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Biomedical subjects

R Hanajima

Publications and source records attributed to R Hanajima.

At least 37 records · Page 2Linked to original sources

Physiological analyses of a patient with extreme widening of Virchow-Robin spaces.

We report on a 60-year-old woman with extreme widening of Virchow-Robin spaces who showed neither neurological symptoms nor signs. Magnetic resonance imagings (MRIs) of her brain disclosed multiple abnormalities located along the perforating medullary arteries in the white matter. Central sensory and motor conduction studies (sensory evoked potentials (SEPs) and magnetic stimulation) showed no conduction delays and several modulatory inputs normally influenced the motor and sensory cortical excitability, as expected from clinical features. These physiological analyses confirmed the functional integrity of the central sensory and motor systems, even though imaging studies showed seemingly serious abnormalities.

Brain↗

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.

Adult↗

Primary motor cortex isolation: complete paralysis with preserved primary motor cortex.

We present a left-sided hemiplegic patient with a cerebrovascular lesion involving the medial part of the right frontal and parietal lobes and the corpus callosum, but sparing the hand area of right primary motor cortex (M1). Several studies using transcranial magnetic stimulation demonstrated functional integrity of the efferent pathways from the right M1, intact sensory afferents to M1, an impairment of transcallosal connection between the bilateral motor cortices, and reduced ipsilateral cortico-cortical inhibition within the right M1. Based on these results, we conclude that the paralysis of this patient was caused by disconnection of the intact M1 from any structures requisite for initiation of movements. The present patient also suggests the importance of various afferents to M1 in voluntary movement. We propose a term of 'primary motor cortex isolation' to designate the paralysis reported here.

Electromyography↗

Localizing the site of magnetic brain stimulation by functional MRI.

In order to locate the site of action of transcranial magnetic stimulation (TMS) within the human motor cortices, we investigated how the optimal positions for evoking motor responses over the scalp corresponded to the hand and leg primary-motor areas. TMS was delivered with a figure-8 shaped coil over each point of a grid system constructed on the skull surface, each separated by 1 cm, to find the optimal site for obtaining motor-evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Magnetic resonance imaging scans of the brain were taken for each subject with markers placed over these sites, the positions of which were projected onto the cortical region just beneath. On the other hand, cortical areas where blood flow increased during finger tapping or leg movements were identified on functional magnetic resonance images (fMRI), which should include the hand and leg primary-motor areas. The optimal location for eliciting MEPs in FDI, regardless of their latency, lay just above the bank of the precentral gyrus, which coincided with the activated region during finger tapping in fMRI studies. The direction of induced current preferentially eliciting MEPs with the shortest latency in each subject was nearly perpendicular to the course of the precentral gyrus at this position. The optimal site for evoking motor responses in TA was also located just above the activated area during leg movements identified within the anterior portion of the paracentral lobule. The results suggest that, for magnetic stimulation, activation occurs in the primary hand and leg motor area (Brodmann area 4), which is closest in distance to the optimal scalp position for evoking motor responses.

Brain Mapping↗

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.

Adult↗

Visualization of the information flow through human oculomotor cortical regions by transcranial magnetic stimulation.

We investigated the topography of human cortical activation during an antisaccade task by focal transcranial magnetic stimulation (TMS). We used a figure-eight shaped coil, with the stimulus intensity set just above the threshold for activation of the hand motor areas but weak enough not to elicit blinks. TMS was delivered at various time intervals (80, 100, and 120 ms) after target presentation over various sites on the scalp while the subjects performed the antisaccade task. It was possible to elicit a mild but significant delay in saccade onset over 1) the frontal regions (a region 2-4 cm anterior and 2-4 cm lateral to hand motor area) and 2) posterior parietal regions (6-8 cm posterior and 0-4 cm lateral to hand motor area) regardless of which hemisphere was stimulated. The frontal regions were assumed to correspond to a cortical region including the frontal eye fields (FEFs), whereas the parietal regions were assumed to represent a wide region that includes the posterior parietal cortices (PPCs). The regions inducing the delay shifted from the posterior parietal regions at an earlier interval (80 ms) to the frontal regions at a later interval (100 ms), which suggested an information flow from posterior to anterior cortical regions during the presaccadic period. At 120 ms, the effect of TMS over the frontal regions still persisted but was greatly diminished. Erroneous prosaccades to the presented target were elicited over a wide cortical region including the frontal and posterior parietal regions, which again showed a forward shift with time. However, the distribution of effective regions exhibited a clear contralateral predominance in terms of saccade direction. Our technique provides a useful method not only for detecting the topography of cortical regions active during saccadic eye movement, but also for constructing a physiological map to visualize the temporal evolution of functional activities in the relevant cortical regions.

