IntroductionThe auditory steady-state response (ASSR) at 40 Hz provides a well-established probe of gamma-band neural synchronization and is thought to reflect excitation–inhibition balance in cortical microcircuits—a mechanism implicated in autism spectrum disorder (ASD). Previous studies focusing on regional ASSR measures have yielded inconsistent findings for ASD, suggesting that system-level approaches may provide complementary information about ASD-related neurophysiological alterations.MethodsWe examined source-level functional brain networks during the 40-Hz ASSR in children with ASD (n = 19) and typically developing (TD) children (n = 34) aged 5–8 years using magnetoencephalography (MEG). Functional connectivity was estimated using the phase lag index (PLI) within the 30–50 Hz band, and graph-theoretical metrics—clustering coefficient (CC), characteristic path length (PL), and small-worldness (SW)—were computed from binary undirected networks. Group differences were assessed using multiple linear regression adjusting for age, sex, and cognitive ability. Associations between network measures and autistic traits, indexed by the Social Responsiveness Scale (SRS), were examined using a regression model including diagnosis and the interaction of diagnosis × graph measure.ResultsThe experimental paradigm elicited ASSR-related cortical activity in both groups. A significant main effect of diagnosis was observed for characteristic PL, with children with ASD exhibiting shorter PL than TD children, indicating altered network topology during 40-Hz ASSR (p = 0.0023). No group differences were found for CC or SW. In the secondary analysis, shorter PL was associated with higher SRS total T-scores in the omnibus model (p = 0.027). The diagnosis × PL interaction was not significant, indicating that this association did not differ detectably between ASD and TD groups.DiscussionThese findings suggest that graph-theoretical analysis of functional brain networks during the 40-Hz ASSR may provide complementary information about ASD-related neural organization beyond conventional ASSR measures. Shorter characteristic PL in ASD, together with its association with autistic-trait severity across the full sample, points to altered large-scale network configuration during externally driven gamma-band synchronization. The results support the value of examining functional brain network topology during the 40-Hz ASSR in ASD.

Abstract Excessive screen use is associated with childhood behavioral problems, but whether associations differ between typically developing (TD) children and those with autism spectrum disorder (ASD) is unclear. Our cross-sectional study included 108 children aged 5–9 years (61 TD, 47 ASD). ASD was diagnosed using standardized clinical instruments. Measures included parent-reported screen time (excluding TV/DVD), cognitive ability (K-ABC), and behavioral problems (Vineland-II). Screen time and externalizing problems were associated in the TD group (Spearman’s ρ = 0.361, p < 0.01), but not in the ASD group. In the regression model, screen time (β = 0.40, t = 2.60, p < 0.05), ASD status (β = 0.70, t = 8.30, p < 0.001), and their interaction (β = −0.34, t = −2.06, p < 0.05) significantly predicted externalizing problems. Considering the diversity within the autism spectrum, future studies with larger sample sizes should consider individual heterogeneity when examining the association between behavioral outcomes and screen time.

Optically pumped magnetometers (OPM) can replace superconducting quantum interference devices (SQUID) as the magnetic sensors in magnetoencephalography (MEG) systems to achieve high spatiotemporal resolution for measuring neuronal activity. OPMs are compact and lightweight, enabling wearable OPM-MEG devices. However, they are susceptible to residual magnetic field gradients within a magnetically shielded room as the sensors are not fixed to the room. Herein, we examined whether a 30Hz steady-state visual evoked field elicited by the hemifield pattern-reversal stimulation procedure could be measured using 18 channel wearable OPM-MEG system without noise cancelling in six healthy adults. Steady-state responses were observed in channels near the visual cortex on the hemifield opposite the visual field where a checkerboard pattern was presented. In the same environment, we successfully verified the cortical oscillatory response using electroencephalography (EEG). Visual evoked field components (e.g. P75m), which follow stimulus onset and are clearly recorded by EEG, were not observed with OPM-MEG. These components were masked by artifacts at 3-5Hz, likely generated by slight body movements. Given the motion artifacts in the low-frequency bandwidth, optimal experimental designs for wearable OPM-MEG measurements without noise canceling need to consider targeting cortical oscillation in the frequency band, which is unaffected by artifacts.

