Effects of repetitive cortical stimulation on the silent period evoked by magnetic stimulation

 The effects of repetitive transcranial stimulation (rTMS) on brain activity remain unknown. In healthy subjects, we studied the effects of rTMS on the duration of the cortical silent period (SP). Repetitive stimuli were delivered with a Cadwell High Speed Magnetic Stimulator and a figure-of-eight coil placed over the hand motor area. rTMS was delivered in trains of 11 or 20 stimuli at frequencies of 3 and 5 Hz and at stimulation intensities of 110 and 120% of motor threshold. The SP was recorded from the forearm muscles during a voluntary contraction (20% of maximum effort). rTMS delivered at a frequency of 3 and 5 Hz and intensities of 110 and 120% motor threshold prolonged the duration of the SP, without modifying either the size or the latency of the muscle-evoked potentials (MEP). A conditioning train of 11 stimuli at 3 Hz had no effect on the duration of the SP evoked by a single magnetic shock delivered 600 ms after the train. These findings show that rTMS increases the duration of the cortical SP, but does so only during the train of stimuli. rTMS probably changes the duration of the SP by facilitating cortical inhibitory interneurons. Received: 4 December 1997 / Accepted: 11 August 1998     

Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period

In healthy subjects, suprathreshold repetitive transcranial magnetic stimulation (rTMS) at frequencies >2 Hz prolongs the cortical silent period (CSP) over the course of the train. This progressive lengthening probably reflects temporal summation of the inhibitory interneurons in the stimulated primary motor cortex (M1). In this study, we tested whether high-frequency rTMS also modulates the ipsilateral silent period (ISP). In nine normal subjects, suprathreshold 10-pulse rTMS trains were delivered to the right M1 at frequencies of 3, 5, and 10 Hz during maximal isometric contraction of both first dorsal interosseous muscles. At 10 Hz, the second pulse of the train increased the area of the ISP; the other stimuli did not increase it further. During rTMS at 3 and 5 Hz, the ISP remained significantly unchanged. Control experiments showed that 10-Hz rTMS delivered at subthreshold intensity also increased the ISP. rTMS over the hand motor area did not facilitate ISPs in the biceps muscles. Finally, rTMS-induced ISP facilitation did not outlast the 10-Hz rTMS train. These findings suggest that rTMS at a frequency of 10 Hz potentiates the interhemispheric inhibitory mechanisms responsible for the ISP, partly through temporal summation. The distinct changes in the ISP and CSP suggest that rTMS facilitates intrahemispheric and interhemispheric inhibitory phenomena through separate neural mechanisms. The ISP facilitation induced by high-frequency rTMS is a novel, promising tool to investigate pathophysiological abnormal interhemispheric inhibitory transfer in various neurological diseases.     

Comparison of motor effects following subcortical electrical stimulation through electrodes in the globus pallidus internus and cortical transcranial magnetic stimulation

Current concepts of transcranial magnetic stimulation (TMS) over the primary motor cortex are still under debate as to whether inhibitory motor effects are exclusively of cortical origin. To further elucidate a potential subcortical influence on motor effects, we combined TMS and unilateral subcortical electrical stimulation (SES) of the corticospinal tract. SES was performed through implanted depth electrodes in eight patients treated with deep brain stimulation (DBS) for severe dystonia. Chronaxie, conduction velocity (CV) of the stimulated fibres and poststimulus time histograms of single motor unit recordings were calculated to provide evidence of an activation of large diameter myelinated fibres by SES. Excitatory and inhibitory motor effects recorded bilaterally from the first dorsal interosseus muscle were measured after SES and focal TMS of the motor cortex. This allowed us to compare motor effects of subcortical (direct) and cortical (mainly indirect) activation of corticospinal neurons. SES activated a fast conducting monosynaptic pathway to the alpha motoneuron. Motor responses elicited by SES had significantly shorter onset latency and shorter duration of the contralateral silent period compared to TMS induced motor effects. Spinal excitability as assessed by H-reflex was significantly reduced during the silent period after SES. No ipsilateral motor effects could be elicited by SES while TMS was followed by an ipsilateral inhibition. The results suggest that SES activated the corticospinal neurons at the level of the internal capsule. Comparison of SES and TMS induced motor effects reveals that the first part of the TMS induced contralateral silent period should be of spinal origin while its later part is due to cortical inhibitory mechanisms. Furthermore, the present results suggest that the ipsilateral inhibition is predominantly mediated via transcallosal pathways.This paper is dedicated to Bernd-Ulrich Meyer, who died in a plane accident     

Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation

 To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation. Received: 24 November 1997 / Accepted: 11 August 1998     

Modulation of intracortical inhibition induced by low- and high-frequency repetitive transcranial magnetic stimulation

We studied the changes of duration of subsequent silent periods (SPs) during repetitive magnetic stimulation (rTMS) trains of ten stimuli delivered at low (1 Hz) and high (7 Hz) frequencies. The effects at different intensities of stimulation (motor threshold, MT, 115% and 130% above the MT) were also evaluated. rTMS was performed in eight healthy subjects with a figure-of-eight coil placed over the hand motor area. The SP was recorded from abductor pollicis brevis (APB) muscle during a voluntary contraction of 30% of maximum effort. rTMS at 1-Hz frequency progressively decreased the duration of SP, whereas an alternating pattern of smaller and larger values was observed during trains at 7-Hz frequency and higher stimulus intensity. The findings show that rTMS changes the duration of cortical SPs; the effect is probably due to the modulation of intracortical inhibitory interneurons depending on the frequency and intensity of stimulation.     

Facilitation of muscle evoked responses after repetitive cortical stimulation in man

The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600–900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex. Received: 12 November 1997 / Accepted: 23 February 1998     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication     

Mechanism of the silent period following transcranial magnetic stimulation Evidence from epidural recordings

We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability. Received: 21 January 1999 / Accepted: 14 April 1999     

Human handedness and asymmetry of the motor cortical silent period

We performed transcranial magnetic stimulation of the motor cortex in 22 left-handed and 25 right-handed subjects during active contraction of a small hand muscle. Motor evoked potentials had the same latency, amplitude and threshold on both sides of the body, whilst the silent period duration was shorter in the dominant hand. Silent periods elicited by nerve and brainstem stimulation were the same in both hands. Since the latter part of the cortical silent period is due mainly to withdrawal of corticospinal input to spinal motoneurones, we speculate that the results are compatible with the suggestion that tonic contractions of the non-dominant hand are associated with a greater involvement of the corticospinal tract than those of the dominant hand. It also seems likely that there is an asymmetry in the excitability of cortical inhibitory mechanisms with those responsible for the cortical silent period being less excitable in the dominant motor cortex. Received: 29 July 1998 / Accepted: 21 April 1999     

Suppression of the motor cortex by magnetic stimulation of the cerebellum

Conditioning magnetic stimulation of the cerebellum suppresses the motor cortex 5-8 ms later, probably through activation of cerebellar Purkinje cells, which inhibit the dentatothalamocortical pathway. To further characterize this pathway, we examined several factors that may modulate its excitability. We tested the effects of different test motor evoked potential (MEP) amplitudes, voluntary activation of the target muscle, and arm extension that required activation of proximal arm muscles while maintaining relaxation of hand muscles. Surface electromyography was recorded from the right first dorsal interosseous (FDI) muscle. A double-cone coil centered 3 cm lateral to the inion was used for right cerebellar stimulation. The stimulus intensity was set at 5% below the threshold for activation of the corticospinal tract. A figure-of-eight coil was used for left motor cortex stimulation. Interstimulus intervals (ISIs) between 3 and 15 ms were studied. Small test MEPs of about 0.5 mV were markedly inhibited at ISIs of 5-8 ms, but there was much less inhibition for test MEPs of about 2 mV. There was no significant MEP suppression during voluntary activation of the FDI muscle or during right arm extension. Left arm extension did not affect inhibition. Our findings indicate that cerebellar stimulation has a much stronger effect on motor cortex neurons activated near threshold intensities than those activated at higher intensities. Activation of contralateral but not ipsilateral proximal arm muscles during arm extension reduced the excitability of the cerebellothalamocortical projections to the hand area of the motor cortex.     

