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BackgroundThe Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH.MethodsSixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity.ResultsFinger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery.ConclusionThe quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH.

Accumulated evidence demonstrate that environmental stress affects the hippocampus, functioning in cognition and sociality, and causes various depressive symptoms. In addition, recent findings showed that environmental stress influenced the hippocampal activity correlated with neuroinflammation, and impaired the hippocampal sharp wave ripples (SWRs), pattens of spike sequences, and the theta rhythms, a strong oscillation observed in the hippocampus. The involvement of the electrophysiological alterations in the etiology of depression has not been appreciated especially in the hippocampus. Furthermore, the pathological markers associated with such alterations have not been identified. In the present study, therefore, the impairment of the SWRs and the theta rhythms in the hippocampus of the restraint stress-induced depression model of mice was analyzed. In the model mice the hippocampal SWRs and theta rhythms were impaired in depression, while physical exercise significantly reverted them. As previously reported, chronic stress induced inflammation in the affected hippocampus in parallel with defects of adult neurogenesis, on the other hand physical exercise ameliorated those pathological conditions of the bran in depression. In conclusion, this study demonstrated the implications of impairment of the hippocampal SWRs and theta rhythms in the etiology of depression and their usefulness as diagnostic markers of depression.

[Purpose] Patients with chronic unilateral vestibular hypofunction show decreased postural stability and low levels of physical activity and also experience much anxiety. Physical activity is known to improve these symptoms; however, no study has reported any positive effects of physical activity, such as symptom reduction or improvement in function in these patients. In this study, we investigated the role of a walking program in improvement of dizziness, anxiety, and postural stability in this patient population. [Participants and Methods] This study included 21 patients with unilateral vestibular hypofunction and chronic dizziness. Patients were instructed to walk 30 min daily for 3 months. Physical activity levels and questionnaires for clinical symptoms, anxiety, and postural stability were evaluated before and after intervention. [Results] We observed significant differences in the amount of moderate-to-vigorous physical activity, clinical symptoms, and self-perceived handicap before and after the intervention. Additionally, anxiety levels were significantly reduced and postural stability was significantly improved in these patients. [Conclusion] A walking program improved physical activity levels, clinical symptoms, and postural stability and reduced self-perceived handicap and anxiety in patients with chronic unilateral vestibular hypofunction. These results highlight the effectiveness of a walking program for these patients and emphasize its role as a complementary vestibular rehabilitation strategy.

Background Mild cognitive impairment (MCI) is a common symptom in the patients with Parkinson’s disease (PD). The characteristics of cognitive impairment in PD are executive function (including working memory) and visuo-perceptual processing. The visuospatial n-back test has the merit of minimizing the influence of educational biases involved in the verbal n-back test. Furthermore, it can assess both visuospatial recognition and working memory in a single test. Methods We aimed to clarify the advantage of the visuospatial n-back test as a tool for detecting impairments of working memory in PD. We enrolled 28 right-handed patients with PD (18 males, 10 females) and 12 age-matched healthy controls (HC; 7 males, 5 females). Thirteen patients were classified as MCI (PD-MCI), and 15 as cognitively normal PD (PD-CN). Using functional MRI (fMRI), we explored the specific brain regions associated with the performance of the n-back test in the PD-MCI, PD-CN, and HC groups. The 0-back test assesses visuospatial recognition, while the 1-back and 2-back tests assess visuospatial working memory. Group comparisons were performed for three loads of this test. Results Patients with PD performed significantly worse in terms of the correct answer rates of all n-back tests compared with HC. fMRI analyses performed during the 2-back test revealed reduced activation in the bilateral dorsolateral prefrontal cortex, middle frontal gyrus (MFG), and parietal lobule in the PD group compared with the HC group. In contrast, the fMRI result during the 0-back test showed only a marginal difference in the frontal lobe. On comparisons of task performance between the PD-MCI and PD-CN groups, we found that the correct answer rate in the 2-back test was lower in the PD-MCI group than in the PD-CN group. However, scores of the 0-back and 1-back tests were not significantly different between the two groups. The fMRI findings revealed that activations within the middle frontal gyrus (MFG) and inferior parietal lobule (IPL) during the 2-back test were reduced in the patients with PD-MCI when compared to those with PD-CN. Conclusions This study reports reduced activation of the MFG and IPL in patients with PD-MCI. These regions may be associated with the pathophysiology of working memory impairment in patients with PD, which involves fronto-striatal network dysfunction.

Background Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F-u-HA/PLLA) implants are widely used in surgeries because they possess high mechanical strength, bioactivity, and radio-opacity. We previously reported that F-u-HA/PLLA implants were useful for treating lateral tibial condylar, lateral humeral condylar, and ankle fractures. The study aim was to investigate the efficacy of F-u-HA/PLLA cannulated screws and FiberLoop® for treating transverse patellar fractures. Methods From April 2013 to February 2019, 15 patients with transverse patellar fractures were treated with F-u-HA/PLLA cannulated screws and FiberLoop® as follows: Open reduction and internal fixation (ORIF) were performed with two F-u-HA/PLLA cannulated screws and a temporary fixation Kirshner wire (K-wire). Three No. 2 FiberLoops® were inserted into these two screw holes and the K-wire hole for temporary fixation. All patients were allowed to full weight-bearing gaits using a knee brace. Knee range of motion exercise was initiated on postoperative day 1. Knee flexion was restricted to ≤90° for 1 month postoperatively. Radiograph was performed to evaluate fracture healing, screw breakage, reduction loss, and screw radio-opacity. Clinical outcomes and postoperative complications were assessed. Results The average follow-up was 16.0 months. All fractures were successfully united. Screw breakage, reduction loss, osteolysis, and radiolucent zones around the screws were not observed at the final radiographic follow-up. All F-u-HA/PLLA screw shadows were observed during the follow-up. The average range of flexion and extension were 132.0° and −2.7°, respectively. No patients experienced deep infection episodes, late aseptic tissue reactions, or foreign body reactions postoperatively. No patients complained of pain at the final follow-up. All patients returned to their pre-injury work level and activities of daily living. Conclusion Our results strongly suggest that ORIF with F-u-HA/PLLA screws and FiberLoop® could be an alternative treatment option for transverse patellar fractures.

