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We previously reported a new quantitative analysis of single-channel surface electromyography (EMG), the "clustering index method" (CI method), in the tibialis anterior muscle, which achieved sufficiently good sensitivity to detect neurogenic or myogenic abnormalities. The window width is a fundamental parameter of the CI method, and was arbitrarily set at 15 ms in that study. In this study, we searched for the most appropriate window width using expanded patient data. The data from our previous study were reanalyzed, and new patients were enrolled. Window width in the CI method was changed from 5 to 27.5 ms with a step of 2.5 ms. For each window width, Z-score values of individual subjects were calculated and the diagnostic yield was investigated. We enrolled 67 controls, 29 subjects with neurogenic disorders, and 39 with myogenic disorders. When the window width was set at 22.5 ms, the highest sensitivity was achieved both for neurogenic (97%) and myogenic (72%) disorders, with a specificity of 97%. Seven of 10 patients with inclusion body myositis were also abnormal. Reliable results were obtained by collecting 15 epochs per subject. There are two conflicting effects that appear to be best balanced at a window width of 22.5 ms: a wider width decreases the chance that a motor unit potential (MUP) is divided into two adjacent windows, and a narrower width reduces the possibility that an MUP firing at a low-frequency is counted twice by the differential sequences. CI is promising as a non-invasive method to diagnose neuromuscular disorders.

INTRODUCTION Needle electromyography (EMG) has been an important diagnostic tool, although discomfort may limit its use in some children. We investigated the diagnostic utility of the clustering index (CI) method, a quantitative analysis for surface EMG (SEMG), in children. METHODS SEMG was recorded from the tibialis anterior muscle. Discriminant analysis between patients with neurogenic disorders and patients with myopathy was performed for whole epochs by using the CI and area values. RESULTS Forty-five children (29 with myopathy, 16 with neurogenic disorders; age 9 ± 3.9 years) were enrolled. The mean discriminant function value of the neurogenic group was 0.58 ± 0.88 (-0.48-2.30), whereas that of the myopathic group was -0.55 ± 0.70 (-2.38-0.68). When the cutoff value was set at the limit of the other group, 17 of 29 children with myopathy and 7 of 16 children with neurogenic disorders were correctly classified. DISCUSSION The CI method can be a useful noninvasive diagnostic tool in children with neuromuscular disorders. Muscle Nerve 58:824-827, 2018.

A 70-year-old man, a urinary retention of unknown origin from 10 years ago, decreased cognitive function from 4 years ago, vision impairment advanced a year ago. Brain MRI with DWI showed high intensity erea in the cortico-medullary junction. We diagnosed as intranuclear inclusion body disease (NIID) because of p62-positive intranuclear inclusion bodies by skin biopsy. Electroretinogram revealed amplitude reduction in the cone response superiority. Nerve conduction test showed mild conduction velocity reduction. Furthermore, in the somatosensory evoked potential of the lower limb, latency of the first cortical component was prolonged. These electrophysiological abnormalities were considered to be associated with the pathological features of NIID.

ObjectivesMultiple system atrophy (MSA) is a refractory neurodegenerative disease, but novel treatments are anticipated. An accurate natural history of MSA is important for clinical trials, but is insufficient. This regional registry was launched to complement clinical information on MSA.SettingPatient recruitment started in November 2014 and is ongoing at the time of submission. The number of participating facilities was 66. Postal surveys were sent to medical facilities and patients with MSA in Hokkaido, Japan.ParticipantsAfter obtaining written consent from 196 participants, 184 overview surveys and 115 detailed surveys were conducted.Primary and secondary outcome measuresAn overview survey evaluated conformity to diagnostic criteria and a detailed survey implemented an annual assessment based on the Unified Multiple System Atrophy Rating Scale (UMSARS).ResultsAt the time of registration, 58.2% of patients were diagnosed with cerebellar symptoms predominant type MSA (MSA-C) and 29.9% were diagnosed with parkinsonism predominant type MSA (MSA-P). UMSARS Part Ⅳ score of 4 or 5 accounted for 53.8% of participants. The higher the UMSARS Part Ⅳ score, the higher the proportion of MSA-P. At baseline, levodopa was used by 69 patients (37.5%) and the average levodopa dose was 406.7 mg/day. The frequency of levodopa use increased over time. Eleven cases changed from MSA-C to MSA-P during the study, but the opposite was not observed. Information about survival and causes of death was collected on 54 cases. Half of deaths were respiratory-related. Sudden death was recorded even in the group with UMSARS Part Ⅳ score of 1.ConclusionsThis study is the first large-scale prospective MSA cohort study in Asia. MSA-C was dominant, but the use of antiparkinsonian drugs increased over the study period. Changes from MSA-C to MSA-P occurred, but not vice versa.

