Examining normative values using the Cambridge neuropsychological test automated battery and developmental traits of executive functions among elementary school-aged children in Japan.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized and child-friendly neuropsychological assessment battery that includes subtests aimed at evaluating some aspects of executive functions. Using the CANTAB, this study aims to establish normative values based on the aspects of executive functions among school-aged children in Japan. The participants included 234 children (135 boys and 99 girls aged 6-12 years) enrolled in regular classes, without any clinical records of developmental disorders or educational support. The participants were grouped according to age (6-7, 8-9, and 10-12 years). Four CANTAB subtests, including spatial working memory (SWM) to assess spatial working memory, Stockings of Cambridge (SOC) to evaluate planning, intra/extradimensional set shift (IED) to evaluate attentional set shifting and flexibility, and stop signal task (SST) to evaluate inhibition, were administered to each participant. The results showed that performance in all the CANTAB subtests administered changed with age. Among the subtests, compared with performances in the SOC and IED, those in the SWM and SST improved earlier, thereby indicating that spatial working memory and inhibition develop earlier than planning as well as attentional set shifting and flexibility. Additionally, in the SST subtest, girls made fewer errors than boys did in the 6-7 years group. This study presents normative data of four CANTAB subtests according to age and sex among school-aged children in Japan. We expect that the findings will be used to develop effective tools for the early detection of and support for children with executive dysfunction.

Child Developmental MRI (CDM) project: protocol for a multi-centre, cross-sectional study on elucidating the pathophysiology of attention-deficit/hyperactivity disorder and autism spectrum disorder through a multi-dimensional approach.

INTRODUCTION: Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration. In addition, we will investigate the relationship between these characteristics and genetic, epigenetic, biochemical markers, and behavioural and psychological measures. METHODS AND ANALYSIS: We will collect resting-state functional MRI (fMRI) and T1-weighted and diffusion-weighted MRI data from 15 healthy adults as travelling subjects and 300 children (ADHD, n=100; ASD, n=100; and typical development, n=100) with multi-dimensional assessments. We will also apply data from more than 1000 samples acquired in our previous neuroimaging studies on ADHD and ASD. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the University of Fukui Hospital (approval no: 20220601). Our study findings will be submitted to scientific peer-reviewed journals and conferences.

What daily factors affect the sleep habits of Japanese toddlers?

STUDY OBJECTIVES: Good sleep, especially during early childhood, is important for development. In Japan, the mean nocturnal sleep duration of toddlers is < 10 hours, and even if toddlers slept for > 11 hours/day, as recommended by the National Sleep Foundation, some of them showed late bedtime and late wake-up time or took long naps. Therefore, we provisionally assumed the minimal sleep conditions for Japanese toddlers, named Nenne-criteria, such as bedtime before 10:00 pm, nocturnal sleep duration of ≥ 9 hours, and < 1 average time of awakening after sleep onset, and investigated the important factors for good sleep. METHODS: We analyzed cross-sectional data from online surveys describing the sleep-related behaviors of 2,124 toddlers and their caregivers. We compared the daily schedules that affect sleep between the Nenne-criteria-meet group and the not-meet group. RESULTS: The Nenne-criteria-meet group showed better daytime behaviors than the not-meet group. Structural equation modeling on daily schedules revealed that, to increase sleep pressure at the appropriate time, it is important to restrict media viewing, play outdoors in the morning, have an early nap ending time, avoid hyperarousal-inducing behaviors before bedtime, maintain daily schedules regularly, and decrease social jetlag. CONCLUSIONS: The Nenne-criteria are useful for screening Japanese toddlers who require intervention for sleep hygiene. To improve toddlers' sleep, it is important not only to guide the ideal bedtime but also to provide tips for improving daily schedules and to avoid suboptimal sleep-related behaviors. CITATION: Murata E, Yoshizaki A, Fujisawa TX, Tachibana M, Taniike M, Mohri I. What daily factors affect the sleep habits of Japanese toddlers? J Clin Sleep Med. 2023;19(6):1089-1101.

Improving Children's Sleep Habits Using an Interactive Smartphone App: Community-Based Intervention Study.