Microsoft Kinect V2Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson's correlation and overall agreement with a method of meta-analysis of Pearson's correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups.The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups.Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

Aphasia is a language disorder that occurs after a stroke and impairs listening, speaking, reading, writing, and calculation skills. Patients with post-stroke aphasia in Japan are increasing due to population aging and the advancement of medical treatment. Opportunities for adequate speech therapy in chronic stroke are limited due to time constraints. Recent studies have reported that intensive speech therapy for a short period of time or continuous speech therapy using high-tech equipment, including speech applications (apps, can improve aphasia even in the chronic stage. However, its underlying mechanism for improving language function and its effect on other cognitive functions remains unclear. In the present study, we investigated whether intensive speech therapy using a newly developed speech support app could improve aphasia and other cognitive functions in patients with chronic stroke. Furthermore, we examined whether it can alter the brain network related to language and other cortical areas. Thus, we conducted a prospective, single-comparison study to examine the effects of a new speech support app on language and cognitive functions and used resting state functional MRI (rs-fMRI) regions of interest (ROI) to ROI analysis to determine changes in the related brain network. Two patients with chronic stroke participated in this study. They used the independent speech therapy system to perform eight sets of 20 randomly presented words/time (taking approximately 20 min), for 8 consecutive weeks. Their language, higher cognitive functions including attention function, and rs-fMRI, were evaluated before and after the rehabilitation intervention using the speech support app. Both patients had improved pronunciation, daily conversational situations, and attention. The rs-fMRI analysis showed increased functional connectivity of brain regions associated with language and attention related areas. Our results show that intensive speech therapy using this speech support app can improve language and attention functions even in the chronic stage of stroke, and may be a useful tool for patients with aphasia. In the future, we will conduct longitudinal studies with larger numbers of patients, which we hope will continue the trends seen in the current study, and provide even stronger evidence for the usefulness of this new speech support app.

Cognitive decline is commonly observed in Parkinson's disease (PD). Identifying PD with mild cognitive impairment (PD-MCI) is crucial for early initiation of therapeutic interventions and preventing cognitive decline.We aimed to develop a machine learning model trained with magnetic susceptibility values based on the multi-atlas label-fusion method to classify PD without dementia into PD-MCI and normal cognition (PD-CN).This multicenter observational cohort study retrospectively reviewed 61 PD-MCI and 59 PD-CN cases for the internal validation cohort and 22 PD-MCI and 21 PD-CN cases for the external validation cohort. The multi-atlas method parcellated the quantitative susceptibility mapping (QSM) images into 20 regions of interest and extracted QSM-based magnetic susceptibility values. Random forest, extreme gradient boosting, and light gradient boosting were selected as machine learning algorithms.All classifiers demonstrated substantial performances in the classification task, particularly the random forest model. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve for this model were 79.1%, 77.3%, 81.0%, and 0.78, respectively. The QSM values in the caudate nucleus, which were important features, were inversely correlated with the Montreal Cognitive Assessment scores (right caudate nucleus: r = -0.573, 95% CI: -0.801 to -0.298, p = 0.003; left caudate nucleus: r = -0.659, 95% CI: -0.894 to -0.392, p 0.001).Machine learning models trained with QSM values successfully classified PD without dementia into PD-MCI and PD-CN groups, suggesting the potential of QSM values as an auxiliary biomarker for early evaluation of cognitive decline in patients with PD.

Kendo, a type of fencing using bamboo swords, is one of the most popular Japanese martial arts that is practiced by over four million people worldwide.1 Kendo players wear face masks that protect their heads, but only from front and side attacks (figure 1A). Repetitive head trauma in athletes engaged in contact sports has been associated with development of neurodegenerative disorders.2 Herein, we present the case of kendo player with a history of chronic headache, depression, and cognitive dysfunction, who developed occipital epilepsy followed by generalized tonic-clonic seizures, as a result of repetitive head injuries.

The Revelation Hip System is a cementless stem with a lateral flare concept. Stable fixation is achieved by fitting the stem to the medullary cavity of the proximal lateral femoral cortex. Patients who have undergone total hip arthroplasty using the Revelation Hip System show good postoperative clinical and radiographic outcomes. However, to the best of our knowledge, no study has reported the relationship between stem fitting and clinical or radiological outcomes after the surgery. In the present study, we investigated the relationship between stem fitting and clinical or radiological outcomes after total hip arthroplasty (THA) using the Revelation Hip System. In this study, 28 hips of 26 patients who were treated with the Revelation Hip System for osteoarthritis, osteonecrosis of the femoral head, rheumatoid arthritis, and rapidly destructive coxarthropathy and were followed up for 5 y were enrolled. These patients were divided into two groups, including the rest fit group (11 hips, group R) and the control group (17 hips, group C), according to the results of the density mapping analysis. In group R, the lateral side of the stem fits on the medullary cavity of the proximal lateral femoral cortex, while in group C, the lateral side of the stem did not fit. Radiographic results showed no significant differences between the groups in terms of stem alignment, subsidence, and stress shielding around the cup. The incidence of stress shielding around the stem in zone 7 was not significant but tended to be higher in group R than in group C (p = 0.052). Clinical outcomes showed no significant differences between group R and group C in terms of the Harris hip score, the Japanese Orthopaedic Association (JOA) score, and the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) total score. However, pain complaints that were assessed by patient-reported outcomes using the 36-Item Short Form Health Survey (SF-36) bodily pain and vitality subscales and the JHEQ pain subscale were significantly higher in group R than in group C at the final follow-up. These results suggest that some patients had pain complaint even if the stems were inserted as per the concept after THA with the Revelation Hip System.Trial Registration911.

