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Objectives: Progressive supranuclear palsy (PSP) is an uncommon progressive neurodegenerative disease with no effective cure at present. The initial symptoms resemble those of Parkinson’s disease; however, the prevalence of PSP is about one-tenth that of Parkinson’s disease. In many cases, dysphagia is severe, and the development of dysphagia is an early predictor of life expectancy. The aim of the current study was to define the effects of Lee Silverman Voice Treatment (LSVT LOUD) on swallowing and voice/speech in seven patients with PSP. Methods : Each patient underwent swallowing and voice/speech evaluations before and after 4 weeks of LSVT. Swallowing motility disorders were defined, temporal measures of swallowing were determined by videofluoroscopic evaluation, and voice measures of maximum phonation and speech intelligibility in reading and monologue were examined. Results: After LSVT, the median duration of opening of the upper esophageal sphincter (from the beginning of the posterior movement of the bolus to upper esophageal sphincter opening) on videofluoroscopy was significantly shortened from 0.42 to 0.38 s (Wilcoxon signed-rank test P=0.016). The oral transit duration was decreased in five patients, but the decrease was not significant. Voice changes after LSVT included increases in voice intensity and in sustained duration were not significant. Conclusion: In this small study, it was found that LSVT may improve swallowing functions in patients with PSP.

Brain activity relating to recognition of action varies among subjects. These differences have been hypothesised to originate from genetic and environmental factors although the extent of their effect remains unclear. Effects of these factors on brain activity during action recognition were evaluated by comparing magnetoencephalography (MEG) signals in twins. MEG signals of 20 pairs of elderly monozygotic twins and 11 pairs of elderly dizygotic twins were recorded while they observed finger movements and copied them. Beamformer and group statistical analyses were performed to evaluate spatiotemporal differences in cortical activities. Significant event-related desynchronisation (ERD) of the β band (13–25 Hz) at the left inferior parietal lobule (IPL) was observed for both action observation and execution. Moreover, β-band ERD at the left IPL during action observation was significantly better correlated among monozygotic twins compared to unrelated pairs (Z-test, p = 0.027). β-band ERD heritability at the left IPL was 67% in an ACE model. These results demonstrate that β-band ERD at the IPL, which is commonly observed during action recognition and execution, is affected by genetic rather than environmental factors. The effect of genetic factors on the cortical activity of action recognition may depend on anatomical location and frequency characteristics.

High gamma band (>50 Hz) activity is a key oscillatory phenomenon of brain activation. However, there has not been a non-invasive method established to detect language-related high gamma band activity. We used a 160-channel whole-head magnetoencephalography (MEG) system equipped with superconducting quantum interference device (SQUID) gradiometers to non-invasively investigate neuromagnetic activities during silent reading and verb generation tasks in 15 healthy participants. Individual data were divided into alpha (8–13 Hz), beta (13–25 Hz), low gamma (25–50 Hz), and high gamma (50–100 Hz) bands and analysed with the beamformer method. The time window was consecutively moved. Group analysis was performed to delineate common areas of brain activation. In the verb generation task, transient power increases in the high gamma band appeared in the left middle frontal gyrus (MFG) at the 550–750 ms post-stimulus window. We set a virtual sensor on the left MFG for time-frequency analysis, and high gamma event-related synchronization (ERS) induced by a verb generation task was demonstrated at 650 ms. In contrast, ERS in the high gamma band was not detected in the silent reading task. Thus, our study successfully non-invasively measured language-related prefrontal high gamma band activity.

Spatiotemporal signal transmission in the human subcortical visual pathway has not been directly demonstrated to date. To delineate this signal transmission noninvasively, we investigated the early latency components between 45 ms (P45m) and 75 ms (N75m) of visually-evoked neuromagnetic fields (VEFs). Four healthy volunteers participated in this study. Hemi-visual field light flash stimuli were delivered a total of 1200 times. Neuromagnetic responses were measured with a 160-channel whole-head gradiometer. In three participants, averaged waveforms indicated a subtle but distinct component that peaked with a very early latency at 44.7 ± 2.1 ms with an initial rise latency of 36.8 ± 3.1 ms, followed by a typical prominent cortical component at 75 ms. The moving equivalent current dipoles continuously estimated from P45m to N75m were first localized in the vicinity of the contralateral lateral geniculate body, then rapidly propagated along the optic radiation and finally terminated in the contralateral calcarine fissure. This result indicates that the source of P45m is the lateral geniculate body and that the early latency components P45m–N75m of the VEFs reflect neural transmission in the optic radiation. This is the first report to noninvasively demonstrate the neurophysiological transmission of visual information through the optic radiation.