Peak alpha frequency (PAF) is a neurophysiological marker of cortical maturation and cognitive function. We aimed to examine PAF reactivity to a visually engaging eyes-open (EO) condition, during which children watched a muted preferred video, compared to a dark-room (DR) resting state without sound, in children with ASD and their TD peers. We analyzed magnetoencephalography data from 68 cortical sources in children aged 5-10 (ASD: n=22; TD: n=29), calculating PAF during a resting-state DR condition and an EO condition involving silent video viewing. Linear mixed-effects models were used to assess the effects of diagnosis, condition, and their interaction on PAF, controlling for age and sex. The results indicated a significant interaction between diagnosis and condition in the right temporal region, where TD children consistently showed a higher PAF in the EO condition relative to the DR condition, whereas children with ASD did not. Furthermore, in TD children, greater PAF reduction in the right temporal region correlated with lower social responsiveness scores, suggesting a link between PAF reactivity and social functioning. These findings suggest that atypical PAF modulation in response to sensory input may reflect altered neural mechanisms underlying social information processing in ASD. Understanding PAF reactivity patterns can inform the development of ASD biomarkers.

Abstract Aim Face‐to‐face communication between caregiver and infant is essential for the development of language and social skills in infancy. A previous study on brain response toward human faces showed that a lateralization right fusiform gyrus (FG) response when viewing faces was associated with better social skills. However, the relationship, between infant face processing and language development remains unclear. This study aimed to examine whether brain responses to faces vary based on the ability level of language expression. Methods Overall, 42 Japanese infants (aged 18–34 months, Mean of age (Mage) = 24.7 months, standard deviation (SD) = 4.57, 47% female) were assessed for expressive communication skills and classified into two groups: a delayed group (20 infants) and a control group (infants with typical expressive language development, 22 infants). Brain activity was recorded using a child‐customized magnetoencephalography during presentation of a mother's face, a stranger's face, and a nonface (scrambled image). The lateralization index of the FG during face viewing was calculated using the following formula: (L − R)/(L + R). Results The results showed a significant difference in the lateralization index between the delayed and control groups. The control group showed rightward dominance of the FG activity when viewing the mother's face and others' faces, whereas the delayed group did not exhibit this lateralization. Based on behavioral observations, 75% of the delayed group met the criteria of autism spectrum disorder (ASD) risk, and infants with a high risk of ASD who had poor expressive language showed poor right hemispheric dominance compared to the control group in their brain responses to their mothers' faces. Conclusion This study suggests that lateralization of face processing in infancy may be a predictor of expressive language abilities.

Advances in perinatal care have improved survival rates of preterm infants; however, concerns regarding their neurodevelopmental outcomes persist. This study investigates the relationship between intraindividual variability (IIV) in sleep duration and crystallized intelligence in very low birth weight (VLBW) children at the preschool stage. This study had 38 participants, including 18 VLBW children and 20 full-term children aged 5 to 6 years. Sleep duration was assessed using actigraphy and sleep diaries, while crystallized intelligence was evaluated using the Achievement Scale (ACH) of the Kaufman Assessment Battery for Children (K-ABC). Statistical analyses, including correlation and multiple regression analyses, were conducted to examine the effect of preterm birth on the relationship between sleep variability and learning outcomes. The results revealed that sleep duration IIV adversely affected ACH scores of preterm children but had no impact on those of full-term children. In multiple regression analysis, the interaction term between sleep variability and preterm birth significantly predicted ACH scores (p = 0.032), suggesting that early childhood learning in preterm children is more vulnerable to the effects of sleep instability. Additionally, among VLBW children, older age was associated with lower ACH scores, implying that learning difficulties may become more pronounced with age. These results show the potential role of sleep regulatory mechanisms in cognitive development. The findings show the importance of monitoring and supporting healthy sleep habits in preterm children to mitigate potential learning difficulties. Early interventions targeting sleep stability may play a critical role in improving academic performance in this high-risk population.

