Paired Magnetic Stimuli Research Articles

Etiology and Recovery of Neuromuscular Fatigue after Simulated Soccer Match Play.

We profiled the etiology and recovery of neuromuscular fatigue after simulated soccer match play. Fifteen semiprofessional players completed a 90-min simulated soccer match. Before, immediately after, and at 24, 48, and 72 h, participants completed a battery of neuromuscular, physical, and perceptual tests. Perceived fatigue and muscle soreness were assessed via visual analog scales. Maximum voluntary contraction (MVC) and twitch responses to electrical (femoral nerve) and magnetic (motor cortex) stimulation during isometric knee extensor contractions and at rest were measured to assess central (voluntary activation) and peripheral (quadriceps potentiated twitch force, Qtw,pot) fatigue, and responses to single and paired magnetic stimuli were assessed to quantify corticospinal excitability and short intracortical inhibition, respectively. Countermovement jump, reactive strength index, and sprint performance were assessed to profile the recovery of physical function. Simulated match play elicited decrements in MVC that remained unresolved at 72 h (P = 0.01). Central fatigue was prominent immediately postexercise (-9% reduction in voluntary activation) and remained depressed at 48 h (-2%, P = 0.03). Qtw,pot declined by 14% postexercise, remained similarly depressed at 24 h, and had not fully recovered 72 h after (-5%, P = 0.01). Corticospinal excitability was reduced at 24 h (P = 0.047) only, and no change in short intracortical inhibition was observed. Measures of jump performance and self-reported fatigue followed a similar time course recovery to neuromuscular fatigue. Central processes contribute significantly to the neuromuscular fatigue experienced in the days after soccer match play, but the magnitude and slower recovery of peripheral fatigue indicates that it is the resolution of muscle function that primarily explains the recovery of neuromuscular fatigue after soccer match play.

Investigating TMS-EEG Indices of Long-Interval Intracortical Inhibition at Different Interstimulus Intervals.

Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes. This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP). In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI100) and 150 ms (LICI150), while TEPs were recorded using simultaneous high-definition EEG. Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced amplitude following LICI100 (P = 0.03) but not LICI150 (P = 0.3). In contrast, the N100 and P180 were significantly reduced by LICI at both intervals (all P-values < 0.05). In addition, topographical analyses suggested that the global change in P30, N40 and P180 differed between LICI conditions. These findings suggest that LICI100 and LICI150 reflect complex measurements of cortical inhibition with differential contributions from comparable circuits.

The modulation of motor cortex excitability during motor imagery depends on imagery quality

Motor imagery (MI) increases corticomotor excitability and modulates intracortical inhibition. This study aimed to relate these neurophysiological mechanisms to imagery quality. Twenty-three healthy adults participated. First, the ability to vividly and accurately imagine performing a finger-to-thumb opposition task was evaluated by calculating a MI index (MII) based on psychological, behavioural and psychophysiological measurements. These scores were used to distinguish good from poor imagers. Transcranial magnetic stimulation was then used to assess modulation of corticomotor excitability, short-interval intracortical inhibition (sICI) and short-interval intracortical facilitation (sICF). Participants imagined abduction of their right thumb paced by a 1-Hz metronome. Single and paired magnetic stimuli were delivered at rest, while listening to the metronome, and during or between imagined movements. Corticomotor excitability was facilitated in the right opponens pollicis for good and poor imagers during MI, and this was positively correlated to the MII score. Poor imagers also facilitated corticomotor excitability of the right abductor digiti minimi, which was not involved in the movement. No interactions were found with sICI and sICF for good imagers, whereas poor imagers recruited intracortical facilitation while imagining. Accurate MI performance was characterised by muscle-specific temporal modulation of corticomotor excitability.