Imitation is a complex process that includes higher-order cognitive and motor function. This process requires an observation-execution matching system that transforms an observed action into an identical movement. Although the low-gamma band is thought to reflect higher cognitive processes, no studies have focused on it. Here, we used magnetoencephalography (MEG) to examine the neural oscillatory changes including the low-gamma band during imitation. Twelve healthy, right-handed participants performed a finger task consisting of four conditions (imitation, execution, observation, and rest). During the imitation and execution conditions, significant event-related desynchronizations (ERDs) were observed at the left frontal, central, and parietal MEG sensors in the alpha, beta, and low-gamma bands. Functional connectivity analysis at the sensor level revealed an imitation-related connectivity between a group of frontal sensors and a group of parietal sensors in the low-gamma band. Furthermore, source reconstruction with synthetic aperture magnetometry showed significant ERDs in the low-gamma band in the left sensorimotor area and the middle frontal gyrus (MFG) during the imitation condition when compared with the other three conditions. Our results suggest that the oscillatory neural activities of the low-gamma band at the sensorimotor area and MFG play an important role in the observation-execution matching system related to imitation.

In this study, we aimed to identify the cerebellum-related electromyographic (EMG) response that appeared in the upper limbs musculature. Thirty times averaged transcranial magnetic stimulation (TMS) with a double-cone coil placed over the cerebellar hemisphere elicited long latency EMG responses at the bilateral extensor carpi radialis (ECR) muscles. The peak latency of this EMG response was 70.7±12.7 ms in the ipsilateral ECR and 62.9±10.2 ms in the contralateral ECR of the TMS side. These latencies were much longer than the latency of the muscle evoked potential when we stimulated pyramidal tracts at the foramen magnum level. Cerebellar hemisphere loading by the finger target pursuit test made this EMG response faster during TMS on the ipsilateral side of the cerebellum and slower during TMS on the contralateral side of the cerebellum. Furthermore, the deeper the level of drowsiness, the slower the peak latency of this EMG response became. These results suggest that this EMG potential is a specific response of the cerebellum and brainstem reticular formation, and may be conducted from the cerebellar structure to the ECR muscle through the polysynaptic transmission of the reticulospinal tract.

Osaka University Center for Twin Research is currently organizing a government-funded, multidisciplinary research project using a large registry of aged twins living in Japan. The purpose of the project is to collect various information as well as biological resources from registered twins, and to establish a biobank and databases for preserving and managing these data and resources. The Center is collecting data from twin pairs, both of whom have agreed to participate in a one-day comprehensive medical examination. The following data are being collected: physical data (e.g., height, body mass, blood pressure, theoretical visceral fat, pulse wave velocity, and bone density), data regarding epidemiology (e.g., medical history, lifestyle, quality of life, mood status, cognitive function, and nutrition), electrocardiogram, ultrasonography (carotid artery and thyroid), dentistry, plastic surgery, positron emission tomography, magnetoencephalogram, and magnetic resonance imaging of brain. These data are then aggregated and systematically stored in specific databases. In addition, peripheral blood is obtained from the participants, and then genomic DNA is purified and sera are stored. A wide variety of studies are ongoing, and more are in the planning stage.

The relationship between M1 activity representing motor information in real and imagined movements have not been investigated with high spatiotemporal resolution using non-invasive measurements. We examined the similarities and differences in M1 activity during real and imagined movements. Ten subjects performed or imagined three types of right upper limb movements. To infer the movement type, we used 40 virtual channels in the M1 contralateral to the movement side (cM1) using a beamforming approach. For both real and imagined movements, cM1 activities increased around response onset, after which their intensities were significantly different. Similarly, although decoding accuracies surpassed the chance level in both real and imagined movements, these were significantly different after the onset. Single virtual channel-based analysis showed that decoding accuracy significantly increased around the hand and arm areas during real and imagined movements and that these are spatially correlated. The temporal correlation of decoding accuracy significantly increased around the hand and arm areas, except for the period immediately after response onset. Our results suggest that cM1 is involved in similar neural activities related to the representation of motor information during real and imagined movements, except for presence or absence of sensory–motor integration induced by sensory feedback.