Children with Autism Spectrum Disorder (ASD) often have more sleep disturbances than typically developing children. These sleep disturbances have been suggested to be associated with atypical sensory features in children with ASD. Sleep habits have also been linked to intelligence and cognitive function in children. However, it remains unclear whether sleep disturbances in children with ASD are related to intelligence or sensory features. This study examined whether sleep disturbances in children can be explained by the presence or absence of ASD characteristics, sensory features, and cognitive skills. Sleep disturbances and atypical sensory features were determined using the Japanese Sleep Questionnaire for Preschoolers and the Caregiver Sensory Profile, as reported by their caregivers. Cognitive skills were assessed using the Japanese translation of the Kaufman Assessment Battery for Children. Consequently, children with below-average cognitive scores demonstrated that higher sensory scores were associated with poorer sleep quality; children with above-average cognitive scores showed no such patterns. These findings may aid in the development of support for sleep disturbances in various subtypes of ASD.

Preterm birth, defined as delivery before 37 weeks of gestation, is associated with alterations in brain development and an increased likelihood of motor difficulties, with effects that often persist across childhood. However, the underlying neurophysiological mechanisms remain insufficiently understood. Oscillatory activity in the primary motor cortex is closely linked to motor execution and reflects the dynamic properties of cortical function, yet motor-related oscillations have rarely been examined directly in children born preterm. In this study, we investigated motor-induced gamma oscillations in school-aged children born preterm using magnetoencephalography (MEG). Eighteen children born preterm and nineteen age- and IQ-matched children born at full term (5 to 7 years old) completed a child-friendly dominant-hand finger movement task during recording with a child-customised MEG system. The preterm group exhibited significantly slower response times and approximately twenty-two per cent weaker contralateral gamma power compared with their full-term peers. They also showed reduced hemispheric lateralisation, indicating greater bilateral cortical engagement. Motor-related gamma power and lateralisation indices were positively associated with perinatal factors and motor performance scores. These findings suggest that attenuated gamma activity and altered lateralisation patterns in children born preterm may relate to delayed maturation of motor cortical circuits and variations in callosal development, potentially affecting interhemispheric communication and motor processing efficiency. This study provides new insight into the neurophysiological basis of motor development following preterm birth. ### Competing Interest Statement The authors have declared no competing interest. Center of Innovation Program, Japan Science and Technology Agency University of Birmingham, https://ror.org/03angcq70

Introduction:Autism spectrum disorders (ASD) represent a heterogeneous group of neurodevelopmental disorders with strong genetic predispositions. Although an increasing number of genetic variants have been implicated in the pathogenesis of ASD, little is known about the relationship between ASD-associated genetic variants and individual ASD traits. Therefore, we aimed to investigate these relationships.Methods:Here, we report a case-control association study of 32 Japanese children with ASD (mainly with high-functioning autism [HFA]) and 36 with typical development (TD). We explored previously established ASD-associated genes using a next-generation sequencing panel and determined the association between Social Responsiveness Scale (SRS) T-scores and intelligence quotient (IQ) scores.Results:In the genotype-phenotype analyses, 40 variants of five genes (SCN1A, SHANK3, DYRK1A, CADPS, and SCN2A) were associated with ASD/TD phenotypes. In particular, 10 SCN1A variants passed permutation filtering (false discovery rate <0.05). In the quantitative association analyses, 49 variants of 12 genes (CHD8, SCN1A, SLC6A1, KMT5B, CNTNAP2, KCNQ3, SCN2A, ARID1B, SHANK3, DYRK1A, FOXP1, and GRIN2B) and 50 variants of 10 genes (DYRK1A, SCN2A, SLC6A1, ARID1B, CNTNAP2, SHANK3, FOXP1, PTEN, SCN1A, and CHD8) were associated with SRS T- and IQ-scores, respectively.Conclusion:Our data suggest that these identified variants are essential for the genetic architecture of HFA.