BACKGROUND: Sleep problems are quite common among young children and are often a challenge for parents and a hinderance to children's development. Although behavioral therapy has proven effective in reducing sleep problems in children, a lack of access to professionals who can provide effective support is a major barrier for many caregivers. Therefore, pediatric sleep experts have begun developing apps and web-based services for caregivers. Despite the substantial influence of cultural and familial factors on children's sleep, little effort has gone into developing cultural or family-tailored interventions. OBJECTIVE: This study aimed to examine the effectiveness of the interactive smartphone app "Nenne Navi," which provides culturally and family-tailored suggestions for improving sleep habits in young Japanese children through community-based long-term trials. The study also aimed to investigate the association between app-driven improvements in sleep and mental development in children. METHODS: This study adopted a community-based approach to recruit individuals from the Higashi-Osaka city (Japan) who met ≥1 of the following eligibility criteria for sleep problems: sleeping after 10 PM, getting <9 hours of nighttime sleep, and experiencing frequent nighttime awakenings. A total of 87 Japanese caregivers with young children (mean 19.50, SD 0.70 months) were recruited and assigned to the app use group (intervention group) or the video-only group (control group). Both groups received educational video content regarding sleep health literacy. The caregivers in the intervention group used the app, which provides family-tailored suggestions, once per month for 1 year. RESULTS: A total of 92% (33/36) of the caregivers in the app use group completed 1 year of the intervention. The participants' overall evaluation of the app was positive. The wake-up time was advanced (base mean 8:06 AM; post mean 7:48 AM; F1,65=6.769; P=.01 and sleep onset latency was decreased (base mean 34.45 minutes; post mean 20.05 minutes; F1,65=23.219; P<.001) significantly in the app use group at the 13th month compared with the video-only group. Moreover, multiple regression analysis showed that decreased social jetlag (ß=-0.302; P=.03) and increased sleep onset latency SD (ß=.426; P=.02) in children predicted a significant enhancement in the development of social relationships with adults. At 6 months after the completion of the app use, all the caregivers reported continuation of the new lifestyle. CONCLUSIONS: The present findings suggest that the app "Nenne Navi" has high continuity in community use and can improve sleep habits in young Japanese children and that interventions for sleep habits of young children may lead to the enhancement of children's social development. Future studies must focus on the effectiveness of the app in other regions with different regional characteristics and neuroscientific investigations on how changes in sleep impact brain development.

The Japanese Sleep Questionnaire for preschoolers within a Malaysian context.

BACKGROUND: Childhood sleep practices impact growth, development, and long-term health. There is a paucity of sleep data pertaining to preschool children in Asia, especially South-East Asia. METHODS: This cross-sectional study involved parents of well siblings, aged 2-6 years. It aimed to: (i) test the reliability of the English version of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P), and (ii) obtain the prevalence, as well as describe, sleep-related issues. Ninety-one (91) parents (74.7%; mothers) self-administered the questionnaire in the pediatric clinic waiting area of a Malaysian tertiary hospital. Recruitment was from August to November 2020. RESULTS: The English version of the JSQ-P has good internal consistency (Cronbach alpha = 0.85). Range of Cronbach alpha values for each item: 0.36-0.87. Many (77%) children slept at 10:00 p.m. or later, similar to parents' late bedtimes. One-third had difficulty waking up in the morning. There were significant strong positive correlations between some features of restless leg syndrome, daytime tiredness, morning symptoms, and obstructive sleep apnea symptoms. Co-sleeping was prevalent (97.9%). Mean screen time for those who had set time limits was 2.35 ± 1.68 h. CONCLUSIONS: The English-language translation of the JSQ-P is a questionnaire with good internal consistency that can be used in non-Japanese speaking countries. Parents need to be educated on healthy sleep and screen time practices to optimize children's sleep quality and quantity.

Effectiveness of a Parent Training Programme for Parents of Adolescents with Autism Spectrum Disorders: Aiming to Improve Daily Living Skills.

Parent training (PT) has been well established in younger children with autism spectrum disorder (ASD) but is less well studied in adolescents. This study examined the effects of attempting PT to enhance the daily living skills (DLSs) of adolescents with ASD. Twenty-five parents of adolescents with ASD participated in either the immediate- or delayed-treatment control condition. Children's DLSs were evaluated using the DLS domain of the Vineland Adaptive Behaviour Scales-II, and the achievement of the DLSs practised by the children at home was the subject of the evaluation. The DLS domain score showed no improvement in the treatment group compared to the control group. However, some parents in the treatment group reported that their children acquired the target DLSs and more sophisticated communication behaviours. In addition, one measure suggested that parents increased their praising behaviours. These changes may have been driven by the completion of the parent training. We discuss several aspects of developing parent-mediated interventions based on the current intervention situation and observed changes.

