Reciprocal first night effect on rhythmic and non-rhythmic oromotor episodes in moderate to severe primary sleep bruxism: A retrospective physiological study.

BACKGROUND: Sleep on the first night in a sleep laboratory is characterized by a lower sleep quality and frequency of rhythmic masticatory muscle activity (RMMA) than that on the second night in moderate to severe sleep bruxism (SB) patients. OBJECTIVE: The aims of this study was to clarify the physiological factors contributing to the first night effect on oromotor activity during sleep and investigate whether physiological factors involved in the first night effect differed between rhythmic and non-rhythmic oromotor activities. METHODS: Polysomnographic data collected on two consecutive nights from 15 moderate to severe SB subjects (F 7: M 8; age: 23.2 ± 1.3 [mean ± SD] years) were retrospectively analysed. Sleep variables, RMMA and non-specific masticatory muscle activity (NSMA) were scored in relation to episode types (i.e. phasic or tonic and cluster or isolated), sleep architecture and transient arousals. The relationships between nightly differences in oromotor and sleep variables were assessed. The distribution of oromotor events, arousals, cortical electroencephalographic power, RR intervals and heart rate variability were examined in relation to sleep cycle changes. These variables were compared between the first and second nights and between RMMA and NSMA. RESULTS: Sleep variables showed a lower sleep quality on Night 1 than on Night 2. In comparisons with Night 1, the RMMA index increased by 18.8% (p < .001, the Wilcoxon signed-rank test) on Night 2, while the NSMA index decreased by 17.9% (p = .041). Changes in the RMMA index did not correlate with those in sleep variables, while changes in the NSMA index correlated with those in arousal-related variables (p < .001, Spearman's rank correlation). An increase in the RMMA index on Night 2 was found for the cluster type and stage N1 related to sleep cyclic fluctuations in cortical and cardiac activities. In contrast, the decrease in the NSMA index was associated with increases in the isolated type and the occurrence of stage N2 and wakefulness regardless of the sleep cycle. CONCLUSION: Discrepancies in first night effect on the occurrence of RMMA and NSMA represent unique sleep-related processes in the genesis of oromotor phenotypes in SB subjects.

Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study.

BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. METHODS: Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual's magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. RESULTS: Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation. CONCLUSIONS: This study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.

Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder.

Bornavirus infection is observed in both animals, including humans. However, bornavirus epidemiology in humans, especially in children, remains unclear. Here, we evaluated antibodies against bornaviruses in Japanese children with autism spectrum disorder (ASD) using immunofluorescence analysis, western blotting, and radio ligand assay. The prevalence of antibodies against bornavirus-specific speckles, N, and P proteins were 22%, 48%, and 33%, respectively, in the ASD children. According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in the ASD children. This is the first report of the serological prevalence of bornavirus in Japanese children. Our results provide valuable baseline-data regarding bornavirus epidemiology in children for future studies.

Abnormal cortical activation during an auditory word comprehension task in benign childhood epilepsy with centrotemporal spikes: A magnetoencephalographic study.

OBJECTIVE: Benign childhood epilepsy with centrotemporal spikes (BECTS), also known as rolandic epilepsy, has recently been reported to be associated with variable degrees of cognitive dysfunction. Many studies reported poor language ability in children with BECTS compared with healthy control children. To elucidate the harmful effects of BECTS on language cognition, we studied the magnetoencephalographic activity elicited by an auditory language comprehension task. METHODS: The participants (N = 20) included 10 children diagnosed with BECTS (aged 10.8 ±â€¯2.8 years) and 10 age-matched healthy children (control) (aged 10.6 ±â€¯1.6 years). Cognitive function was assessed using general intellectual function and language ability. In patients with BECTS, we reviewed the clinical course and electroencephalogram (EEG) findings. We recorded the cortical responses elicited by an auditory language comprehension task using magnetoencephalography (MEG). We compared those results between groups and analyzed the correlation with cognitive scores and frequency of spikes. RESULTS: The full-scale intelligence quotient (FSIQ) by the Wechsler Intelligence Scale for Children-4th edition was significantly reduced in the group with BECTS (96.4 ±â€¯12.3) compared with the control group (110.0 ±â€¯7.4). In half of the group with BECTS, the auditory comprehension score fell below the age-standard level. In the group with BECTS, the cortical activation during the task showed reduced intensity in language-associated areas such as the bilateral primary auditory cortex, left superior and mid-temporal areas, and inferior frontal area compared with those in the control group. In addition, the cortical activation in the left superior temporal area was negatively correlated with spike frequency and positively correlated with FSIQ in the group with BECTS. Conversely, the right inferior frontal and mid-temporal areas had increased the activations in the group with BECTS. From the time frequency analysis, low gamma band event-related desynchronization was reduced in the group with BECTS. CONCLUSION: Epileptic spikes negatively influenced responsiveness to the auditory language comprehension task in the language-associated cortices. These findings suggest that epileptic spikes could have a negative impact on the functional activity in rolandic areas and become a reason to change the functional development of the language network.