In previous magnetoencephalography (MEG) studies, children with autism spectrum disorder (ASD) have been shown to respond differently to speech stimuli than typically developing (TD) children. Quantitative evaluation of this difference in responsiveness may support early diagnosis and intervention for ASD. The objective of this research is to investigate the relationship between syllable-induced P1m and social impairment in children with ASD and TD children. We analyzed 49 children with ASD aged 40-92 months and age-matched 26 TD children. We evaluated their social impairment by means of the Social Responsiveness Scale (SRS) and their intelligence ability using the Kaufman Assessment Battery for Children (K-ABC). Multiple regression analysis with SRS score as the dependent variable and syllable-induced P1m latency or intensity and intelligence ability as explanatory variables revealed that SRS score was associated with syllable-induced P1m latency in the left hemisphere only in the TD group and not in the ASD group. A second finding was that increased leftward-lateralization of intensity was correlated with higher SRS scores only in the ASD group. These results provide valuable insights but also highlight the intricate nature of neural mechanisms and their relationship with autistic traits.

Children born with very low birth weight (VLBW) are at higher risk for cognitive impairment, including language deficits and sensorimotor difficulties. Voice-evoked response (P1m), which has been suggested as a language development biomarker in young children, remains unexplored for its efficacy in VLBW children. Furthermore, the relation between P1m and sensory difficulties in VLBW children remains unclear. 40 children with VLBW were recruited at 5-to-6 years old (26 male, 14 female, mean age of months ± SD, 80.0 ± 4.9). We measured their voice-evoked brain response using child-customized magnetoencephalography (MEG) and examined the relation between P1m and language conceptual inference ability and sensory characteristics. The final sample comprised 36 children (23 boys, 13 girls; ages 61–86 months; gestational ages 24–36 weeks). As a result of multiple regression analysis, voice-evoked P1m in the left hemisphere was correlated significantly with language ability (β = 0.414 P = 0.015) and sensory hypersensitivity (β = 0.471 P = 0.005). Our findings indicate that the relation between P1m and language conceptual inference ability observed in term children in earlier studies is replicated in VLBW children, and suggests P1m intensity as a biomarker of sensory sensitivity characteristics.

Verbal interaction and imitation are essential for language learning and development in young children. However, it is unclear how mother-child dyads synchronize oscillatory neural activity at the cortical level in turn-based speech interactions. Our study investigated interbrain synchrony in mother-child pairs during a turn-taking paradigm of verbal imitation. A dual-MEG (magnetoencephalography) setup was used to measure brain activity from interactive mother-child pairs simultaneously. Interpersonal neural synchronization was compared between socially interactive and noninteractive tasks (passive listening to pure tones). Interbrain networks showed increased synchronization during the socially interactive compared to noninteractive conditions in the theta and alpha bands. Enhanced interpersonal brain synchrony was observed in the right angular gyrus, right triangular, and left opercular parts of the inferior frontal gyrus. Moreover, these parietal and frontal regions appear to be the cortical hubs exhibiting a high number of interbrain connections. These cortical areas could serve as a neural marker for the interactive component in verbal social communication. The present study is the first to investigate mother-child interbrain neural synchronization during verbal social interactions using a dual-MEG setup. Our results advance our understanding of turn-taking during verbal interaction between mother-child dyads and suggest a role for social "gating" in language learning.

