Effects of Lee Silverman Voice Treatment (LSVT LOUD) on Swallowing in Patients with Progressive Supranuclear Palsy: A Pilot Study.

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.

Neural Processing Mechanism of Mental Calculation Based on Cerebral Oscillatory Changes: A Comparison Between Abacus Experts and Novices.

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.

Frequency-specific genetic influence on inferior parietal lobule activation commonly observed during action observation and execution.

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 ß band (13-25 Hz) at the left inferior parietal lobule (IPL) was observed for both action observation and execution. Moreover, ß-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). ß-band ERD heritability at the left IPL was 67% in an ACE model. These results demonstrate that ß-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.

Non-invasive detection of language-related prefrontal high gamma band activity with beamforming MEG.

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.

Noninvasive spatiotemporal imaging of neural transmission in the subcortical visual pathway.

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.

Frequency-dependent oscillatory neural profiles during imitation.

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.

Heritability of brain volume on MRI in middle to advanced age: A twin study of Japanese adults.

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.

Within-pair differences of DNA methylation levels between monozygotic twins are different between male and female pairs.

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.

Language-related cerebral oscillatory changes are influenced equally by genetic and environmental factors.

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.

Common neural correlates of real and imagined movements contributing to the performance of brain-machine interfaces.

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.

Categorical discrimination of human body parts by magnetoencephalography.

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.

Closed-Loop Control of a Neuroprosthetic Hand by Magnetoencephalographic Signals.

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.

Temporospatial identification of language-related cortical function by a combination of transcranial magnetic stimulation and magnetoencephalography.

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.

Facilitated lexical ambiguity processing by transcranial direct current stimulation over the left inferior frontal cortex.

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.

Alpha band functional connectivity correlates with the performance of brain-machine interfaces to decode real and imagined movements.

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.

Genetic and environmental influences on motor function: a magnetoencephalographic study of twins.

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.

Cerebellar-related long latency motor response in upper limb musculature by transcranial magnetic stimulation of the cerebellum.

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.

Cerebral oscillatory activity during simulated driving using MEG.

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.

Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

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.

The midline electroneurography method for facial palsy reflects total nerve degeneration.

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.