Adult↗

Preferential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil.

Transcranial magnetic stimulation (TMS) over the human primary motor cortex (MI) evokes motor responses in the contralateral limb muscles. The latencies and amplitudes of those responses depend on the direction of induced current in the brain by the stimuli (Mills et al. 1992, Werhahn et al. 1994). This observation suggests that different neural elements might be activated by the differently directed induced currents. Using a figure-of-eight-shaped coil, which induces current with a certain direction, we analyzed the effect of direction of stimulating current on the latencies of responses to TMS in normal subjects. The latencies were measured from surface electromyographic responses of the first dorsal interosseous muscles and the peaks in the peristimulus time histograms (PSTHs) of single motor units from the same muscles. The coil was placed over the MI, with eight different directions each separated by 45 degrees. Stimulus intensity was adjusted just above the motor threshold while subjects made a weak tonic voluntary contraction, so that we can analyse the most readily elicited descending volley in the pyramidal tracts. In most subjects, TMS with medially and anteriorly directed current in the brain produced responses or a peak that occurred some 1.5 ms later than those to anodal electrical stimulation. In contrast, TMS with laterally and posteriorly directed current produced responses or a peak that occurred about 4.5 ms later. There was a single peak in most of PSTHs under the above stimulation condition, whereas there were occasionally two peaks under the transitional current directions between the above two groups. These results suggest that TMS with medially and anteriorly directed current in the brain readily elicits I1 waves, whereas that with laterally and posteriorly directed current preferentially elicits I3 waves. Functional magnetic resonance imaging studies indicated that this direction was related to the course of the central sulcus. TMS with induced current flowing forward relative to the central sulcus preferentially elicited I1 waves and that flowing backward elicited I3 waves. Our finding of the dependence of preferentially activated I waves on the current direction in the brain suggests that different sets of cortical neurons are responsible for different I waves, and are contrarily oriented. The present method using a figure-of-eight-shaped coil must enable us to study physiological characteristics of each I wave separately and, possibly, analyse different neural elements in MI, since it activates a certain I wave selectively without D waves or other I waves.

Adult↗

Shortening of simple reaction time by peripheral electrical and submotor-threshold magnetic cortical stimulation.

Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can shorten the simple reaction time in contralateral arm muscles if the cortical shock is given at about the same time as the reaction stimulus. The present experiments were designed to investigate whether this phenomenon is due to a specific facilitatory effect on cortical circuitry. The simple visual reaction time was shortened by 20-50 ms when subthreshold TMS was given over the contralateral motor cortex. Reaction time was reduced to the same level whether the magnetic stimulus was given over the bilateral motor cortices or over other points on the scalp (Cz, Pz). Indeed, similar effects could be seen with conventional electrical stimulation over the neck, or even when the coil was discharged (giving a click sound) near the head. We conclude that much of the effect of TMS on simple reaction time is due to intersensory facilitation, although part of it may be ascribed to a specific effect on the excitability of motor cortex.

Electric Stimulation↗

Motor cortical reflex myoclonus: a case study with MEG.

Cortical reflex myoclonus usually depends for its generation on the hyperexcitability of sensory cortex, which manifests itself as an enhanced somatosensory evoked potential (SEP). A 25-year-old female, presenting with involuntary jerky dorsiflexion of the left foot, was found to have cortical reflex myoclonus which was aggravated during intended movements. The jerks were also elicited by electrical stimulation of the posterior tibial nerve, although the SEP evoked by the same stimulus was normal in latency and amplitude. Both the spontaneous spikes and the premyoclonus spike demonstrated by jerk-locked back averaging were localized to the superior frontal gyrus, just anterior to the paracentral sulcus. Paired-pulse magnetic stimulation disclosed lack of inhibition in the right hemisphere leg motor area, whereas the excitability of sensory cortex as studied by paired SEP testing was normal. This suggests that the myoclonus was caused mainly by enhanced excitability of the motor cortex and that this alone was enough for the production of long loop reflexes. We propose to designate this type of cortical myoclonus as motor cortical reflex myoclonus. It is generated in the motor cortex, but is at the same time stimulus-sensitive.

