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The guidelines provided by American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) (ACMG/AMP guidelines) suggest a framework for the classification of clinical variants. However, the interpretations can be inconsistent, with each definition sometimes proving to be ambiguous. In particular, there can be difficulty with interpretation of variants related to the X-linked recessive trait. To confirm whether there are biases in the interpretation of inherited traits, we reanalyzed variants reported prior to the release of the ACMG/AMP guidelines. As expected, the interpretation ratio as pathogenic or likely pathogenic was significantly lower for variants related to the X-linked recessive trait. Evaluation of variants related to the X-linked recessive trait, hence, need to consider whether the variant is identified only in males in accordance with the X-linked recessive trait. The ACMG/AMP guidelines should be revised to eliminate the bias revealed in this study.

Background: An individual with autism spectrum disorder (ASD) has social skill, motor skill, and motion perception deficits. However, the relationship among them was not clarified. Therefore, this study aimed to evaluate the effects of motor skills on social skills and motion perception.Methods: Five typically developed children and fourteen children with ASD participated in our study. The N200 component, a brain activity indicating motion perception, was induced in mid-temporal (MT/V5) brain area by watching a random dot kine-matograph, and was recorded using a scalp electroencephalogram. Furthermore, the social responsiveness scale (SRS) indicating the social skill deficit, the developmental coordination disorder questionnaire (DCDQ) estimating the developmental coordination disorder (DCD), and the movement assessment battery for children second edition (MABC-2) indicating motor skills were recorded in the children with ASD. A hierarchical multiple regression analysis was conducted to examine the modulation effects of motor skills on the relationship between social skills and motion perception. The dependent variable was the N200 latency, and the inde-pendent variables were SRS, MABC-2, and combined MABC-2 and SRS.Results: The N200 latency was more delayed in children with ASD relative that in typically developed children. Intact balance ability modulated the relationship between social skills and N200 latency in children with ASD. Within the high balance ability, when the social skills worsened, the N200 latency was shortened. Conclusions: This is the first report that intact motor skills could modulate the relationship between social skills and motion perception.(c) 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Patients with major depressive disorder (MDD) exhibit several clinical symptoms including difficulties in flexible thinking. Flexible thinking mainly relies on a cognitive ability called shifting; however, the mechanisms underlying shifting in patients with MDD have not yet been clarified. Therefore, we conducted a preliminary intervention study to clarify the association between depression and shifting ability. We examined the hemodynamic responses in the frontal regions during the shifting task using functional near-infrared spectroscopy (fNIRS) in 21 patients with MDD who were treated using high-frequency repetitive transcranial magnetic stimulation (rTMS). Behavioral performance on the shifting task did not change between pre- and posttreatments, whereas patients who responded well to rTMS treatment showed a significant decrease in hemodynamic responses posttreatment. On the other hand, the poor responders did not show significant changes in the hemodynamic responses between pre- and posttreatments. These results suggest that the good responders were successfully remedied with rTMS treatment and did not need effortful activity in frontal regions for shifting, which made their brain activity more efficient.

To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis.We enrolled 13 infants with posterior quadrant dysplasia aged2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated.Overall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs.Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement.PLI quantifies neurodevelopmental improvements after posterior quadrantectomy.

Introduction An alteration in postoperative cognitive function varies according to the patients’ background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills. We examined the relationship between alterations of executive function (EF) and adaptive behavior in school children undergoing surgery for intractable epilepsy. Methodology We enrolled 31 children with focal resection or corpus callosotomy for intractable epilepsy [mean age at surgery, 12.5 years; 16 boys; mean intellectual quotient, 73.3]. We surveyed answered questionnaires on attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and adaptive behavior using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II), and performed continuous performance tests (CPTs) on children pre- and postoperatively. Result ADHD and ASD symptoms improved after epilepsy surgery. The omission error (OE) in the CPT variable improved after epilepsy surgery, especially in children with a shorter preoperative period. Improved ASD symptoms led to an increased score of the coping skills subdomain. The reduced OE observed after surgery also increased the score of the community skills subdomain. Conclusion Improvement in EF and ASD symptoms resulted in better adaptive behavior postoperatively. These results were important for the pre- and postoperative evaluation and re-evaluation of children with epilepsy requiring special education and related services.