A preliminary study of sleep spindles across non-rapid eye movement sleep stages in children with autism spectrum disorder.

Study Objectives: Sleep spindles play a crucial role in multiple neuronal network functions. Initiation and termination of spindles are regulated by the thalamic reticular nucleus and thalamocortical network, and the spindle can be an index for brain organization. We conducted a preliminary study of the parameters of sleep spindles, focusing on sleep-stage temporal distribution in children with autism spectrum disorder (ASD) with normal intelligence/developmental quotients. Methods: We performed overnight polysomnography in 14 children with ASD (4-10 years) with normal full-scale intelligence quotient/developmental quotient (≥75) and 14 community samples (CS) of children. Sleep stages were scored according to the Rechtschaffen and Kales criteria. Spindle parameters were quantified and compared between these groups and the identified subgroups. Results: Sleep parameters did not differ between the ASD and CS groups, except for a higher rate of rapid eye movement (REM) sleep duration in ASD. Spindle parameters did not significantly differ between the groups, but spindle density was distributed in a broader range in the ASD group. Five children with ASD had a higher spindle density in stage 3 than in stage 2. The ratio of spindle density in stage 3 to that in stage 2 (stage 3/2 ratio) was significantly higher in ASD than in CS cases. Conclusions: The lower spindle density in stage 2 and relatively higher density in stage 3 in children with ASD may represent an abnormal generation of spindles due to insufficient maturation of the thalamic reticular nucleus and thalamocortical network.

Abnormal cortical responses elicited by audiovisual movies in patients with autism spectrum disorder with atypical sensory behavior: A magnetoencephalographic study.

BACKGROUND: Atypical sensory behavior disrupts behavioral adaptation in children with autism spectrum disorder (ASD); however, neural correlates of sensory dysfunction using magnetoencephalography (MEG) remain unclear. METHOD: We used MEG to measure the cortical activation elicited by visual (uni)/audiovisual (multisensory) movies in 46 children (7-14 years) were included in final analysis: 13 boys with atypical audiovisual behavior in ASD (AAV+), 10 without this condition, and 23 age-matched typically developing boys. RESULTS: The AAV+ group demonstrated an increase in the cortical activation in the bilateral insula in response to unisensory movies and in the left occipital, right superior temporal sulcus (rSTS), and temporal regions to multisensory movies. These increased responses were correlated with severity of the sensory impairment. Increased theta-low gamma oscillations were observed in the rSTS in AAV+. CONCLUSION: The findings suggest that AAV is attributed to atypical neural networks centered on the rSTS.

Relationships between cortical, cardiac, and arousal-motor activities in the genesis of rhythmic masticatory muscle activity across sleep cycles in primary sleep bruxism children.

STUDY OBJECTIVES: The present study aimed to clarify the physiological relationships between rhythmic masticatory muscle activity (RMMA) and cyclic changes in cortical, autonomic, and arousal-motor activities during sleep in sleep bruxism (SB) children. METHODS: Polysomnographic recordings were performed on 15 SB children (9 boys, 6 girls, 10.3 ± 2.5 years) and 18 control children (5 boys, 13 girls, 10.7 ± 3.1 years) free from sleep and developmental disorders. Sleep and RMMA were scored by the standard rules. Sleep cycle was divided into NREM and REM sleep segments and the frequency of RMMA, transient arousal and movement, and cortical and cardiac activities were then quantitatively analyzed in relation to sleep cycles. RESULTS: Neither sleep architecture nor sleep stage distribution of RMMA significantly differed between the two groups. In sleep cycles, SB children showed more frequent RMMA in all segments than controls, while cyclic changes in cortical and autonomic activities did not significantly differ between the two groups. In SB children, RMMA was the most frequent in the last NREM segment before REM sleep and was associated with increases in cortical beta activity and arousal; more than 70% of RMMA time-dependently occurred with cortical and motor arousals. CONCLUSIONS: This is the first study to suggest that the potentiation of RMMA occurrence was associated with transient arousal under cyclic sleep processes in primary SB children.

Use of a Sensing Device to Visualizes Group Participation in Social Skills Learning Groups.