The midline electroneurography (ENoG) method might reflect total facial nerve degeneration.We compared ENoG values in patients with facial palsy using two different methods, the midline method and five electroneurogram recordings, to reveal whether the ENoG value obtained with the midline method reflects total facial nerve degeneration.Forty patients with facial palsy were enrolled. Compound muscle action potentials (CMAPs) were recorded using the midline method, in which the anode was placed on the mental protuberance and the cathode was placed on the philtrum. Additionally, five electroneurogram recordings were obtained by placing the anode on the skin of the parietal region and five cathodes on the skin over five facial muscles (frontalis, orbicularis oculi, nasalis, orbicularis oris, and depressor anguli oris muscles). ENoG values recorded using the two methods were compared.The ENoG values of the five facial muscles did not differ from those obtained using the midline method. The total ENoG value calculated by summing five CMAPs from five facial muscles, which is considered to reflect total facial nerve degeneration, was not significantly different from that using midline methods; moreover, a strong positive correlation coefficient (r = 0.87) was found between them.

The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it.

Objective Though a cortical visual prosthesis is a promising method for treating severe visual disturbances, long-term blindness is known to depress visual cortex activity. We examined the use of repetitive transcranial magnetic stimulation (rTMS) with a navigation system as a direct functional assessment tool for the visual cortex. Methods We performed rTMS of the occipital cortex at three different stimulus frequencies (1 Hz, 5 Hz, and 20 Hz), on five stimulus targets around the calcarine fissure in 10 healthy subjects and 3 patients with visual impairment. Results In the subjects with normal vision, phosphenes were mostly induced in the visual hemifield contralateral to the stimulation site, and stimulation on the targets inferior to the calcarine fissure predominantly induced phosphenes in the upper visual hemifield. High-frequency stimulation induced larger and complicated-shaped phosphenes at higher rates. The phosphenes induced rate and spatial distribution were altered in the blind patients. Conclusions The rTMS has the ability to directly assess the regional visual function of the occipital cortex both in normal-sighted subjects and blind patients. Precise targeting with a navigation system appropriately stimulated the lingual gyri, which contributed to consistently inducing the phosphenes in the upper visual fields. Atypical representation of the phosphenes in patients with visual impairment suggests the alteration of regional cortical excitations and spatial representation due to the cortical reorganization after the loss of visual inputs.

Object Event-related cerebral oscillatory changes reflect regional brain activation. In a previous study, the authors proposed a new method to determine language dominance: examine frontal oscillatory changes during silent reading by using synthetic aperture magnetometry (SAM). The authors' aims in the present study were to establish a normal template for this method, to confirm the results of their previous study with a larger patient population, and to evaluate their method with respect to language localization. Methods A statistical group analysis of 14 healthy volunteers was conducted to establish a normal control. Language dominance and localization were then evaluated in a larger population of 123 consecutive patients. Study participants were instructed to silently read 100 visually presented words. Using SAM, the spatial distribution of the oscillatory changes was obtained as the Student t statistic by comparing the current density for each voxel between 1 second before and 1 second after each word presentation. Group analyses of the healthy volunteers were performed using statistical nonparametric mapping. Language dominance in the patients was determined according to the laterality index (LI) calculated using peak t values of the left and right frontal desynchronizations. Language dominance was prospectively assessed, and the results were compared with those of the Wada test (63 patients). Language localization results were quantitatively compared with those of stimulation mapping (17 patients). Results Group analysis of the healthy volunteers indicated β to low γ band desynchronization in the left frontal area and α to β desynchronization in the left parietotemporal areas. In patients, the frontal language areas were detected in 118 persons (95.9%). Lateralization of β or low γ desynchronization in the inferior or middle frontal gyri corresponded well with language dominance. The introduction of the LI resulted in a quantitative evaluation of language dominance, whose results were concordant with those of the Wada test in 51 (85.0%) of 60 cases. The distance between the estimated frontal language areas and stimulation-positive sites was 6.0 ± 7.1 mm (mean ± SD). Conclusions This study is the first in which magnetoencephalography (MEG) was used to determine language dominance in a large population, and the results were compared with those of the Wada test. Moreover, language localization results obtained using MEG were compared with those obtained by invasive mapping. The authors' method, which is based on neuromagnetic oscillatory changes, is a new approach for noninvasively evaluating the frontal language areas, a procedure that has been problematic using MEG dipole methods. Synthetic aperture magnetometry is a noninvasive alternative to Wada testing for language dominance and helps to determine stimulation sites for invasive mapping.

