Intraoperative recording of the very fast oscillatory activities evoked by median nerve stimulation in the human thalamus.
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Biomedical subjects
Publications and source records attributed to R Hanajima.
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OBJECTIVES: We tried to determine which neural elements were activated in awake subjects by stimulation through contacts placed chronically on the motor cortex. METHODS: We recorded the motor effects of stimulation through 4 disc contacts placed in the subdural space over the motor cortex in 9 patients undergoing chronic stimulation for the control of pain or for the control of the rigidity of multiple system atrophy. RESULTS: Single stimuli could elicit short latency motor evoked potentials or facilitate active motoneurons in the contralateral limbs. The responsible neural elements had a short chronaxie (the pulse duration necessary to reach threshold with a stimulus intensity twice that required to reach threshold at the longest pulse duration used) and refractory period implying that they were myelinated axons. The facilitation was larger with cathodal than with anodal monopolar stimulation. The short latency facilitation in response to the second of two stimuli was greater at condition test intervals of 2-5 ms. This enhancement could be demonstrated with conditioning stimuli subthreshold for the excitation of active motoneurons suggesting that it arose, in part, at the level of the cortex. Single cortical stimuli could result in inhibition of voluntarily activated motoneurons. The inhibition was larger with cathodal than anodal monopolar stimulation. The responsible neural elements also had a short chronaxie and refractory period. CONCLUSIONS: Stimulation in awake subjects through contacts placed chronically over the motor cortex appears to activate axons in the cortex, which excite both corticospinal neurons and inhibitory neurons.
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 > or = 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.
To investigate the cortical information processing during the preparation of vocalization, we performed transcranial magnetic stimulation (TMS) over the cortex while the subjects prepared to produce voice in response to a visual cue. The control reaction time (RT) of vocalization without TMS was 250-350 msec. TMS prolonged RT when it was delivered up to 150-200 msec before the expected onset of voice (EOV). The largest delay of RT was induced bilaterally over points 6 cm to the left and right of the vertex (the left and right motor areas), resulting in 10-20% prolongation of RT. During the early phase of prevocalization period (50-100 msec before EOV), the delay induced over the left motor area was slightly larger than that induced over the right motor area, whereas, during the late phase (0-50 msec before EOV), it was significantly larger over the right motor area. Bilateral and simultaneous TMS of the left and right motor areas induced delays not significantly different from that induced by unilateral TMS during the early phase, but induced a large delay well in excess of the latter during the late phase. Thus, during the cortical preparation for human vocalization, alternation of hemispheric lateralization takes place between the bilateral motor cortices near the facial motor representations, with mild left hemispheric predominance at the early phase switching over to robust right hemispheric predominance during the late phase. Our results also suggested involvement of the motor representation of respiratory muscles and also of supplementary 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.
OBJECTIVE: To study interhemispheric interaction between the hand motor areas of both hemispheres through the corpus callosum in myoclonus epilepsy. SUBJECTS: Five patients with benign myoclonus epilepsy and ten age matched normal volunteers. METHODS: We studied effects of a medially directed conditioning stimulus over the right hand motor area on responses in the right first dorsal interosseous muscle to a posteriorly directed test stimulus over the left hand motor area. RESULTS: In normal subjects, inhibition was evoked at interstimulus intervals (ISIs) of 8-20ms (late inhibition). In contrast, facilitation occurred in patients at ISIs of 4-6ms (early facilitation) with no late inhibition. CONCLUSIONS: The lack of late inhibition in the patients is consistent with the idea that cortical inhibitory interneurones are affected in myoclonus epilepsy. We propose that this releases interhemispheric facilitation from powerful surround inhibition. The consequence is a predominant early facilitation between the hemispheres in patients with myoclonus epilepsy.
OBJECTIVE: To evaluate recovery functions of the sensory cortex using somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median nerve in patients with myotonic dystrophy (MD). SUBJECTS/METHODS: Twelve MD patients were enrolled in the present investigation. Five patients with facioscapulohumeral muscular dystrophy (FSH) and 12 healthy volunteers were studied as control groups. SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single pulse or paired-pulse stimuli at various interstimulus intervals (ISIs) (10, 20, 40, 60, 80, 100, 150, 200 and 300 ms) were given. Recovery functions of N9, N20onset-N20peak, N20-P25 and P25-N33 components were studied. RESULTS: Conventional SEPs to a single stimulus were normal in the latency and amplitude in all the patients. Recovery functions of both N9 and N20o-N20p components were normal in the patients. In contrast, in MD patients, disinhibited or hyperexcitable recovery pattern was observed in recovery curves of the N20-P25 or P25-N33 components, whereas those were normal in FSH patients. CONCLUSIONS: Disinhibited cortical excitability (or hyperexcitability) is present in the sensory cortex in patients with myotonic dystrophy. This may reflect cortical pathology or functional alteration of the sensory cortex in MD.
OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.
Transcranial magnetic stimulation (TMS) has been used to study several aspects of movement disorders: central motor conduction time (CMCT), electromyographic (EMG) silence evoked by TMS, reset of tremor rhythm by TMS, GABAergic inhibitory interneuronal function of the motor cortex studied with paired-pulse TMS. In this communication, We briefly summarize results of paired-pulse TMS in movement disorders. NORMAL SUBJECTS: A subthreshold conditioning stimulus over the motor cortex reduced the size of EMG responses to a succeeding suprathreshold test stimulus given to the same motor cortex. This inhibition is considered to be an inhibitory effect on the motor cortex because the same conditioning stimulus has no influence on H-reflexes or electrical cortical responses. Pharmacological effects on this inhibition suggested that it is mediated by GABAergic inhibitory systems in the motor cortex. PATIENTS: The cortical inhibition was reduced in cortical myoclonus, which is consistent with the notion that the studied effect is mediated by GABAergic systems. The inhibition was disturbed in focal dystonia, whereas normal inhibition was elicited in Segawa's disease. Reduced inhibition was seen in Parkinson's disease (PD), whereas normal inhibition in essential tremor. Normal inhibition was evoked in all patients with chorea. Abnormal inhibition in basal ganglia disorders must reflect damaged movement selection in the motor cortex secondary to the primary lesion in the basal ganglia. This abnormality occurs in some movement disorders and does not occur in the others, which indicates different pathomechanisms for involuntary movements. It is conspicuous that normal inhibition was evoked in Segawa's disease even though the patients had dystonia.
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.
We have studied the function of inhibitory interneurons within the motor cortex in several movement disorders using a paired-pulse magnetic stimulation technique. Their function was disturbed in patients with dystonia or focal lesions of the basal ganglia. On the other hand, the inhibition was normal in patients with chorea or essential tremor. The inhibitory circuit in the motor cortex must be functionally involved in some movement disorders probably because of changes of the inputs from basal ganglia to motor cortices, but not involved in the others. This difference in the functional involvement of inhibitory interneurons of the motor cortex may reflect different pathogenesis of these movement disorders.
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.
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.
OBJECTIVE: A well-organized input-output relation similar to that of the monkey motor cortex has been demonstrated in the human hand motor area (Terao Y, Ugawa Y, Uesaka Y, Hanajima R, Gemba-Shimizu K, Ohki Y, Kanazawa I. Input-output organization in the hand area of the human motor cortex, Electroenceph clin Neurophysiol 1995;97:375-381). The aim of this study is to investigate the input-output organization of the human foot motor area. METHODS: We studied the effect of tactile stimuli given to the toe tip on the sizes of following responses; motor evoked potentials (MEPs) elicited by transcranial magnetic or electrical stimulation (TMS or TES) over the motor cortex and magnetic stimulation at the foramen magnum level. RESULTS: Air stimuli applied to the toe tip facilitated magnetically evoked MEPs of mainly the muscle attached to that toe, although a less prominent facilitation was also noted in muscles attached to the adjacent toes. Neither responses evoked by TES, nor those by stimulation at the foramen magnum level, were affected by air stimuli. These results suggest that the observed facilitatory effect occurs at the cortical level. CONCLUSION: A fairly well-organized input-output relation is present also in the foot motor area in humans, although the facilitatory effect is not so topographically restricted as is noted for the hand motor area.
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.
We report a case of Lambert-Eaton myasthenic syndrome (LEMS) associated with idiopathic thrombocytopenic purpura (ITP) and diffuse panbronchiolitis (DPB). An extensive search for malignancy yielded negative results. Interestingly, ITP and DPB developed simultaneously when the patient suffered from myasthenic symptoms. This is the first report in the Japanese or English literature of an association of LEMS, ITP, and DPB. The use of cholinesterase blocker alone did not improve the myasthenic symptoms, and the symptoms and signs relapsed with the tapering of prednisolone (PSL) dosage. However, after administration of immunoglobulin (IVIG) (0.4 g/kg/day x 5 days), low-dose PSL (20 mg/day) alleviated the LEMS and ITP, and the diseases have remained in remission for 8 months without additional IVIG. We suspect that there is a synergistic relationship between IVIG and PSL.
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.
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