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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., Competing Interests: CONFLICTS OF INTEREST: The authors have no conflicts of interests directly relevant to the content of this article., (©2021 The Japanese Association of Rehabilitation Medicine.)

Background : Abacus experts could mentally calculate fast some mathematical operations using multi-digit numbers. The temporal dynamics of abacus mental calculation are still unknown although some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor neural process during abacus mental calculation. Therefore, this contribution aims to clarify the significant similarities and the differences between experts and novices by investigating calculation-induced neuromagnetic responses based on cerebral oscillatory changes. Methods : Twelve to 13 healthy abacus experts and 17 non-experts participated in two experimental paradigms using non-invasive neuromagnetic measurements. In experiments 1 and 2, the spatial distribution of oscillatory changes presented mental calculations and temporal frequency profiles during addition while examining multiplication tasks. The MEG data were analyzed using synthetic aperture magnetometry (SAM) with an adaptive beamformer to calculate the group average of the spatial distribution of oscillatory changes and their temporal frequency profiles in source-level analyses. Results : Using a group average of the spatial distribution of oscillatory changes, we observed some common brain activities in both right-handed abacus experts and non-experts. In non-experts, we detected the right dorsolateral prefrontal cortex (DLPFC) and bilateral Intraparietal sulcus (IPS); whereas in experts, detected the bilateral parieto-occipital sulcus (POS), right inferior frontal gyrus (IFG), and left sensorimotor areas mainly. Based on the findings generated, we could propose calculation processing models for both abacus experts and non- experts conveniently. Conclusion : The proposed model of calculation processing in abacus experts and novices revealed that the novices could calculate logically depending on numerical processing in the left IPS. In contrast, abacus experts are utilizing spatial processing using a memorized imaginary abacus, which distributed over the bilateral hemispheres in the IFG and sensorimotor areas., (Copyright © 2020 Belkacem, Kiso, Uokawa, Goto, Yorifuji and Hirata.)

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.

Brain atrophy is part of the aging process and accelerated by neurodegenerative diseases, so an understanding of the background heritability of brain volume is essential. The purpose of this study was to determine the heritability of brain volume in middle to advanced age East Asian adults, an age group less studied and an ethnicity not previously studied. 3T magnetic resonance images were obtained and volumetric analyses conducted for a total of 74 individuals, 20 monozygotic twin pairs (mean age 61y min 41y max 75y) and 17 dizygotic twin pairs (mean age 64y min 41y max 85y). Total brain volume and a further seven regions were assessed, including lobar volumes, lateral divisions, and separated grey and white matter. Additive genetics and unique environment (AE) models for global brain volumes including total brain (90%), grey matter (91%) and white matter (84%) and many lobar volumes demonstrated high heritability in our study population. Our results present the heritability of brain volume in middle to advanced age as possibly higher in East Asian adults.

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.

Twin studies have suggested that there are genetic influences on inter-individual variation in terms of verbal abilities, and candidate genes have been identified by genome-wide association studies. However, the brain activities under genetic influence during linguistic processing remain unclear. In this study, we investigated neuromagnetic activities during a language task in a group of 28 monozygotic (MZ) and 12 dizygotic (DZ) adult twin pairs. We examined the spatio-temporal distribution of the event-related desynchronizations (ERDs) in the low gamma band (25-50Hz) using beamformer analyses and time-frequency analyses. Heritability was evaluated by comparing the respective MZ and DZ correlations. The genetic and environmental contributions were then 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 improve our understanding of how genetic and environmental factors influence cerebral activities during linguistic processes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic analysis of DNA methylation in monozygotic twins, an optimal model to evaluate them because the genetic backgrounds are the same., Results: We examined 30 male and 43 female older monozygotic twin pairs recruited from the registry established by the Center for Twin Research, Osaka University. Their methylation levels were determined using the Infinium HumanMethylation450 BeadChip Kit (Illumina), which interrogated 485577 highly informative CpG sites at the single-nucleotide resolution, and the median methylation level was calculated for each of the 25657 CpG islands. Within-pair differences of methylation levels (WPDMs) were greater in male pairs than female pairs for 86.0 % of autosomal CpG islands, but were higher in female pairs than male pairs for 76.7 % of X chromosomal CpG islands. Mean WPDMs of CpG islands in each autosomal chromosome were significantly higher in male pairs than in female whereas that in X chromosome was significantly higher in female pairs than in male. Multiple comparison indicated that WPDMs in three autosomal and two X-chromosomal CpG islands were significantly greater in male pairs, whereas those in 22 X-chromosomal CpG islands were significantly greater in female pairs., Conclusion: Sex-related differences were present in the WPDMs of CpG islands in individuals with the same genetic background. These differences may be associated with the sexual influences in susceptibility of some diseases.