Situs inversus totalis (SI) is a rare condition in which all visceral organs are arranged as mirror images of the usual pattern. The objective of this study was to determine whether SI individuals have reversed brain asymmetries. We performed a neuroimaging study on 3 SI subjects and 11 control individuals with normally arranged visceral organs. The language-dominant hemisphere was determined by magnetoencephalography. Left-hemispheric dominance was observed in 1 SI subject and all controls, whereas right-hemispheric dominance was observed in the remaining 2 SI subjects. Statistical analysis revealed that language dominance patterns in SI subjects were different from those in the controls, suggesting that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying functional brain asymmetry. Anatomical brain asymmetries were determined by magnetic resonance imaging. SI subjects had the same planum temporale (PT) asymmetry pattern as the controls, but a reversed petalia asymmetry pattern. The inferior frontal gyrus (IFG) asymmetry pattern varied within both groups, indicating a relationship between the rightward IFG and right-hemispheric language dominance. These results suggest that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying petalia asymmetry but not to those underlying PT and IFG asymmetries, and that brain asymmetries might develop via multiple region-dependent mechanisms.

Imitating the mosquito's proboscis, the combined microneedles comprising a central straight needle and two outer jagged needles have been already proposed by the authors, and the effectiveness of these needles for easy insertion was investigated by the finite element method (FEM) simulation. Following this, in the present paper, silicon microneedles are practically fabricated by using a silicon on insulator (SOI) wafer and deep reactive ion etching (DRIE) process. A sole straight needle, a sole jagged needle, and combined jagged needles are employed. The fabricated shape and size of the harpoon-like jagged protrusions are almost the same as the mosquito's. The resistance force during inserting these fabricated needles into an artificial skin of silicone rubber is experimentally investigated. Comparing the results, the effect of combining needles for easy insertion is confirmed. It is also confirmed that applying vibration to the needles with jagged shape is fairly effective for easy insertion. The mechanisms of employing jagged shape needles, applying vibration, and combining needles are discussed. For practical medical applications, a silicon needle is not safe enough on the human body owing to its brittleness. To cope with this problem, coating the silicon surface with biocompatible parylene is proposed. It is proved that parylene-coated needle surely penetrates silicone rubber, although the necessary force increases. © 2008 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

The aim of this study is to reveal the oscillatory change and subjective arousal level during simulated driving using synthetic aperture magnetometry (SAM). Subjects were instructed to perform the driving simulation task using a steering wheel, accelerator and brake pedals. The subjective arousal level was estimated using a visual analog scale. The subjective arousal level was reduced and the activities of theta band (4–8 Hz) in frontal areas were increased as driving time advanced. It is well known that the theta wave increases during rest state. Our previous studies also demonstrated that pseudo- Z value in the theta band inversely correlates with subjective arousal level. The present study demonstrated that this relation holds true even during driving state.

Objective A neuroprosthesis using a brain–machine interface (BMI) is a promising therapeutic option for severely paralyzed patients, but the ability to control it may vary among individual patients and needs to be evaluated before any invasive procedure is undertaken. We have developed a neuroprosthetic hand that can be controlled by magnetoencephalographic (MEG) signals to noninvasively evaluate subjects’ ability to control a neuroprosthesis. Method Six nonparalyzed subjects performed grasping or opening movements of their right hand while the slow components of the MEG signals (SMFs) were recorded in an open-loop condition. The SMFs were used to train two decoders to infer the timing and types of movement by support vector machine and Gaussian process regression. The SMFs were also used to calculate estimated slow cortical potentials (eSCPs) to identify the origin of motor information. Finally, using the trained decoders, the subjects controlled a neuroprosthetic hand in a closed-loop condition. Results The SMFs in the open-loop condition revealed movement-related cortical field characteristics and successfully inferred the movement type with an accuracy of 75.0 ± 12.9% (mean ± SD). In particular, the eSCPs in the sensorimotor cortex contralateral to the moved hand varied significantly enough among the movement types to be decoded with an accuracy of 76.5 ± 10.6%, which was significantly higher than the accuracy associated with eSCPs in the ipsilateral sensorimotor cortex (58.1 ± 13.7%; p = 0.0072, paired two-tailed Student’s t-test). Moreover, another decoder using SMFs successfully inferred when the accuracy was the greatest. Combining these two decoders allowed the neuroprosthetic hand to be controlled in a closed-loop condition. Conclusions Use of real-time MEG signals was shown to successfully control the neuroprosthetic hand. The developed system may be useful for evaluating movement-related slow cortical potentials of severely paralyzed patients to predict the efficacy of invasive BMI.

