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BackgroundAtypical peak alpha frequency (PAF) has been reported in children with autism spectrum disorder (ASD); however, the relationships between PAF, age, and autistic traits remain unclear. This study was conducted to investigate and compare the resting-state PAF of young children with ASD and their typically developing (TD) peers using magnetoencephalography (MEG).MethodsNineteen children with ASD and 24 TD children, aged 5-7 years, underwent MEG under resting-state conditions. The PAFs in ten brain regions were calculated, and the associations between these findings, age, and autistic traits, measured using the Social Responsiveness Scale (SRS), were examined.ResultsThere were no significant differences in PAF between the children with ASD and the TD children. However, a unique positive association between age and PAF in the cingulate region was observed in the ASD group, suggesting the potential importance of the cingulate regions as a neurophysiological mechanism underlying distinct developmental trajectory of ASD. Furthermore, a higher PAF in the right temporal region was associated with higher SRS scores in TD children, highlighting the potential role of alpha oscillations in social information processing.ConclusionsThis study emphasizes the importance of regional specificity and developmental factors when investigating neurophysiological markers of ASD. The distinct age-related PAF patterns in the cingulate regions of children with ASD and the association between right temporal PAF and autistic traits in TD children provide novel insights into the neurobiological underpinnings of ASD. These findings pave the way for future research on the functional implications of these neurophysiological patterns and their potential as biomarkers of ASD across the lifespan.

Transformer models have revolutionized fields like Natural Language Processing (NLP) by enabling machines to accurately understand and generate human language. However, these models’ inherent complexity and limited interpretability pose barriers to their broader adoption. To address these challenges, we propose a simplified query-only attention mechanism specifically for encoder-based transformer models to reduce complexity and improve interpretability. Unlike conventional attention mechanisms, which rely on query (Q), key (K), and value (V) vectors, our method uses only the Q vector for attention calculation. This approach reduces computational complexity while maintaining the model’s ability to capture essential relationships, enhancing interpretability. We evaluated the proposed query-only attention on an EEG conformer model, a state-of-the-art architecture for EEG signal classification. We demonstrated that it performs comparably to the original QKV attention mechanism, while simplifying the model’s architecture. Our findings suggest that query-only attention offers a promising direction for the development of more efficient and interpretable transformer-based models, with potential applications across various domains beyond NLP.

Abstract 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.

Abstract 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.

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.

Abstract 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.

Measuring whole brain networks is a promising approach to extract features of autism spectrum disorder (ASD), a brain disorder of widespread regions. Objectives of this study were to evaluate properties of resting-state functional brain networks in children with and without ASD and to evaluate their relation with social impairment severity. Magnetoencephalographic (MEG) data were recorded for 21 children with ASD (7 girls, 60–89 months old) and for 25 typically developing (TD) control children (10 girls, 60–91 months old) in a resting state while gazing at a fixation cross. After signal sources were localized onto the Desikan–Killiany brain atlas, statistical relations between localized activities were found and evaluated in terms of the phase lag index. After brain networks were constructed and after matching with intelligence using a coarsened exact matching algorithm, ASD and TD graph theoretical measures were compared. We measured autism symptoms severity using the Social Responsiveness Scale and investigated its relation with altered small-worldness using linear regression models. Children with ASD were found to have significantly lower small-worldness in the beta band (p = 0.007) than TD children had. Lower small-worldness in the beta band of children with ASD was associated with higher Social Responsiveness Scale total t-scores (p = 0.047). Significant relations were also inferred for the Social Awareness (p = 0.008) and Social Cognition (p = 0.015) sub-scales. Results obtained using graph theory demonstrate a difference between children with and without ASD in MEG-derived resting-state functional brain networks, and the relation of that difference with social impairment. Combining graph theory and MEG might be a promising approach to establish a biological marker for ASD.

