1. Dehesh T, Mosleh-Shirazi MA, Jafari S, Abolhadi E, Dehesh P. A assessment of the effects of parental age on the development of autism in children: a systematic review and a meta-analysis. BMC Psychol. 2024; 12(1): 685.

OBJECTIVE: There has been conflicting evidence in earlier research on the association between parental age and autism risk. To clarify this association, we conducted a comprehensive meta-analysis of observational studies. The primary objective of this study was to determine the association between parents’ age and the risk of autism in the offspring. METHODS: PubMed, EMBASE and Web of Science were searched for reports published up to November 2023. Results from relevant studies were pooled using random effects models. Subgroup analyses and meta-regression were performed to examine heterogeneity between the studies. Studies were included in this meta-analysis that focused on children with autism and examined the relationship between parents’ age (mother or father) and the risk of autism.The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: This meta-analysis included 41 articles. The low age of mother (OR = 0.96, (95% CIs: 0.88-1.05) and father (OR = 1.11, (95% CIs: 0.98-1.24) was not significantly associated with lower risk of autism in children. Conversely, greater paternal and maternal ages were associated with an increased risk of autism in their children. The adjusted odds ratios for mothers’ and fathers’ ages were 1.47 (95% CIs: 1.33-1.62) and 1.51 (95% CIs: 1.40-1.62), respectively. CONCLUSION: Increased risk of autism in children is significantly associated with greater parents’ ages. Further research is needed to gain further insight into the mechanisms responsible for the effects of parents’ ages on the risk of autism in children. The findings of previous studies on the association between parents’ ages and their children’s autism risk have been mixed. Therefore, by carefully examining a number of previous investigations, in this study we aimed to determine the exact relationship between parental age and autism risk. According to the study’s findings, parents who are older have a higher chance of their child getting autism. In other words, children of older parents are more likely to develop autism. The exact causes of this relationship, however, are still unclear. This study shows that higher age of parents can be one of the risk factors for autism in their childs.

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2. Ferguson EF, Spackman E, Cai RY, Hardan AY, Uljarević M. Exploring the Heterogeneity of Self-Injurious Behaviors in Autistic Youth: Patterns, Predictors, and Implications for Intervention. Autism Res. 2024.

Self-injurious behaviors (SIB) encompass a heterogeneous set of self-inflicted aggressive behaviors that are highly prevalent in autistic youth. Existing research on SIB in autism spectrum disorder (ASD) has been limited by significant methodological and conceptual inconsistencies. Thus, the current study leveraged item-level data capturing the severity of unique SIB topographies to further understanding of factors associated with distinct SIB in a sample of 582 autistic youth (M(age) = 12.12, SD(age) = 3.68; range: 3-19 years; 13% females). Results suggest variation in severity endorsements for specific SIB topographies amongst autistic youth, such that 30%-50% of caregivers endorsed slight to very serious concern regarding the SIB topographies of bites nails/skin/fingers, scratches self, hits head/face/neck, bangs head against things, and picks skin. Generalized additive models demonstrated distinct patterns of associations between each SIB topography and dysregulation, sensory hypersensitivity, age, sex, IQ, and language level. Findings underscore the importance of exploring SIB as a multifaceted construct to capture unique correlates of distinct SIB that vary in severity and functional impact, which is critical for the development of effective interventions. This study represents an important step towards more individualized characterization of SIB and support for diverse presentations of these behaviors in autistic youth.

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3. Islam MI, Stubbs T, Esgin T, Martiniuk A. Impact of healthy pregnancy and lifestyle in mothers on developmental delay in their offspring: a strength-based analysis of a longitudinal study among indigenous children in Australia. BMC Pregnancy Childbirth. 2024; 24(1): 776.