Objective Children with attention deficit hyperactivity disorder (ADHD) exhibit deficits in executive function. Since there are no clear biomarkers for the disorder, this study aimed to investigate the neurophysiological biomarkers for deficits in executive function in children with ADHD using functional near-infrared spectroscopy (fNIRS) and electroencephalography. Methods Twenty patients diagnosed with ADHD and 19 typically developing children (TDC; 8–11 years old) were included. Event related potentials (ERPs) were recorded using an electroencephalogram (EEG) and oxygenated hemoglobin concentrations (Oxy-Hb) were recorded using fNIRS during a colored Go/NoGo task, simultaneously. Latencies and amplitudes of NoGo-N2 and NoGo/Go-P3 tasks were measured using EEG. Results Children with ADHD showed significantly decreased Oxy-Hb in the right frontal cortex as well as longer NoGo-P3 latencies and a decreased NoGo/Go-P3 amplitude. There was a significant positive correlation between the Oxy-Hb and NoGo/Go-P3 amplitude. Conclusions These results suggest that children with ADHD experience executive dysfunction. Hemodynamic and electrophysiological findings during the Go/NoGo task might be useful as a biomarker of executive function. Significance These findings have key implications for understanding the pathophysiology of deficits in executive function in ADHD.

Background Children with Williams syndrome (WS) show a marked interest in music, a characteristic often explored in clinical settings. However, the actual musical abilities of patients with WS remain debatable due to some of the relevant data being derived from experimental tasks that require a verbal response, despite the known language impairments in WS. The present study aimed to examine musical ability in children with WS using a newly invented pitch discrimination task with minimal involvement of language and clarify its relationship with language skill. Methods Eleven children with WS participated in the study. We used a novel pitch discrimination task that required minimal language use. Two piano tones were presented sequentially, and children were asked to give a non-verbal response as to whether the second tone was higher than, lower than, or the same as the first tone. Results Pitch discrimination performance in children with WS was lower than the level predicted for their chronological age (CA), even in the non-verbal task. Pitch discrimination ability and verbal mental age (VMA) were shown to be dissociated, such that children with WS with a lower skill level for language showed an unexpectedly higher level of pitch discrimination ability and vice versa. Conclusions Our results indicated reduced musical ability with respect to CA in children with WS. The dissociation between musical ability and language skills may indicate unique developmental relationships that differ from those in normal children. These findings provide new evidence to support the importance of assessing actual musical ability in WS prior to implementing interventional music therapy.

The third G20 Health Ministers' Meeting was held in Okayama, Japan on October 19-20, 2019. The authors were involved in the decision making of the substantial issues of this meeting including theme setting, schedule management, facilitating the discussion, and preparation for the ministers' meeting. Here, we summarize our lessons of experience from hosting G20 Okayama Health Ministers' Meeting as: i) Utilizing the occasion of existing major health related meeting to gain efficiency; ii) Collaboration with other G20 tracks such as finance can function as a tool to facilitate inter-sectoral collaboration within other G20 members; iii) Two-day Health Working Group before the ministerial meeting provides sufficient time for negotiation of the declaration text; and iv) Inclusion of residents and representatives of the host city provides great opportunity to create G20 legacy. Such an experience of Japanese policymaking is rarely shared in English and the lessons learned from our experience shall provide meaningful advice for Saudi Arabia colleagues who are to hold the next G20 Health Ministers' Meeting as well as for the preparation of other G20 ministerial meetings.

BACKGROUND Oral support during feeding was clinically provided to patients with severe motor and intellectual disabilities (SMID) for the prevention of dysphasia. The present study anatomically and functionally investigated the advantages of oral support. METHODS A videofluoroscopic swallowing study was conducted on nine patients with SMID (age = 5-41 years; mean age = 15.0; four males, five females) and twenty-four healthy adults (age = 26-67 years; mean age = 44.3; 16 males, eight females). The movements of the hyoid bone and mandible during pharyngeal swallowing were tracked, and the pharyngeal residues were evaluated. The temporal and spatial features of the movements were compared between patients with and without oral support as well as healthy adults. RESULTS The mandible moved downward earlier and showed larger displacement in the patients with SMID. The patients also had insufficient anterior displacement of the hyoid, which was associated with pharyngeal residue. This displacement was enhanced, and the pharyngeal residue decreased with oral support. CONCLUSIONS Oral support to hold the mandible successfully improved hyoid excursion and reduced pharyngeal residue during swallowing, which is a simple and reliable strategy for the prevention of dysphasia in patients with SMID.