Adult↗

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 Fisher's 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.

Adult↗

Magnetic stimulation of the descending and ascending tracts at the foramen magnum level.

To test the possibility that stimulation over the foramen magnum activates ascending tracts as well as descending tracts, we studied 4 patients with myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs) and 10 normal subjects, using our previously reported method (Ugawa et al., Ann. Neurol., 1994, 36: 618-624). For latency comparisons, peripheral nerve stimulation at the elbow and spinal motor root were also performed. In all patients, magnetic stimulation at the foramen magnum consistently elicited long loop reflexes as well as direct responses caused by stimulation of the descending tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies of both types of response were the same whether stimulation used upward or downward current in the brain, although the former was always more effective. This indicates that stimulation at the level of the foramen magnum activates ascending tracts as well as descending tracts at a fixed position. The threshold for LLRs was lower than that for activation of the descending tracts. This threshold difference is compatible with the hypothesis that large diameter fibers from muscle afferent conduct the central afferent volley for LLRs (Marsden et al., Brain, 1977, 100: 185-200).

Afferent Pathways↗

Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders.

We used a paired-pulse magnetic stimulation technique to study ipsilateral cortico-cortical inhibition of the motor cortex in 48 patients with various neurological disorders and in 20 normal volunteers. In the normal subjects, the first subthreshold conditioning stimulus suppressed responses to the second suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-5 ms (inhibition at short intervals), and facilitated them at ISIs of 8-15 ms (facilitation at long intervals). Patients with motor neuron disease, except those in whom brain stimulation produced control responses that were generated by direct activation of corticospinal neurons (D-waves), had normal inhibition at short intervals. Facilitation at long intervals was not elicited in some patients with amyotrophic lateral sclerosis. Less inhibition at short intervals and normal facilitation at long intervals was found for all the patients with progressive myoclonic epilepsy, a condition in which the excitability of cortical inhibitory interneurons is thought to be affected. Inhibition at short intervals was disturbed, but facilitation at long intervals was intact in the patients with movement disorders (Parkinson's disease, corticobasal degeneration, and Wilson's disease). In these patients, positron emission tomography (PET) studies showed decreased regional cerebral blood flow (rCBF) in the basal ganglia in the relaxed state. However, normal suppression was elicited in the patients with Parkinson's disease with normal rCBF. In four patients with chorea, the time-course of inhibition and facilitation was normal, even though PET studies showed decreased rCBF in the basal ganglia in two of them. Normal inhibition could not be elicited in patients who had a small lesion in the basal ganglia or in the pathway from basal ganglia to the primary motor cortex; the putamen, globus pallidus, and supplementary motor cortex. In contrast, patients who had a lesion in a sensory system (sensory cortex or sensory thalamus) or in the pontine nucleus had normal suppression. We conclude that the results of ipsilateral cortico-cortical inhibition with paired magnetic stimulation reflect the excitability of inhibitory interneurons in the motor cortex and that outputs from the basal ganglia markedly affect this inhibition, but outputs from somato-sensory systems or cerebellum do not. Moreover, dysfunction of the corticospinal tract or spinal motoneurons does not affect results obtained by the paired magnetic stimulation technique when the control responses are generated by I-waves (i.e. descending volleys are produced by transsynaptic activation of the corticospinal tract neurons.

Adult↗

Magnetoencephalographic analysis of cortical myoclonic jerks.

We studied the pre-myoclonus spike using magnetoencephalography in patients with cortical myoclonus (6 with cortical reflex myoclonus and one with epilepsia partialis continua). The spike was estimated as a single current dipole on the pre-central gyrus in one patient with epilepsia partialis continua. In contrast, it was estimated as a single dipole on the post-central gyrus in 5 of 6 patients with cortical reflex myoclonus, and as two dipoles on the pre- and post-central gyrus in the remaining patient. We conclude that there are 3 physiological types of cortical myoclonus: (1) abnormal discharges in the motor cortex produce the myoclonus; (2) the source of the myoclonus is mainly the sensory cortex; (3) both the motor and sensory cortices play important roles in the production of myoclonus.

Epilepsies, Myoclonic↗

Clinical utility of magnetic corticospinal tract stimulation at the foramen magnum level.

