Conditioning-test Intervals Research Articles

Excitability changes in human peripheral nerve axons in a paradigm mimicking paired-pulse transcranial magnetic stimulation.

A peripheral nerve model was developed to determine whether changes in axonal excitability could affect the findings in studies of cortical processes using paired-pulse transcranial magnetic stimulation (TMS). The recovery of axonal excitability from a conditioning stimulus smaller than the test stimulus was qualitatively similar to that with suprathreshold conditioning stimuli. There was an initial decrease in excitability, equivalent to refractoriness at conditioning-test intervals < 4 ms, an increase in excitability, equivalent to supernormality, at intervals of 5-20 ms and a second phase of decreased excitability, equivalent to late subnormality at intervals > 30 ms. H reflex studies using conditioning stimuli below threshold for the H reflex established that these excitability changes could be faithfully translated across an excitatory synapse. Changing membrane potential by injecting polarising current altered axonal excitability in a predictable way, and produced results similar to those reported for many disease states using paired-pulse TMS. Specifically, axonal hyperpolarisation produced a smaller decrease in excitability followed by a greater increase in excitability. This study supports the view that changes in excitability of the stimulated axons should be considered before synaptic mechanisms are invoked in the interpretation of findings from paired-pulse TMS studies.

Effects of acute stimulation through contacts placed on the motor cortex for chronic stimulation

Objectives: We tried to determine which neural elements were activated in awake subjects by stimulation through contacts placed chronically on the motor cortex.Methods: We recorded the motor effects of stimulation through 4 disc contacts placed in the subdural space over the motor cortex in 9 patients undergoing chronic stimulation for the control of pain or for the control of the rigidity of multiple system atrophy.Results: Single stimuli could elicit short latency motor evoked potentials or facilitate active motoneurons in the contralateral limbs. The responsible neural elements had a short chronaxie (the pulse duration necessary to reach threshold with a stimulus intensity twice that required to reach threshold at the longest pulse duration used) and refractory period implying that they were myelinated axons. The facilitation was larger with cathodal than with anodal monopolar stimulation.The short latency facilitation in response to the second of two stimuli was greater at condition test intervals of 2–5 ms. This enhancement could be demonstrated with conditioning stimuli subthreshold for the excitation of active motoneurons suggesting that it arose, in part, at the level of the cortex.Single cortical stimuli could result in inhibition of voluntarily activated motoneurons. The inhibition was larger with cathodal than anodal monopolar stimulation. The responsible neural elements also had a short chronaxie and refractory period.Conclusions: Stimulation in awake subjects through contacts placed chronically over the motor cortex appears to activate axons in the cortex, which excite both corticospinal neurons and inhibitory neurons.

Excitability changes in human corticospinal projections to forearm muscles during voluntary movement of ipsilateral foot.

Excitability of the H-reflex in the relaxed flexor carpi radialis (FCR) muscle was tested during voluntary oscillations of the ipsilateral foot at five evenly spaced delays during a 600 ms cycle. In some experiments the H-reflex was conditioned by transcranial magnetic stimulation (TMS). With the hand prone, the amplitude of the FCR H-reflex was modulated sinusoidally with the same period as the foot oscillation, the modulation peak occurring in coincidence with contraction of the foot plantar-flexor soleus and the trough during contraction of the extensor tibialis anterior. When the H-reflex was facilitated by TMS at short latency (conditioning-test interval: -2 to -3.5 ms), the modulation was larger than that occurring with an unconditioned reflex of comparable size. This suggests that both the peripheral and the corticospinal components of the facilitated response were modulated in parallel. When the H-reflex was tested 40-60 ms after conditioning, i.e. during the cortical "silent period" induced by TMS, no direct effect was produced on the reflex size but the foot-associated modulation was deeply depressed. These results suggest that the reflex modulation may depend on activity fluctuations in the cortical motor area innervating the forearm motoneurones. It is proposed that when the foot is rhythmically oscillated, along with the full activation of the foot cortical area a simultaneous lesser co-activation of the forearm area produces a subliminal cyclic modulation of cervical motoneurones excitability. Should the two limbs be moved together, the time course of this modulation would favour isodirectional movements of the prone hand and foot, indeed the preferential coupling observed when hand and foot are voluntarily oscillated.