Abstract Aim This study aimed to investigate gamma oscillations related to face processing of children with autism spectrum disorders and typically developed children using magnetoencephalography. Methods We developed stimuli that included naturalistic real‐time eye‐gaze situations between participants and their mothers. Eighteen young children with autism spectrum disorders (62−97 months) and 24 typically developed children (61−79 months) were included. The magnetoencephalography data were analyzed in the bilateral banks of the superior temporal sulcus, fusiform gyrus, and pericalcarine cortex for frequency ranges 30–59 and 61–90 Hz. The gamma oscillation normalized values were calculated to compare the face condition (children gazing at mother's face) and control measurements (baseline) using the following formula: (face − control)/(face + control). Results The results revealed significant differences in gamma oscillation normalized values in the low gamma band (30–59 Hz) in the right banks of the superior temporal sulcus, right fusiform gyrus, and right pericalcarine cortex between children with autism spectrum disorders and typically developed children. Furthermore, there were significant differences in gamma oscillation normalized values in the high gamma band (61–90 Hz) in the right banks of the superior temporal sulcus, bilateral fusiform gyrus, and bilateral pericalcarine cortex between the groups. Conclusion This report is the first magnetoencephalography study revealing atypical face processing in young children with autism spectrum disorders using relevant stimuli between participants and their mothers. Our naturalistic paradigm provides a useful assessment of social communication traits and a valuable insight into the underlying neural mechanisms in children with autism spectrum disorders.

Abstract Aim Although atypical sensory motor processing has been investigated in children with autism spectrum disorder (ASD), whether or not atypical sensory motor processing is related to altered language function in children with ASD remains unclear. Methods This study examined the relationship between sensory motor processing and language conceptual inference ability in 3–10‐year‐old children with (n = 61) and without (n = 114) ASD. Language performance was assessed using the language conceptual inference task of the Kaufman Assessment Battery for Children (K‐ABC). Sensory processing was assessed using the Caregiver Sensory Profile. Results In children with ASD, altered processing of the fine motor/perceptual factor scored by sensory profile was found to be significantly related to language conceptual inference ability in the K‐ABC, representing the integrated abilities of language comprehension and language expression, which reflect language semantic concept formation. Conclusions For children with ASD, the results suggest a relationship between difficulties of integrating sensory information perceived from the body adjusting fine movement and deficiencies of language semantic conceptual formation.

In children with autism spectrum disorder (ASD), impairment of joint attention and language function are observed frequently from early childhood. Earlier reports have described these two phenomena as mutually related. For this study, developing past research, the relation between joint attention and the ability of conceptual inference is examined in 113 Japanese children (67.9 months mean age, 75% male) with ASD. We calculated Pearson’s correlation coefficients between their Joint attention abnormality evaluated by ADOS-2 and “Riddle” subscale in K-ABC, then they are negatively correlated: r (104) = -.285. A larger abnormality of joint attention is associated with a lower ability of conceptual inference. New findings were obtained indicating that, in children of this age group with ASD, the degree of joint attention impairment is correlated negatively with conceptual inference ability, but not with expressive and receptive language abilities. Consideration of the mechanism of this relation is presented in this report.

Individuals with sub-threshold autism spectrum disorder (ASD) are those who have social communication difficulties but do not meet the full ASD diagnostic criteria. ASD is associated with an atypical brain network; however, no studies have focused on sub-threshold ASD. Here, we used the graph approach to investigate alterations in the brain networks of children with sub-threshold ASD, independent of a clinical diagnosis. Graph theory is an effective approach for characterizing the properties of complex networks on a large scale. Forty-six children with ASD and 31 typically developing children were divided into three groups (i.e., ASD-Unlikely, ASD-Possible, and ASD-Probable groups) according to their Social Responsiveness Scale scores. We quantified magnetoencephalographic signals using a graph-theoretic index, the phase lag index, for every frequency band. Resultantly, the ASD-Probable group had significantly lower small-worldness ( SW ) in the delta, theta, and beta bands than the ASD-Unlikely group. Notably, the ASD-Possible group exhibited significantly higher SW than the ASD-Probable group and significantly lower SW than the ASD-Unlikely group in the delta band only. To our knowledge, this was the first report of the atypical brain network associated with sub-threshold ASD. Our findings indicate that magnetoencephalographic signals using graph theory may be useful in detecting sub-threshold ASD.