Although several studies have demonstrated correlation between white matter hyperintensities (WMH) and impairment of executive functions, the underlying anatomical-functional relationships are not fully understood. The present study sought to investigate the correlations between the volume of WMH and medial temporal lobe atrophy (MTA) using quantitative magnetic resonance image (MRI) and a variety of executive function assessments. A total of 91 patients ranging in age from 58 to 90 years with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or early phase AD were recruited from the outpatient clinic at the Department of Neurology of Nagoya City University Hospital. We administered neuropsychological batteries evaluating verbal memory, orientation, spatial ability, sustained attention, and a variety of executive functions, including verbal fluency, flexibility, inhibition, and working memory. Quantitative MRI analyses were performed using Dr. View/Linux software and a voxel-based specific regional analysis system. Significant correlations were observed between WMH, as well as MTA, and some executive function scores. Regression analysis revealed that MTA was the strongest predictor of flexibility and verbal fluency. These findings provide new insight into the relationship between quantitative MRI analyses and various types of executive dysfunction in elderly people with MCI due to AD and/or early phase AD. When cognitive function is examined in elderly patients with MCI due to AD or early phase AD, it is important to consider the involvement of WMH and MTA, which is indicative of AD pathology in cognitive dysfunction, particularly executive function.

[Purpose] Sports activity has been shown to improve postural stability and vestibular function in healthy older adults. The hypothesis was that healthy young adults undertaking sports activity will also have better postural stability and vestibular function compared with healthy young adults who do not undertake sports activity. The purpose of this study was to investigate the differences in postural stability and vestibular function between healthy young adults who undertake sports activity and those who do not undertake such activity. [Participants and Methods] Thirty-nine healthy young adults were recruited and divided into sports and non-sports groups on the basis of their response to a questionnaire concerning regular participation in sports activities over the past 12 months. In both groups, postural stability was measured during quiet standing and standing during head rotation, and dynamic visual acuity was assessed during head rotation. [Results] The results showed significant differences in postural stability during head rotation and dynamic visual acuity between the two groups, whereas no significant differences were found in postural stability during quiet standing. [Conclusion] The results suggest that healthy young adults who undertake sports activity have better postural stability during head rotation and better dynamic visual acuity. The causal effect of these differences is not clear and further investigation is warranted.

We describe the pathology and treatment of flexible flat foot in children. The flexible flat foot is seen in the overly flexible foot and usually involves hypermobility of the subtalar joint. It typically occurs in childhood and may continue to adulthood. The arch develops spontaneously during the first decade of life in most children and comes within the normal range observed in adult feet. We prescribed orthoses for the treatment of flexible flat foot patients. Lateral weight-bearing radiographs and ultrasonography were helpful for the evaluation of the flat foot. Bleck recommended the UCBL shoe insert in cases of flexible flat foot if the standing or lateral rentgenogram demonstrates a talar plantar flexion angle (TPF) of 45° or greater. Bordelon suggested that cases of flexible flat foot should be treated if the standing or lateral roentgenogram demonstrates a Meary's talo-1st metatarsal angle (T1-MTA) of -15°or greater. However, the radiograph of a young child's foot poses some difficulties in making an accurate evaluation, because of the radiolucent cartilage zone. In this situation, a sagittal image obtained by ultrasonography has proved to be a powerful aid to evaluate the type of the flat foot. We classified the flat foot into three types: talo-navicular sag (T-N sag), naviculo-cuneiform sag (NC sag) and talo-navicular and naviculo-cuneiform sag (Mixed sag) following the criteria of Tachdjian. We recommended the NC sag and Mixed sag groups to be treated by using orthoses, while we kept a status of watchful waiting for the T-N sag group. However, we should consider the increasing complaints of children and their parents during the orthotic treatment. A through discussion between the parents of patients and the pediatric orthopedic doctors is necessary before orthotic treatment is started.

Introduction: Trochanteric femoral fracture is one of the most common fractures in the elderly. Trochanteric femoral fracture with involvement of the lesser trochanter is considered unstable and recognized as having a poor prognosis. However, fixation of lesser trochanter fragment is scarce because of technical difficulties. In this study, we reported the simple surgical procedure and the effect of using nonabsorbable tape in lesser trochanter fixation. Methods: From January 2014 to December 2017, 114 patients treated with proximal intramedullary nailing for trochanteric fractures with the lesser trochanter fragment were reviewed. Among patients enrolled in this study, 73 were followed up until radiographic bone union, of which 26 were treated with lesser trochanter fragment banding (group B) and 47 without banding (group N). Radiographs and/or computed tomography images were used to evaluate bone union of the lesser trochanter fragment at three months postoperatively. Results: The bone union of the lesser trochanter fragment was achieved in 24 cases (92%) in group B and 30 cases (64%) in group N. Compared with group N, group B showed a significantly increased number of mild and moderate deformities but decreased number of severe deformity and nonunion (P < 0.001). Postoperative complications were not observed in both groups. Conclusions: From the viewpoint of increasing lesser trochanteric bone union ratio, fixation of the lesser trochanter fragment using nonabsorbable tape in the treatment of trochanteric fractures could be an effective procedure.

BackgroundCognitive impairment is a common symptom in the patients with Parkinson’s disease (PD). In delineating a therapeutic plan, the early diagnosis of mild cognitive impairment in PD (PD-MCI) is important. Patients with PD-MCI have severe impairment in frontal executive function and/or visuospatial recognition. However, the clinical assessment of these functions is not routinely performed.MethodIn this study, we aimed to clarify the advantage of visuospatial version of the n-back test as a tool for the early detection of neuropsychological change in the patients with PD-MCI. The score of 0-back test reflects visuospatial recognition, and the scores of 1-back and 2-back reflect visuospatial working memory. PD-MCI was classified according to the criteria provided by the Movement Disorder Society Task Force for mild cognitive impairment in PD. We recruited 13 patients with PD-MCI, and 15 patients with cognitive normal PD. Using functional MRI (fMRI), we also aimed to clarify the specific brain regions associated with the impairment of visuospatial working memory.ResultWe demonstrated that the correct answer rate of patients with PD-MCI was lower in the 2-back test than patients with PD-CN. However, we did not find statistical difference in the 0-back test. These results indicate the preservation of visuospatial recognition and the impairment of visuospatial working memory in the patients with PD-MCI. We revealed the reduced activation within the middle frontal gyrus (MFG) and the inferior parietal lobule (IPL) during the 2-back test in the patients with PD-MCI. It may be associated with the severity of cortico-striatal dysfunction in the dopaminergic neural network which is associated with Lewy body pathology.ConclusionThe visuospatial n-back test has advantages for use in rapid and early detection of impaired visual recognition and working memory. The combination of functional neuroimaging and neuropsychological tests may provide markers for the increased risk of dementia before the development of an irreversible disease-specific pathology.