Effect of vagal afferent conditioning on trigeminal motor neuron activity associated with tooth-pulp-evoked jaw-opening reflex

To clarify the vagal afferent modifying effect on the neurons constituting the nociceptive jaw-opening reflex (JOR), we conducted extracellular recording of trigeminal motor nucleus (TMN) neuron activity in pentobarbital-anesthetized rats. Of 12 TMN neuron responses evoked by tooth pulp (TP) stimulation, 10 were suppressed by vagal afferent conditioning (83%). The mean time of the suppressive effect on the TMN neurons paralleled that found with the digastric electromyogram (dEMG), and maximal inhibition of both TMN neuronal spikes and the dEMG amplitude were observed at a 50-ms conditioning-test interval. The ratio of inhibition was approximately 38%. Seven of 12 units were activated antidromically by digastric muscle stimulation (1-3 mA, 0.1 ms, 2 Hz) and fulfilled the criteria for antidromic activation. Vagal afferent conditioning stimulation had no effect on the antidromic TMN neuronal responses to digastric muscle stimulation. These results suggest that suppression of the TP-evoked JOR in response to vagal afferent stimulation in rats is the result of an inhibitory effect on the sensory neurons rather than on the motor neurons.

A comparison of the different interpair intervals in the conditioning–testing P50 paradigms

The conditioning–testing P50 paradigm is used to demonstrate sensory gating of responsiveness to auditory stimuli. Sensory gating is measured in terms of a suppression of the second (test) P50 component in that paradigm. The time course of sensory gating can be determined by examining subjects’ gating of responsiveness to stimuli repeated at various interpair intervals. In the present study auditory evoked potentials were recorded using a paired click, conditioning–testing P50 paradigm in 11 normal subjects with no family history of any psychotic disorder. Recordings were made at conditioning–testing intervals of 250 ms, 500 ms, 750 ms and 1000 ms. Whereas the grand averages of the P50 conditioning–testing response for the 250- and 500-ms intervals were 3.07% and 37.2%, respectively, indicating almost complete suppression, the grand averages of the ratios for the 750- and 1000-ms intervals were 114.35% and 92.92%, respectively, indicating little or no suppression. There was significant correlation in the C–T ratios with the increasing intervals. Our results suggest that the mechanism(s) responsible for sensory gating is activated mostly during the 500 ms after stimulus presentation. Other gating mechanism(s) functioning at longer intervals appear to be uncertain.

Cerebellar stimulation in acute cerebellar ataxia

Objectives: To report follow-up studies of cerebellar stimulation in patients with acute cerebellar ataxia (ACA). Methods: We studied two patients with ACA. One patient also had decreased deep sensations in the feet due to combined diseases such as diabetic polyneuropathy and lumbosacral radiculopathies. We applied the technique of electrical stimulation over the cerebellum which was reported previously (Ugawa et al., J Physiol 441 (1991a) 57). Results: Conditioning stimulation over the cerebellum did not reduce the size of motor-evoked potentials to test magnetic stimulation of the motor cortex at conditioning–test intervals of 5, 6, and 7 ms in the acute stage in both patients. However, normal suppression was recognized in the recovery stage in both patients. Conclusions: This technique was useful for follow-up evaluation of cerebellar function in patients with ACA and was also useful for distinguishing cerebellar ataxia from sensory ataxia in a patient with combined diseases.

Abnormalities of sensorimotor integration in focal dystonia: a transcranial magnetic stimulation study.