Daytime physical activity and sleep in pre-schoolers with developmental disorders.

AIM: This study aims to investigate the association between daytime physical activity (PA) and sleep in pre-schoolers with or without autism spectrum disorders (ASDs). METHOD: Thirty-one pre-school children with ASD and 16 age-matched controls were recruited. Sleep and PA patterns were measured with an Actiwatch for 7 days. After average PA values were calculated for three periods (morning, afternoon and evening) of each day for each child, the days with maximum (active) and minimum (inactive) PA values for these three periods were determined. The Wilcoxon signed-rank test was used to compare sleep following active mornings, afternoons and evenings with that following inactive time periods. RESULTS: In control children, sleep onset time following active mornings/afternoons did not differ from that following inactive mornings/afternoons. In contrast, sleep onset following the most inactive morning (median sleep onset time: 9:57 pm) and the most inactive afternoon (median sleep onset time: 10:24 pm) began significantly later than that following the most active mornings (median sleep onset time: 9:21 pm) and the most active afternoons (median sleep onset time: 9:39 pm) in children with ASD. The percentage of sleep for control children following active mornings was significantly higher (median: 93.2%) than that following inactive ones (median: 91.7%). Significant associations were not found between evening PA and sleep in either ASD or control children. CONCLUSIONS: A high level of morning and afternoon PA can advance the sleep phase in children with ASD.

Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series.

Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication.

[An analysis of the developmental trajectory of children with autism spectrum disorders].

OBJECTIVE: To investigate the factors that affect the developmental trajectory in autism spectrum disorders (ASD) by means of a questionnaire-based retrospective analysis. METHOD: This study included 292 consecutive Japanese children with ASD who visited the pediatric developmental clinic at the Osaka University Hospital. Questionnaires were completed by caregivers on their first visit and were used for obtaining demographic information as well as nurturing environment and history of supportive intervention. Caregivers also fulfilled out The Infant Behavior Checklist (revised, in Japanese), and The Children's Behavior Questionnaire (revised, in Japanese). The scores for autistic traits during infancy and at present were compared in order to evaluate the developmental trajectory. RESULTS: Early intervention may attenuate ASD symptoms, whereas unfavorable domestic conditions, any psychiatric or neurological disorder in a family member, and epilepsy as a co-morbidity may aggravate these symptoms. In addition, impaired social interaction among all other ASD symptoms was specifically improved by early intervention, even if such intervention was not tailored to ASD. CONCLUSION: Early intervention and family support are important for children with ASD to promote their social development.

Development of a rating scale for maladaptive symptoms by maltreatment: Perspectives of attachment and dissociation.

Child abuse has been increasing in Japan. Abused children's behavior may often be confused with neurodevelopmental disorders; therefore, specialized tools to identify these cases and specific care for maltreatment are crucial. This study aimed to develop an objective early screening scale for abuse-related maladaptive symptoms. To do this, two surveys were conducted. Survey 1 included 60 children attending public elementary schools, who had been admitted to orphanages due to abuse (maltreated group), and 154 children attending public elementary schools with no reported maltreatment (control group). In this survey, 40 existing scale items related to attachment behavior and dissociative symptoms were evaluated. Childcare staff and homeroom teachers evaluated children's behaviors. Receiver operating characteristic (ROC) curves were drawn to determine optimal cut-off values. In Survey 2, 39 children in the maltreatment group and 186 children in the control group were subjected to confirmatory factor analysis to examine the new scale's reliability and validity. Based on the results of an exploratory factor analysis, a two-factor, 20-item rating scale for maladaptive symptoms due to maltreatment (RS-MSM) was developed. The receiver operating characteristic curve indicated that cutoff values set in Survey 1 were appropriate for screening the general population and children in the clinical range. The results confirmed a two-factor structure with high reliability and convergent validity in the Survey 2 sample. Therefore, the developed RS-MSM scale is valid and will allow for easy screening of maltreated children at school.