OBJECTIVE The objective of this study was to assess the relationship between nigrostriatal magnetic susceptibility and dopamine transporter abnormality and their associations with behavioral and cognitive impairments in patients with Parkinson's disease (PD). METHODS For this case-control study, we enrolled 41 patients with PD and 20 age-matched healthy controls. All participants underwent global physical and cognitive assessments, 3-Tesla brain magnetic resonance imaging including quantitative susceptibility mapping (QSM; iron deposition measure), and 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane single-photon emission computed tomography (dopamine transporter measure). We subdivided the striatum into the putamen, caudate nucleus, and nucleus accumbens and measured the nigrostriatal QSM values and dopamine transporter-specific binding ratios using an atlas-based approach. RESULTS The patients with PD had higher QSM values in the substantia nigra and subdivisions of the striatum than did the healthy controls. The striatal dopamine transporter-specific binding ratios were not correlated with the QSM values of the substantia nigra but were inversely correlated with those of the striatum (putamen, r = -0.478, P = 0.009; caudate nucleus, r = -0.462, P = 0.011). The QSM values of the putamen were positively correlated with motor parkinsonism scores (Movement Disorder Society Unified Parkinson's Disease Rating Scale, r = 0.505, P = 0.003), and those of the caudate nucleus were negatively correlated with cognitive impairment scores (Montreal Cognitive Assessment, r = -0.525, P

Highlights • R2* relaxometry analysis combined with QSM revealed detail of WM alteration in PD-MCI. • R2* relaxometry analysis can detect slight demyelination in PD-MCI. • R2* value shows potential for early evaluation of cognitive decline in PD., Background R2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson’s disease (PD) using R2* relaxometry analysis combined with QSM. Materials and methods We enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed. Results In the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere. Conclusion R2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD.

Introduction: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. Methods: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson’s correlation and overall agreement with a method of meta-analysis of Pearson’s correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. Results: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. Conclusions: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

IgG4-related disease (IgG4-RD) is a recently recognized disease entity. A 74-year-old male presented with transient headache. He was diagnosed IgG4-RD by pancreatic biopsy at the age of 72. Magnetic Resonance Imaging (MRI) showed disseminated cerebral microbleeds and microinfarctions in time and space. It suggested cerebral vasculitis, however any causative factor were not confirmed. IgG4-RD rarely causes cerebral vasculitis. This might be a first case of an asymptomatic cerebral vasculitis due to IgG4-RD. Patient was started on oral prednisolone, and no neurological or neuropsychological symptom was clinically observed. The MRI findings improved after treatment, and revealed no indication of newly lesions at 6-months follow-up. Early treatment for IgG4-RD may be recommended to prevent irreversible cognitive dysfunction., Highlights • Cerebral vasculitis is uncommon in IgG4-RD. • This report is a first case of IgG4-RD where treatment for cerebral involvement was underwent in an asymptomatic stage. • Early treatment for IgG4-RD may be recommended to prevent irreversible cognitive dysfunction.

ObjectiveTo assess the relationship among iron accumulation, blood–brain barrier (BBB) damage, and cognitive function in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).MethodsWe enrolled 21 patients with NOTCH3 mutations and 21 age-matched healthy controls in this cross-sectional study. All participants underwent global physical and cognitive assessments and brain MRI using voxel-based quantitative susceptibility mapping (QSM; iron deposition measure) and dynamic contrast-enhanced MRI (BBB permeability measure). We compared behavioral and imaging data between the groups and analyzed the correlations in each group.ResultsAmong 21 NOTCH3 mutation carriers, 10 were symptomatic and 11 asymptomatic. Montreal Cognitive Assessment scores were significantly different among the groups (symptomatic < asymptomatic < control participants). Voxel-based QSM analysis revealed that the symptomatic group had higher QSM values than did the asymptomatic group in the putamen, caudate nucleus, temporal pole, and centrum semiovale. These QSM values were positively correlated with regional BBB permeabilities (putamen: r = 0.57, p = 0.006; caudate nucleus: r = 0.51, p = 0.019; temporal pole: r = 0.48, p = 0.030; centrum semiovale: r = 0.45, p = 0.044) and negatively correlated with Montreal Cognitive Assessment scores (caudate nucleus: r = −0.53, p = 0.012; temporal pole: r = −0.56, p = 0.008).ConclusionsThis study showed that cerebral iron burden was associated with regional BBB permeability and cognitive dysfunction in patients with CADASIL, highlighting the potential of these imaging techniques as auxiliary biomarkers to monitor the course of small vessel disease.

Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.

This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel-based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T1 -weighted and multi-echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP-QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP-spoiled gradient echo (MP-GRE) in healthy volunteers to validate the availability of MP-QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel-based comparisons of susceptibility and morphometry in MP-QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP-QSM, MP-GRE, and mGRE were 0.14 ± 0.011, 0.17 ± 0.015, and 0.045 ± 0.010, respectively. Segmented GM and WM volumes in the MP-QSM closely coincided with those in the MP-GRE. Region of interest analyses indicated that the mean susceptibility values in MP-QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP-QSM sequence makes it possible to acquire acceptable-quality images for simultaneous analysis and determine brain atrophy and susceptibility distribution without image registration by using voxel-based analyses.

