Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson’s disease

Motor cortex excitability was assessed in 12 patients with Parkinson’s disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated (“ON”) and when immobile after medication withdrawal (“OFF”). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in “ON” and “OFF” states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either “ON” or “OFF” states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.     

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.     

Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease and dyskinesia

IntroductionLevodopa-induced dyskinesia in patients with Parkinson's disease (PD) has been shown to be associated with an abnormal plasticity in the motor cortex. We investigated whether changes in the excitability of inhibitory and excitatory motor circuits could underlie maladaptive mechanisms associated with dyskinesia.MethodsUsing single and paired transcranial magnetic stimulation (TMS), we studied motor threshold, silent period (SP) duration, intracortical facilitation (ICF), short intracortical inhibition (SICI) and low- and high-intensity long intracortical inhibition (LICI) in 10 dyskinetic and 10 non-dyskinetic patients, matched for disease and treatment duration, before (OFF state) and after (ON state) levodopa, and in 10 healthy controls.ResultsIn the OFF state, the two groups of patients showed similar motor cortex excitability with a reduced SICI compared to controls. LICI was weaker and increasing stimulation intensity had a lower effect on SP duration in dyskinetic patients than in controls. In dyskinetic patients, in contrast to non-dyskinetic patients, levodopa failed to increase SICI and SP duration, and potentiated to a lesser extent the effect of increasing the stimulation intensity on LICI. Although levodopa improved motor symptoms to a similar extent in both dyskinetic and non-dyskinetic patients, it failed to activate effectively the excitability of the inhibitory systems in dyskinetic patients.DiscussionThese findings suggest that dyskinesia is associated with an abnormal effect of levodopa on cortical motor inhibitory circuits.     

Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson's disease

BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found abnormalities in several excitatory and inhibitory circuits in the motor cortex in PD. These include motor evoked potential (MEP) recruitment curve, silent period duration (SP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI). METHODS: The authors studied the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on these circuits in 12 patients with PD treated with STN DBS. Data from nine patients who completed the study were analyzed. Patients remained on their usual medications. The stimulators were set at the optimal parameters (ON), half the optimal amplitude (HALF), and switched off (OFF) in random order. RESULTS: The Unified PD Rating Scale motor scores were significantly lower in the ON compared to the HALF and OFF conditions. Resting SICI, studied with paired-pulse TMS at interstimulus interval of 2 ms, was reduced in the OFF and HALF conditions compared to normal subjects. STN stimulation restored SICI to normal levels. STN stimulation had no effect on motor threshold, MEP recruitment curve, SP, active SICI, ICF, and LICI. CONCLUSIONS: Although restoration of short-interval intracortical inhibition by STN stimulation is similar to the effects of dopaminergic drugs, it has no effect on silent period duration and long-interval intracortical inhibition, which are also influenced by dopaminergic drugs. A previous study found that internal globus pallidus (GPi) stimulation reduced SP but did not change SICI. Thus, GPi and STN stimulation may affect different circuits in the motor cortex.     

Stimulus-response properties of motor system in patients with cerebellar ataxia.

OBJECTIVE: The aim of the study was to examine the stimulus-response properties of the excitatory and inhibitory components of corticospinal projections at rest and during voluntary contraction in cerebellar patients. METHODS: We investigated motor evoked potential (MEP) and cortical silent period recruitment curves in response to increasing intensities of transcranial magnetic stimulation in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched controls. The transcranial magnetic stimulation intensity was increased from 90 to 180% of the resting motor threshold. MEP recruitment curves were recorded at rest and during voluntary contraction in the right abductor pollicis brevis muscle. RESULTS: No statistical differences were found between patients and controls in MEP recruitment curves in either the resting or active condition. A significant difference was found between patients and controls in the cortical silent period threshold (patients: 33.2+/-3.4% of maximal stimulator output; controls 39.4+/-3.2%; P=0.01) and recruitment curve, the duration of the cortical silent period being longer in patients at transcranial magnetic stimulation intensities ranging from 90 to 130% of the resting motor threshold (patients: 135-191 ms; controls: 53-158 ms). No changes were found in the silent period evoked by peripheral nerve stimulation. CONCLUSIONS: Inhibitory components of corticospinal projections were recruited with a lower threshold in patients. No abnormalities were found in the recruitment of the excitatory networks. Our data show a prevalence of inhibitory phenomena in the motor cortex of cerebellar patients. These findings would appear to be specific to cerebellar diseases and are the opposite of those previously documented in movement disorders such as dystonia and Parkinson's disease. Our results suggest that the cerebellum and the basal ganglia may counteract each other in modulating the level of motor system excitability.     