Influence of 5 Hz repetitive transcranial magnetic stimulation on motor learning

The aim of our study was to assess a possible improvement in motor learning induced by 5 Hz repetitive transcranial magnetic stimulation (rTMS) of human motor cortex. The same stimulation protocol previously enhanced perceptual learning as assessed by tactile discrimination performance when applied to the human primary somatosensory cortex. We applied 1250 pulses of 5 Hz “real” rTMS at 90% of resting motor threshold to the motor hotspot of the abductor pollicis brevis (APB) muscle in 15 healthy subjects before 1 h of motor training. Furthermore, 15 subjects received 5 Hz “sham” rTMS and served as control group. The motor task consisted of a synchronized co-contraction of the right APB and deltoid muscle. The latency between the onsets of muscle contractions was measured during training and served as a parameter for motor learning. MEP amplitudes were assessed in a subgroup of 10 subjects before and after rTMS as a parameter of corticospinal excitability. We found a significant learning effect in both groups as indicated by a reduction of latencies between the onsets of muscle contractions in the course of the training. Corticospinal excitability increased after “real”, but not after “sham” rTMS. However, “real” rTMS did not significantly influence motor learning as compared to “sham” rTMS. We conclude that 5 Hz rTMS of human primary motor cortex is not able to improve motor learning in healthy subjects, which might be due to the higher complexity of motor learning as compared to perceptual learning in the tactile domain.     

Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation

Many studies show consistently that repetitive transcranial magnetic stimulation (rTMS) with a frequency of 1 Hz and an intensity above the resting motor threshold (RMT) performed for several minutes over the primary motor cortex (M1) leads to a depression of cortical excitability. Furthermore, most studies concur on a facilitation of the non-stimulated contralateral M1. Little is known, however, about the physiological mechanisms underlying these effects. In 11 healthy volunteers, we stimulated the left M1 for 15 min with 1 Hz-rTMS of 115% RMT. Before, immediately after, and 30 min after the rTMS train, we examined short-interval intracortical inhibition (SICI; interstimulus interval (ISI) of 2 and 4 ms), intracortical facilitation (ICF; ISI 10 ms), and short-interval intracortical facilitation (SICF; ISI 1.5 ms) with established paired-pulse protocols. Mean unconditioned motor evoked potential (MEP) amplitudes and RMT were also measured. Two sessions were run at least 1 week apart, in one excitability of the stimulated M1 was tested, in the other one excitability of the non-stimulated M1. rTMS led to the expected reduction of MEP amplitude of the stimulated M1, which was significant only immediately after the rTMS train. rTMS increased MEP amplitude of the non-stimulated M1, which lasted for at least 30 min. RMT, SICI, ICF and SICF did not show any significant change in either M1, except for a long lasting increase of SICF in the non-stimulated M1. In conclusion, the MEP increase in the non-stimulated M1 lasted longer than the MEP decrease in the stimulated M1. Only the long-lasting MEP increase was associated with a specific change in intracortical excitability (increase in SICF). Modulation of motor cortical inhibition did not play a role in explaining the rTMS induced changes in MEP amplitude.     

Changes of blood lactate levels after repetitive transcranial magnetic stimulation

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 μV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1 Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood–brain barrier.     

Paired-pulse repetitive transcranial magnetic stimulation of the human motor cortex

In nine healthy humans we modulated corticospinal excitability by using conditioning-test paired-pulse transcranial magnetic stimulation in a repetitive mode (rTMS), and we compared its effect to conventional single-pulse rTMS. We applied 80 single pulses or 80 paired pulses to the motor cortex at frequencies ranging from 0.17 to 5 Hz. The conditioning-test intervals were 2, 5, or 10 ms. Motor evoked potential (MEP) amplitudes from the abductor digiti minimi (ADM) as target muscle and extensor carpi radialis (ECR) indicated the excitability changes during and after rTMS. During paired-pulse rTMS at a facilitatory conditioning-test interval of 10 ms, we observed a facilitation of MEPs at 1, 2, and 5 Hz. A similar facilitation was found during single-pulse rTMS, when stimulus intensity was adjusted to evoke MEPs of comparable size. Using an inhibitory conditioning-test interval of 2 ms, paired-pulse rTMS at frequencies of 1 and 2 Hz caused no change in MEP size during the train. However, paired-pulse rTMS at 5 Hz caused a strong enhancement of MEP size, indicating a loss of paired-pulse inhibition during the rTMS train. Since no facilitatory effect was observed during single-pulse rTMS with an adjusted stimulus intensity, the MEP enhancement during 5 Hz rTMS was specific for "inhibitory" paired-pulse rTMS. After 5 Hz rTMS MEPs were facilitated for 1 min, and this effect was not substantially different between paired-pulse rTMS and single-pulse rTMS. The correlation between ADM and ECR was most pronounced at 5 Hz rTMS. We conclude that paired-pulse rTMS is a suitable tool to study changes in corticospinal excitability during the course of rTMS. In addition, our data suggest that short trains of paired-pulse rTMS are not superior to single-pulse rTMS in inducing lasting inhibition or facilitation. Electronic Publication     