Recent non-invasive brain stimulation techniques in combination with motor training can enhance neuroplasticity and learning. It is reasonable to assume that such neuroplasticity-based interventions constitute a useful rehabilitative tool for patients with Parkinson's Disease (PD). Regarding motor skill training, many kinds of tasks that do not involve real motor movements have been applied to PD patients. The purpose of this study is to elucidate whether motor skill training using mirror visual feedback (MVF) is useful to patients with PD in order to improve untrained hand performance dependent on the time course of training; and whether MVF combined with anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) causes an additional effect based on increased motor cortical excitability. Eighteen right-handed patients with PD in the off-medication state and 10 age-matched healthy subjects (HS) performed four sessions of right-hand ball rotation using MVF (intervention) on two separate days, 1 week apart (day 1 and day 2). HS subjects received only sham stimulation. The intervention included four sessions of motor-skill training using MVF for 20 min comprised of four sets of training for 30 s each. PD patients were randomly divided into two intervention groups without or with anodal tDCS over the right M1 contralateral to the untrained hand. As the behavior evaluation, the number of ball rotations of the left hand was counted before (pre) and immediately after (post) intervention on both days (pre day 1, post day 1, pre day 2, and post day 2). Motor evoked potential (MEP), input-output function, and cortical silent period were recorded to evaluate the motor cortical excitatory and inhibitory system in M1 pre day 1 and post day 2. The number of ball rotations of the left hand and the facilitation of MEP by intervention were significantly impaired in patients with PD compared to HS. In contrast, if anodal tDCS was applied to right M1 of patients with PD, the number of ball rotations in accordance with I-O function at 150% intensity was significantly increased after day 1 and retained until day 2. This finding may help provide a new strategy for neurorehabilitation improving task-specific motor memory without real motor movements in PD.

OBJECTIVE Brain iron accumulation has been proposed as one of the pathomechanisms in Parkinson's disease (PD). This study aimed to examine the whole-brain pattern of iron accumulation associated with cognitive impairment in patients with PD using voxel-based quantitative susceptibility mapping analysis. METHODS We enrolled 24 patients with PD and mild cognitive impairment, 22 patients with PD and normal cognition, and 20 age-matched healthy controls in this cross-sectional study. All participants underwent global cognitive and physical assessments and brain MRI. Using a combined method of voxel-based morphometry and quantitative susceptibility mapping, we compared the voxel-wise magnetic susceptibility of the whole brain between the groups and analyzed its correlation with the cognitive and behavioral data. RESULTS The PD and mild cognitive impairment group had lower Montreal Cognitive Assessment (MoCA) score than the PD and normal cognition and healthy control groups. There were no gray matter volumetric differences between the groups. In contrast, the voxel-based quantitative susceptibility mapping analysis showed that the PD and mild cognitive impairment group had significantly higher quantitative susceptibility mapping values in the cuneus, precuneus, caudate head, fusiform gyrus, and orbitofrontal cortex than did the PD and normal cognition group. These quantitative susceptibility mapping values were negatively correlated with the MoCA scores in the PD patients (cuneus: r = -0.510, P < .001; caudate head: r = -0.458, P = 0.002). CONCLUSIONS This study suggests that cognitive impairment in PD is associated with cerebral iron burden and highlights the potential of quantitative susceptibility mapping as an auxiliary biomarker for early evaluation of cognitive decline in patients with PD. © 2019 International Parkinson and Movement Disorder Society.

Intra-articular fractures of the posterior malleolus are common in ankle fractures and are frequently difficult to treat during surgery. Posterolateral and posteromedial approaches are commonly used to access the fracture fragments. However, visualization of fragments during surgery is limited because of the thick soft tissue surrounding the fracture fragments. In this study, a new technique of preoperative simulation was used to achieve the optimal position of the fracture fragments, plate, and screws, namely “software-based reduction and fixation,” using a three-dimensional (3D) workstation software, following which the surgery was performed. A 71-year-old man who presented with posterior dislocation of the left ankle with trimalleolar fracture was hospitalized following a fall. The position of the posterior malleolus fracture fragment was preoperatively determined using computed tomography (CT) and reduced using the 3D workstation software. The imported implant data were overlaid on the patient's dataset, enabling determination of the precise position of the plate and the trajectories of the screws. Finally, surgery was performed by referring to the displays of the preoperative simulation and image intensifier. Postoperative radiographs and CT scans showed that the fracture fragments were well reduced and that the implant position and screw trajectories were precisely reproduced in accordance with the preoperative simulation. All fracture fragments were united 3 months after surgery without any complications. This clinical case demonstrated that preoperative simulations using a 3D workstation software and “software-based reduction and fixation” are useful for treating posterior malleolus fractures.

A 50-year-old man with acute myelogenous leukemia underwent allogeneic bone-marrow transplantation (BMT). He presented with severe diarrhoea 86 days post BMT and was diagnosed with graft-versus-host disease (GVHD) based on skin and rectal biopsies. He complained of numbness and weakness in the distal extremities at 114 days after BMT. His symptoms rapidly deteriorated and he required mechanical ventilation for respiratory failure. His clinical course and the findings of a nerve conduction study fulfilled the criteria for diagnosis of Guillain–Barré syndrome (GBS). Sural nerve biopsy revealed active demyelination and infiltration of macrophages and CD8+ T-cells. After three cycles of intravenous immunoglobulin therapy, his symptoms gradually improved, and he could eventually walk unassisted. Although GBS has been known to develop after allogeneic BMT, the pathogenesis remains unclear, and specific treatment regimens have not been well established. Here, we report a case of GBS, caused by an immune-mediated mechanism related to GVHD, which was successfully treated using intravenous immunoglobulin therapy., Highlights • AIDP occurs in the clinical setting of graft-versus-host-disease. • Pathological findings confirmed the infiltration of macrophages and CD8+ T cells. • Three rounds of intravenous immunoglobulin yielded a good prognosis.