Needle electromyography (EMG) has been an important diagnostic tool, although discomfort may limit its use in some children. We investigated the diagnostic utility of the clustering index (CI) method, a quantitative analysis for surface EMG (SEMG), in children.SEMG was recorded from the tibialis anterior muscle. Discriminant analysis between patients with neurogenic disorders and patients with myopathy was performed for whole epochs by using the CI and area values.Forty-five children (29 with myopathy, 16 with neurogenic disorders; age 9 ± 3.9 years) were enrolled. The mean discriminant function value of the neurogenic group was 0.58 ± 0.88 (-0.48-2.30), whereas that of the myopathic group was -0.55 ± 0.70 (-2.38-0.68). When the cutoff value was set at the limit of the other group, 17 of 29 children with myopathy and 7 of 16 children with neurogenic disorders were correctly classified.The CI method can be a useful noninvasive diagnostic tool in children with neuromuscular disorders. Muscle Nerve 58:824-827, 2018.

Introduction: A reliable electrophysiological marker for clinical trials is increasingly needed in spinal and bulbar muscular atrophy (SBMA). We previously developed a quantitative analysis method for surface electromyography (SEMG), the clustering index (CI) method. Our purpose was to test the utility of the CI method for evaluating lower motor neuron involvement in SBMA patients. Methods: Subjects included 29 SBMA patients and 27 healthy controls. The recording electrode was placed over the abductor digiti minimi (ADM) muscle with a proximal reference. The Z-score, based on the CI method, was compared with compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE), with regard to sensitivity. Results: The Z-scores of the CI method, CMAP amplitude, and MUNE were abnormal in 100%, 72%, and 93% of the patients, respectively. Interrater reliability of the CI method was sufficiently high. Conclusion: The CI method is promising as a non-invasive electrophysiological marker in SBMA. Muscle Nerve, 2011

Objective To establish a non-invasive and quantitative analysis method using single-channel surface EMG (SEMG) for diagnosing neurogenic and myopathic changes. Methods The subjects consisted of 66 healthy controls, 12 patients with neurogenic diseases, and 18 patients with myopathic diseases. The tibialis anterior muscle was examined using a belly to the adjacent bone lead. From each subject, 20–40 signals of 1s length were collected of various strengths. A new parameter, the "Clustering Index (CI)", was developed to quantify the uneven distribution of the SEMG signal, and was plotted against the SEMG area. The results were expressed as the Z -score of each subject calculated using linear regression from the normative data. Results When ±2.5 was used as the cut-off value of the Z -score, the specificity was 95%, whereas the sensitivity was 92% (11/12) and 61% (11/18) for the neurogenic and myopathic patients, respectively. There was no overlap of the Z -score values between the neurogenic and myopathic groups. Conclusions The CI method achieved a reasonably high diagnostic yield in detecting neurogenic or myopathic changes. Significance This is a new simple and quantitative analysis method using SEMG with good reproducibility, and is promising as a non-invasive complement to needle EMG.