Analysis of stimuli triggering attacks of paroxysmal dystonia induced by exertion

In a patient with a familial form of paroxysmal exertion induced dyskinesia (PED), the efficacy of different stimuli and manoeuvres in triggering dystonic attacks in the arm was studied. As a new approach, transcranial magnetic stimulation (TMS) of the motor cortex was used to trigger motor paroxysms and to monitor cortical excitability during attacks. Motor paroxysms could be provoked by muscle vibration, passive movements, TMS, magnetic stimulation of the brachial plexus, and electrical nerve stimulation. Sham stimulation over the motor cortex and thermal and tactile cutaneous stimuli were ineffective in triggering attacks. It is concluded that dystonic attacks are triggered by proprioceptive afferents rather than cutaneous stimuli or the descending motor command itself. Outside the attacks, motor cortical excitatory and inhibitory neuronal mechanisms as assessed by TMS (response threshold and amplitudes, duration of the contralateral and ipsilateral silent period, corticocortical inhibition, and facilitation) were normal, which underlines the paroxysmal character of the disorder.     

Modulation of motor activity by cutaneous input: inhibition of the magnetic motor evoked potential by digital electrical stimulation

We examined the inhibitory effect of a brief train of digital (D2) electrical stimuli at 4 times perception threshold on transcranial magnetic motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles ipsilateral to the side of D2 stimulation. We compared this to the inhibitory effect of ipsilateral D2 stimulation on averaged rectified EMG recorded at 10% maximum voluntary contraction and on F-responses and H-reflexes recorded from these same muscles. We also compared MEPs recorded following D2 stimulation just above perception threshold to MEPs following higher intensity D2 stimulation. As well, we assessed the effect of preceding D2 stimulation on MEPs recorded from a relaxed versus tonically contracted hand muscle. D2 stimulation elicited a triphasic response of modest MEP facilitation followed by inhibition and further facilitation. The duration and onset of MEP inhibition correlated with those of the initial period of rectified EMG inhibition, however, the magnitude of MEP inhibition was generally less than the magnitude of EMG inhibition, consistent with a greater inhibitory effect of digital afferents on smaller motor neurons. MEN were not facilitated during the rebound of EMG activity (the E2 period) that usually followed the initial period of EMG inhibition (I1 period). The behavior of H-reflexes and F-responses following ipsilateral D2 stimulation suggested that inhibition of both EMG and MEPs is not mediated via presynaptic inhibition of la afferents, and that inhibition is augmented by descending rather than segmental input to spinal motor neurons. Tonic contraction of the target muscle during D2 stimulation decreased the inhibitory effect of the preceding digital stimulus possibly due to recruitment of larger spinal motor neurons less likely to be inhibited by cutaneous input.     

The silent period threshold as a measure of corticospinal inhibition.

Corticomotor threshold is a clinically useful concept for defining motor cortex excitability using transcranial magnetic stimulation. Although the silent period duration can be a quantitative measure of corticospinal inhibitory function, its threshold value has not been formally determined. The authors studied 20 right-handed normal subjects and found that silent period threshold was a reproducible parameter that did not vary with age and sex. Its value was significantly lower with left-sided transcranial magnetic stimulation and right-hand recordings. The silent period threshold may be a novel parameter useful for future studies of cortical inhibitory function.     

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.     

A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia

It has been proposed that inhibitory deficits play a crucial role in the pathophysiological process of schizophrenia as suggested by post-mortem, neuropsychological and neurophysiological evidence. We hypothesised that patients with schizophrenia would demonstrate abnormalities of cortical inhibition in the motor cortex with single and paired pulse transcranial magnetic stimulation (TMS). Patients with DSM-IV schizophrenia (n=22) and normal volunteers (n=21) participated in the study. Electromyographic recordings from the abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the contra-lateral motor cortex. The threshold intensity to produce a motor response, the size of the motor evoked potential, the duration of the silent period, and the cortical inhibition and facilitation to paired pulse TMS were measured. The patient group demonstrated a reduction in length of the silent period and a reduction in cortical inhibition with paired stimuli. No changes were found in motor threshold, motor evoked potential size, or cortical facilitation. The study demonstrated deficits of cortical inhibition in the motor cortex of patients with schizophrenia. These deficits appear to be of cortical origin. Their relationship to dysfunction in other cortical networks requires further elucidation.     