Background The mental rotation task is well-known for the assessment of visuospatial function; however, it has not been used for screening of dementia patients. Objective The aim of this study was to create a simple screening test for patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by focusing on non-amnestic symptoms. Methods Age-matched healthy controls (age 75.3±6.8), patients with MCI (76.5±5.5), and AD (78.2±5.0) participated in this study. They carried out mental rotation tasks targeting geometric graphics or alphabetical characters with three rotating angles (0°, 90°, and 180°) and indicated the correct answer. Response accuracy and reaction time were recorded along with their eye movements using an eye tracker. To quantify their visual processing strategy, the run count ratio (RC ratio) was calculated by dividing the mean number of fixations in incorrect answers by that in correct answers. Results AD patients showed lower accuracy and longer reaction time than controls. They also showed a significantly greater number of fixation and smaller saccade amplitude than controls, while fixation duration did not differ significantly. The RC ratio was higher for AD, followed by MCI and control groups. By setting the cut-off value to 0.47 in the 180° rotating angle task, we could differentiate MCI patients from controls with a probability of 80.0%. Conclusions We established a new screening system for dementia patients by evaluating visuospatial function. The RC ratio during a mental rotation task is useful for discriminating MCI patients from controls.

The objective screening of infant hips using ultrasonography (Graf method) is gaining favor in the diagnosis of developmental dysplasia of the hip in Japan. However, the accuracy of the Graf method is dependent on the examiner’s experience and technique. The purpose of this study was to investigate the reproducibility of acquiring ultrasonic hip images and their evaluation after examiners attended an infant hip ultrasound training course. Ultrasonic images of 70 hips of 35 newborns who were screened by ultrasonography using the Graf method, were evaluated. The images were acquired by two inexperienced examiners who attended the training course. The inter- and intra-examiner measurement errors as well as reproducibility were calculated based on the images obtained. The intra-examiner measurement error in the acquired images of the same hip was minor. The inter-examiner measurement error was also small. The intra- and inter-examiner agreements of the Graf classification were high. The intra-examiner reproducibility of the acquired ultrasonic images was substantial, and the inter-examiner reproducibility was almost perfect. Our results demonstrated that inexperienced examiners could obtain ultrasonic infant hip joint images with minor differences and high reproducibility after the training course. Our findings raise the possibility of extending the infant hip ultrasound course in Japan.

Hippocampal cholinergic neurostimulating peptide (HCNP) regulates acetylcholine synthesis in the septal hippocampus through the quantitative increase of choline acetyltransferase levels in the septal nucleus both in vitro and in vivo. Additionally, HCNP-precursor protein transgenic (HCNP-pp Tg) mice display depressive behavior. To examine the physiological function of HCNP and/or HCNP-pp on hippocampal neural activity, we investigated whether overexpression of HCNP-pp strengthened the efficiency of neural activity in the hippocampus. Long-term potentiation (LTP) of excitatory synaptic transmission was induced by a tetanic stimulation of the Schaffer collateral-commissural fibers (SCs) in mouse hippocampal slices. LTP in HCNP-pp Tg mice was significantly enhanced when compared with wild-type littermate (WT) mice. This facilitation of LTP in HCNP-pp Tg mice was blocked by atropine or pirenzepine, but not by mecamylamine. In contrast, LTP in WT mice was not affected by atropine, but enhanced by carbachol. However, neither difference in the input-output relationship of field excitatory postsynaptic potentials nor in the facilitation ratio in paired-pulse stimulation of the SCs was observed between HCNP-pp Tg and WT mice, indicating that presynaptic glutamate release in HCNP-pp Tg mice is similar to that of WT mice. These results suggest that muscarinic (M1) modulation of glutamatergic postsynaptic function may be involved in strengthening LTP in HCNP-pp Tg mice.

Start hesitation in patients with Parkinson's disease (PD) occurs predominantly during distractive and conflictual situations. The aim of this study was to investigate how differently an auditory stimulus (AS) influences execution function and execution time during a cognitively demanding stepping task in PD patients as compared to healthy controls. PD patients and healthy controls stepped forward in response to a visual imperative stimulus of an arrow. We applied a Simon task that comprised congruent and incongruent conditions. Direction and location of the arrow matched in the congruent condition, while they didn't in the incongruent condition. AS were randomly and simultaneously presented with the visual stimulus. An error in the direction of an anticipatory postural adjustment (APA), termed an APA error, and temporal parameters (reaction onset of APA and APA duration) were analyzed. As a result, the AS increased the APA error rate in the control group regardless of the condition, but they did not influence it in the PD group. The AS also speeded the reaction onset in both groups regardless of the condition. The APA duration was prolonged by the AS for the control group, while it was unaffected by the AS for the PD group in both conditions. These findings indicate that AS could facilitate a step initiation, conceivably by facilitating a stimulus identification process and increasing attentional control of stepping behavior, without influencing a decision-making process even in a cognitively demanding condition in patients with PD.

Objective Dizziness is one of the most common symptoms in the general population. Patients with dizziness experience balance problems and anxiety, which can lead to decreased physical activity levels and participation in their daily activities. Moreover, recovery of vestibular function from vestibular injury requires physical activity. Although there are reports that decreased physical activity is associated with handicap, anxiety, postural instability and reduced recovery of vestibular function in patients with chronic dizziness, these data were collected by self-report questionnaires. Therefore, the objective data of physical activity and the relationships between physical activity, handicap, anxiety and postural stability in patients with chronic dizziness are not clear. The purpose of this research was to objectively measure the physical activity of patients with chronic dizziness in daily living as well as handicap, anxiety and postural stability compared to healthy adults. Additionally, we aimed to investigate the relationships between physical activity, handicap, anxiety and postural stability in patients with chronic dizziness. Methods Twenty-eight patients with chronic dizziness of more than 3 months caused by unilateral vestibular hypofunction (patient group) and twenty-eight age-matched community dwelling healthy adults (healthy group) participated in this study. The amount of physical activity including time of sedentary behavior, light physical activity, moderate to vigorous physical activity and total physical activity using tri-axial accelerometer, self-perceived handicap and anxiety using questionnaires, and postural stability were measured using computerized dynamic posturography. Results The results showed worse handicap, anxiety and postural stability in the patient group compared to the healthy group. Objective measures of physical activity revealed that the patient group had significantly longer time of sedentary behavior, shorter time of light physical activity, and shorter time of total physical activity compared to the healthy group; however, time of moderate to vigorous physical activity was not significantly different between groups. Moreover, there were correlations between physical activity and postural stability in the patient group, while there were no correlations between physical activity, handicap or anxiety in the patient group. Conclusion These results suggest that objectively measured physical activity of the patients with chronic unilateral vestibular hypofunction is lower compared to the healthy adults, and less active patients showed decreased postural stability. However, the details of physical activity and causal effect between physical activity and postural stability were not clear and further investigation is needed.