Children with autism spectrum disorders (ASD) have difficulties in developing stable peer relationships. Interventions for learning social skills (SS) for such children are often conducted in a group. Behavioral imaging and social imaging, which have been called for in recent years, are methods for visualizing children's behaviors and interpersonal relationships. To examine the usefulness of visualizing face-to-face interaction with others in the social skills learning scene of children with ASD, we use a business microscope that can qualify and visualize face-to-face interactions automatically. We highlight two boys' face-to-face interaction changes in the same SS learning group of five children. The device's use may provide a more objective measurement that complements the observer's subjective evaluation in case of the intervention's validation. It is expected that information on face-to-face interactions will be used to determine the SS learning process in the future.

Sleep and the General Behavior of Infants and Parents during the Closure of Schools as a Result of the COVID-19 Pandemic: Comparison with 2019 Data.

This study compared cross-sectional data from online surveys describing the sleep behavior of infants and caregivers in March 2020 (the school closure period during the early stages of the COVID-19 pandemic; n = 295, 23.8 ± 3.8 months old) and March 2019 (before the pandemic; n = 2017, 24.2 ± 3.8 months old). In comparing those two points in time, no significant differences were found in wake-up times (2019: 7:19 ± 0:46 am vs. 2020: 7:18 ± 0:47 am, p = 0.289), bedtimes (21:01 ± 0:48 pm vs. 21:04 ± 0:53 pm, p = 0.144), or nocturnal sleep times (593.7 ± 43.9 min vs. 588.1 ± 50.3 min, p = 0.613). Regarding the caregivers, in 2020, wake-up times (2019: 6:46 ± 0:50 am vs. 2020: 6:39 ± 0:50 am, p = 0.017) and bedtimes (22:53 ± 1:17 pm vs. 22:42 ± 1:04 pm, p = 0.016) became significantly earlier compared to 2019. Among infants staying at home, total sleep time and percentage of outdoor play decreased significantly, and media use increased significantly in 2020. Lower levels of exercise and more frequent media viewing may have caused prolonged sleep latency in these children. The percentage of caregivers responding with "negative childcare feelings" was significantly higher in the group with less than three nursery school attendance days. Caregivers and infants staying at home are a high-risk group during the pandemic.

An Interactive Smartphone App, Nenne Navi, for Improving Children's Sleep: Pilot Usability Study.

BACKGROUND: Healthy sleep is important not only for physical health but also for brain development in children. Several reports have revealed that Japanese adults and children have later bedtimes and shorter sleep durations compared with those in other countries, possibly because of Japanese culture and lifestyles. Therefore, an intervention tool that is suitable to the Japanese sociocultural environment is urgently needed to improve children's sleep problems in their early years. OBJECTIVE: To provide appropriate sleep health literacy to caregivers and change their parenting behavior, we developed a smartphone app that allows reciprocal interaction between caregivers and pediatric sleep experts. This paper describes a preliminary study to examine the app's basic design and functions and to establish its acceptability and usability in a small sample. METHODS: A total of 10 caregivers and 10 infants (aged 18-28 months; 4/10, 40% boys) living in Japan participated in the study. At the start of the trial, the e-learning content regarding sleep health literacy was delivered via a smartphone. Thereafter, caregivers manually inputted recorded data about their own and their infant's sleep habits for 8 consecutive days per month for 2 months. After pediatric sleep experts retrieved this information from the Osaka University server, they specified the problems and provided multiple sleep habit improvement suggestions to caregivers. Caregivers then selected one of the feasible pieces of advice to practice and reported their child's sleep-related behaviors via the app. Actigraphy was used to monitor children's sleep behaviors objectively. The concordance between the information provided by caregivers and the actigraphy data was assessed. The acceptability and usability of the app were evaluated using self-report questionnaires completed by caregivers; qualitative feedback was obtained via semistructured interviews after the intervention. RESULTS: There was no significant difference between the information provided by the caregivers and the actigraphy data for bedtimes and wake-up times (P=.13 to P=.97). However, there was a difference between the actigraphy data and the caregivers' reports of nighttime sleep duration and nighttime awakenings (P<.001 each), similar to prior findings. User feedback showed that 6 and 5 of the 10 caregivers rated the app easy to understand and easy to continue to use, respectively. Additionally, 6 of the 10 caregivers rated the app's operativity as satisfactory. Although this was a short-term trial, children's sleep habits, caregivers' sleep health consciousness, and parenting behaviors improved to some extent. CONCLUSIONS: The present findings suggest that the app can easily be used and is acceptable by Japanese caregivers. Given the user feedback, the app has the potential to improve children's sleep habits by sending individualized advice that fits families' backgrounds and home lives. Further studies are needed to confirm the efficacy of the app and facilitate social implementation.