Excitability changes at brainstem and cortical levels in blind subjects

Objectives This study was designed to search potential changes in trigemino-facial system in blind subjects by the use of relatively well-established electrophysiological methods. Excitability changes in the motor cortex were also investigated by transcranial magnetic stimulation studies (TMS) with the expectation of finding some abnormal interactions between the cortex and brainstem. Methods Twenty blind (BS) and 13 control subjects (CoS) were included in the study. Blink reflex and its recovery with paired electrical stimulation were studied at 150, 200, 300, 400 and 500 ms interstimulus intervals (ISI). Facial F waves elicited by buccal branch stimulation were recorded from nasalis muscles. Motor cortex excitability with recordings from left first dorsal interosseus muscle was studied by using magnetically elicited silent periods and paired magnetic stimuli, subthreshold conditioning and suprathreshold test, given at ISIs of 2, 3, 4, 10, 12, 15 and 20 ms. Results Blink reflex recovery was significantly reduced in BS group comparing to CoS at 400 and 500 ms ISIs. This difference between the groups was more prominent for the responses evoked by the initial stimulation side and faded away with stimulations on the contralateral side. Facial F wave amplitudes and F/M amplitude ratios were higher in BS group. In TMS studies, the early inhibitions at 2 and 4 ms were found to be significantly less in BS as compared to that of CoS. Conclusions The reduced blink reflex recovery and its fast restoration with continuing stimulation might be explained by conditioning and extinction processes which have been shown to be mainly carried out by cerebellar–brainstem pathways. Our TMS studies showed reduced intracortical inhibition in the motor cortices of BS cases and facial F wave studies revealed the possible effect of this altered excitability on the facial motor nuclei. Significance Firing probabilities of facial motor neurons in BS are probably determined by the equilibrium between the low-set excitability of blink reflex interneurons and the enhanced excitability brought on by the descending motor pathways.

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

To examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS). Twenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated. After MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation. We provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes. Present results prove the MG stimulation to be a promising tool in neurorehabilitation.

Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans

We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean +/- SE maximum O(2) uptake (Vo(2 max)) = 56.5 +/- 2.7 ml x kg(-1) x min(-1)] cycled at > or =90% Vo(2 max) to exhaustion in normoxia [NORM-EXH; inspired O(2) fraction (Fi(O(2))) = 0.21, arterial O(2) saturation (Sp(O(2))) = 93 +/- 1%] and hypoxia (HYPOX-EXH; Fi(O(2)) = 0.13, Sp(O(2)) = 76 +/- 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; Sp(O(2)) = 96 +/- 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10-100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (-39 +/- 4 vs. -24 +/- 3%, P < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 +/- 0.5 vs. 13.4 +/- 0.8 min, P < 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH (-34 +/- 4 vs. -39 +/- 4%, P > 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.

Visual Cortex Excitability in Migraine Evaluated by Single and Paired Magnetic Stimuli

To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.

Effect Of Severe Hypoxia On Endurance Capacity And Quadriceps Muscle Fatigue In Healthy Humans

Severe hypoxia elicits a significant decrease in whole body endurance capacity. It is unclear whether this decrease in endurance capacity is accompanied by an increase in the severity of exercise-induced locomotor muscle fatigue. PURPOSE To determine the effect of severe hypoxia on endurance capacity and quadriceps muscle fatigue. METHODS On separate occasions (order randomised), 9 male subjects (mean ± SEM VO2peak= 56.5 ± 2.7 ml/kg/min) cycled to exhaustion at > 90% VO2peak under conditions of normoxia (2peakFI,O2= 0.21; NORM-EXH) and acute hypoxia (2peakFI,O2= 0.13; HYPOX). The subjects also exercised in normoxia for a time equal to that achieved during hypoxia (NORM-CTRL). Quadriceps twitch force (Qtw), in response to supramaximal paired magnetic stimuli of the femoral nerve (1–100 Hz), was assessed pre- and up to 70 min post-exercise. RESULTS End-exercise measurements are contained in table.TableCONCLUSIONS Severe hypoxia affects performance during heavy-intensity exercise in part because of the direct effect of decreased systemic O transport on the force output of the limb locomotor muscles, shown by the reduced twitch force after hypoxia vs. normoxia at exercise iso-time. An additional effect of severe hypoxemia on exercise capacity was not dependent upon end-organ limb muscle fatigue, as implicated by the finding that the reduction in force output after hypoxic exercise to exhaustion was only about one-half that observed after exercise to exhaustion in normoxia. This comparison implies that reflex-induced inhibition of motor output to locomotor muscles may have occurred during exercise in severe hypoxia. Supported by NHLBI.