Objective To determine the efficacy and safety of unilateral deep brain stimulation on the posterior subthalamic white matter, including the zona incerta (ZI) and the prelemniscal radiation (PRL), for tremor-dominant parkinsonian patients and to determine the exact location of electrodes that were most effective. Methods Eight parkinsonian patients with severe resting tremor underwent unilateral stimulation of the ZI/PRL by use of stereotactic guidance. Electrophysiological targeting was obtained by macrostimulation and by somatosensory evoked potentials recorded directly through a quadripolar deep brain stimulation lead. Postoperative computed tomographic scans and magnetic resonance images were performed to confirm anatomic location of the electrode. Parkinsonian motor disabilities were evaluated by use of the Unified Parkinson's Disease Rating Scale in the medication-off state before surgery and every 6 months after electrode implantations. Results The mean location of the clinically effective contacts was in the posterior subthalamic white matter, including the ZI and the PRL (mean, 5.6 +/- 1.2 mm posterior to the midcommissural point, 3.2 +/- 1.1 mm inferior to the anterior commissure-posterior commissure line, and 10.5 +/- 1.2 mm lateral to the midline). At 24 months after operation, ZI/PRL stimulation resulted in significant improvement in mean Unified Parkinson's Disease Rating Scale motor score by 44.3%, contralateral tremor by 78.3%, contralateral rigidity by 92.7%, and contralateral akinesia by 65.7% above the "off-stimulation" scores. Handwriting, posture, and gait were also improved. There were no or only mild adverse events. Conclusion Unilateral ZI/PRL stimulation is a reliable and long-term therapeutic modality and can be considered another surgical target for the treatment of tremor-dominant Parkinson's disease.

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45° steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.

Objective : To study the effect of a loud auditory stimulus on the excitability of the human motor cortex. Methods : Ten normal volunteers participated in this study. The size of responses to transcranial magnetic or electrical cortical stimulation (TMS or TES) given at different times (ISIs) after a loud sound were compared with those to TMS or TES alone (control response). Different intensities and durations of sound were used at several intertrial intervals (ITIs). In addition, we examined how the presence of a preceding click modulated the effect of a loud sound (prepulse inhibition). The incidence of startle response evoked by various stimuli was also studied. Results : A loud auditory stimulus suppressed EMG responses to TMS when it preceded the magnetic stimulus by 30–60 ms, whereas it did not affect responses to TES. This suggests that the suppression occurred at a cortical level. Significant suppression was evoked only when the sound was louder than 80 dB and longer than 50 ms in duration. Such stimuli frequently elicited a startle response when given alone. The effect was not evoked if the ITI was 5 s, but was evoked when it was longer than 20 s. A preceding click reduced the suppression elicited by loud sounds. Conclusions : Auditory stimuli that produced the greatest effect on responses to TMS had the same characteristics as those which yielded the most consistent auditory startle. We suggest that modulation of cortical excitability occurs in parallel with the auditory startle and both may arise from the same region of the brain-stem.

Air-puff stimulation applied to a fingertip is known to exert a location-specific facilitatory effect on the size of the motor evoked potentials elicited in hand muscles by transcranial magnetic stimulation. In order to clarify its nature and the pathway responsible for its generation, we studied 27 patients with discrete lesions in the brain (16, 9 and 2 patients with lesions in the cerebral cortex, thalamus and brainstem, respectively). Facilitation was absent in patients with lesions affecting the primary sensorimotor area, whereas it was preserved in patients with cortical lesions that spared this area. Facilitation was abolished with thalamic lesions that totally destroyed the nucleus ventralis posterolateralis (VPL), but was preserved with lesions that at least partly spared it. Lesions of the spinothalamic tract did not impair facilitation. The size of the N20-P25 component of the somatosensory evoked potential showed a mild correlation with the amount of facilitation. The facilitation is mainly mediated by sensory inputs that ascend the dorsal column and reach the cortex through VPL. These are fed into the primary motor area via the primary sensory area, especially its anterior portion, corresponding to Brodmann areas 3 and 1 (possibly also area 2), without involving other cortical regions. The spinothalamic tract and direct thalamic inputs into the motor cortex do not contribute much to this effect. Some patients could generate voluntary movements despite the absence of the facilitatory effect. The present method will enable us to investigate in humans the function of one of the somatotopically organized sensory feedback input pathways into the motor cortex, and will be useful in monitoring ongoing finger movements during object manipulation.