It has been postulated that sensorimotor integration is abnormal in dystonia. We investigated changes in motor cortical excitability induced by peripheral stimulation in patients with focal hand dystonia (12 patients with hand cramps) and with cervical dystonia (nine with spasmodic torticollis) compared with 16 age-matched normal controls. Motor evoked potentials (MEP) to focal (figure-of-eight coil) transcranial magnetic stimulation of the hand area were recorded from the right abductor pollicis brevis (APB), first dorsal interosseus (FDI), flexor carpi radialis and extensor carpi radialis muscles. Changes of test MEP size following conditioning stimulation of the right median nerve (or of the index finger) at conditioning-test (C-T) intervals of 50, 200, 600 and 1000 ms were analysed. Peripheral stimulation significantly reduced test MEP size in the APB and FDI muscles of normal control and spasmodic torticollis patients. The inhibitory effect was larger upon median nerve stimulation and reached a maximum at the C-T interval of 200 ms. On the contrary, hand cramp patients showed a significant facilitation of test MEP size. This study suggests that MEP suppression following peripheral stimulation is defective in patients with focal hand dystonia. Central processing of sensory input is abnormal in dystonia and may contribute to increased motor cortical excitability.

Voluntary contraction impairs the refractory period of transmission in healthy human axons.

1. Voluntary contraction of a muscle causes substantial hyperpolarization of the active motor axons due to activation of the electrogenic Na+-K+ pump. The present study was undertaken to determine whether voluntary effort produces a significant impairment in impulse transmission in normal axons and whether mechanisms other than membrane hyperpolarization contribute to the changes in axonal excitability. 2. The compound muscle action potential (CMAP) was recorded after median nerve stimulation at the wrist using sub- and supramaximal stimuli, delivered singly and in pairs at conditioning-test intervals of 2-15 ms. Axonal excitability parameters (threshold, refractoriness, supernormality, and strength-duration time constant (tauSD)) were measured using threshold tracking. Impulse transmission was assessed using supramaximal stimuli. 3. Maximal voluntary contractions of the abductor pollicis brevis for 1 min produced a substantial increase in threshold, an increase in supernormality and a decrease in tauSD, all of which lasted approximately 10 min and indicate axonal hyperpolarization. However, immediately after the contraction there was an unexpected increase in refractoriness. The post-contraction increase in refractoriness could not be mimicked by an imposed ramp of hyperpolarization that produced changes in the other indices to an extent that was similar to voluntary contraction. 4. The contraction had relatively little effect on the size of the unconditioned maximal CMAP. However, there was failure of transmission of supramaximal conditioned volleys when the conditioning-test interval was short. 5. The relationships between axonal excitability and supernormality and tauSD following voluntary contraction differed significantly from those recorded during the hyperpolarization produced by DC current. It is argued that these differences probably result from extra-axonal K+ accumulation with the voluntary contraction but not with the DC polarization. I6. It is concluded that, following maximal voluntary contraction of a normal muscle, the refractory period of transmission is impaired distal to the stimulus site sufficient to cause transmission failure of the second of a pair of closely spaced impulses. The site of transmission failure is likely to be the terminal axon, presumably at branch points, possibly in the unmyelinated pre-terminal segment.

Spinal and cortical inhibition in Huntington's chorea.

In this article we studied spinal and cortical inhibitory mechanisms in patients with Huntington's disease. To evaluate spinal cord inhibitory circuitries, we assessed reciprocal inhibition between antagonist forearm muscles and the recovery cycle of the H reflex in the flexor carpi radialis. Patients showed a significant decrease in the presynaptic phase of reciprocal inhibition reaching a minimum at the conditioning-test interval of 20 msec and an abnormal facilitation of the test H reflex at the conditioning test interval of 40 to 60 msec. Throughout its time course (10-200 msec), the H reflex recovery cycle showed a more prominent facilitation in patients than in control subjects. To assess whether the observed pathophysiological abnormalities might have arisen from an abnormal motor cortical excitability, we examined the recovery cycle of the motor potentials evoked by paired transcranial magnetic stimuli. We found that the inhibitory mechanisms controlling motor cortical excitability were normal. An interpretation of the spinal cord abnormalities is that the intrinsically normal but deafferentated motor cortex in Huntington's disease partly loses its inhibitory control, thus disinhibiting spinal cord circuitry. Our findings from paired transcranial magnetic stimulation suggest that cortical motor areas are not hyperexcitable in Huntington's disease. Hence, the postulated thalamocortical overactivity in experimental models of Huntington's disease needs to be reappraised.