Evaluation of the validity of psychological preparation for children undergoing polysomnography.

STUDY OBJECTIVES: Nocturnal polysomnography (PSG) is an essential diagnostic technique to assess sleep abnormalities, including sleep-disordered breathing (SDB). Although low in invasiveness, it is extremely difficult to conduct PSG with children who are not cooperative with wearing electrodes and sensors. Particularly, it is difficult to conduct PSG on children with autism spectrum disorder (ASD) because they have poor predictive ability, exhibit extreme anxiety about novel and unfamiliar things, and have difficulty understanding verbal instructions. Recently, the usefulness of psychological preparation was reported. The primary aim of this study was to assess the usefulness of psychological preparation for PSG. METHODS: The goal of our study was to assess the usefulness of psychological preparation for PSG. A total of 253 children were enrolled in the study: 131 in the control group (19 with ASD) and 122 selected for psychological preparation (51 with ASD). RESULTS: In the preparation group, 110 of 122 (90.2%) could undergo regular PSG, a significantly higher percentage than the control group at 104 of 131 (79.4%), P = .018. Regarding hypnotic drugs, in the preparation group 111 of 122 (91.0%) underwent PSG without hypnotic drugs, which was a significantly higher percentage than in the control group at 107 of 131 (81.7%), P = .032. Additionally, 45 of 51 children with ASD in the preparation group (88.2%) could undergo PSG without hypnotic drugs. CONCLUSIONS: This study indicated that psychological preparation was effective in facilitating PSG without hypnotic drugs in children who have difficulty cooperating with PSG, including those with ASD.

Examining the Treatment Efficacy of PEERS in Japan: Improving Social Skills Among Adolescents with Autism Spectrum Disorder.

This study examines the efficacy of the Japanese version of the Program for the Education and Enrichment of Relational Skills (PEERS), which focuses on improving social functioning through making friends and maintaining good relationships for adolescents with autism spectrum disorder (ASD) without intellectual disabilities. Originally developed in the United States, PEERS is one of the few evidence-based social skills training programs for youth with ASD. The present study shows that with linguistic and cultural modifications, PEERS is effective in improving social functioning for adolescents with ASD in Japan. Positive results were found specifically in the areas of socialization, communication, knowledge of social skills, autistic mannerisms, and behavioral and emotional problems. In addition, most treatment gains were maintained at a 3-month follow-up assessment. These findings suggest that the Japanese version of PEERS is beneficial across multiple socio-emotional and behavioral domains for adolescents with ASD.

Structural brain abnormalities in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share high rates of comorbidity, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition now acknowledging the comorbid diagnosis of ASD and ADHD. Although structural abnormalities in the prefrontal cortex, cerebellum, and basal ganglia occur in both ASD and ADHD, no structural studies have focused exclusively on patients with comorbid ASD and ADHD. We thus aimed to clarify the structural features and developmental changes in patients with comorbid ASD and ADHD in a relatively large sample from two sites. Ninety-two patients were age-matched to 141 typically developing (TD) controls (age range: 5-16 years) and assessed for volumetric characteristics using structural magnetic resonance imaging (i.e. surface-based morphometry). While there were no significant differences in prefrontal cortex, cerebellum, and basal ganglia volumes, patients with ASD and ADHD exhibited significantly lower left postcentral gyrus volumes than TD controls. We observed significantly lower postcentral gyrus volumes exclusively in children and preadolescents, and not in adolescents. Our findings suggest that abnormal somatosensory, attributed to delayed maturation of the left postcentral gyrus, leads to the core symptoms experienced by patients with comorbid ASD and ADHD.

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study.

BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 ± 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 ± 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention.

White Matter Tract-Cognitive Relationships in Children with High-Functioning Autism Spectrum Disorder.