Intracortical inhibition of the motor cortex was investigated using a paired pulse magnetic stimulation method in 14 patients with chorea caused by various aetiologies (six patients with Huntington's disease, one with chorea acanthocytosis, a patient with systemic lupus erythematosus with a vascular lesion in the caudate, three with senile chorea and three with chorea of unknown aetiology). The time course and amount of inhibition was the same in the patients as in normal subjects, suggesting that the inhibitory mechanisms of the motor cortex studied with this method are intact in chorea. This is in striking contrast with the abnormal inhibition seen in patients with Parkinson's disease or focal hand dystonia, or those with a lesion in the putamen or globus pallidus. It is concluded that the pathophysiological mechanisms responsible for chorea are different from those producing other involuntary movements.

Aim : A high-frequency oscillation in the range of 600–900 Hz has been shown to be a component of the somatosensory evoked potential (SEP) in humans. In the present communication, we studied these oscillation potentials in two neurological disorders. Subjects and methods : Subjects were 20 healthy volunteers, 17 patients with Parkinson's disease (PD) and 3 with myoclonus epilepsy (ME). Median nerve SEPs were recorded using filters set at 0.5 and 3000 Hz. Several peaks of oscillation were obtained by digitally filtering raw SEPs from 500 to 1000 Hz, and their amplitudes and onset latencies were measured. Results : In normal subjects, several oscillation potentials were observed at the latency of 0 to 8 ms after the onset of N20. In PD patients, the oscillation potentials at normal latencies were significantly larger than those of normal subjects. Moreover, in 7 of 17 PD patients, they were extremely enlarged (>mean±3 SD of normal values). In contrast, in patients with ME, abnormally enlarged oscillation potentials were seen at longer latencies (7–14 ms) in spite of normal-sized early oscillation potentials. Magnetoencephalographic analyses showed that any oscillation potentials originated from the primary sensory cortex. Conclusions : There are at least two mechanisms for producing the oscillation potentials of SEP. Those around N20 have some relation with the basal ganglia function and are enlarged in PD patients, the others around P25-N33 are enhanced in ME patients.

There have been few previous studies trying to evaluate neuromuscular disorders using surface electro myography (SEMG). The greatest obstacle to such an approach must be the difficulty in identifying individual motor unit potentials (MUPs) on the SEMG signal under voluntary contraction because of their dense overlap. We tried to solve this problem by reducing the overlap of MUPs using appropriate electrode setting, as well as by developing a new method of interference pattern analysis. The tibialis anterior muscle was examined in our first study. A new method to analyse SEMG signal, the Clustering Index (CI) method, achieved 100% and 61% sensitivities for neurogenic and myopathic patients, and 97% specificity for control subjects. In the second study, the abductor digiti minimi muscle was examined. Subjects were 29 spinal and bulbar muscular atrophy patients and 27 controls. The CI method was compared with the motor unit number estimation, and the amplitude of compound muscle action potential. As results, the CI method achieved the best sensitivity and among these three techniques. The CI method is a novel, simple, and quantitative analysis method without using any special equipments, and is promising as a non-invasive complement to needle EMG.

Anti-aquaporin-4 (AQP4) antibody is highly specific for neuromyelitis optica (NMO) and NMO spectrum disorder. Brainstem lesions sometimes show involvement in NMO and NMO spectrum disorder, and onset is usually diagnosed in young or middle-aged adults. Here, we report the case of an 87-year-old woman with recurrent brainstem lesions and subsequent severe longitudinally extensive cervical cord lesions who was found to be positive for anti-AQP4 antibody. In patients with recurrent brainstem lesions, even in the elderly and those with symptoms mimicking infarction, NMO spectrum disorder should be considered as a differential diagnosis.