Effects of antiepileptic drugs on motor cortex excitability in humans: A transcranial magnetic stimulation study

The effect of a single oral dose of various antiepileptic drugs on the excitability of the motor system was studied in healthy volunteers by means of transcranial magnetic stimulation. Motor threshold, duration of the cortical silent period, and intracortical excitability after double-shock transcranial stimulation were tested before and at defined intervals after drug intake. Antiepileptic drugs that support the action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold. Gabapentin, whose mechanism of action has not yet been unequivocally identified, showed a similar profile. By contrast, sodium and calcium channel blockers without considerable neurotransmitter properties (carbamazepine, lamotrigine, losigamone) elevated motor threshold but did not change intracortical excitability. The cortical silent period was lengthened by gabapentin and carbamazepine. Changes in peripheral motor excitability (maximum M wave, peripheral silent period) were not observed. We conclude that the changes in intracortical excitability are caused by GABA-controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability. Transcranial magnetic stimulation may be a promising noninvasive approach to study the selective effects of antiepileptic drugs on brain function.     

Intracranial inhibitory mechanisms in clinically diagnosed corticobasal degeneration: a study of a silent period followed by transcranial magnetic stimulation]

A 52-year-old man with clinically diagnosed corticobasal degeneration (CBD) who developed the asymmetric akinetic-rigid syndrome was studied by means of transcranial magnetic stimulation (TMS) after an interval of two years. TMS of the motor cortex during tonic muscle contraction causes a silent period immediately after a motor evoked potential in an electromyogram. This silent period is considered to reflect activity of an intracortical inhibitory mechanism. In this patient, the motor symptoms started from the left half of the body and spread to the right. The major neurological findings were dystonia, rigidity, clumsiness, and hyperreflexia. The involuntary contraction of the muscles, which was unrelated to voluntary movement, seemed to be responsible for his signs and symptoms. There was laterality of the threshold intensity and the duration of the silent period after a motor evoked potential; the threshold was higher and the duration was shorter on the affected side. Also, we found that the threshold increased and the duration decreased as his motor dysfunction progressed, which has not been reported before. A comparison of the clinical symptoms and the results of TMS in this case together with previous TMS data on CBD suggests that a disorder of the intracortical inhibitory mechanism is closely related to the movement impairment in CBD.     

Corticospinal physiology in patients with Prader-Willi syndrome: a transcranial magnetic stimulation study

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic developmental disorder, mostly caused by a deletion on the paternal chromosome 15 or by a maternal uniparental disomy 15. Some PWS clinical and neurochemical features suggest an involvement of the corticospinal motor structures. OBJECTIVE: To explore the corticospinal physiology of PWS by transcranial magnetic stimulation. SETTING: A community-based hospital. METHODS: We studied motor evoked potentials in the first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured the following variables: relaxed motor threshold, central motor conduction time, duration of the central silent period, and short-interval intracortical inhibition and facilitation. We also recorded F waves in the first dorsal interosseous muscle. We had 11 normal controls. RESULTS: In the whole PWS group, motor threshold was higher as compared with controls (P<.05). The central motor conduction time, central silent period, and F waves were normal. Intracortical facilitation was reduced significantly (P<.001). Patients with PWS and a deletion had a weaker intracortical inhibition as compared with patients with PWS and a uniparental disomy (P<.05). CONCLUSIONS: Transcranial magnetic stimulation changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect.     

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 418–424, 1997.     

Effects of internal globus pallidus stimulation on motor cortex excitability

BACKGROUND: Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD. METHODS: The physiologic effects of internal globus pallidus (GPi) stimulation in seven patients with PD and seven age-matched healthy volunteers were studied. The stimulators were set at the optimal parameters (ON), at half the optimal amplitude (Half-Amp), or switched off (OFF) in random order. Patients were taking their usual medications. Magnetic stimulation was applied to the motor cortex, and motor evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous muscle. Several excitatory and inhibitory pathways that have been found to be abnormal in PD were tested. RESULTS: The motor threshold (MT), MEP recruitment curve (stimulus intensities from 100 to 150% of MT), short and long interval intracortical inhibition, and intracortical facilitation were similar in the three stimulator conditions tested both at rest and during voluntary contraction. The silent period (SP) was longer in the OFF and Half-Amp conditions than in normal control subjects. In the stimulator ON condition, the SP was significantly reduced compared with the OFF condition and became similar to that in normal control subjects. CONCLUSIONS: GPi stimulation while on dopaminergic medications reduced the SP following magnetic stimulation but did not change corticospinal excitability or other measures of intracortical inhibition and facilitation. The reduction of SP may be related to the antidyskinetic and levodopa-blocking effects of ventral GPi stimulation.     