We report on a case with periodic nystagmus on lateral gaze during vertigo attack. The case is a 19-year-old woman who had repeated vertigo attacks in the early stage of the disease. During remission, she had continuous nystagmus on lateral gaze with a large amplitude. During vertigo attack, she had periodic nystagmus with a small amplitude on lateral gaze with null periods of 8s. At onset, her tentative diagnosis was spinocerebellar degeneration such as dentatorubral-pallidoluysian atrophy because of brain stem tegmentum and cerebellar vermis atrophy identified on MRI, but brainstem encephalitis and cerebellitis couldn't be excluded. Periodic nystagmus during vertigo attack may be induced by the depression of higher neural control which was indicated by lesions in the cerebellar vermis shown on MRI.

Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures.

The aim of this study was to verify the relation between gamma-band activity and process of function words. We recorded the neuromagnetic signals in six healthy volunteers during silent reading of verbs (verb task) and forming of the past tenses (past-tense task) and investigated the spatio-temporal distribution of event-related desynchronization (ERD) and synchronization using synthetic aperture magnetometry. In both tasks, ERDs were observed simultaneously at multiple language-related areas. The left junctional area of inferior frontal sulcus and precentral sulcus and the left supramarginal gyrus showed stronger and/or longer-lasting ERDs in past-tense task than in verb task. This result suggests that the gamma-activities reflect the syntactic process of words.

To evaluate the gamma-band activity related to somatosensory processing, we recorded neuromagnetic signals from seven healthy subjects. The source power changes evoked by electrical stimulation of the median nerve were estimated with synthetic aperture magnetometry (SAM). Source power in the low gamma band (40 Hz) decreased in the contralateral primary somatosensory cortex (SI) for a few hundred milliseconds (i.e. middle and long latency) and then increased inversely. Source power in the high gamma band (70-90 Hz) increased simultaneously both in the contralateral SI and contra/ipsilateral secondary somatosensory cortex (SII) in 80-180 ms. These results suggest that low and high gamma oscillations work under independent mechanisms during somatosensory processing. In particular, high gamma oscillations may play an essential role in making a functional connection between SI and SII.

Twin studies have suggested that there are genetic influences on inter-individual variation in regard to linguistic abilities. However, the brain activities under genetic influence during linguistic processing remain unclear. In this study, we investigated neuromagnetic activities during a verb generation task in a group of 28 monozygotic (MZ) and 12 dizygotic (DZ) adult Japanese twins. We examined the spatio-temporal distribution of the event-related desynchronizations (ERDs) in the low gamma band (25–50 Hz) using beamformer and time–frequency analyses. Heritability was evaluated by comparing the respective MZ and DZ intra-class correlations. The genetic and environmental contributions were estimated by structural equation modeling (SEM). We found that the peaks of the low gamma ERDs were localized to the left frontal area. The power of low gamma ERDs in this area exhibited higher similarity between MZ twins than that between DZ twins. SEM estimated the genetic contribution as approximately 50%. In addition, these powers were negatively correlated with the behavioral verbal scores. These results shows that low gamma ERDs in the left frontal area during a language task are influenced equally by genetic and environmental factors, and the subjects with higher verbal scores had lower powers for these ERDs.

Previous studies suggest that the left inferior frontal cortex is involved in the resolution of lexical ambiguities for language comprehension. In this study, we hypothesized that processing of lexical ambiguities is improved when the excitability of the left inferior frontal cortex is enhanced. To test the hypothesis, we conducted an experiment with transcranial direct current stimulation (tDCS). We investigated the effect of anodal tDCS over the left inferior frontal cortex on behavioral indexes for semantic judgment on lexically ambiguous and unambiguous words within a context. Supporting the hypothesis, the RT was shorter in the anodal tDCS session than in the sham session for ambiguous words. The results suggest that controlled semantic retrieval and contextual selection were facilitated by anodal tDCS over the left inferior frontal cortex.

We performed numerical simulations of the eddy current induced by transcranial magnetic stimulation (TMS) to the cerebellum. Solutions were obtained on a three-dimensional human head model with inhomogeneous conductivity. The stimulating coil consisted of a pair of circular coil elements with a diameter of 110 mm. Electric current applied to the coil had an intensity of 44.2 kA middot Turn, which resulted in a magnetic field intensity of 0.56 T at the center of a coil element. The maximum current density in the cerebellum was 2.9 A/m2. Distribution of the eddy current in the cerebellum was limited to approximately 1 cm beneath the surface of the cerebellum. The eddy current had a localized distribution in the cerebellum, while the magnetic field had a broad distribution

非侵襲ハンディ酸素モニタを用いて,mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)患者のエルゴ負荷時の血液量と組織酸素レベルの測定を行った.正常コントロールとは異なり負荷時の血液量の滅少と組織酸素レベルの上昇が患者では認められずに異なったパターンが認められた.