Altered microstructural connectivity of the superior cerebellar peduncle is related to motor dysfunction in children with autistic spectrum disorders.

Many studies have reported motor impairments in autistic spectrum disorders (ASD). However, the brain mechanism underlying motor impairment in ASD remains unclear. Recent neuroimaging studies have suggested that underconnectivity between the cerebellum and other brain regions contributes to the features of ASD. In this study, we investigated the microstructural integrity of the cerebellar pathways, including the superior, middle, and inferior cerebellar peduncles, of children with and without ASD by using diffusion tensor imaging (DTI) tractography to determine whether the microstructural integrity of the cerebellar pathways is related to motor function in children with ASD. Thirteen children with ASD and 11 age-, gender-, handedness-, and IQ-matched typically developing (TD) controls were enrolled in this study. DTI outcome measurements, such as fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), for the cerebellar pathways were calculated. The Movement Assessment Battery for Children 2 (M-ABC 2) was used for assessing motor functions. There were no significant differences between the two groups in RD. However, compared to the TD subjects, patients with ASD had a significantly lower FA in the right superior cerebellar peduncle and lower AD in the left superior cerebellar peduncle, in addition to a significantly lower score in ball skills and the total test score of M-ABC 2. There was a significant positive correlation between the total test score of M-ABC 2 and FA in the right superior cerebellar peduncle in the ASD group. These findings suggest that the altered microstructural integrity of the superior cerebellar peduncle may be related to motor impairment in ASD.

A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia.

We reported on a male patient with rare leukoencephalopathy and skeletal abnormalities. The condition was first noticed as a developmental delay, nystagmus and ataxia at 1 year of age. At 4 years of age, he was diagnosed as hypomyelination with skeletal abnormalities from clinical features, brain magnetic resonance imaging (MRI) and skeletal X-rays. His brain MRI revealed diffuse hypomyelination. These findings suggested the classical type of Pelizaeus-Merzbacher disease (PMD) caused by proteolipid protein (PLP)-1 gene or Pelizaeus-Merzbacher-like disease (PMLD). However, we found neither mutation nor duplication of PLP-1. The patient had severe growth retardation and general skeletal dysplasia compatible with spondylo-epi-metaphyseal dysplasia; however the mutation of discoidin domain receptor (DDR) 2 gene was absent. The co-morbidity of hypomyelination with skeletal abnormalities is rare. We performed array CGH and no causal copy number variation was recognized. Alternatively, this condition may have been caused by a mutation of the gene encoding a molecule that functions in both cerebral myelination and skeletal development.

[Effectiveness of a modified parent training of smaller groups and shorter schedules for children with pervasive developmental disorders].

OBJECTIVE: We have previously reported the modified parent training of smaller groups and shorter schedules (PTSS). In this study, we applied PTSS to the mothers of children with pervasive developmental disorder (PDD) and revealed the new evidence for its effectiveness. METHODS: The participants were 30 mothers of children with PDD aged from 4.2 to 9.6 years. The effectiveness of PTSS was assessed with the confidence degree questionnaire (CDQ) and the child behavior checklist (CBCL), before and after each PTSS course. The recorded interviews were qualitatively analyzed using the KJ (Kawakita Jiro) methods. RESULTS: Average CDQ scores were clearly improved as previously reported. In addition, the CBCL total T-score was significantly improved, which was not observed in the previous study. About KJ methods, six factors that change of mothers recognition were identified. CONCLUSIONS: Our findings provides additional evidence for the usefulness of PTSS for children with PDD.

Subjective sleep assessments are correlated with EEG-related sleep measurements of the first sleep cycle in healthy young adults.