The factors associated with the clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) remain largely unexplored. Therefore, this study aimed to examine whether rTMS can change the functional laterality of the prefrontal hemodynamic response and whether baseline functional laterality can predict the clinical outcomes of rTMS using functional near-infrared spectroscopy (fNIRS). We included 19 patients with MDD who were treated with high-frequency rTMS. The verbal fluency task was used as the activation task. We calculated the laterality index (LI) based on the task-related oxygenation response in the frontal region. First, the LI was compared before and after rTMS treatment. Second, the reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) score was compared between the rightward dominance group (pre-LI0) and the leftward dominance group (pre-LI ≥ 0). The findings showed a significant change in the LI after rTMS treatment. The rightward dominance group had a significantly greater reduction in MADRS score than the leftward dominance group. Subsequently, the laterality of the task-related hemodynamic response of the prefrontal region shifted leftward following left high-frequency rTMS treatment. Thus, the pre-LI calculated using fNIRS data is a possible predictor of rTMS outcomes in patients with MDD.

Aim The prevalence estimates of neurodevelopmental disorders have been calculated by questionnaire surveys scored by a single rater, which introduces inherent rater biases. The present study aimed to estimate the prevalence and comorbidity rates of four neurodevelopmental disorders based both on parent and teacher rating scales. Methods We performed a community sample survey recruiting 3852 children aged 6?9?years. Both parents and teachers evaluated clinical conditions in children using questionnaire-style scales. These scales with the cut-off values were used to estimate the prevalence and comorbidity rates of attention deficit / hyperactive disorder, autism spectrum disorder, specific learning disorder (or developmental dyslexia), and developmental coordination disorder. Results The prevalence estimates were separately confirmed according to the raters. Some estimates were higher than those in the previous studies conducted in other countries. We also found a large disagreement between the parent and teacher rating scores. Moreover, the degree of agreement between two raters varied depending on the severity of clinical condition in the child. Conclusion These estimates are the first findings based on evaluating children by two raters. The prevalence and comorbidity estimates are informative to the researchers and clinicians of pediatric neurology. The disagreement between two raters raises questions about previous estimates of neurodevelopmental disorders. This article is protected by copyright. All rights reserved.

Objectives Dysphagia is linked to mortality risk among patients with profound intellectual and multiple disabilities (PIMD); the present study therefore aimed to clarify the characteristics of hyoid movements during swallowing and to examine the mechanism of dysphagia in patients with PIMD. Methods A retrospective video fluoroscopic swallowing study was conducted on 43 patients with PIMD (mean age = 25.4; 25 males, 18 females) and 24 healthy adults (mean age = 44.3; 16 males, 8 females). The movements of the hyoid bone and mandible were tracked frame by frame in the video footage, and their range of movements and trajectories were analyzed. Results Most patients showed atypical movement trajectories of the hyoid, such as insufficient anterior movement and increased range of mandibular downward movement, compared with normal adults. Moreover, the mechanism of dysphagia was revealed by structural equation modeling, indicating that insufficient anterior movement could lead to pharyngeal residue in the pyriform sinus. Conclusion The insufficient anterior movement of the hyoid could be caused by weak ventral suprahyoid muscles and atypical head and neck posture characteristic of patients with PIMD. It may be useful to predict pharyngeal residue from the range of hyoid movements and trajectories for the prevention of aspiration.