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.

Humans recognize body parts in categories. Previous studies have shown that responses in the fusiform body area (FBA) and extrastriate body area (EBA) are evoked by the perception of the human body, when presented either as whole or as isolated parts. These responses occur approximately 190 ms after body images are visualized. The extent to which body-sensitive responses show specificity for different body part categories remains to be largely clarified. We used a decoding method to quantify neural responses associated with the perception of different categories of body parts. Nine subjects underwent measurements of their brain activities by magnetoencephalography (MEG) while viewing 14 images of feet, hands, mouths, and objects. We decoded categories of the presented images from the MEG signals using a support vector machine (SVM) and calculated their accuracy by 10-fold cross-validation. For each subject, a response that appeared to be a body-sensitive response was observed and the MEG signals corresponding to the three types of body categories were classified based on the signals in the occipitotemporal cortex. The accuracy in decoding body-part categories (with a peak at approximately 48%) was above chance (33.3%) and significantly higher than that for random categories. According to the time course and location, the responses are suggested to be body-sensitive and to include information regarding the body-part category. Finally, this non-invasive method can decode category information of a visual object with high temporal and spatial resolution and this result may have a significant impact in the field of brain-machine interface research.

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.

Introduction: Identification of language-related cortical functions can be carried out noninvasively by transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), which allow for lesion-based interrogation and global temporospatial investigation of cortices, respectively. Combining these two modalities can improve the accuracy of the identification, but the relationships between them remain unclear. We compared TMS and MEG responses during the same language task to elucidate their temporospatial relationships and used the results to develop a novel method to identify language-related cortical functions., Methods: Twelve healthy right-handed volunteers performed a picture-naming task during TMS and MEG. TMS was applied on the right or left inferior frontal gyrus (IFG) at five time points, and the reaction times (RTs) for naming the pictures were measured. The temporospatial oscillatory changes measured by MEG during the same task were then compared with the TMS results., Results: Transcranial magnetic stimulation of the left IFG significantly lengthened RTs at 300 and 375 msec after picture presentation, whereas TMS of the right IFG did not change RTs significantly. Interestingly, the stimulus time point at which RTs increased significantly for each individual was correlated with when the low gamma event-related desynchronizations (ERDs) peaked in the left IFG. Moreover, combining the results of TMS and MEG improved the detection rate for identifying the laterality of language function., Conclusions: These results suggest that the low gamma ERDs measured by MEG strongly relate to the language function of picture naming in the left IFG. Finally, we propose a novel method to identify language-related cortical functions by combining TMS and MEG.

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 aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG) during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a non-parametric permutation test. Oscillatory differences were calculated by comparison between "passive viewing" and "active driving." "Passive viewing" was the baseline, and oscillatory differences during "active driving" showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG) during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior cingulate gyrus (PCiG) during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition.

Brain signals recorded from the primary motor cortex (M1) are known to serve a significant role in coding the information brain-machine interfaces (BMIs) need to perform real and imagined movements, and also to form several functional networks with motor association areas. However, whether functional networks between M1 and other brain regions, such as these motor association areas, are related to the performance of BMIs is unclear. To examine the relationship between functional connectivity and performance of BMIs, we analyzed the correlation coefficient between performance of neural decoding and functional connectivity over the whole brain using magnetoencephalography. Ten healthy participants were instructed to execute or imagine three simple right upper limb movements. To decode the movement type, we extracted 40 virtual channels in the left M1 via the beam forming approach, and used them as a decoding feature. In addition, seed-based functional connectivities of activities in the alpha band during real and imagined movements were calculated using imaginary coherence. Seed voxels were set as the same virtual channels in M1. After calculating the imaginary coherence in individuals, the correlation coefficient between decoding accuracy and strength of imaginary coherence was calculated over the whole brain. The significant correlations were distributed mainly to motor association areas for both real and imagined movements. These regions largely overlapped with brain regions that had significant connectivity to M1. Our results suggest that use of the strength of functional connectivity between M1 and motor association areas has the potential to improve the performance of BMIs to perform real and imagined movements.