Introduction Gait disturbance of Parkinsonian syndrome is characterized by dysrhythmic gait cycle including freezing, small steps and slowness. These symptoms are often not sufficiently responsive to dopaminergic therapy. Recently, we developed new rehabilitation system using non-invasive closed–circuit brain stimulation targeting on dysrhythmic gait dysfunction. Methods The objective of this study is to investigate whether the oscillatory closed-circuit brain stimulation mimicking the appropriate gait cycle can modulate the gait speed and cycle in patients with parkinsonian syndrome. Six patients with Parkinsonian syndrome participated in this study. Three were diagnosed as Parkinson’s disease, two as corticobasal syndrome and one as vascular parkinsonism. Before gait rehabilitation, we decided optimal brain stimulation frequency to each subject as 1/averaged gait cycle when they were best on condition. All participants performed gait rehabilitation for total ten days which contained 4 sessions (4 min. walk and 3 min. rest) per each day. During gait rehabilitation, slow oscillatory DC stimulation (current intensity 0–2 mA) was applied over ipsilateral cerebellum as symptom dominant side, which was triggered by their flat foot switch attached to the ipsilateral heels. Closed-circuit system enabled the implementation of the oscillatory brain stimulation with a fixed pre-set phase lag with respect to the intrinsic gait cycle. Ten m gait speed, cadence, laterality of gait cycle and frozen of gait questionnaire (FOGQ) were evaluated before and after gait rehabilitation. Results Gait speed and cadence were significantly increased after gait rehabilitation (speed: 98 ± 39 cm/s before and 116 ± 38 cm/s after, cadence: 114 ± 18 steps/min before and 124 ± 20 steps/min after). Laterality of gait cycle and FOGQ were significantly decreased after the rehabilitation (laterality: 0.07 ± 0.05 before and 0.0021 ± 0.004 after, FOGQ: 10 ± 7 before and 7 ± 5 after). Conclusion Closed-circuit brain stimulation during walking is useful method to parkinsonian gait disturbance possibly by normalizing dysrhythmic and lateralized gait control system in patients with Parkinsonian syndrome. This new system may provide the personalized rehabilitation in patients with Parkinson related disorders.

Background: This study aimed to evaluate the efficacy of assessing positive remodeling for predicting future stroke events in the internal carotid artery. We therefore assessed narrowing of the carotid artery lumen using multidetector-row computer tomography (MDCT) angiography and carotid plaque characteristics using black-blood (BB) magnetic resonance (MR). Methods: We retrospectively selected 17 symptomatic and 11 asymptomatic lesions with luminal narrowing >50%. We compared remodeling parameters of luminal stenosis (remodeling ratio, RR/remodeling index, RI) using MDCT and MR intensities of atherosclerotic plaque contents using the BB technique (relative signal intensity, rSI). We also confirmed the validity of the relationship between MR intensity and atherosclerotic plaque contents by histology. The levels of biological markers related to vessel atherosclerosis were measured. Results: Plaque lesions with positive remodeling in carotid arteries were associated with a significantly higher prevalence of stroke compared with plaques with negative remodeling (p < 0.05). Radiologic and histologic analyses determined that plaques with positive remodeling had higher signal intensities (with respect to their lipid-rich content or to hemorrhage) compared with negative remodeling (correlation coefficients: RI and rSI, r = 0.41, p < 0.05; RR and rSI, r = 0.50, p < 0.05). Levels of biological markers, including high-sensitivity C-reactive protein, hemoglobin A1C, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were not useful for predicting stroke events. Conclusions: The results of this study suggest that the combined analysis of RR, RI and rSI could potentially help to predict future stroke events.

The evaluation of cranial nerves in magnetic resonance imaging (MRI) at early developmental stage has not been established in amyotrophic lateral sclerosis (ALS). A 23-year-old man with familial ALS developed peripheral facial nerve palsy, and showed the striking gadolinium enhancement on MRI in those nerves at an early stage. His symptoms progressed rapidly and he died approximately 3 months after onset. We identified a missense mutation in exon 1 of the Cu/Zn superoxide dismutase gene (SOD-1), resulting in a Cys6Gly (C6G) amino acid substitution. Based on the rapid progression and neurotoxicity resulting from SOD-1 protein aggregation, the gadolinium enhancement of facial nerves might be caused by the rapid Wallerian degeneration and blood–brain barrier disruption at the early phase of progression.

1389-9457/$ see front matter 2013 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2013.07.020 ⇑ Corresponding author. Address: Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuhoku, Nagoya, Aichi 467-8601, Japan. Tel.: +81 (0) 52 853 8094; fax: +81 (0) 52 852 3590. E-mail address: toguri@mac.com (T. Oguri). sleep/) Guide for Authors for instructions. We hope this section will be enriched by the contributions of our colleagues who wish to offer stimulating opportunities for discussion and new insights into the field of sleep.