Task dependence of Ia presynaptic inhibition in human wrist extensor muscles: a single motor unit study

Objective: Task-dependent changes in the Ia presynaptic inhibition generated by flexor group I afferents were investigated in 25 identified motor units (MUs) located in human extensor carpi radialis (ECR) muscles. Methods: Seven subjects had to voluntarily contract their ECR muscles either alone during isometric wrist extension or concurrently with their wrist and finger flexor muscles while clenching their hand around a manipulandum. The MU reflex responses to the radial nerve stimulation (test stimulation) yielded narrow peaks in the post-stimulus time histograms (PSTH). The Ia presynaptic inhibition induced while stimulating the median nerve (conditioning stimulation) 20 and 40 ms before the radial nerve was assessed from the changes in the contents of the first 0.5 ms in the peaks. Results: With both stimulation intervals, the Ia presynaptic inhibition, as assessed from the first 0.5 ms of the PSTH peaks, was consistently weaker during hand clenching. With both motor tasks, the Ia presynaptic inhibition was strongest at the 20 ms interval, in which it showed a downward gradient, working from slow to fast contracting MUs. With both intervals, the presynaptic inhibition was consistently weaker during hand clenching. The decrease in the Ia presynaptic inhibition observed at the 40 ms conditioning-test interval was less pronounced during wrist extension. Conclusion: It is suggested that the reason why Ia presynaptic inhibition was weaker during hand clenching may have been that this task involved numerous cutaneous inputs originating from the palm and finger tips. During gripping tasks, these cutaneous inputs may therefore contribute to adjusting the wrist stiffness by relieving the presynaptic inhibition.

Monitoring of head injury by myotatic reflex evaluation

OBJECTIVES(1) To establish the feasibility of myotatic reflex measurement in patients with head injury. (2) To test the hypothesis that cerebral dysfunction after head injury causes myotatic reflex abnormalities through...

The effects of a volatile anaesthetic on the excitability of human corticospinal axons.

The recovery of excitability following a conditioning volley and the strength-duration properties of corticospinal axons were measured in 10 neurologically normal patients in whom corticospinal function was being monitored during scoliosis surgery. Corticospinal volleys were produced using transcranial electrical stimulation of the motor cortex, and recorded from the spinal cord using epidural leads. Administration of a volatile anaesthetic, sevoflurane 2%, increased the threshold current required to produce a submaximal test volley by 35.8% (P = 0.0005), indicating that the anaesthetic depressed the excitability of the site at which the transcranial stimulus activated the corticospinal system. Following a strong transcranial stimulus, axons were relatively refractory for conditioning-test intervals up to approximately 2.5 ms, and then superexcitable for intervals of >10 ms. In two patients, the time course and extent of refractoriness and superexcitability did not differ when receiving sevoflurane 2% and after its withdrawal. Strength-duration properties were determined by measuring the stimulus current required to produce a submaximal corticospinal volley of fixed amplitude using test stimuli of different duration, from 50 micros to 1 ms. Strength-duration curves were well described by a hyperbolic function, with which there is a linear relationship between stimulus charge and stimulus duration. In the absence of sevoflurane, the strength-duration time constant (tau(SD)) was 432.2 +/- 70.5 micros. When sevoflurane 2% was administered to 6 patients, tau(SD) decreased to 203.7 +/- 93.8 micros, a change that was significant (P = 0.04). The decrease in tau(SD) was accompanied by an increase in rheobase. These findings imply that the lowest-threshold component of the corticospinal volley produced by transcranial electrical stimulation probably arises from nodes of Ranvier of corticospinal axons, where it would not be affected by changes in the excitability of cortical neurons. It is suggested that the increase in threshold produced by sevoflurane is due to depression of Na(+) currents at the nodes of Ranvier of corticospinal axons.