To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities and differences of movement-related cortical fields (MRCFs) in middle-aged and elderly monozygotic (MZ) twins. MRCFs were measured using a 160-channel magnetoencephalogram system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1) between 16 MZ twins and 16 pairs of genetically unrelated pairs. Differences in latency and dipole location between MZ twins were significantly less than those between unrelated age-matched pairs. However, amplitude and dipole intensity were not significantly different. These results suggest that the latency and dipole location of MEF1 are determined early in life by genetic and early common environmental factors, whereas amplitude and dipole intensity are influenced by long-term environmental factors. Improved understanding of genetic and environmental factors that influence cerebral motor function may contribute to evaluation and improvement for individual motor function.

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.

Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation-guided 5 Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ≥ 30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P=.035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P=.035 and P=.019), and significantly increased after rTMS (P=.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD)., Methods: Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting., Results: The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α., Conclusion: The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.

Conclusion: The midline electroneurography (ENoG) method might reflect total facial nerve degeneration., Objective: 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., Methods: 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., Results: 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.

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We report the case of a 70-year-old female patient with granulomatous interstitial nephritis (GIN) induced by carbamazepine (CBZ). The patient had a 22-year history of bipolar disorder. Approximately 50 days before admission to our hospital, she was switched from valproic acid to 200 mg/day CBZ for mood swings. Forty days later, she presented with mild transient platelet depletion and liver dysfunction along with a C-reactive protein (CRP) level of 2.65 mg/dL. At that time, she discontinued CBZ without consulting the doctor. She subsequently developed high fever and a pruritic maculopapular rash. Laboratory tests revealed an elevated CRP level (11.98 mg/dL) and serum creatinine (sCr) of 1.6 mg/dL. Hence, she was admitted to our hospital, where she showed eosinophilia and immunoglobulin suppression. She was diagnosed with atypical drug-induced hypersensitivity syndrome (DIHS). All drugs prescribed by the previous doctor were discontinued. A lymphocyte transformation test showed CBZ positivity; a renal biopsy revealed many granulomatous lesions connected to arterioles, without angionecrotic findings. The patient had no history of allergic disorders or tuberculosis. Because of psychological instability, we treated her conservatively without steroid administration. She had a good recovery except for mild residual renal insufficiency (sCr, 1.0 mg/dL). Although granuloma formation has been observed in kidney biopsy specimens of rare cases with DIHS, no previous studies have reported on the relationship between arterioles and granuloma formation.

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., (© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.)

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.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The frequency profiles and time courses of oscillatory changes when reading words are not fully understood, although there have been many reports that oscillatory dynamics reflect local brain function. In order to clarify oscillatory dynamics, we investigated the frequency and spatiotemporal distributions of neuromagnetic activities during silent reading of words in 23 healthy subjects. Individual data were divided into the following frequency bands: theta (5-8 Hz), alpha (8-13 Hz), beta (13-25 Hz), low gamma (25-50 Hz), and high gamma (50-100 Hz), and were analyzed by synthetic aperture magnetometry (SAM). The time window was consecutively moved in steps of 50 ms. Group analysis was performed to delineate common areas of brain activation. A transient power increase in the theta band occurred first in the bilateral occipital cortices, and then rapidly propagated to the left temporo-occipital areas, left inferior and middle frontal gyri, bilateral medial prefrontal cortices, and finally to the left anterior temporal cortices, which possibly reflects a serial cognitive process. This serial propagation of the transient power increase in the theta band was followed by sustained power decreases in the alpha, beta and low gamma bands. These results suggest that the transient power increase in the theta bands may be associated with priming and propagation of local activities, while sustained power decreases in the alpha, beta and low gamma bands reflect parallel neural processes related to silent reading words. Our results showed a relationship between frequency bands of oscillatory changes and locations. This may have implications in the relationship between frequency bands and functions., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A 59-year-old Japanese man admitted to our hospital complaining of anasarca, body weight gain, and elevation of blood pressure. Serum creatinine(Cre), albumin(Alb), cholesterol(chol), and urinary protein were 1.3 mg/dL, 2.5 g/dL, 527 mg/dL, and 10 g/gCr, respectively. An abdominal echography showed a renal mass, which was diagnosed to be a hypertrophic column of Bertin by enhanced CT. His serum Cre and Alb had worsened to 1.6 mg/dL and 1.7 g/dL, respectively, and a renal biopsy was performed. The results showed a segmental sclerotic lesion associated with hypertrophy and proliferation of podocytes in several glomeruli, hence we diagnosed a focal segmental glomerulosclerosis collapsing variant. After steroid pulse therapy and LDL apheresis, his serum Cre level had decreased to 1.1 mg/dL and the urinary protein level to 2.5 g/gCr. Patients with a focal segmental glomerulosclerosis collapsing variant are poor responders to standard therapies, and have a very poor prognosis. For this case, combined steroid pulse and LDL apheresis therapy was effective.