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 disorders (ASD) are characterized by impaired social cognition and communication. In addition to social impairment, individuals with ASD often have intellectual disability. Intelligence is known to influence the phenotypic presentation of ASD. Nevertheless, the relation between intelligence and social reciprocity in people with ASD remains unclear, especially in childhood. To elucidate this relation, we analyzed 56 typically developing children (35 male, 21 female, aged 60-91 months) and 46 children with ASD (35 male, 11 female, aged 60-98 months) from university and affiliated hospitals. Their cognitive function was evaluated using the Kaufman Assessment Battery for Children. Their social cognition was assessed using the Social Responsiveness Scale. We used linear regression models to ascertain whether the associations between intelligence and social cognition of typically developing children and children with ASD are significantly different. Among the children with ASD, scores on the Kaufman Assessment Battery for Children correlated significantly with social cognition, indicating that higher intelligence is associated with better social cognition. For typically developing children, however, no significant correlation was found. One explanation might be that children with ASD fully use general intelligence for successful learning in social cognition, although extensive use of intelligence might not be necessary for TD children. Alternatively, autistic impairment in social cognition can be compensated by intelligence despite a persistent deficit in social cognition. In either case, when using the SRS as a quantitative phenotype measure for ASD, the influence of intelligence must be considered.

Abstract Background A growing body of anecdotal evidence indicates that the use of robots may provide unique opportunities for assisting children with autism spectrum disorders (ASD). However, previous studies investigating the effects of interventions using robots on joint attention (JA) in children with ASD have shown insufficient results. The robots used in these studies could not turn their eyes, which was a limitation preventing the robot from resembling a human agent. Methods We compared the behavior of children with ASD with that of children with typical development (TD) during a JA elicitation task while the children interacted with either a human or a robotic agent. We used the robot “CommU,” which has clear eyes and can turn its eyes, for the robotic intervention. The age range of the participants was limited to 5–6 years. Results Sixty-eight participants participated in this study, including 30 (10 females and 20 males) children with ASD and 38 (13 females and 25 males) children with TD. The participants were randomly assigned to one of the following two groups: the robotic intervention group or the control group. JA in the children with ASD was better during the robotic intervention than during the human agent intervention. These children exhibited improved performance in the JA task with human after interacting with the robot CommU. JA was differentially facilitated by the human and robotic agents between the ASD and TD children. Conclusions The findings of this study significantly contribute to the literature on the impact of robots on JA and provide information regarding the suitability of specific robot types for therapeutic use.

Objectives: Insomnia, characterized by difficulty initiating or maintaining sleep, affects a significant portion of the global population. Bedtime procrastination, which is a voluntary delay in going to bed, is a major contributing factor to the prevalence of sleep deprivation in modern societies. Hwanglyeonhaedok-tang (HJD decoction) has shown promise in improving the symptoms of insomnia. This study aimed to evaluate the efficacy of HJD decoction in patients with insomnia and bedtime procrastination.Methods: This study employs a parallel-group design, comparing HJD decoction to usual care in a 1:1 ratio. Sixty participants with insomnia and bedtime procrastination will be enrolled. The experimental group will receive HJD decoction for 4 weeks, while both groups will undergo a brief behavioral treatment for insomnia. The primary outcome will be the change in the Insomnia Severity Index score (ISI) from baseline to 4 weeks. Secondary outcomes include sleep diary metrics, the Pittsburgh Sleep Quality Index (PSQI), and Bedtime Procrastination Scale (BPS). The exploratory outcomes include perceived stress, anxiety, smartphone use, and heart rate variability.Conclusion: This trial examines the role of herbal medicine in treating a specific type of insomnia that is increasingly common in modern society. The combination of HJD decoction with behavioral intervention offers a comprehensive approach to treating insomnia complicated by bedtime procrastination. The results will provide valuable insights into integrative treatment strategies for sleep disorders in the digital age.