Modulation of corticospinal excitability and intracortical inhibition during motor imagery is task-dependent

Previous studies have clearly shown that motor imagery modulates corticospinal excitability. However, there is no clear evidence for the modulation of intracortical inhibition (ICI) during imagined task performance. The aim of this study was to use transcranial magnetic stimulation (TMS) to assess changes in corticospinal excitability and ICI during the imagined performance of two types of task. In Experiment 1, eight subjects performed phasic depression of a computer mouse button using the dominant index finger in time with a 1 Hz auditory metronome. Single and paired pulse magnetic stimuli were delivered at rest, and during the 'on' and 'off' phases of actual and imagined task performance. Motor evoked potentials (MEPs) were recorded from FDI and APB. In Experiment 2, eight subjects performed phasic isometric abduction of the dominant thumb in time with a 1 Hz auditory metronome. As before, single and paired pulse magnetic stimuli were delivered at rest, and during the 'on' and 'off' phases of actual and imagined task performance. In both experiments, the conditioning stimulus intensity was set to produce 50% inhibition at rest, to enable both increases and decreases in ICI during task performance to be detected. No significant temporal or spatial modulation of MEP amplitude or ICI was observed in Experiment 1. In contrast, MEP amplitude was significantly greater, and ICI significantly lower during the 'on' phase of imagined task performance in Experiment 2. These results are most likely related to the higher levels of target muscle activation required during actual task performance and the greater anatomical distance between target and control muscles in Experiment 2. These task characteristics may influence the observed degree of corticospinal excitability and ICI modulation.

Focal reduction of intracortical inhibition in the motor cortex by selective proprioceptive stimulation

The influence of proprioception on motorcortical excitability was assessed by muscle vibration (MV; 80 Hz, 0.5 mm amplitude) of the flexor carpi radialis muscle (FCR) and compared to voluntary contraction and relaxation conditions. Motor thresholds, motor-evoked potentials (MEPs) in response to single pulses of transcranial magnetic stimulation (TMS) and the intracortical inhibition (ICI) and facilitation (ICF) after paired magnetic stimuli were studied. A control experiment using TMS inducing posteriorly directed current was performed. MEPs were recorded simultaneously from the FCR, the extensor carpi radialis, the abductor pollicis brevis and the first dorsal interosseus. In the FCR, MV led to an increase of excitability shown by a decrease of motor threshold, a facilitation of MEPs in response to single-pulse TMS, a reduction of ICI and an increase of ICF. Since especially the ICI and ICF remain unchanged in other recorded muscles, this increase of excitability is specific for the vibrated muscle. With posteriorly directed current the ICI in the FCR was reduced as well, showing an involvement of later I-waves. We suggest that MV induces a focused motorcortical activation which relies on a reduced activity of intracortical inhibitory interneuronal circuits targeting selectively the motorcortical representation of the vibrated muscle.

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson's disease (PD). Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

Mechanisms of motor‐evoked potential facilitation following prolonged dual peripheral and central stimulation in humans

1. Repetitive electrical peripheral nerve or muscle stimulation can induce a lasting increase in the excitability of the corticomotor projection. By pairing peripheral stimulation with transcranial magnetic brain stimulation it is possible to shorten the duration of stimulation needed to induce this effect. This ability to induce excitability changes in the motor cortex may be of significance for the rehabilitation of brain-injured patients. The mechanisms responsible for the increases in excitability have not been investigated thoroughly. 2. Using two paired transcranial magnetic stimuli protocols we investigated the excitability of intracortical inhibitory and excitatory systems before and following a period of repetitive dual muscle and brain stimulation. The dual stimulation consisted of motor point stimulation of first dorsal interosseous (FDI; 10 Hz trains of 1 ms square waves for 500 ms) delivered at one train every 10 s, paired with single transcranial magnetic stimulation given 25 ms after the onset of the train. 3. Following 30 min of dual stimulation, motor-evoked potentials (MEPs) were significantly increased in amplitude. During this period of MEP facilitation there was no significant difference in the level of intracortical inhibition. There was, however, a significant increase in the intracortical facilitation demonstrated with paired magnetic stimuli. The increase in facilitation was seen only at short interstimulus intervals (0.8-2.0 ms). These intervals comprised a peak in the time course of facilitation, which is thought to reflect I wave interaction within the motor cortex. 4. The relevance of this finding to the MEP facilitation seen following dual peripheral and central stimulation is discussed.

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.

Intracortical excitatory and inhibitory phenomena to paired transcranial magnetic stimulation in healthy human subjects: differences between the right and left hemisphere

Intracortical inhibition (ICI) and facilitation (ICF) to paired magnetic stimuli reflect the activation of interneuronal circuits within the motor cortex. Intersubjects physiological variability of these phenomena, partly limits the usefulness of such method. Therefore, interhemispheric ICI/ICF differences might represent a more sensitive and less variable neurophysiological parameter to test the motor cortex excitability. Motor evoked potentials from the hand muscles were recorded in ten healthy subjects in a paired-pulse paradigm. Interstimulus intervals (ISIs) from 1 to 50 ms were used. The time course of ICI and ICF in the two hemispheres is consistent with minimal interhemispheric asymmetries. The interhemispheric differences of ICI and ICF could be a valuable neurophysiological marker for the diagnosis, prognosis and follow-up of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