Background: Secondary hyperparathyroidism is one of the critical complications of end-stage renal disease patients. Conventionally intact parathyroid hormone (iPTH) was used to assess secondary hyperparathyroidism, but this assay measures both PTH(1-84) (full-length parathyroid hormone) and PTH(7-84) (amino (N)-terminal-cleaved parathyroid hormone). PTH(7-84) is biologically inactive or antagonistic for PTH. In this study, we examined the relationship between serum calcium concentration and PTH(7-84)/PTH(1-84) ratio and the effect of calcimimetics on the ratio in hemodialysis (HD) patients., Methods: Ionized-calcium (iCa), iPTH, and whole PTH (wPTH) were measured at the start of HD sessions on HD patients. Patients were divided into four groups by presence (+) or absence (-) of vitamin D (VD) and calcimimetics (CM)., Result: PTH(7-84)/PTH(1-84) ratios of the four groups [VD(-)CM(-), VD(+)CM(-), VD(-)CM(+) and VD(+)CM(+)] were 0.735, 0.799, 0.844, and 1.156, respectively. In VD(-)CM(-) and VD(+)CM(-) groups, iCa and PTH(7-84)/PTH(1-84) ratio showed equilateral correlation (r = 0.634, p < 0.001 and r = 0.360, p < 0.01, respectively). In calcimimetics-treated group, iCa and PTH(7-84)/PTH(1-84) ratio did not show correlation., Conclusion: Whereas in the absence of calcimimetics cleavage of N-terminal PTH was regulated by serum calcium concentration, this regulation was abolished in the presence of calcimimetics. This suggests that cleavage of N-terminal PTH is regulated by calcium concentration via a calcium-sensing receptor and that calcimimetics may have a novel effect to reduce PTH level.

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 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)., 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.

Various renal vascular lesions are complicated with systemic lupus erythematosus (SLE), and are often overlooked in the actual renal biopsy specimen. We report a case of biopsy-proven lupus vasculopathy, with lupus nephritis class IV-G (A). She developed SLE at 15 years of age, and was treated with prednisolone(PSL) and cyclophosphamide (CTX). Sometimes she experienced a flare-up clinically or serologically, requiring a dose increase of oral PSL. At 40 years of age, she visited our hospital after discontinuation of hospital visits for about 4 months. Oral PSL at 30 mg per day was not effective for urinary abnormalities, increase of anti double-stranded DNA (ds-DNA) antibody titer and decrease in complement components. On admission she had hypertension (180/92 mmHg) and signs of microangiopathic hemolytic anemia. Renal biopsy findings showed the glomerular changes of lupus nephritis, WHO class IV-G (A), and lupus vasculopathy, which is marked luminal narrowing or total occlusion by abundant subendothelial accumulation of immunoglobulins and complement components. In addition to PSL, intravenous pulse CTX promptly achieved clinical remission. When lupus vasculopathy is complicated, CTX may be useful.

We followed eight hereditary motor and sensory neuropathy patients with proximal dominance (HMSN-P) in Shiga prefecture from 1984 to 2007. There were 4 men and 4 women from two families showing autosomal and dominant prepotency. These families were related by marriage. The average onset of disease was at 53.4 +/- 8.9 (40-68) years-old. Initial symptoms were difficulty of standing up, difficulty elevating their arms, limping, or numbness. The main feature was neurogenic muscular atrophy with proximal dominance. All deep tendon reflexes were decreased or nonexistent. Paresthesia in the hands and feet and/or decreased vibratory sense in the legs were found in six patients. High CK blood levels were recognized in three patients. EMG in four patients revealed neurogenic pattern. Nerve conduction study was conducted in two patients. MCV of the median nerve and of the tibial posterior nerve, also SCV of the median nerve and of the sural nerve were within normal range in all nerves. Amplitudes of sensory action potential or of M wave were decreased or nonexistent in five of eight nerves, and distal latency of M waves was delayed in three of four nerves. These data suggests dysfunction of distal parts of the peripheral nerve fibers and axonal degeneration of the nerve trunk. Seven patients have died, and their average death age was 69.1 +/- 8.2 (52-77) years-old. Their average affected period was 16.6 (4-30) years. Their clinical history resembles Okinawa-type HMSN-P, but without the painful muscle cramps which are distinctive Okinawa-type signs.