In healthy subjects, we studied the late electromyographic response elicited by transcranial magnetic stimulation (TMS) applied at the level of the foramen magnum in the left soleus muscle in an upright and supine posture. The late response at the latency of approximately 40 ms was constantly elicited during both postures. It was elicited during planter flexion, but not dorsi flexion. Additionally, no response appeared in the relaxed muscle. Those behaviours are the same as that of the long-loop reflex (LLR). We believe that the late response may be a long-loop reflex.

Three patients with motor neuron disease had eyelid "apraxia" with impaired voluntary but preserved involuntary eyelid movements. Attempts were made to localise the lesions responsible with neuroimaging and neuropathological examination.

We performed extensive quantitative analyses of the peripheral nervous system (PNS) of two siblings with familial amyloid polyneuropathy (FAP) caused by a transthyretin (TTR) Gly42 mutation. Pronounced amyloid deposition was found in the sympathetic ganglia (SyG), dorsal root ganglia (DRG) and throughout the length of the peripheral nerve fibers with some accumulation in the more proximal portion. There was severe neuronal loss in the SyG and DRG together with nerve fiber depletion in the nerve trunk, while only a small amount of amyloid deposition with mild fiber loss was seen in the spinal roots. Sprouts of regenerating axons were very scanty even in the spinal nerves or roots. A teased fiber study mainly showed demyelinating fibers, but axonal degeneration was also present throughout peripheral nerves. An electron microscopic study showed fine amyloid fibrils in direct contact with the axoplasmic membrane of demyelinated axons and destruction of axons in some areas. Amyloid deposition within the PINS in this type of FAP resembled that in type I FAP (TTR Met30). However, direct axonal damage by amyloid fibrils appeared to be more prominent in our cases than in type I FAP. Lectin histochemistry using Ulex europaeus agglutinin I demonstrated preferential depletion of small neurons in the DRG and their primary afferent fibers in the spinal dorsal horn. Primary axonal degeneration and ganglionopathy due to amyloid deposition appear to be the pathogenetic mechanisms for peripheral neuropathy in this type of FAP.

This is the first report with histochemical and immunohistochemical techniques of an autopsy case with mitochondrial encephalomyopathy caused by the mitochondrial tRNAIle (nt4269) A to G mutation showing focal cytochrome c oxidase (COX) deficiency of neuronal cells. The 18-year-old male patient had cardiomyopathy, hearing disability, mental retardation, and seizures. Muscle biopsy exhibited many ragged-red fibers and focal COX deficiency. A postmortem histochemical study on frozen sections of the cerebral cortex, cerebellum, brain stem, and dorsal root ganglia revealed a loss of COX activity in some neuronal cells. On immunohistochemical staining, COX was also defective in a mosaic pattern. Focal COX deficiency may cause variable neurological manifestations in mitochondrial encephalomyopathies.

In 2011, nine brain and six nerve and muscle physiological examinations were covered by the national health insurance in Japan. The greatest recent change was the digitalization of electroencephalography in the neurophysiological laboratory. This change is good for hospital affairs both economically and ecologically. Board certified doctors or technologists by the Academic Society in Neurophysiology are increasing each year and are improving the clinical level in daily laboratory work. One problem is that the level of neurophysiological laboratory examinations differs among hospitals in Japan, but they are showing a gradual improvement. Future development is promising in this field. Technological progress in neurophysiological functions is remarkable, including magnetic methods. Magnetoencephalography has powerful spatiotemporal resolution and can analyze higher brain function such as language, memory, calculation and so on. Transcranial magnetic stimulation is also available for laboratory examination of the nervous system, including motor and higher brain functions. In this symposium we showed cerebellar-related motor potentials in the soleus muscle by transcranial magnetic stimulation of the posterior fossa. This report summarizes the present status and future development of the neurological field in physiological laboratory examinations.