Background Striatal dopamine is functionally important for the acquisition of motor skills. However, it remains controversial as to whether intrinsic processing of motor learning is impaired in patients with Parkinson’s disease (PD), and if yes, whether the impairment is associated with altered striatal dopamine release. Additionally, most neuro-imaging studies of patients with PD have focused on motor sequence learning. In contrast, skill acquisition, specifically, the reconstruction of muscle control of isolated movements, has barely been studied. Method In this study, we used a repetitive skill training task to measure the peak acceleration of left thumb movement during a process to achieve fine tuning of motor skill. Using 11C-raclopride (RAC) positron emission tomography, we investigated changes in striatal dopamine levels in two conditions of a skill acquisition task: initial skill training (Day 1) and acquired condition (Day 2) with eight patients with PD and age-matched healthy subjects (HS). Result In HS, the mean acceleration of each session improved through repeated training sessions on Day 1. However, in patients with PD, the training-associated increase was less than that for HS, and this suggests that repetitive skill training does not result in the effective improvement of motor performance. The regions of interest (ROI) analysis revealed that the RAC-binding potential (BP) was significantly reduced in the right putamen on Day 1 compared with Day 2 in HS. In patients with PD, BP within the right putamen was unchanged. Further, we found that patients with PD had increased dopamine levels within the right ventral striatum (VST) and right caudate (CAU) on Day 2, which was greater than that in HS. These results suggest the impaired activation of the putamen during skill acquisition in patients with PD and compensated hyperactivation of the VST and CAU for the reduced dopamine release within the dorsal putamen (DPU). Conclusion Our findings suggest that patients with PD had insufficiency in the process to improve motor skills. Different patterns of striatal dopamine release are relevant to the impairment of these motor functions in patients with PD, at the early stage of the disease.

Paired associative stimulation (PAS) is an effective non-invasive method to induce human motor plasticity by the repetitive pairing of peripheral nerve stimulation and transcranial magnetic stimulation (TMS) at the primary motor cortex (M1) with a specific time interval. Although the repetitive pairing of two types of afferent stimulation might be a biological basis of neural plasticity and memory, other types of paired stimulation of the human brain have rarely been studied. We hypothesized that the repetitive pairing of TMS and interhemispheric cortico-cortical projection or paired bihemispheric stimulation (PBS), in which the right and left M1 were serially stimulated with a time interval of 15 ms, would produce an associative long-term potentiation (LTP)-like effect. In this study, 23 right-handed healthy volunteers were subjected to a 0.1 Hz repetition of 180 pairings of bihemispheric TMS, and physiological and behavioural measures of the motor system were compared before, immediately after, 20 min after and 40 min after PBS intervention. The amplitude of the motor evoked potential (MEP) induced by the left M1 stimulation and its input–output function increased for up to ∼20 min post-PBS. Fine finger movements were also facilitated by PBS. Spinal excitability measured by the H-reflex was insensitive to PBS, suggesting a cortical mechanism. The associative LTP-like effect induced by PBS was timing dependent, occurring only when the interstimulus interval was 5–25 ms. These findings demonstrate that using PBS in PAS can induce motor cortical plasticity, and this approach might be applicable to the rehabilitation of patients with motor disorders.

We present two cases of young adults with acute disseminated encephalomyelitis (ADEM) who developed severe conscious and motor disturbances. Despite their similar initial clinical course and MRI findings, their motor function outcomes were quite different. In both cases, fluid attenuated inversion recovery (FLAIR) sequenced MRI showed multiple symmetric hyperintense lesions in the internal capsule and the brainstem at the subacute stage. However, in case 1 the apparent diffusion coefficient (ADC) was pathologically decreased in the internal capsule, whereas the ADC for case 2 was normal. At the end of the examination period, severe motor disability (bedridden state) with brain atrophy apparent on MRI remained in case 1, whereas case 2 made an almost full recovery without brain atrophy. These two cases suggest that altered ADC in the internal capsules at the subacute stage may reflect a different pathogenesis between cytotoxic and vasogenic edema, and may be a valuable indicator for the prognosis of motor disturbance.

Object substitution masking is a form of visual backward masking in which a briefly presented target is rendered invisible by a lingering mask that is too sparse to produce lower image-level interference. Recent studies suggested the importance of an updating process in a higher object-level representation, which should rely on the processing of visual motion, in this masking. Repetitive transcranial magnetic stimulation (rTMS) was used to investigate whether functional suppression of motion processing would selectively reduce substitution masking. rTMS-induced transient functional disruption of cortical area V5/MT+, which is important for motion analysis, or V1, which is reciprocally connected with V5/MT+, produced recovery from masking, whereas sham stimulation did not. Furthermore, masking remained undiminished following rTMS over the region 2 cm posterior to V5/MT+, ruling out nonspecific effects of real stimulation and confirming regional specificity of the rTMS effect. The results suggest that object continuity via the normal function of the visual motion processing system might in part contribute to this masking. The relation of these findings to the reentrant processing view of object substitution masking and other visual phenomena is discussed.

An interventional paired associative stimulation (IPAS) combining the peripheral nerve and the cortical stimulation can induce a long-lasting increase in the excitability of the motor cortex, when two inputs were synchronous at the level of the motor cortex (associative long-term potentiation (LTP)-like effect). The aim of this study is to elucidate whether the dopaminergic system can modulate the associative LTP-like effect in the motor cortex by applying this method to Parkinson's disease (PD). Ten right-handed patients with PD without dopamine replacement therapy for the previous 12 h and five right-handed age-matched healthy volunteers were studied. IPAS consisted of an electrical stimulation of the right median nerve and a following suprathreshold magnetic stimulation over the left primary motor cortex (M1) with the delay of 25 ms. A total of 240 pairs of stimuli were given at 0.2 Hz. Motor evoked potentials (MEPs) were measured from the right abductor pollicis brevis (APB) muscles before (baseline) and immediately after IPAS. IPAS was capable of inducing increased MEP amplitude of the right APB in age-matched healthy volunteers, whereas it did not change MEP amplitude in PD. This result suggests that the dopaminergic system modulates the associative plasticity of the human motor cortex, which may be achieved via basal–ganglia–thalamocortical loops.

To clarify the mechanism of congenital mirror movements.The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones.Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions.The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.