We previously demonstrated that late electromyographic responses with a latency of 100 ms were evoked bilaterally in soleus muscles following transcranial magnetic stimulation over the left cerebellum. Efferent fibers from the left cerebellum modulate vestibulospinal tract influences on the extensor muscles of the left hindlimb. Here, we investigated whether the vestibulospinal tract mediates this late response. We activated the vestibulospinal tract by optokinetic stimulation. Our results show that the latency of the soleus electromyographic response is shortened by optokinetic stimulation, but the latency of the motor response evoked by the corticospinal tract is unchanged. These findings support our hypothesis that vestibulospinal tracts mediate late electromyographic responses, and allow the development of techniques to assess the human vestibulospinal system function.

Recent changes in Japanese social environments consequently dropped total fertility rate, and poor interpersonal relationships in local communities have aggravated the environments for childbirth and child-rearing. Under such circumstances, we introduced a bulletin board system (BBS) to an official web-site of a maternity hospital to set up a community for its patients for communication regarding childbirth and the like. Based on the logs from BBS, we graphed types of communication among its users with to describe topologies. Additionally, we calculated degrees of centralization of entire networks and found the hospital role as the administrator becomes smaller as inter-user communication becomes more brisk. The analysis of contents of respective threads also revealed that main topics shifted from gestational matters to postnatal and child-rearing as communication became more brisk, which indicates those postnatal users are also strongly conscious with gestational and progestational contents and contribute to supporting the entire BBS.

The objective of this study was to elucidate how and where emotional connotations in words influenced linguistic processing in the language-related areas. We recorded neuromagnetic signals in nine right-handed and one left-handed healthy volunteers while they silently read emotional and emotionless words written in Japanese kanji characters, and investigated the distribution of the cerebral oscillatory changes using synthetic aperture magnetometry. Event-related desynchronizations (ERDs) in the beta-low gamma bands were observed in the anterior cingulate cortex (ACC) that were specific to the reading of emotional words in seven of nine right-handers. Beta-low gamma band ERDs were also detected in the left inferior or middle frontal gyrus (IFG or MFG) in nine right-handers regardless of the tasks. The magnitude of the ERDs in the IFG or MFG was significantly greater during emotional-word reading than during emotionless-word reading in nine right-handers. Left-dominant ERDs in the beta and gamma bands were observed in the prefrontal cortex (PFC) when negative emotional words were read (i.e. sadness), while right-dominant ERDs were observed for positive emotional words (i.e. happiness) in seven of nine right-handers (p=0.012, corrected). In one left-hander, the ERD in the ACC and the greater ERD that occurred in the IFG that was specific to emotional-word reading were also observed, but their lateralities in the IFG and PFC were reversed. These results suggest that emotional connotations in words facilitated the ERDs in the frontal language-related areas, and that these facilitations might be modulated by emotional processing in the ACC. Furthermore, negative and positive emotional words may be processed by different mechanisms.

The education system for medical technologists has recently been revolutionized, their educational periods vary from 2 to 9 years, and some already have doctoral degrees. In such a new situation, our faculty thinks that the most important point for new medical technologists is the ability to have a broad view of the clinical fields, especially the view of patients. Special training in bed-side education and a stint in several divisions, such as the surgical operation room, rehabilitation. radiological examination room, pharmacy, central storage room of medical records, and medical informatics, and so on, of the hospital is a powerful tool to obtain a broad view of the various clinical fields and can be essential for developing high performance medical technologists. As nine years have passed since starting this education, we evaluated this practice through systematic personal communication. As a result, it was found to be extremely effective for many reasons such as having a continuous image of the patient when they examine the blood sample in the hospital laboratory, showing advanced laboratory performance, and having no mental barrier to visiting the wards and so on. The abilities of our alumni are praised highly by many large scale hospitals around the country and 50% of them are working in the clinical laboratory division of these hospitals. About 40% are working in the division of research and development in various companies. We express sincere thanks to the director and all cooperative individuals for this course in the Osaka University Hospital.

We performed magnetic stimulation at the level of foramen magnum in healthy subjects to evaluate the long latency response in lower limb muscle. Subjects assumed an upright stance and we recorded electromyographic activities in soleus muscle. A late response at the onset latency of approximately 40 ms was elicited. The late response wasn't induced in other lower limb muscles; anterior tibial muscle, quadriceps femoris muscle, and biceps femoris muscle. Additionally, magnetic stimulation to foot motor cortex, basal occiput and cervical nerve roots did not evoke the response with latency of 40 ms. These results reveal the late response in soleus muscle that has not been previously reported. We speculate that it is involved with the long-loop reflex.