Inhibitory phenomena in individual motor units induced by transcranial magnetic stimulation

It is well known that a silent period (SP) can be observed in voluntary tonic EMG activity starting directly after the initial early response when magnetic stimuli are delivered through the skull over the contralateral primary motor cortex. It is, however, unknown as to how an individual motoneurone (MN) contributes to the SP observed in the surface EMG. The present investigation was conducted to investigate inhibitory phenomena at the level of individual motor units. It demonstrates that the duration of the SP in single motor units is inhomogeneously distributed within the pool of active MNs. At various stimulation strengths, SP durations in single motor units can be similar or longer when compared to that observable in surface EMG records. In some motor units, which show low thresholds for early excitation and appearance of the SP, durations of SP can exceed 1000 msec. The length of suppression of spontaneous MN firing is maximal at stimulus intensities a little higher than those required for an early excitatory response. Although in general thresholds for early excitation and appearance of SPs are similar, at threshold stimulation in a number of trials inhibitory effects on the firing of voluntarily activated motoneurones were present, even in the absence of early excitations. This proves the independent nature of inhibitory as opposed to excitatory effects induced by transcranial magnetic stimulation. An SP in the absence of early excitation underlines its cortical origin. Inhibition and excitation of single MNs were maximal over the same small scalp area. We suggest that cortical inhibitory control plays an important role in the organization of natural movements.     

The silent period induced by transcranial magnetic stimulation in muscles supplied by cranial nerves: normal data and changes in patients.

The silent period induced by transcranial magnetic stimulation of the sensorimotor cortex (Magstim 200, figure of eight coil, loop diameter 7 cm) in active muscles supplied by cranial nerves (mentalis, sternocleidomastoid, and genioglossus) was studied in 14 control subjects and nine patients with localised lesions of the sensorimotor cortex. In the patients, measurements of the silent period were also made in the first dorsal interosseus and tibialis anterior muscles. In the controls, there was a silent period in contralateral as well as ipsilateral cranial muscle and the duration of the silent period increased with increasing stimulus intensities. The mean duration of the silent period was around 140 ms in contralateral mentalis muscle and around 90 ms in contralateral sternocleidomastoid muscle at 1.2 x threshold stimulation strengths. Whereas the duration of the silent period in ipsilateral mentalis muscle was shorter than on the contralateral side it was similar on both sides in sternocleidomastoid muscle. In patients with focal lesions of the face associated primary motor cortex and corresponding central facial paresis, the silent period in mentalis muscle was shortened whereas it was unchanged or prolonged in limb muscles (first dorsal interosseus, tibialis anterior) with stimulation over the affected hemisphere. By contrast, in a patient with a lesion within the parietal cortex, the silent period in mentalis muscle was prolonged with stimulation of the affected side.     

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.

OBJECTIVE: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755-64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. METHODS: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. RESULTS: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. CONCLUSIONS: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.     

Covariation of corticospinal efficiency and silent period in motoneuron diseases

For a better understanding of the changes affecting the cortically induced silent period (SP) in motoneuron disease, the excitatory and inhibitory effects of transcranial magnetic stimulation were explored repeatedly in 8 patients with amyotrophic lateral sclerosis (ALS), 3 patients with Kennedy's disease (KD), and 10 healthy subjects. In KD, the background electromyogram (EMG) and the motor evoked potential (MEP) area were both enhanced. However, neither the corticospinal efficiency (MEP gain, the ratio between MEP and background EMG) nor the duration of the SP differed from healthy subjects. In ALS patients, the MEP gain and the SP duration decreased conspicuously with time. We conclude that use of the MEP gain improves detection of corticospinal dysfunction in ALS patients. Part of the SP shortening in ALS seems to reflect the reduced activation of cortical or spinal inhibitory networks by the abnormal corticospinal pathway.     

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.