This study aimed to reveal how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders and their parents and to identify possible factors that enabled them to maintain their QOL. We enrolled 136 school-aged children (intellectual quotient ≥ 50) and their parents and administered QOL questionnaires to assess the maladaptive behavior of the children; depression, anxiety, and stress of the parents; and activities of their daily lives. The relationship between their QOL and clinical features was examined. The decrease in QOL of children and parents was associated with the mother’s limited job flexibility. Decreased QOL was also associated with changes in the sleep rhythms of the children. Maladaptive behaviors in children were associated with parental stress. However, maintained QOL of some families who faced these same conditions of job stress and sleep disorders was associated with less parental stress, less parental depression and anxiety, and milder maladaptive behavior in children. Both mothers with limited job flexibility and changes in the sleep rhythm of children were associated with reduced QOL of children and their parents. Low parental stress was associated with decreased maladaptive behavior in children and with maintained QOL of the family.

Nogo-N2 is associated with the premotor cognitive process that precedes motor response (e.g., conflict monitoring), whereas Nogo-P3 is related to the inhibition of the actual motor response. We examined the influence of motor clumsiness of developmental coordination disorder (DCD) on components of the event-related potential in a Go/Nogo task. Participants were healthy adults (N = 81) that were classified into control and DCD groups based on the Movement Assessment Battery for Children Second Edition. We manipulated the difficulty in stopping a response by varying the frequency of Nogo stimuli in a response task into rare (20%) and frequent (80%) conditions, and Nogo-N2 and Nogo-P3 were calculated from electroencephalograms (EEGs) during the Go/Nogo tasks. The commission error rate in the rare condition was significantly higher in the DCD group than in the control group, indicating that motor clumsiness decreases task performance. There were no differences in Nogo-N2 between DCD and control groups. However, Nogo-P3 in the rare condition was reduced in the DCD group compared to the control group. These results suggest that the influence of motor clumsiness is limited to the cognitive process after the initiation of the actual motor response.

Objective We aimed to clarify the strengths and weaknesses in adaptive behavior in children with focal epilepsy and show children-associated factors related to adaptive behavior. Materials and methods Sixty-three children with focal epilepsy aged 5–18 years with intellectual quotient (IQ) ranging from 67 to 135 were enrolled in this study. Adaptive behavior was evaluated using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II). The children performed continuous performance test and tests of reading, writing, and IQ; parents answered questionnaires regarding attention-deficit hyperactivity disorder and autism spectrum disorder (ASD). Participants were categorized into four groups based on IQ and adaptive behavior scores for statistical comparisons. Results and discussion Children with low adaptive behavior were more likely to show a reduction in daily living skills, and those with both low adaptive behavior and IQ were more likely to show a reduction in daily living skills and communication. Lower adaptive behavior was related to more severe autistic symptoms, lower academic achievement in children with IQ > 85, and lower executive function in children with IQ ≤ 85. There was a qualitative difference of cognitive dysfunction in adaptive behavior between both groups. Conclusions There were differences in VABS-II domain and subdomain characteristics between children with focal epilepsy and those with ASD; however, it was more difficult for children with more severe ASD and coexisting focal epilepsy to show age-equivalent adaptive behavior.

Objective The right prefrontal cortex (PFC) plays an essential role in active processing within visuospatial working memory (VSWM). The aim of this study was to examine developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks in school-age participants. Methods We recruited 80 school-age children who were classified into three age groups: 7- to 8-year-old, 9- to 10-year-old, and 11- to 12-year-old children. We used near infrared spectroscopy (NIRS) to measure PFC activity during visuospatial memory task. Memory stimuli were presented either sequentially or simultaneously. Results In all three groups, right-lateralized PFC activity was observed during sequential presentation, suggesting specialization of the right PFC for VSWM. During simultaneous presentation, right-lateralized PFC activity was not observed in 7- to 8-year-old children or 9- to 10-year-old children. In contrast, PFC activity was right-lateralized in 11- to 12-year-old children. Conclusions We suggest that specialization of the right PFC for VSWM is already present before school-age, but widely distributed activity in response to visuospatial memory tasks changes to more focal activity in VSWM-specific regions during the early school years. Significance Using NIRS, we showed developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks.