This study examined whether subjective and objective sleep parameters (sleep stage, electroencephalography [EEG] power, heart rate variability) are related to the progression of sleep cycles using differences in the variables between two nights. We hypothesized that the association between night-to-night differences between subjective and objective sleep variables reflect the difference in objective sleep variables in the first sleep cycle. Seventy-seven healthy adults (23.8 ± 2.2 years; 41 females) participated in polysomnographic recordings on two consecutive nights. To extract the variables that represent the difference between the nights, the sleep parameters of Night 1 were subtracted from those of Night 2. Spearman's rho was used to assess correlations between subjective sleep assessments and objective sleep parameters, with false discovery rate correction for multiple comparisons. Subjective sleep assessments were significantly correlated with whole-night sleep architecture and quantitative EEG activity, but not with heart rate variability during the night. Among sleep cycles, subjective sleep parameters were correlated with the objective sleep parameters in the first sleep cycle ("Ease of falling asleep" vs. waking after sleep onset [r = - 0.382], "Depth of sleep" vs. EEG theta power [r = 0.404], "Quality of sleep" vs. the percentage of stage N3 [r = 0.412] and EEG delta power [r = 0.458], all p < 0.05). These results suggest the importance of taking the difference among the nights into account when assessing subjective sleep quality. This study clarified that sleep in the first sleep cycle has a dominant influence on subjective sleep assessments. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00437-x.

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.

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.

Extension of microglial activation is associated with epilepsy and cognitive dysfunction in Tuberous sclerosis complex: A TSPO-PET study.

BACKGROUND AND OBJECTIVES: Neuroinflammation contributes to the severity of various neurological disorders, including epilepsy. Tuberous sclerosis complex (TSC) is a condition that results in the overactivation of the mammalian target of rapamycin (mTOR) pathway, which has been linked to the activation of microglia responsible for neuroinflammation. To clarify the involvement of neuroinflammation in the neuropathophysiology of TSC, we performed a positron emission tomography (PET) study using the translocator protein (TSPO) radioligand, [11C] DPA713, and investigated microglial activation in relation to neurological manifestations, especially epilepsy and cognitive function. METHODS: This cross-sectional study included 18 patients with TSC (6 in the no-seizure group, 6 in the refractory seizure group, and 6 in the mTOR-inhibitor [mTOR-i] group). All participants underwent [11C] DPA713-PET. PET results were superimposed with a 3D T2-weighted fluid-attenuated inversion-recovery (FLAIR) and T1-weighted image (T1WI) to evaluate the location of cortical tubers. Microglial activation was assessed using the standardized uptake value ratio (SUVr) of DPA713 binding. The volume ratio of the DPA713-positive area to the intracranial volume (volume ratio of DPA713/ICV) was calculated to evaluate the extent of microglial activation. A correlation analysis was performed to examine the relationship between volume ratio of DPA713/ICV and severity of epilepsy and cognitive function. RESULTS: Most cortical tubers with hyperintensity on FLAIR and hypo- or isointensity on T1WI showed microglial activation. The extent of microglial activation was significantly greater in the refractory seizure group than in the no-seizure or mTOR-i groups (p < 0.001). The extent of microglial activation in subjects without mTOR-i treatment correlated positively with epilepsy severity (r = 0.822, P = 0.001) and negatively with cognitive function (r = -0.846, p = 0.001), but these correlations were not present in the mTOR-i group (r = 0.232, P = 0.658, r = 0.371, P = 0.469, respectively). CONCLUSION: Neuroinflammation is associated with the severity of epilepsy and cognitive dysfunction in brains with TSC. mTOR-i may suppress the extent of neuroinflammation in TSC. Investigating the spread of microglial activation using TSPO-PET in these patients may help to predict the progression of neuropathy by assessing the degree of neuroinflammation and therefore be useful for determining how aggressive the treatment should be and in assessing the effectiveness of such treatment in patients with TSC.

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.

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.

[Effects of botulinum toxin therapy for respiratory distress in patients with cervical hypertonia].

Botulinum toxin A (BTX-A) therapy has been approved as a first-line therapy for spastic torticollis. However it has been suggested as that its use in patients with respiratory distress should be decided cautiously. We treated 5 patients with abnormal posture, cervical hypertonia and obstructive respiratory distress by BTX-A, and analyzed its efficacy for respiratory distress by their Tsui score and respiratory status after BTX-A therapy. All 5 patients clinically had some degree of dysphagia before BTX-A therapy. Cervical hypertonia and induced abnormal posture were improved in all patients. The youngest patient could control muscle tone after only 2 doses of BTX-A and subsequently maintained a good condition without additional BTX-A. BTX-A therapy can decrease torsion and hyperextension of the upper respiratory tract by reducing cervical hypertonia. Consequently, it may improve respiratory status. On the other hand, mild dysphagia and excessive salivation was noted in one patient for each symptom. It is safe to avoid BTX-A invasion to the anterior muscle of neck and rapid changes in the swallowing pattern.

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.

Objective: Tuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI). Methods: A total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers. Results: The TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC. Conclusion: The disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.

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.