A brain machine interface (BMI) provides the possibility of controlling such external devices as prosthetic arms for patients with severe motor dysfunction using their own brain signals. However, there have been few studies investigating the decoding accuracy for multiclasses of useful unilateral upper limb movements using non-invasive measurements. We investigated the decoding accuracy for classifying three types of unilateral upper limb movements using single-trial magnetoencephalography (MEG) signals. Neuromagnetic activities were recorded in 9 healthy subjects performing 3 types of right upper limb movements: hand grasping, pinching, and elbow flexion. A support vector machine was used to classify the single-trial MEG signals. The movement types were predicted with an average accuracy of 66 ± 10% (chance level: 33.3%) using neuromagnetic activity during a 400-ms interval (− 200 ms to 200 ms from movement onsets). To explore the time-dependency of the decoding accuracy, we also examined the time course of decoding accuracy in 50-ms sliding windows from − 500 ms to 500 ms. Decoding accuracies significantly increased and peaked once before (50.1 ± 4.9%) and twice after (58.5 ± 7.5% and 64.4 ± 7.6%) movement onsets in all subjects. Significant variability in the decoding features in the first peak was evident in the channels over the parietal area and in the second and third peaks in the channels over the sensorimotor area. Our results indicate that the three types of unilateral upper limb movement can be inferred with high accuracy by detecting differences in movement-related brain activity in the parietal and sensorimotor areas.

To confirm the clinical utility of selegiline (L-deprenyl), a selective inhibitor of monoamine oxidase B, as an anti-Parkinson's disease (PD) agent, the first Japanese multi-center, double-blind comparative study of this drug was conducted. The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment. A total of 112 patients in two groups, one given selegiline at a dose of 7.5 mg/day (Group D, n = 60) and another given a placebo (Group P, n = 52), were compared over an 8-week treatment period. The percentage patients showing "moderate improvement" or better was 34.5% in Group D, while that in Group P was 11.5% (P < 0.01). In the assessment of overall safety, 66.7% in Group D showed no adverse reactions, which was not significantly different from the result of 78.9% for Group P.

In order to clarify whether neurophysiological profiles affect the performance of brain machine interfaces (BMI), we examined the relationships between amplitudes of movement-related cortical fields (MRCFs) and decoding performances during movement. Neuromagnetic activities were recorded in nine healthy participants during three types of unilateral upper limb movements. The movement types were inferred by a support vector machine. The amplitude of MRCF components, motor field (MF), movement-evoked field I (MEFI), and movement-evoked field II (MEFII) were compared with the decoding accuracies in all participants. Decoding accuracies at the latencies of MF, MEFI, and MEFII surpassed the chance level in all participants. In particular, accuracies at MEFI and MEFII were significantly higher in comparison with that of MF. The amplitudes and decoding accuracies were strongly correlated (MF, r(s)=0.90; MEFI, r(s)=0.90; and MEFII, r(s)=0.87). Our results show that the variation of MRCF components among participants reflects decoding performance. Neurophysiological profiles may serve as a predictor of individual BMI performance and assist in the improvement of general BMI performance.

The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherry-red spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of alpha-neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system: lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis.

A modified sensory “inching” method for the electrodiagnosis of carpal tunnel syndrome (CTS) Is described. The median nerve as stimulated at the cubital portion, with 8 channel recording electrodes placed along the nerve across the carpal tunnel. In most of the CTS cases, there was a conductive abnormality from 3 to 4.5 cm distal to the proximal ending of the flexor retinaculum. Subjects'; values, obtained by subtracting the theoretical latency from the measured latency, which were more than 0.6 ms, could not be improved by conservative therapy. As we could determine from subtle change at the short span of nerve condcution, below the electrodes from the proximal to the affected site of the carpal tunnel, this method provides high sensitivity and specificity for the diagnosis of CTS.

Renal handling of urate, xanthine and hypoxanthine was studied in a hypouricemic patient who had increased plasma concentrations of xanthine and hypoxanthine. The patient, a 50-year-old man, had been suffering from Parkinson's disease, while neither systemic disorders nor particular renal diseases known to affect plasma purine levels were found. His serum urate level was 58 +/- 6 mumol/l (healthy controls for males, 310 +/- 48 mumol/l, mean +/- SD) and the renal uric acid clearance was 3 times higher than that of the controls, establishing a diagnosis of renal hypouricemia. Xanthine and hypoxanthine concentrations in the plasma were elevated to 1.3 +/- 0.1 mumol/l (controls, 0.5 +/- 0.3) and 5.9 +/- 3.5 mumol/l (controls, 1.6 +/- 0.4), respectively. Both renal xanthine and hypoxanthine clearance was only half the value of the controls, indicating reduced urinary excretion of xanthine, and hypoxanthine appears to be responsible for their elevation in plasma. A probenecid loading test revealed no response of urinary urate excretion but normal responses of xanthine and hypoxanthine excretion. However, urinary excretion of urate, xanthine or hypoxanthine did not respond at all to pyrazinamide administration. These findings indicate that the patient had a defective renal handling of xanthine and hypoxanthine as well as urate.