Facilitation of rhythmic events in progressive myoclonus epilepsy: a transcranial magnetic stimulation study

Twelve subjects with progressive myoclonus epilepsy (PME) were studied with transcranial magnetic stimulation (TMS), using single and paired magnetic stimuli at different interstimulus intervals (ISIs), and polygraphic recording. Motor threshold (T) and silent period (SP) were normal. Paired TMS showed a loss of inhibition at 100–150 ms ISI and a marked facilitation at 50 ms ISI of conditioned motor evoked potential (MEP). Polygraphic analysis showed 20 Hz oscillatory activity over the sensorimotor area coupled to contralateral myoclonic jerks. These findings suggest a condition of increased supraspinal excitability and support the evidence of a cortical rhythm in the range of 20 Hz. No direct evidence exists that these findings are mediated by the same intracortical pathway. Furthermore, the normal SP and T suggest that the abnormal excitability is not a constant feature but is evident during rhythmic events.

Cortical excitability in patients with essential tremor.

We used transcranial magnetic stimulation in 10 patients with essential tremor and 8 matched healthy subjects. A round stimulating coil was placed over the vertex and electromyographic activity was recorded from the first dorsal interosseous muscle. Paired transcranial stimuli were delivered at interstimulus intervals of 3, 5, 20, 100, 150, and 200 ms. The intensity of the conditioning stimulus was 80% of motor threshold at short and 150% at long interstimulus intervals (ISIs). We also measured the silent period obtained after a single magnetic pulse delivered at 150% of motor threshold during a submaximal muscle contraction. Patients and controls had similar motor threshold and similar latencies. Paired magnetic stimuli given at short and long ISIs at rest, and during a voluntary muscle contraction, elicited similar responses in both groups. The silent period evoked by transcranial magnetic stimulation had a similar duration in patients with ET and controls. In conclusion, these findings suggest that patients with essential tremor have normal cortical motor area excitability.

Asymmetry of cortical excitability revealed by transcranial stimulation in a patient with focal motor epilepsy and cortical myoclonus

Motor cortex excitability was analyzed with transcranial stimulation in a patient with motor focal epilepsy and cortical myoclonus originating from the right motor cortex. The motor threshold to single transcranial magnetic shocks, but not to electric stimuli, was higher in the epileptic motor cortex than the normal left motor cortex. Single magnetic shocks elicited a short cortical silent period (50 ms) in the epileptic motor cortex. Paired magnetic stimuli also showed reduced cortico-cortical inhibition. These findings reveal an asymmetry in cortical excitability presumably due to impaired inhibition in the epileptic motor cortex

Alterations of motor cortical inhibition in patients with dystonia.

Cortical inhibitory mechanisms were investigated with the technique of paired transcranial magnetic stimulation in 10 patients with dystonia of the right arm: six patients had focal, task-specific dystonia (writer's cramp) and three had segmental and one had generalized dystonia. Paired stimuli were delivered in a conditioning-test design during slight voluntary activation of the target muscle, with subthreshold conditioning stimuli at short intervals (3-20 ms) and suprathreshold conditioning stimuli at long intervals (100-250 ms). The amount of inhibition at short interstimulus intervals did not differ significantly between patients and normal subjects. With long interstimulus intervals, patients showed more inhibition of the test response, which was significant at the 150-ms interval. The cortical silent period following a single suprathreshold magnetic stimulus was slightly shorter in patients. No significant difference was detected between the affected side and the unaffected side in patients with unilateral task-specific dystonia, neither in the duration of the silent period nor in the response to paired magnetic stimuli. These results indicate that the different types of motor cortical inhibition are produced by different inhibitory circuits. We propose that the alterations observed in patients with dystonia are the result of impaired feedback from the basal ganglia to motor cortical areas, with the ultimate effect of a flattening of the excitability curve of the cortical motoneuron pool during voluntary muscle activation.

Intracortical inhibition of lower limb motor-evoked potentials after paired transcranial magnetic stimulation.

The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33+/-5%). The test stimulus (67+/-2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1-15 ms were examined. Conditioned TA MEPs were significantly suppressed (P<0.01) at ISIs of less than 5 ms (relative amplitude from 20-50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P<0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34+/-6%, 61+/-5%, and 98+/-9% for conditioning intensities of 0.95, 0.90, and 0.85x active threshold, respectively (P<0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area.