Background: Invasive laser acupuncture (ILA) involves simultaneous application of focused laser irradiation and acupuncture. This study aims to explore the effects of ILA on knee osteoarthritis (KOA) through a pilot clinical trial. Methods: This prospective, patient-blinded, single-center, and parallel-arm pilot randomized controlled trial will enroll 45 patients with KOA randomized to the control, 830, and 650 groups. All patients will receive education on exercise and self-care. Their ILA treatment will correspond to their group (control group, sham; 830 group, 830 nm; 650 group, 650-nm wavelength laser) for 10 minutes once daily, twice weekly for 6 weeks at EX-LE4, ST35, ST34, SP10, SP9, GB34, and EXLE2 acupoints. Results: The primary endpoint will be changes in the visual analog scale (VAS) score of pain at rest and during activity 1 week after interventions (week 7). The secondary outcomes will be the responder rate; VAS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain subscale, WOMAC function subscale, European quality of life five-dimension five-level scale, and patient global assessment scores; and rescue medication doses. Safety outcome measures will include blood chemistry parameters, occurrence of adverse events, pulse rate, and blood pressure. The efficacy outcomes will be measured at baseline, visit after six treatments, 1 week after the last treatment, and 6 weeks after the last treatment. Conclusion: The findings will provide preliminary data on the effects of ILA on KOA.

Electroencephalograms of individuals with autism spectrum disorders (ASD) show higher rates of interictal epileptiform discharges (IEDs), which are known to have an inverse association with cognitive function in typically developed (TD) children. Nevertheless, that phenomenon has not been investigated adequately in children with ASD. From university and affiliated hospitals, 163 TD children (84 male, 79 female, aged 32–89 months) and 107 children (85 male, 22 female, aged 36–98 months) with ASD without clinical seizure were recruited. We assessed their cognitive function using the Kaufman Assessment Battery for Children (K-ABC) and recorded 10 min of MEG. Original waveforms were visually inspected. Then a linear regression model was applied to evaluate the association between the IED frequency and level of their cognitive function. Significantly higher rates of IEDs were found in the ASD group than in the TD group. In the TD group, we found significant negative correlation between mental processing scale scores (MPS) and the IED frequency. However, for the ASD group, we found significant positive correlation between MPS scores and the IED frequency. In terms of the achievement scale, correlation was not significant in either group. Although we found a correlative rather than a causal effect, typically developed children with higher IED frequency might better be followed up carefully. Furthermore, for children with ASD without clinical seizure, clinicians might consider IEDs as less harmful than those observed in TD children.

The COVID-19 pandemic forced the rapid development of methods to measure humoral and cellular immunity against SARS-CoV-2. The lack of a global standardized protocol and the high variability of intra- and inter-assay precision of the T-cell response made it difficult to compare T-cell assay results with those of other laboratories. The interferon-gamma enzyme-linked immunosorbent spot (IFN-γ ELISpot) assay for immunogenicity evaluation was validated using naturally infected donor peripheral blood mononuclear cells, a commercially available IFN-γ ELISpot kit, and a SARS-CoV-2 specific peptide pool. Depending on anti-CD3 and peptide pool stimulation, the mean coefficients of variation (CVs) of the intra-assay precision were 19.0% and 13.4%, respectively. The mean CVs of the inter-assay precision were 26.1% and 25.4%, and the mean CVs for reproducibility were 6.7% and 15.9%, respectively. Linearity with an R-squared value between 0.98 and 0.99 was established, and the mean CVs between the lots were 17.6% and 6.6%, depending on the anti-CD3 and peptide pool stimulation, respectively. The limit of detection was 11 spot-forming counts per well. Taken together, we demonstrated that the IFN-γ ELISpot assay is feasible for evaluating SARS-CoV-2-specific cell-mediated immune function through validation based on standard operating procedures.

Phase-amplitude coupling (PAC) plays an important role in neural communication and computation. Interestingly, recent studies have indicated the presence of ubiquitous PAC phenomenon even during the resting state. Despite the importance of PAC phenomenon, estimation of significant physiological PAC is challenging because of the lack of appropriate surrogate measures to control false positives caused by non-physiological PAC. Therefore, in the present study, we evaluated PAC phenomenon during resting-state magnetoencephalography (MEG) signal and considered various surrogate measures and computational approaches widely used in the literature in addition to proposing new ones. We evaluated PAC phenomenon over the entire length of the MEG signal and for multiple shorter time segments. The results indicate that the extent of PAC phenomenon mainly depends on the surrogate measures and PAC computational methods used, as well as the evaluation approach. After a careful and critical evaluation, we found that resting-state MEG signals failed to exhibit ubiquitous PAC phenomenon, contrary to what has been suggested previously.