Event-related cerebral oscillatory changes reflect regional brain activation. In a previous study, the authors proposed a new method to determine language dominance: examine frontal oscillatory changes during silent reading by using synthetic aperture magnetometry (SAM). The authors' aims in the present study were to establish a normal template for this method, to confirm the results of their previous study with a larger patient population, and to evaluate their method with respect to language localization.A statistical group analysis of 14 healthy volunteers was conducted to establish a normal control. Language dominance and localization were then evaluated in a larger population of 123 consecutive patients. Study participants were instructed to silently read 100 visually presented words. Using SAM, the spatial distribution of the oscillatory changes was obtained as the Student t statistic by comparing the current density for each voxel between 1 second before and 1 second after each word presentation. Group analyses of the healthy volunteers were performed using statistical nonparametric mapping. Language dominance in the patients was determined according to the laterality index (LI) calculated using peak t values of the left and right frontal desynchronizations. Language dominance was prospectively assessed, and the results were compared with those of the Wada test (63 patients). Language localization results were quantitatively compared with those of stimulation mapping (17 patients).Group analysis of the healthy volunteers indicated beta to low gamma band desynchronization in the left frontal area and alpha to beta desynchronization in the left parietotemporal areas. In patients, the frontal language areas were detected in 118 persons (95.9%). Lateralization of beta or low gamma desynchronization in the inferior or middle frontal gyri corresponded well with language dominance. The introduction of the LI resulted in a quantitative evaluation of language dominance, whose results were concordant with those of the Wada test in 51 (85.0%) of 60 cases. The distance between the estimated frontal language areas and stimulation-positive sites was 6.0 +/- 7.1 mm (mean +/- SD).This study is the first in which magnetoencephalography (MEG) was used to determine language dominance in a large population, and the results were compared with those of the Wada test. Moreover, language localization results obtained using MEG were compared with those obtained by invasive mapping. The authors' method, which is based on neuromagnetic oscillatory changes, is a new approach for noninvasively evaluating the frontal language areas, a procedure that has been problematic using MEG dipole methods. Synthetic aperture magnetometry is a noninvasive alternative to Wada testing for language dominance and helps to determine stimulation sites for invasive mapping.

Single-strand conformation polymorphism (SSCP) was analyzed to detect a mutation in the transthyretin (TTR) gene from the mother and son showing polyneuropathy with carpal tunnel syndrome. DNA segments containing TTR coding sequence were amplified by polymerase chain reaction, heat denatured and electrophoresed on a neutral polyacrylamide gel. The single-stranded DNA fragments in the gel were transferred to a nylon membrane and hybridized with biotinylated TTR cDNA probe, followed with chemiluminescent DNA detection. The mobility shift was found in the fragments of exon 3 from the patients' DNA. Sequencing analyses of the exon 3 confirmed a T----G base change, resulting in a Leu 58----Arg substitution. TTR Arg 58 is the first mutant TTR gene that has been detected by SSCP analysis. The rapid and sensitive detection of new mutations at various sites on the TTR gene is hereafter possible by the present method in the facilities for non-radioactive experiments.

Many CoQ trials for mitochondrial encephalomyopathy are reported, however, the action of CoQ in the central nervous system is unknown. We administered CoQ to a patient with MELAS, and decreasing CSF lactate and pyruvate levels were revealed. This reduction in CSF lactate and pyruvate may be evidence that CoQ acts directly on the CNS. There have been no other descriptions of evidence of CoQ effective action in the central nervous system, a finding unique to this report.

We studied the expression of mRNAs coding for the alpha-subunit of the muscle nicotinic acetylcholine receptor (AChR) in thymomas from patients with myasthenia gravis (MG). Northern blot analysis failed to detect the expression, but amplification of mRNAs derived from thymomas by reverse transcription and polymerase chain reaction produced the DNA fragments containing the nucleotide sequence coding for part of the alpha-subunit. We further revealed that the alpha-subunit mRNA was derived from neoplastic epithelial cells of thymoma. Our results support the hypothesis that AChR expressed in thymoma is a candidate for the primary antigen which induces autoimmune responses to muscle AChR. The close relationship between MG and thymoma may be at least in part explained by this hypothesis.