OBJECTIVE: The purpose of the present study was to clarify the relationship between white matter tracts and cognitive symptoms in children with high-functioning autism spectrum disorder (ASD). METHODS: We examined the cognitive functions of 17 children with high-functioning ASD and 18 typically developing (TD) controls and performed diffusion tensor imaging (DTI) tractography. We compared the results between the groups and investigated the correlations between the cognitive scores and DTI parameters within each group. RESULTS: The Comprehension scores in the ASD group exhibited a positive correlation with mean diffusivity (MD) in the forceps minor (F minor). In the TD group, the Comprehension scores were positively correlated with fractional anisotropy (FA) in the right inferior fronto-occipital fasciculus (IFO) and left anterior thalamic radiation (ATR), and negatively correlated with MD in the left ATR, radial diffusivity (RD) in the right IFO, and RD in the left ATR. Additionally, a positive correlation was observed between the Matching Numbers scores and MD in the left uncinate fasciculus and F minor, and RD in the F minor. Furthermore, the Sentence Questions scores exhibited a positive correlation with RD in the right inferior longitudinal fasciculus. Relative to TD controls, the specific tract showing a strong correlation with the cognitive scores was reduced in the ASD group. CONCLUSION: Our findings indicate that white matter tracts connecting specific brain areas may exhibit a weaker relationship with cognitive functions in children with ASD, resulting in less efficient cognitive pathways than those observed in TD children.

Abnormal cortical activation during silent reading in adolescents with autism spectrum disorder.

OBJECTIVE: Autism spectrum disorder (ASD) is a developmental disorder characterized by communication deficits and social difficulties, and individuals with ASD frequently exhibit varied levels of language abilities. However, the neurophysiological mechanisms underlying their language deficits remain unclear. To gain insight into the neurophysiological mechanisms of receptive language deficits, we assessed cortical activation patterns in adolescents with ASD during silent word-reading. METHODS: We used magnetoencephalography to measure cortical activation during a silent word-reading task in 14 adolescent boys with high-functioning ASD and 17 adolescent boys with typical development (TD). RESULTS: Compared with participants with TD, those with ASD exhibited significantly decreased cortical activation in the left middle temporal gyrus, left temporoparietal junction, bilateral superior temporal gyrus, left posterior insula, and right occipitotemporal gyrus, and increased activation in the right anterior insula. Participants with ASD also exhibited a lack of left-lateralization in the central sulcus and abnormal right-lateralization in the anterior insula area. Furthermore, in participants with ASD, we found that abnormal activation of the right central sulcus correlated significantly with lower visual word comprehension scores, and that decreased activation of the right anterior insula correlated significantly with the severity of social interaction difficulties. CONCLUSION: Our findings suggest that atypical cortical activation and lateralization in the temporal-frontal area, which is associated with higher-order language processing functions, such as semantic analysis, may play a crucial role in visual word comprehension and social interaction difficulties in adolescents with ASD.

Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains. METHODS: Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed. RESULTS: Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains. CONCLUSION: Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.

Aberrant Cerebellar-Cerebral Functional Connectivity in Children and Adolescents With Autism Spectrum Disorder.

The cerebellum, which forms widespread functional networks with many areas in the cerebral cortices and subcortical structures, is one of the brain regions most consistently reported to exhibit neuropathological features in patients with autism spectrum disorder (ASD). However, cerebellar functional connectivity (FC) studies in patients with ASD have been very sparse. Using resting state functional connectivity (rsFC) analysis, we investigated the FC of the hemispheric/vermal subregions and the dentate nucleus of the cerebellum with the cerebral regions in 36 children and adolescents [16 participants with ASD, 20 typically developing (TD) participants, age: 6-15 years]. Furthermore, an independent larger sample population (42 participants with ASD, 88 TD participants, age: 6-15 years), extracted from the Autism Brain Imaging Data Exchange (ABIDE) II, was included for replication. The ASD group showed significantly increased or decreased FC between "hubs" in the cerebellum and cerebral cortices, when compared with the TD group. Findings of aberrant FCs converged on the posterior hemisphere, right dentate nucleus, and posterior inferior vermis of the cerebellum. Furthermore, these aberrant FCs were found to be related to motor, executive, and socio-communicative functions in children and adolescents with ASD when we examined correlations between FC and behavioral measurements. Results from the original dataset were partially replicated in the independent larger sample population. Our findings suggest that aberrant cerebellar-cerebral FC is associated with motor, socio-communicative, and executive functions in children and adolescents with ASD. These observations improve the current knowledge regarding the neural substrates that underlie the symptoms of ASD.