INTRODUCTION: Extensive literature has investigated the prenatal risk factors of developmental delay in children, with evidence highlighting the impact of prenatal health, mental health, and behavioural factors. While a deficit discourse has underscored Indigenous health research and policies, strengths-based approaches provide an opportunity to reframe this discourse, to illustrate and celebrate the strength and resilience of Australian Indigenous families. As such, this study aimed to identify the protective impact of healthy pregnancy and lifestyle in mothers on developmental delay in Indigenous Australian children; and whether it varies by child birthweight adjusted for gestational age. Further, we also tested whether child birthweight for adjusted gestational age mediates the association between a healthy pregnancy and lifestyle in mothers and developmental delay in their Indigenous offspring. METHODS: Strength-based analysis was conducted using data from 8 longitudinal waves of LSIC study in Australia. Random-effect models were used to longitudinally measure the impact of maternal healthy pregnancy and lifestyle on developmental delays in their children between 2008 and 2018. A composite score (ranging from 0 to 3, score = 3 refers to most healthy pregnancy) was created for a healthy pregnancy and lifestyle variable using three criteria - (1) a lack of medical conditions, (2) no substance use including smoking/alcohol/illicit drugs, and (3) intake of iron/folic acid during pregnancy. All models were adjusted for potential covariates. RESULTS: Of the 780 mother-child dyads analysed, 65.4% of mothers reported healthy pregnancy and lifestyle; while 73.5% of children born with a recommended appropriate birthweight adjusted for gestational age, and 91.4% reported no developmental delays. In children born in the recommended range of appropriate birthweight adjusted for gestational age, healthy pregnancy in mothers (most healthy, aOR: 4.76, 95% CI: 1.12-20.18; and 2nd most healthy, aOR: 4.02, 95% CI: 1.09-14.83) was protective against development delay compared to maternal unhealthy pregnancy. Living in remote areas (vs. major city, and regional) was also found to be protective against developmental delay in those who were born within the recommended range of birthweight adjusted for gestational age. Further, the current study found that child birthweight for adjusted gestational age does not have any mediating effect on the association between healthy pregnancy in mothers and developmental delay in their children. CONCLUSION: This strengths-based study suggests healthy pregnancy in mothers should be advocated to prevent developmental delay in their offspring in the Australian Indigenous population. The findings also found living in remote areas has a protective effect against developmental delay in Indigenous children who born within the recommended range of birthweight adjusted for gestational age. These findings have implications for challenging and reframing the deficit discourse surrounding Indigenous Australian health research and policymaking. Further studies are needed to investigate the positive relationship between Indigenous Australians’ health and social and emotional well-being (SEWB) and their connection to their country and culture.

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4. Li Y, Xie T, Vos M, Snieder H, Hartman CA. Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue. Transl Psychiatry. 2024; 14(1): 476.

Autism spectrum disorder (ASD) often co-occurs with functional somatic syndromes (FSS), such as irritable bowel syndrome (IBS), multisite pain, and fatigue. However, the underlying genetic mechanisms and causality have not been well studied. Using large-scale genome-wide association study (GWAS) data, we investigated the shared genetic architecture and causality between ASD and FSS. Specifically, we first estimated genetic correlations and then conducted a multi-trait analysis of GWAS (MTAG) to detect potential novel genetic variants for single traits. Afterwards, polygenic risk scores (PRS) of ASD were derived from GWAS and MTAG to examine the associations with phenotypes in the large Dutch Lifelines cohort. Finally, we performed Mendelian randomization (MR) to evaluate the causality. We observed positive genetic correlations between ASD and FSS (IBS: r(g) = 0.27, adjusted p = 2.04 × 10(-7); multisite pain: r(g) = 0.13, adjusted p = 1.10 × 10(-3); fatigue: r(g) = 0.33, adjusted p = 5.21 × 10(-9)). Leveraging these genetic correlations, we identified 3 novel genome-wide significant independent loci for ASD by conducting MTAG, mapped to NEDD4L, MFHAS1, and RP11-10A14.4. PRS of ASD derived from both GWAS and MTAG were associated with ASD and FSS in Lifelines, and MTAG-derived PRS showed a bigger effect size, larger explained variance, and smaller p-values. We did not observe significant causality using MR. Our study found genetic associations between ASD and FSS, specifically with IBS, multisite pain, and fatigue. These findings suggest that a shared genetic architecture may partly explain the co-occurrence between ASD and FSS. Further research is needed to investigate the causality between ASD and FSS due to current limited statistical power of the GWASs.

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5. Lundin Remnélius K, Bölte S. Moving Beyond the Phenotypic Correlation Between Anorexia Nervosa and Autism. Int J Eat Disord. 2024.