Needle electromyography (EMG) of the tongue is traditionally used as a key to the diagnosis of amyotrophic lateral sclerosis (ALS), although relaxation of the tongue is often difficult to achieve. Recently, frequent abnormalities in the EMGs of the sternocleidomastoid (SCM) and upper trapezius muscles in ALS have been reported. To elucidate the diagnostic utility of these muscles we performed a multicenter prospective study to examine EMGs of the tongue (genioglossus), SCM, and trapezius in 104 ALS or suspected ALS patients. We also examined EMGs of the SCM and trapezius in 32 cervical spondylosis (CS) patients. We mainly evaluated fibrillation potentials/positive sharp waves (Fib/PSWs) and fasciculation potentials. Complete relaxation was achieved in 85% of ALS patients in the trapezius, but in only 6% of patients in the tongue. Fib/PSWs were observed in 8%, 13%, and 45% of ALS patients in the tongue, SCM, and trapezius, respectively, whereas fasciculation potentials were observed in 1%, 7%, and 39%, respectively. Abnormal spontaneous activity of any type was found in 9%, 17%, and 63% of patients, respectively. The high frequency of abnormal spontaneous activity in the trapezius was similar among the different diagnostic categories, and even 72% of clinically suspected ALS (progressive muscular atrophy) patients showed them in their trapezius. We did not observe Fib/PSWs or fasciculation potentials in any of our CS patients, thus these findings have excellent specificity. Tongue EMG added little utility over the clinical sign of tongue atrophy. Abnormal spontaneous activity in the trapezius would be more useful for the early diagnosis of ALS.

Object The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads. Methods Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism. Results Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 ± 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 ± 1. 3 mm posterior to the midcommissure point, 4.8 ± 1.2 mm inferior to the anterior commissure–posterior commissure line, and 9.7 ± 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive–negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 ± 1.1 msec and 16.4 ± 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus. Conclusions The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.

Tremor in the proximal arm muscle, trunk, or legs is often resistant to the standard stereotactic surgery of the thalamic ventrointermediate nucleus. We have performed deep brain stimulation (DBS) of the posterior subthalamic area for those intractable tremors. The white matter area between the red nucleus and the subthalamic nucleus was targeted on the T2-weighted MR-CT fused image. Inhibitory effect on the tremor was tested with macrostimulation. The somatosensory-evoked potential recorded through DBS contacts demonstrated characteristic biphasic pattern. Eight cases with severe essential tremor and 18 of tremor-dominant Parkinson disease were treated with unilateral DBS of the area including the zona incerta and the prelemniscal radiation (Zi/Raprl). Tremors including the proximal part have been well controlled for 24 months after the operation. The stimulation parameters have been almost stable during the follow-up period. There was no obvious adverse effect of stimulation. We conclude that Zi/Raprl-DBS is a safe and effective treatment on Parkinsonian and essential tremor.

Electrical stimulation over the cerebellum is known to transiently suppress the contralateral motor cortex in humans. However, projections from the cerebellar nuclei to the primary motor cortex are disynaptic excitatory pathways through the ventral thalamus. In the present investigation we studied facilitatory effects on the motor cortical excitability elicited by electrical stimulation over the cerebellum by recording surface electromyographic (EMG) responses from the first dorsal interosseous (FDI) muscle in nine normal volunteers. For primary motor cortical activation magnetic stimuli were given over the contralateral hand motor area with a figure-of-eight shaped coil with a current to preferentially elicit I3-waves (test stimulus). For cerebellar stimulation high-voltage electric stimuli were given with an anode on the ipsilateral mastoid process and a cathode over the contralateral process as previously described (conditioning stimulus). The effect of conditioning-test interstimulus intervals was investigated. Anodal cerebellar stimuli increased the size of EMG responses to magnetic cortical stimulation at an interstimulus interval of 3 ms. Reversing the current of conditioning stimulus abolished the facilitation. The same (anodal) conditioning stimuli did not affect electrically evoked cortical responses. Based on the effective polarity of the conditioning stimulus and the time course of facilitation we consider that this effect is due to motor cortical facilitation elicited by activation of the excitatory dentatothalamocortical pathway at the deep cerebellar nuclei or superior cerebellar peduncle. We conclude that the motor cortical facilitation is evoked by cerebellar stimulation in humans.

Object. Tremors, including its proximal component, are often refractory to standard thalamic surgery. In the 1960s the posterior part of the subthalamic white matter was reported to be a promising target in treating various forms of tremor, but was also found to be associated with adverse effects. Advances involving a less invasive method, that is, deep brain stimulation (DBS), has led to a reappraisal of this target. Methods. Eight patients with severe essential tremor involving the proximal arm were treated using unilateral stimulation of the posterior part of the subthalamic white matter. The tentative target was situated in the area lateral to the red nucleus and posteromedial to the subthalamic nucleus. Macrostimulation was used to find the optimal site to suppress tremor. Through a quadripolar DBS lead, somatosensory evoked potentials (SSEPs) were recorded. Improvement of tremor was evaluated based on a modified clinical tremor rating scale. Anatomical locations of all contacts were assessed using stereotactic guidance and represented on the Schaltenbrand—Wahren atlas. Conclusions. A characteristic diphasic pattern of SSEPs reaffirmed the electrophysiological endorsement of this target. Tremors, both proximal and distal, were remarkably improved in all patients. The rate of improvement, as indicated by the total tremor score, was a mean of 81%. Axial tremors in the legs and head were also improved. Most of the contacts associated with remarkable improvement were located in the posterior part of the subthalamic white matter (the zona incerta and prelemniscal radiation). Neither major complications nor neurological deterioration was observed. The authors concluded that DBS of the posterior part of the subthalamic white matter together with SSEP recording is a safe and effective method to ameliorate severe intractable tremors.

In order to elucidate the mechanisms underlying intracortical I-wave facilitation elicited by paired-pulse magnetic stimulation, we compared intracortical facilitation of I1-waves with that of I3-waves using single motor unit and surface electromyographic (EMG) recordings from the first dorsal interosseous muscle (FDI). We used a suprathreshold first stimulus (S1) and a subthreshold second stimulus (S2). In most experiments, both stimuli induced currents in the same direction. In others, S1 induced posteriorly directed currents and S2 induced anteriorly directed currents. When both stimuli induced anteriorly directed currents (I1-wave effects), an interstimulus interval (ISI) of 1.5 ms resulted in extra facilitation of the responses to S1 alone. The latency of this effect was equivalent to that of the I2-wave from S1. When S1 evoked posteriorly directed currents (I3-wave recruitment), facilitation occurred at a latency corresponding to the I3-wave from S1. This facilitation occurred at an ISI of 1.5 ms when both S1 and S2 flowed posteriorly, and at an ISI of approximately 3.5 ms when S1 was posteriorly and S2 was anteriorly directed. Based on these findings, we propose the following mechanisms for intracortical I-wave facilitation. When S1 and S2 induce currents in the same direction, facilitation is produced by summation between excitatory postsynaptic potentials (EPSPs) elicited by S1 and subliminal depolarization of interneurones elicited by S2 directly. When S1 and S2 induce currents in the opposite direction, facilitation is produced by the same mechanism as above or by temporal and spatial summation of EPSPs elicited by two successive stimuli at interneurones or corticospinal neurones of the motor cortex.

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.

The corpus callosum is involved in interhemispheric transfer of cognitive and sensory information. In anatomical studies on animals, callosal projection cells and terminal ramifications of their fibres were identified in the motor cortex (Jenny, 1979; Jones et al. 1979; Castman-Berrevoets et al. 1980), which indicates the presence of transcallosal outputs from and inputs to the motor cortex. The importance of transcallosal information for motor execution was also suggested in humans, for example interhemispheric facilitatory influences on the motor cortex in visuomotor tasks (Lassonde, 1986) and the gradual maturation of interhemispheric inhibition between the motor cortices in the two hemispheres during the development of hemispheric dominance (Thut et al. 1997). The transcallosal connection between the motor cortices has been studied in humans using transcranial stimulation. Transcallosally evoked potentials could be recorded from the motor cortex after electrical (Amassian & Cracco, 1987) or magnetic (Cracco et al. 1989) stimulation of the contralateral frontal cortex. Interhemispheric inhibitory connections between the motor cortices have also been observed (Ferbert et al. 1992; Meyer et al. 1995; Boroojerdi et al. 1996; Meyer et al. 1998). Ferbert et al. (1992) reported that magnetic conditioning stimuli over the motor cortex in one hemisphere reduced the size of responses to magnetic stimuli over the motor cortex in the other hemisphere. They considered that this effect was produced by interhemispheric inputs through the corpus callosum. They also described capricious interhemispheric facilitatory influences between the motor cortices in the two hemispheres. Ferbert et al. (1992) sometimes, but not always, observed the interhemispheric facilitation at shorter interstimulus intervals than those for transcallosal inhibition. In our previous report (Ugawa et al. 1993), weak facilitation was observed consistently when the conditioning and test stimuli were positioned strictly over the motor points in both hemispheres and their intensities were appropriately adjusted. Both the conditioning and test stimuli should have been just above the threshold for active muscles. Probably because this facilitatory effect on I1-waves was very weak, facilitation did not occur on responses larger than 0.2 mV (if the test stimulus was fixed at a slightly higher intensity) and this effect was masked by inhibition when using a higher intensity conditioning stimulus. In another report (Salerno & Georgesco, 1996), a facilitatory effect was evoked by a strong conditioning stimulus. In spite of these previous works, details of the facilitatory connection remain to be investigated. In the present paper, we tried to clarify the details of interhemispheric facilitation by studying transcallosal facilitatory effects on responses preferentially produced by I1-waves (indirect-waves: descending volleys produced by indirect activation of pyramidal tract neurones via presynaptic neurones), those produced by I3-waves and those elicited by D-waves (direct waves; descending volleys produced by direct activation of pyramidal tract neurones). From differences in the effects on different descending volleys (D-, I1- and I3-waves), we can speculate where facilitation occurs (at the cortex or spinal cord). We used a previously reported method (Sakai et al. 1997) which relies on the fact that the lowest threshold I-wave depends on the direction of currents induced in the brain by magnetic stimulation. Usually, anteriorly directed currents in the brain preferentially elicit I1-waves, whereas posteriorly directed currents elicit I3-waves.

Objective : To compare voluntary single fiber electromyography (v-SFEMG) and repetitive nerve stimulation (RNS) at the same extensor digitorum communis (EDC) muscle in myasthenia gravis (MG). Methods : We examined v-SFEMG and RNS successively on the same day in the same EDC muscle. We studied 45 examinations of both v-SFEMG and RNS in 29 patients suffering from MG, together with examinations of RNS in 30 control subjects. Results : Forty-one of 45 (91%) v-SFEMGs showed abnormal results, whereas only 18/45 (40%) RNSs showed an abnormal decrement. The percentage of decrement showed similar correlations with 3 v-SFEMG parameters: percentage of abnormal pairs, percentage of blocking pairs, and the mean MCD value. Examinations showing a significant decrement in RNS had at least 60%, and usually no less than 90%, abnormal pairs, and 10–80% blocking pairs. Some muscles without a decrement had up to 50% blocking pairs. Conclusions : These results suggest that the blocking phenomenon observed in v-SFEMG is not a direct counterpart of the decrement in RNS. This must be partly because fibers contributing to the decrement are continuously blocked during voluntary contraction, and partly, because smaller motor units explored by v-SFEMG are probably more abnormal in MG than larger motor units mainly contributing to a decrement. Both factors make v-SFEMG much more sensitive than RNS.

Objectives: To investigate whether the cortico–cortical inhibition originally reported for the human hand motor area is present in the motor cortex for sternocleidomastoid muscle (SCM) and to evaluate the amount of inhibition in spasmodic torticollis and essential tremor. Methods: Subjects were 14 normal healthy volunteers, 10 patients with spasmodic torticollis and 5 with essential tremor involving neck muscles. A paired-pulse magnetic stimulation was performed for the SCMs and first dorsal interosseous muscles (FDIs). Results: In normal subjects, a subthreshold magnetic conditioning stimulus suppressed responses to a suprathreshold magnetic test stimulus when their interval was 1–5 ms in SCM. This indicates that the similar cortico–cortical inhibitory mechanism is present in the motor cortex for SCM as in the hand motor area. In the patients with spasmodic torticollis, the cortico–cortical inhibitory effect was reduced or absent in SCM, but normal in the FDI. In contrast, in patients with essential tremor, normal cortico–cortical inhibition was seen in both the SCM and FDI. Conclusions: The cortico–cortical inhibitory mechanisms of the motor cortex for SCM can be studied by a paired-pulse magnetic stimulation method. Our result of reduced cortico–cortical inhibition in torticollis patients suggests abnormal excitability (hyperexcitable or disinhibited) of the motor cortex for SCM in spasmodic torticollis.