Near-infrared spectroscopy studies in children with attention deficit hyperactivity disorder (ADHD) have shown excessive prefrontal activity responsible for coping with interference. However, it is possible that the previous results were influenced by verbal, reading, and memory developments. The flanker task is an interference task that does not require a verbal response, reading, or memorization. We examined activity in the superior frontal cortex (SFC) during the flanker task in 12 children with ADHD and 14 children with typical development using near-infrared spectroscopy. SFC activity was significantly greater in children with ADHD than in those with typical development. The results showed excessive interference coping activity in children with ADHD irrespective of verbal, reading, and memory development. Moreover, SFC activity was positively correlated with the inattention subscale score of the ADHD rating scale. We suggest that children with ADHD need greater SFC activation to cope with interference, and the inefficient mechanism is demanding and hard to sustain, which causes inattention symptoms of children with ADHD.

Early detection and treatment promote positive outcomes in mental health problems among infants. This study developed a simple and reliable screening inventory for infants’ mental health. Participants were 579 primary caregivers who had Japanese infants aged 2–6 years. Participants evaluated their children using the Mental Health Inventory for Infants (MHII; developed in this study), which contains 24 items. Exploratory factorial analysis identified the MHII factor structure; confirmatory factorial analysis examined its factorial validity. Internal consistency and criterion-related validity were also examined. Irritability (8 items), somatic symptoms (6 items), and signs of insecurity (4 items) were identified as factors in the MHII; each of these factors measures a critical aspect of infants’ mental health. The MHII’s internal consistency and scale homogeneity were acceptable; its criterion-related validity was supported. In this study, male infants exhibited greater irritability and less insecurity than females. The present results support the MHII’s reliability and validity; additionally, they indicate that caregivers may use the MHII to quickly screen for three critical aspects of infants’ mental health. We expect that the MHII will be used for early detection of mental health difficulties in infants to facilitate treatment.

Background The diagnosis of Developmental Coordination Disorder (DCD) requires a precise assessment of motor skills via a standardized tool such as the Movement Assessment Battery for Children-Second Edition (MABC-2). Although the MABC-2 has been widely used in English-speaking countries, to the best of our knowledge, no studies have examined its applicability to Japanese children. Thus, it has been difficult to diagnose DCD in Japan. Aims As a preliminary investigation preceding its formal standardization in Japan, we examined the applicability of the MABC-2. Methods and procedures Participants comprised 132 typically developing Japanese children who completed a test set of the MABC-2 for Age Band 2. We analyzed both internal consistency and factorial validity for our Japanese sample. We also included a comparison between our sample of Japanese children and the normative sample of the MABC-2, as well as an examination of gender differences. Outcomes and results Our results indicated acceptable internal consistency and scale homogeneity. High factorial validity, which has not been examined in other populations, was also confirmed for the test set. Moreover, we found differences in component scores between the Japanese and normative children with respect to Manual Dexterity and Balance. We also found that girls obtained superior Manual Dexterity and Balance scores compared with boys. Conclusions and Implications The present findings represent the first step towards the standardization of the MABC-2 in a Japanese population.

This study investigated the applicability of the Movement Assessment Battery for Children - Second Edition (MABC-2) for 3- to 6-year-old Japanese children, particularly addressing its internal consistency and factorial validity. The MABC-2 test set for 3- to 6-year-old children was administered to 252 children. Differences between Japanese children and those of the original normative sample (i.e. United Kingdom children) were investigated along with sex differences. The Japanese children aged 3-6 years were found to have higher Manual Dexterity and Balance component scores than children of the normative sample. Girls scored higher than boys on the Balance component. Results of several analyses showed good internal consistency of the MABC-2. Confirmatory factor analysis revealed that a theoretical three-component model of the MABC-2 was not fitted to Japanese children aged 3-6 years. Instead, a new three-component model was postulated and discussed. The new three-component model of the MABC-2, with Manual Dexterity, Static Balance and Ball Skills, and Dynamic Balance, has high factorial validity in Japanese children aged 3-6 years.

