-sensitive reticular reflex myoclonus in man.

The reduced responsiveness of neurones in nucleus reticularis gigantocellularis following their excitation by peripheral nerve stimulation.

1. Post-stimulus histograms of neuronal activity, constructed from extracellular recordings in decerebrate, decerebellate cats, have been used to investigate the responsiveness of neurons in nucleus reticularis gigantocellularis following their excitation by a peripheral nerve stimulus. 2. The response to a testing stimulus applied to a peripheral nerve was depressed following the response to a conditioning stimulus applied to the same or a different peripheral nerve. This reduction in responsiveness was maximal within 50 msec of the peak of the response to the conditioning stimulus. Response latencies to the testing stimulus were increased during the period of reduced responsiveness. 3. Responsiveness to a peripheral nerve stimulus was also reduced following a spontaneous or an antidromically evoked spike, but this effect was weaker and much shorter-lasting than that following a nerve-evoked spike. Thus, the reduced responsiveness cannot be solely due to phenomena which are an inevitable consequence of an action potential in the neurone. 4. In spontaneously firing neurones, the duration of the reduced responsiveness to a testing stimulus generally outlasted the depression of spontaneous activity which often followed an excitation evoked by a peripheral nerve conditioning stimulus. 5. The reduction in responsiveness to a testing stimulus applied to the same nerve as the conditioning stimulus was greater and longer-lasting than that to a testing stimulus applied to a different nerve. 6. When stimuli were applied to one nerve at a relatively high rate, the neurone became much less responsive to that input, but simultaneously became more responsive to low rate stimulation of other nerves. 7. It is concluded that the greater part of the reduced responsiveness is due to events occurring on the input pathway to a reticular neurone, or possibly in the region of the afferent endings on its dendrites. These processes may allow selective changes in responsiveness to different inputs, and enable the units to act as novelty detectors.

Effect of etorphine, morphine and diprenorphine on neurones of the cerebral cortex and spinal cord of the rat.

1. The actions of etorphine, morphine and diprenorphine were investigated on neurones of the cerebral cortex and spinal cord of rats anaesthetized with pentobarbitone.2. In the cerebral cortex, intravenous etorphine increased the latency of the primary evoked response to a peripheral nerve stimulus and suppressed the rhythmical after-discharge. Diprenorphine reversed this effect. These actions were demonstrated on both field potentials and unit firing.3. Morphine had no effect on the primary response but the frequency of after-discharge bursts was reduced and there was an increase in firing between bursts.4. In the cerebral cortex, electrophoretically applied etorphine reduced after-discharges when applied for long periods but had no effect on the depressant actions of glycine and gamma-aminobutyric acid (GABA) nor on the excitant action of acetylcholine and L-glutamate. Similarly there was no alteration by etorphine of the effects of glycine, GABA and L-glutamate on spinal cord neurones.5. It is concluded that etorphine may act pre-synaptically in the cerebral cortex.

Cortically induced inhibition in the dorsal column nuclei of monkeys.

Corticofugal inhibition of somatosensory transmission in the cuneate nucleus of monkeys under chloralose was investigated with particular reference to the time course of primary afferent depolarization (PAD), the cortical origin of its pathway, and its sensitivity to small additional doses of Nembutal. Corticofugal effects were also compared with PAD elicited by conditioning peripheral nerve stimuli. It is concluded that the pathway mediating corticofugal inhibition has its origin in areas in front of the Rolandic fissure. It is suggested that the pathway is indirect and involves the bulbar reticular formation.