We applied magnetic stimulation of the corticospinal tract at the foramen magnum level to 19 patients with various neurological disorders. Results were consistent with our previous speculation that activation occurs at the foramen magnum level. This method was clinically useful for the following conditions. (1) Detection of subclinical lesion: one patient who had transient ischemic attack that caused no clinical symptoms at examination was shown to have dysfunction of the corticospinal tract. (2) Multiple lesions: our method disclosed at least one lesion above and below the foramen magnum in two patients with multiple sclerosis. (3) Unmasking of dysfunction of the corticospinal tract masked by peripheral neuropathy: magnetic stimulation showed conduction delay in the corticospinal tract in two patients in whom no pyramidal signs were evident because of muscular atrophy due to neuropathy. One patient had multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy, the other had degenerative ataxia and neuropathy. (4) Association of disorders: conduction delay rostral to the foramen magnum, which should not occur in patients with only cervical myelopathy, was shown in a patient with cervical myeloradiculopathy and amyotrophic lateral sclerosis. We conclude that this magnetic stimulation method which is less painful than electrical stimulation has extensive clinical usefulness.

Adult↗

[Involuntary movements observed in a patient with Russian spring summer encephalitis].

A 38-year-old woman had an episode of headache, fever and convulsion in October, 1993. She became alert in two weeks, though weakness and atrophy remained in the upper limb muscles. She was diagnosed as Russian spring summer encephalitis (RSSE) based on several serological studies. Three kinds of involuntary movements were noted after recovery. These were spontaneous muscle jerks in the left arm, action tremor in the right arm and pathological associated-movement in the right leg. The movements were studied physiologically by electroencephalogram (EEG)-electromyogram (EMG) polygraphic recordings, jerk-locked averaging (JLA), magnetencephalography (MEG), and sensory evoked potentials (SEPs). The jerky movements in her left arm were observed at rest and aggravated by emotional stress. EEG-EMG polygraph showed that the jerks were sometimes associated with small spikes thus were considered to be due to epilepsia partialis continua (EPC). JLA analysis revealed a pre-myoclonus spike on the right hemisphere which preceded the onset of the jerk in the left first dorsal interosseous muscle by 25.2ms, which was equal to the magnetic cortical latency of that muscle. Jerk-locked magnetic field, obtained by averaging neuromagnetic activities with respect to the onset of myoclonus, showed that the spike preceding the jerk, originated from the right motor cortex. The spontaneous spikes were localized mainly on the right motor cortex. Sensory evoked potentials (SEPs) were normal in both size and latency. No hyperexcitability of the sensory cortex was demonstrated even by using paired stimulation SEPs. Based on these results, we conclude that the jerky movements in this patient were produced by abnormal spontaneous discharges in the motor cortex. The action tremor had a frequency of 4-5 Hz and its clinical features were compatible with cerebellar tremor. This is thought to result from a lesion in the left thalamus, affecting the cerebellothalamic pathways. Her right leg unintentionally moved whenever she began to move the hands. This was considered to be a pathological associated-movement due to dysfunction of the pyramidal tracts.

Adult↗

Magnetic stimulation over the cerebellum in humans.

Magnetic stimulation performed with a double-cone coil placed over appropriate positions on the back of the head reduced the size of electromyographic responses evoked by magnetic cortical stimulation in the first dorsal interosseous muscle when it preceded the cortical stimulus by 5, 6, and 7 msec. No suppression of responses to electrical cortical stimulation occurred. Greater suppression was evoked by stronger cerebellar stimuli; lesser suppression was elicited by stronger cortical stimuli. These physiological findings correspond to those obtained with electrical cerebellar stimulation. The most effective position for magnetic stimulation over the back of the head was slightly rostral to the foramen magnum level on the ipsilateral side of the muscle studied. This indicates that the conditioning stimulus activates certain structures at the back of the head on the ipsilateral side of the muscle, consistent with the cerebellum, because the part of the cerebellum regulating limb muscles is positioned about there on the ipsilateral side. In 2 patients with only cerebellar dysfunction, this suppression effect was not elicited, which also supports that the suppression is caused by activity in cerebellar structures. We conclude that magnetic stimulation over the cerebellum with a double-cone coil elicits the same suppressive effect on the motor cortex as electrical stimulation, but with less discomfort; moreover, we believe that this effect is produced by activation of certain cerebellar structures.

Adult↗