The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation.

The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.

Soleus Stretch Reflex Inhibition in the Early Swing Phase of Gait Using Deep Peroneal Nerve Stimulation in Spastic Stroke Participants

Objectives. To investigate the feasibility of inhibiting the stretch reflex of the soleus muscle by a conditioning stimulus applied to the deep peroneal nerve in spastic stroke participants during the early swing phase of gait. Materials and Methods. This study investigated the effect of an electrical conditioning stimulus applied to the deep peroneal nerve on the magnitude at the peak of the soleus stretch reflex in the early swing phase of gait in six spastic stroke participants. Results. Five of the six participants showed a reduced stretch reflex of more than 80%. On average (n= 4), it was shown that maximal inhibition occurred at a conditioning-test interval of 114 ms and had a magnitude of more than 90% (p < 0.05). For all five participants investigated, there was a significant reduction in the sensitivity of the soleus stretch reflex after conditioning (p < 0.02). Conclusions. It is concluded that the inhibition of the soleus stretch reflex with an electrical conditioning stimulus applied to the deep peroneal nerve is feasible in the early swing phase of walking. This shows a potential for being used in the rehabilitation of walking by spastic stroke persons.

Ischaemic changes in refractoriness of human cutaneous afferents under threshold-clamp conditions.

1. A technique was developed to counteract the changes in threshold to electrical stimuli of large myelinated cutaneous afferents in the human median nerve induced by ischaemia for 13 min. Intermittent application of polarizing currents was used in five subjects, in whom refractoriness, supernormality and the strength-duration time constant (tauSD) were tracked to determine whether compensating for the ischaemia-induced changes in threshold also controlled the ischaemic changes in these excitability parameters. 2. The threshold compensation prevented the ischaemic changes in tauSD, an excitability parameter dependent on nodal Na+ channels. Threshold compensation did not prevent the changes in refractoriness and supernormality, whether the compensation began 10, 100 or 200 ms prior to the test stimuli. 3. In three subjects, continuous polarizing current was injected for 13 min to compensate for the ischaemic change in threshold, thus clamping threshold at the pre-ischaemic level. Again, tauSD was effectively controlled, but there were still ischaemic changes in refractoriness and supernormality. 4. The effective control of tauSD suggests that both the intermittent threshold compensation and the continuous threshold clamp effectively controlled membrane potential at the node of Ranvier. 5. The ischaemic increase in refractoriness when threshold was kept constant could be due to interference with the processes responsible for refractoriness by a metabolic product of ischaemia. The ischaemic change in supernormality during effective compensation probably results from the intrusion of refractoriness into the conditioning-test intervals normally associated with maximal supernormality. 6. The present results indicate that ischaemia has effects on axonal excitability that cannot be readily explained by changes in membrane potential. Specifically, it is suggested that ischaemic metabolites interfere with the recovery of Na+ channels from inactivation.

Reproducibility of indices of axonal excitability in human subjects

Objectives: Different indices of axonal excitability are now being measured in human subjects, both normal volunteers undergoing some test manoeuvre and patients with a variety of peripheral nerve disorders. The reproducibility of these indices has not previously been established, and was determined for cutaneous afferents in the median nerve of 12 healthy subjects, using threshold tracking techniques.Methods: Refractoriness and supernormality were determined as the change in stimulus current required to produce a predetermined target potential when conditioned by a supramaximal stimulus at appropriate conditioning-test intervals. Strength-duration time constant was calculated from the threshold currents using unconditioned test stimuli of 0.1 ms and 1.0 ms. The effects of changes in membrane potential on these indices was assessed by applying subthreshold DC currents (from 50% depolarizing to 50% hyperpolarizing), using the reciprocal of threshold (i.e., ‘excitability’) as an indicator of membrane potential. The intraindividual reproducibility was determined by repeating the study on each subject up to 10 times.Results: Refractoriness and supernormality were variable between subjects (mean±SD of 31.5±9.5% and 13.2±3.8%, respectively) and within subjects (coefficient of variation 0.2104 and 0.21849, respectively). τSD showed even greater interindividual variability (499.2±115 μs) and intraindividual variability (coefficient of variation 0.2339). The slopes of relationships between each of the indices and axonal ‘excitability’ suggest that refractoriness is extremely sensitive to changes in excitability (0.9767±0.1907), τSD less so (0.3766±0.1322), supernormality least (0.2223±0.1268).Conclusions: Under controlled conditions, refractoriness is the most sensitive and least variable of the indices of axonal excitability. However, small decreases in temperature greatly increase refractoriness but have little effect on τSD. Given that 3 indices reflect different biophysical mechanisms, nodal and internodal, greater insight into the functional state of peripheral nerve axons will come when there are coherent changes in all 3 indices.