AIM:The receptive language ability of individuals with autism spectrum disorder (ASD) seems to lag behind expressive language ability. Several autism-related genes may influence this developmental delay. Polymorphism of one such gene, namely, the contactin-associated protein-like 2 gene (CNTNAP2), affects receptive language in individuals with language delay. However, the association between CNTNAP2 polymorphism and receptive language in individuals with no language delay remains unclear.METHODS:We included 59 children with ASD and 57 children with typical development in this study and investigated this association using coarse-grained exact matching.RESULTS:We present the first evidence of an association between CNTNAP2 rs2710102 (A-allele carrier) and reduced receptive language ability in children with ASD whose language development was not delayed. Similarly, among children with typical development, A-allele carriers had lower receptive language ability, but the difference was non-significant.CONCLUSIONS:It is possible that the effect of rs2710102 on receptive language ability is larger in the presence of autism-related genes. Consequently, we speculate that the effect of rs2710102 on receptive language ability would be exerted in combination with other genes. These findings provide new insights into the genetic interactions between mutations associated with common language disorders and ASD and identify molecular mechanisms and risk alleles that contribute to receptive vocabulary. These findings also provide practical guidance in terms of providing candidate genetic markers that may provide opportunities for targeted early intervention to stratify risk and improve prognosis for poor receptive language development in children with ASD.

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.

Autism spectrum disorder (ASD) often involves dysfunction in general motor control and motor coordination, in addition to core symptoms. However, the neural mechanisms underlying motor dysfunction in ASD are poorly understood. To elucidate this issue, we focused on brain oscillations and their coupling in the primary motor cortex (M1). We recorded magnetoencephalography in 18 children with ASD, aged 5 to 7 years, and 19 age- and IQ-matched typically-developing children while they pressed a button during a video-game-like motor task. The motor-related gamma (70 to 90 Hz) and pre-movement beta oscillations (15 to 25 Hz) were analyzed in the primary motor cortex using an inverse method. To determine the coupling between beta and gamma oscillations, we applied phase-amplitude coupling to calculate the statistical dependence between the amplitude of fast oscillations and the phase of slow oscillations. We observed a motor-related gamma increase and a pre-movement beta decrease in both groups. The ASD group exhibited a reduced motor-related gamma increase and enhanced pre-movement beta decrease in the ipsilateral primary motor cortex. We found phase-amplitude coupling, in which high-gamma activity was modulated by the beta rhythm in the primary motor cortex. Phase-amplitude coupling in the ipsilateral primary motor cortex was reduced in the ASD group compared with the control group. Using oscillatory changes and their couplings, linear discriminant analysis classified the ASD and control groups with high accuracy (area under the receiver operating characteristic curve: 97.1%). The current findings revealed alterations in oscillations and oscillatory coupling, reflecting the dysregulation of motor gating mechanisms in ASD. These results may be helpful for elucidating the neural mechanisms underlying motor dysfunction in ASD, suggesting the possibility of developing a biomarker for ASD diagnosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an early onset and a strong genetic origin. Unaffected relatives may present similar but subthreshold characteristics of ASD. This broader autism phenotype is especially prevalent in the parents of individuals with ASD, suggesting that it has heritable factors. Although previous studies have demonstrated brain morphometry differences in ASD, they are poorly understood in parents of individuals with ASD. Here, we estimated grey matter volume in 45 mothers of children with ASD (mASD) and 46 age-, sex-, and handedness-matched controls using whole-brain voxel-based morphometry analysis. The mASD group had smaller grey matter volume in the right middle temporal gyrus, temporoparietal junction, cerebellum, and parahippocampal gyrus compared with the control group. Furthermore, we analysed the correlations of these brain volumes with ASD behavioural characteristics using autism spectrum quotient (AQ) and systemizing quotient (SQ) scores, which measure general autistic traits and the drive to systemize. Smaller volumes in the middle temporal gyrus and temporoparietal junction correlated with higher SQ scores, and smaller volumes in the cerebellum and parahippocampal gyrus correlated with higher AQ scores. Our findings suggest that atypical grey matter volumes in mASD may represent one of the neurostructural endophenotypes of ASD.