Persistent effects of high frequency repetitive TMS on the coupling between motor areas in the human

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a treatment for various movement and psychiatric disorders. How rTMS may have persistent effects on cortical function remains unclear. We hypothesised that it may act by modulating cortico-cortical connectivity. To this end we assessed cortico-cortical coherence before and after high frequency rTMS of the motor cortex. Sixteen healthy subjects received a single train (5 Hz, active motor threshold, 50 stimuli) of rTMS to the left motor hand area. Spectral power and coherence estimates were calculated between different EEG signals at rest and while muscles of the distal upper limb were tonically contracted. Repetitive TMS over the left motor hand area caused a significant decrease in the intrahemispheric EEG-EEG coherence between motor and premotor cortex in the 10.7–13.6 Hz (upper alpha band) lasting a few minutes after stimulation. There was no significant change in interhemispheric EEG-EEG coherence between motor areas. Thus, high frequency rTMS of the motor cortex decreases ipsilateral cortico-cortical intrahemispheric in the upper alpha band. Electronic Publication     

The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects

It has been suggested that the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are mediated through changes in cortical inhibition (CI). However, in healthy human subjects the effects of rTMS on CI have been inconsistent. Therefore, this study sought to improve on the methodological limitations of previous studies by exploring several different rTMS-stimulus conditions on inhibition in the human motor cortex. In the first experiment, 12 healthy control subjects were randomly assigned to receive regular 1, 10 or 20 Hz rTMS in a counterbalanced order with sessions separated by at least 1 week. In the second experiment, 10 of these 12 subjects received priming rTMS (600 stimuli at 6 Hz followed by 600 stimuli at 1 Hz). Cortical inhibition was indexed using short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Corticospinal excitability was indexed using motor threshold and MEP amplitude. We found no significant overall change in SICI, although there was a significant correlation between changes in SICI with baseline SICI. Subjects with greater SICI at baseline tended to have reduction in SICI post-rTMS, whereas subjects with less SICI tended to have increase in SICI post-rTMS. There was also a significant lengthening of the CSP with higher stimulation frequencies compared to lower stimulation frequencies. These findings suggest that rTMS increases CI, particularly in subjects with reduced baseline inhibition, a finding consistent with the concept of homeostatic plasticity. Baseline physiological characteristics may be further explored as a method to select patients who may benefit from rTMS treatment.     

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.     

Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects

Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5 Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5 Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.     

Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation

Introduction

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent.

Materials and methods

Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5 Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10 min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables.

Results

Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved.

Conclusions

Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.     

Priming theta-burst repetitive transcranial magnetic stimulation with low- and high-frequency stimulation

Repetitive transcranial magnetic stimulation (rTMS) can be used to study metaplasticity in human motor cortex. The term metaplasticity describes a phenomenon where the prior synaptic history of a pathway can affect the subsequent induction of long-term potentiation or depression. In the current study, we investigated metaplasticity in human motor cortex with the use of inhibitory continuous theta-burst stimulation (cTBS). cTBS involves short bursts of high frequency (50 Hz) rTMS applied every 200 ms for 40 s. In the first series of experiments, cTBS was primed with 10 min of intermittent 2 or 6 Hz rTMS. Subjects (n = 20) received priming stimulation at 70% of active motor threshold or 90% of resting motor threshold. In another series of experiments, cTBS was primed with excitatory intermittent theta-burst stimulation (iTBS). iTBS involves a 2 s train of theta-burst stimulation delivered every 10 s for 190 s. Stimuli were delivered over the first dorsal interosseus motor area.. The effect of cTBS alone and primed cTBS on motor cortical excitability was investigated by recording motor-evoked potentials (MEP) in the first dorsal interosseus following single-pulse TMS. MEP area in the cTBS alone condition was not significantly different from cTBS primed with 2 or 6 Hz rTMS. However, priming cTBS with iTBS suppressed MEP area to a greater extent than in cTBS alone. Our results provide further evidence of metaplasticity in human motor cortex when appropriate priming protocols are employed.