Demonstration of half-metallicity in fermi-level-tuned Heusler alloy Co2FeAl0.5Si0.5 at room temperature.

Fermi level tuning has been successfully demonstrated in Co-based full-Heusler alloy Co(2)FeAl(0.5)Si(0.5) (CFAS). The half-metallic band gap of CFAS was proved by the behavior of differential conductance of CFAS/(MgAl(2))O(x)/CoFe magnetic tunneling junctions with an unexplored crystalline (MgAl(2))O(x) barrier. CFAS exhibits the highest effective spin polarization (P_{eff}) at 300 K and the weakest temperature dependence of P_{eff} among all known half metals. Further study shows that P_{eff} of CFAS decays with increasing temperature (T) following T;{3/2} law perfectly, which indicates that the depolarization of CFAS is determined by spin wave excitation only.

Difference in intracortical inhibition of the motor cortex between cortical myoclonus and focal hand dystonia.

OBJECTIVE: The short interval intracortical inhibition (SICI) of the motor cortex (M1) is reduced in both cortical myoclonus and focal hand dystonia. This reduction has been attributed to the dysfunction of GABAergic system within the motor cortex. However, the precise mechanisms underlying the reduction may not be entirely identical in these two disorders, being due to primary pathological involvement in M1 or secondary to functional changes outside M1. The aim of this study was to elucidate possible differences in intracortical inhibition between these two disorders. METHODS: Subjects were 11 patients with benign myoclonus epilepsy, 7 with focal hand dystonia, and 11 normal volunteers. We studied SICI using anterior-posterior (AP) directed and posterior-anterior (PA) directed induced currents in the brain. RESULTS: In both disorders, SICI with PA-directed currents was reduced as reported previously. In contrast, SICI studied with AP currents was normal in patients with focal hand dystonia, but reduced in patients with cortical myoclonus. CONCLUSIONS: The difference between the two disorders might reflect the underlying pathological difference. In cortical myoclonus, the inhibitory interneurons of the motor cortex are affected, whereas the same interneurons are intact in dystonia. The difference in SICI induced by AP and PA directed currents in dystonia may be explained by the following possibilities: the difference in composition of I-waves contributing to EMG generation and the difference in modulation of the interneuronal activity by voluntary contraction. These changes may be secondary to dysregulation of the motor cortex by the basal ganglia or related cortices in dystonia. SIGNIFICANCE: The SICI using AP directed currents together with the conventional SICI using PA directed currents was able to demonstrate some difference in the intrinsic circuits of M1 between myoclonus and focal hand dystonia. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.

Magnetic relaxations of antiferromagnetic nanoparticles in magnetic fields.

We reexamine anomalous magnetic relaxations of ferritin in magnetic fields, the presence of which has been regarded as evidence suggesting the existence of thermally assisted macroscopic quantum tunneling in antiferromagnetic nanoparticles. In the present study, relaxation curves of ferritin are examined using an approach that is free from assumptions regarding distributions of various parameters of polydispersive particles. The results are not anomalous. In other words, the relaxation is accelerated by the field, as expected for classical superparamagnetic fluctuations.

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

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.

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 > 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.

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation.

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.

Hemispheric lateralization in the cortical motor preparation for human vocalization.

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.

Phase transitions of iron-nitride magnetic fluids.

Phase transitions of magnetic fluids in the zero field were studied from the viewpoint of static susceptibility and typical relaxation time in order to distinguish between the transitions and the blocking phenomena. We used iron-nitride magnetic fluids containing nearly uniform particles so as to remove the effects of particle-size distribution. In the densest sample, we observed the growth of ferromagnetic fluctuations and, in the diluted samples, a temperature-induced first-order phase transition.

Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells.

The effects of various experimental conditions on in vitro drug permeability to Caco-2 monolayers were investigated to determine the optimized conditions for the prediction of intestinal drug absorption. Concerning the pH of the transport medium in the Caco-2 study, two different pH values, 6.0 and 7.4, were tested for the apical medium with the pH of the basolateral medium fixed to 7.4. The change in the apical pH showed pronounced effects on the permeability of both passively and actively transported drugs. It was found that the transport study under the condition of an apical pH value of 6.0 showed a better prediction of in vivo drug absorption in human. The appropriate conditions for determining the permeability of poorly soluble drugs were also examined. First, the effects of bile acids, surfactant and some agents used for solubilizing drugs on the permeability and transepithelial electrical resistance (TEER) of Caco-2 monolayers were investigated. Taurocholic and cholic acid showed no effects on the permeability of 3H-Dexamethasone (DEX) and TEER at 10 mM concentration, suggesting the possibility of use in the Caco-2 study. Polyethyleneglycol-400 and dimethylsulfoxide reduced the permeability of DEX concentration dependently, whereas ethanol induced no significant changes in the permeability. Furthermore, it was demonstrated that the addition of plasma protein (bovine serum albumin) to the basolateral medium apparently facilitated the transport of poorly soluble drugs with high lipophilicity across Caco-2 monolayers. These findings clearly suggest the importance of considering the physiological conditions of in vivo drug absorption in optimizing the in vitro experimental conditions for transport study using Caco-2 cells, in order to obtain a satisfactory in vitro-in vivo correlation.

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.

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.

Air-puff-induced facilitation of motor cortical excitability studied in patients with discrete brain lesions.

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.

Input-output organization of the foot motor area in humans.

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.

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 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.

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.

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.

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.

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.

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.