Modulation of reciprocal inhibition between ankle extensors and flexors during walking in man.

1. The modulation of disynaptic reciprocal inhibition between antagonistic ankle muscles during walking was investigated in 17 healthy human subjects. Inhibition from ankle dorsiflexors to ankle plantar flexors was evoked by stimulation of the common peroneal nerve (CPN) and evaluated as the stimulus-induced depression of rectified soleus EMG activity (latency approx. 40 ms) or the short-latency depression of the soleus H-reflex (conditioning-test intervals around 2-3 ms). In some experiments the inhibition from ankle plantar flexors to ankle dorsiflexors was investigated. In these experiments the tibial nerve was stimulated and the amount of inhibition was evaluated from the short-latency depression of the voluntary rectified tibialis anterior (TA) EMG. 2. The short-latency inhibition of the soleus H-reflex following the CPN stimulation (1.1 x motor threshold; MT) was strongly modulated during walking, being large in the swing phase and absent in the stance phase. 3. A smaller amount of EMG depression following the CPN stimulation (1. 1-1.2 x MT) was observed in the stance phase of walking as compared to tonic or dynamic plantar flexion at a similar background EMG activity level in standing or sitting subjects. 4. In four subjects a depression of the TA EMG activity was produced by stimulation of the tibial nerve (1.1-1.2 x MT). In all subjects a smaller amount of inhibition was observed in the swing phase of walking as compared to tonic dorsiflexion at a comparable EMG activity level. 5. It is concluded that the transmission in the disynaptic Ia reciprocal pathway between ankle plantar flexors and dorsiflexors is modulated during walking. Inhibition from dorsiflexors to plantar flexors seems to be large in swing and small in stance, whereas inhibition from plantar flexors to dorsiflexors seems to be small in swing.

Temperature dependence of excitability indices of human cutaneous afferents.

The temperature dependence of different indices of axonal excitability (threshold, latency, refractoriness, supernormality, strength-duration time constant, and rheobase) was studied for cutaneous afferents of 8 healthy human volunteers using threshold tracking. Cooling from approximately 32 - approximately 22 degrees C dramatically increased the threshold for a conditioned potential evoked during the relatively refractory period (average increase 573%) but had little effect on the threshold for unconditioned potentials (increased by 4% with 0.1-ms test stimuli), strength-duration time constant (increased by 18%), or rheobase (decreased by 12%). Cooling increased the latency of the unconditioned test potential by 41%, but this slowing was small compared with the effect of cooling on the latency slowing attributable to refractoriness. This measure of refractoriness was initially 0.17 ms at a conditioning-test interval of 2 ms, and increased with cooling to 1.30 ms at the same interval. With cooling, refractoriness was both greater at any one conditioning-test interval and longer in duration, extending into intervals normally associated with supernormality. It is concluded that, although cooling affects all excitability indices to some extent, the most prominent feature is the increase in refractoriness. By contrast, strength-duration time constant is influenced little by temperature.

Modulation of motor cortex excitability by median nerve and digit stimulation.

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200-600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation.

Evidence suggesting that a transcortical reflex pathway contributes to cutaneous reflexes in the tibialis anterior muscle during walking in man.

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70-95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0-2.5x perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be -- at least partly -- mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2x motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50-80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking.