Katsuyuki Machii

Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves.

1 In paired‐pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1‐5 ms) and facilitate them at long ISIs (8‐15 ms). 2 We made paired‐pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes. 3 In post‐stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves. 4 Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1‐20 ms, compatible with the duration of GABA‐mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus. 5 We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.

Interhemispheric facilitation of the hand motor area in humans

1 We investigated interhemispheric interactions between the human hand motor areas using transcranial cortical magnetic and electrical stimulation. 2 A magnetic test stimulus was applied over the motor cortex contralateral to the recorded muscle (test motor cortex), and an electrical or magnetic conditioning stimulus was applied over the ipsilateral hemisphere (conditioning motor cortex). We investigated the effects of the conditioning stimulus on responses to the test stimulus. 3 Two effects were elicited at different interstimulus intervals (ISIs): early facilitation (ISI = 4–5 ms) and late inhibition (ISI ≥ 11 ms). 4 The early facilitation was evoked by a magnetic or anodal electrical conditioning stimulus over the motor point in the conditioning hemisphere, which suggests that the conditioning stimulus for early facilitation directly activates corticospinal neurones. 5 The ISIs for early facilitation taken together with the time required for activation of corticospinal neurones by I3‐waves in the test hemisphere are compatible with the interhemispheric conduction time through the corpus callosum. Early facilitation was observed in responses to I3‐waves, but not in responses to D‐waves nor to I1‐waves. Based on these results, we conclude that early facilitation is mediated through the corpus callosum. 6 If the magnetic conditioning stimulus induced posteriorly directed currents, or if an anodal electrical conditioning stimulus was applied over a point 2 cm anterior to the motor point, then we observed late inhibition with no early facilitation. 7 Late inhibition was evoked in responses to both I1‐ and I3‐waves, but was not evoked in responses to D‐waves. The stronger the conditioning stimulus was, the greater was the amount of inhibition. These results are compatible with surround inhibition at the motor cortex.

Magnetic stimulation over the cerebellum in patients with ataxia

We studied 20 patients with ataxia caused by various disorders using magnetic stimulation over the cerebellum. Results were compared with normal values found for 12 normal volunteers. In normal subjects, a magnetic stimulus over the cerebellum reduced the size of responses evoked by magnetic cortical stimulation when it preceded cortical stimulus by 5, 6 and 7 ms. The grand average of the ratios of the areas of conditioned responses at intervals of 5, 6 and 7 ms to those of control responses was designated the average area ratio (5-7 ms). Suppression of motor cortical excitability was reduced or absent in patients with a lesion in the cerebellum or cerebellothalamocortical pathway, but was normal in patients with a lesion in the afferent pathway to the cerebellum. Normal suppression was observed in Fishers syndrome. The average area ratio (5-7 ms) correlated well with the severity of ataxia in patients with degenerative late-onset ataxia. These results are consistent with those for electrical stimulation of the cerebellum reported previously. We conclude that magnetic stimulation over the cerebellum produces the same effect as electrical stimulation even in ataxic patients. This less painful method can be used clinically to clarify the pathomechanisms for ataxia. Two other clinical uses of this technique were that it revealed clinically undetectable cerebellar dysfunction in patients whose extrapyramidal signs masked cerebellar signs, and that the slow progression of ataxia could be followed quantitatively in patients with degenerative late-onset ataxia.

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation.

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 degrees 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.

Visual Phosphene Perception Modulated by Subthreshold Crossmodal Sensory Stimulation

Crossmodal sensory interactions serve to integrate behaviorally relevant sensory stimuli. In this study, we investigated the effect of modulating crossmodal interactions between visual and somatosensory stimuli that in isolation do not reach perceptual awareness. When a subthreshold somatosensory stimulus was delivered within close spatiotemporal congruency to the expected site of perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse delivered to the occipital cortex evoked a visual percept. The results suggest that under subthreshold conditions of visual and somatosensory stimulation, crossmodal interactions presented in a spatially and temporally specific manner can sum up to become behaviorally significant. These interactions may reflect an underlying anatomical connectivity and become further enhanced by attention modulation mechanisms.

The human hand motor area is transiently suppressed by an unexpected auditory stimulus

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.

Somatosensory evoked high-frequency oscillation in Parkinson's disease and myoclonus epilepsy

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 Parkinsons 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.

Cortico–cortical inhibition of the motor cortical area projecting to sternocleidomastoid muscle in normals and patients with spasmodic torticollis or essential tremor

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.

Intracortical inhibition of the motor cortex is normal in chorea

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.

Recovery function of and effects of hyperventilation on somatosensory evoked high-frequency oscillation in Parkinson's disease and myoclonus epilepsy

To evaluate recovery function of and effects of hyperventilation (HV) on high-frequency oscillations (HFOs) of median nerve somatosensory evoked potential (SEP), we recorded SEPs in 8 Parkinsons disease (PD) patients with enlarged HFOs, 4 myoclonus epilepsy (ME) patients and 10 healthy volunteers (N). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Responses were amplified with filters set at 0.5 and 3000 Hz. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz. We measured amplitudes of the N20 onset-peak (N20o-p), N20 peak-P25 peak (N20p-P25p), P25 peak-N33 peak (P25p-N33p), the early (1st-2nd) and late (3rd) HFOs. For the recovery function study, paired-pulse stimuli at various interstimulus intervals (20, 50, 100, 150, 200 and 300 ms) were given. To investigate effects of HV, amplitudes of several components of SEPs recorded after HV were compared with those before HV. In PD and ME, the N20o-p recovery curve showed significantly less suppression as compared with those of N. The P25p-N33p recovery curve of ME showed longer suppression than those of N and PD. There were no significant differences in the early or late HFOs recovery curves among three groups. At the dysinhibited state after HV, the late HFO was reduced in association with a significant enlargement of the N20p-P25p amplitude in normal subjects. This suggests that the late HFOs should reflect bursts of inhibitory interneurons. In the ME patients, the early HFOs significantly decreased by HV. The pattern in ME patients may be explained by a kind of compensation for already enhanced SEPs (giant SEP) in the dysinhibited situation. We conclude that (1) Giant HFOs are normally regulated by inhibitory neuronal systems involving in paired stimulation SEP. (2) The late HFOs must reflect bursts of GABAergic inhibitory interneurons.