Although atypical processing of biological motion (BM) in individuals with autism spectrum disorder (ASD) has been reported, the temporal profile of the neural response to BM is not well explored. In the current study, event-related potentials (ERPs) were measured in 12 individuals with ASD, aged 8–22 years, and 12 age- and gender-matched normal controls, to investigate the electrophysiological response to BM and a control visual stimulus. By introducing a novel experimental paradigm that can dissociate the electrophysiological responses to motion processing and the global shape processing of BM, we found that: (1) the timing of the response was preserved in ASD groups, whereas (2) the ERP response to BM was significantly enhanced compared with scrambled point-light motion (SM) in normal controls; the responses to both BM and SM were not significantly different in subjects with ASD. Because we did not find a significant group effect on the peak and mean amplitude induced by BM, it is presumed that this atypical response in individuals with ASD was due to over-sensitivity to the local motion signals. This experimental paradigm showed atypical local motion processing of BM in individuals with ASD.

BackgroundJapan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level.MethodsWe used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations.FindingsLife expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from -32·4% (-34·8 to -30·0) to -22·0% (-20·4 to -20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015.InterpretationJapan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment.FundingBill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund.

Although phonics is the most frequently used approach in treating students with reading difficulties, its effects have not been fully clarified at either a behavioral or neurophysiological level. The present case study administered pure and short-term (i.e., 10 minutes per day for five weeks) phonics-training to a 13-year-old Japanese girl with severe difficulty in learning English. As a result, a drastic improvement in reading accuracy was associated with the enhancement of print-specific N170 in event-related potentials (ERPs) elicited by the trained words. The present finding indicates that phonics training can, by itself, remediate English reading and affect its neurophysiological bases.

Neurofeedback (NF) training aims the enhancement of self-regulation over brain activities. While it is largely recognized as an effective treatment for attention deficit hyperactivity disorder (ADHD), the existence of non-learners has also been reported. The present study explored pre-training assessment indices that could predict learners prior to NF training.Twenty-two children with ADHD participated in slow cortical potential (SCP) NF training and completed pre- and post-training assessments. Participants were classified into learners or non-learners based on their progress in the SCP regulation, and pre-training indices that differentiate the two groups were examined by decision tree analysis.The learner rate in NF training was 45.5%. Learners were predicted by pre-training cognitive and neurophysiological measures regarding Stroop tasks, which suggested relatively intact executive function as their characteristics. Given that NF training is not universally effective for children with ADHD, further studies are necessary to establish application criteria.

Activity in the alpha band of the electroencephalogram (EEG) reflects functional inhibition of the cerebral cortex. The superior frontal cortex (SFC) is known to control alpha activity. Based on this relationship between SFC and alpha, we hypothesized that SFC controlled alpha mediates proactive control over interference. In this study, we examined the relationship between SFC and alpha in the flanker task by simultaneously recording EEG and near infrared spectroscopy (NIRS). Forty participants performed a flanker task with occasional (compatible 75%, incompatible 25%) and successive (incompatible 100%) conditions. In the occasional condition, larger SFC activity was related to pre-stimulus alpha enhancement under occipital electrodes. This is consistent with a model in which SFC enhances pre-stimulus alpha activity, leading to proactive control over interference. However, we could not detect a correlation between SFC activity and alpha activity in the successive condition. Active inhibition may have been reduced by a need to continuously inhibit brain regions associated with the irrelevant information. This may have reduced the role of the SFC in controlling alpha activity. Based on these findings, we postulate that there are two cerebral mechanisms of proactive control over interference.

Spatial working memory (SWM) involves both simultaneous and sequential encoding, but the differences in their neural correlates are unclear. We investigated the differences in prefrontal cortex activity related to these SWM encoding types. We also examined the patterns of brain activity influencing individual visuospatial abilities (VSA). We conducted SWM tasks with two different conditions, sequential and simultaneous encoding, and examined hemodynamic activity in 39 healthy adults using near-infrared spectroscopy. The bilateral dorsolateral prefrontal cortex was activated more strongly in the sequential condition compared with the simultaneous condition. This suggests that prefrontal cortex activity underlying SWM is modulated by the type of encoding. We also found that individuals with high VSA showed weaker activation in the right-dorsolateral prefrontal cortex compared with those with lower VSA during the simultaneous condition. This hypoactivation is thought to reflect neural efficiency in the individuals with high ability. These findings are expected to lead to a better understanding of neural substrates for SWM.