The recent systematic review and meta-analysis by Inal-Kaleli et al. is situated within a growing area of research, investigating the relationship between anorexia nervosa and autistic characteristics. Their synthesis of research within the topic finds support for elevated autistic characteristics and autism in individuals with anorexia nervosa and a small but significant correlation between autistic traits and level of eating disorder symptoms. In this commentary, we discuss the findings of Inal-Kaleli and colleagues and propose further research to generate insights into the nature of this link. We focus on the potential origins of the observed relationship, specific mechanisms, and manifestation of anorexia nervosa in autistic populations, and the influence of sex and gender on the intersection of eating disorders and autism. By addressing these largely unexplored research avenues, future investigations can go beyond the phenotypic correlations and facilitate the development of prevention and intervention suited for individuals experiencing both disordered eating and elevated autistic traits.

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6. Manning BL, Hosseini K, Yang E, Buzzell GA, Landi N, Kim SH. Neural Processing of Speech Sounds in Autistic Kindergarteners as a Predictor of Reading Outcomes. J Autism Dev Disord. 2024.

Phonology is an important foundation of reading development; however, little is known about the neural substrates of speech sound processing and reading development in autistic children. We investigated early auditory event-related potentials (ERPs) in response to speech sounds and their association with reading ability (word recognition and reading comprehension). 56 kindergarteners (28 ASD, 28 TD) completed an ERP task using rhyming, bisyllabic pseudowords (/gibu/ and /bidu/) in an old/new design: 50% « old » and 50% « new » stimuli presented following a sensitization block of 100% « old » stimuli. Behavioral measures of reading ability were completed at kindergarten entry and exit. Results from generalized linear mixed models revealed a significant three-way interaction between stimuli (« new » vs. « old »), diagnosis (ASD vs. TD), and reading ability (for word recognition and reading comprehension) for P1 and P2 amplitude. Follow-up analyses revealed that autistic children with lower reading abilities showed greater P1 and P2 amplitudes for « new » vs. « old » stimuli, with effects ranging from marginal to significant (p’s 0.04-0.07). Regression analyses revealed that old/new ERP difference scores significantly predicted later word recognition at kindergarten year-end (P1 amplitude: p = .05; P2 amplitude: p = .04), but not reading comprehension, controlling for sex and nonverbal IQ. Autistic children with poorer reading skills, specifically those with weaker word recognition abilities, show neural differences when processing speech sounds compared to autistic peers with greater reading ability and typically developing children. A better understanding of the neural basis of speech sound processing could enhance our insight into the heterogeneity in reading among individuals with ASD and guide future treatment approaches.

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7. Nelson MA, Schmitt LM, Horn PS, Berry-Kravis E, Hessl D, Shaffer RC, Carpenter R, Budimirovic DB, Wang P, Reisinger DL, Walton-Bowen K, Erickson CA. Parent-Reported Outcome Measures for Individuals with Fragile X Syndrome: Clinically Meaningful Change Thresholds. J Autism Dev Disord. 2024.

Estimating meaningful change thresholds (MCT) on clinical outcome assessments is an important consideration when evaluating treatments. In fragile X syndrome (FXS) research, there has been no consensus on how to define MCT’s on several commonly used outcome measures. The purpose of the current study was to determine clinically relevant MCT’s of caregiver-rated assessments using data from a phase 3 clinical trials of arbaclofen (Berry-Kravis et al., 2017). Data were collected as a part of previous phase 3, double-blind, placebo-controlled studies of arbaclofen in individuals with FXS (Berry-Kravis et al., 2017). The two studies enrolled age groups of 5-11-years (n = 159) and 12-50-years (n = 119). The current study examines meaningful within-patient change thresholds from baseline to treatment week 8 across several measures: ABC-C(FXS); PSI; Vineland-II; and a Visual Analog Scale (VAS) of Anxiety and Disruptive Behaviors. MCT’s were established by using anchor-based methods, using the CGI-S and CGI-I as anchors. Examining the results of the anchor-based analyses and visual CDF plots, MCT’s were observed for the pediatric study for the ABC-C(FXS) subscales (with a range depending on use of CGI-S or CGI-I as anchor): Irritability: 11.1-14.8 points; Hyperactivity: 6.7-8.9 points; and Socially Unresponsive/Lethargic: 6.6-8.1 points; as well both VAS subscales: Anxiety: 28.3-36.2 mm; and Disruptive Behavior: 22.4-27.4 mm. Such thresholds were not observed for the Vineland-II and PSI subscales. Our analysis of MCT’s helps set the stage for interpreting clinical trial results in FXS. This may include use of relevant subscales of the ABC-C(FXS) and VAS as primary outcomes using the MCT’s for response definition. This work may help define future study inclusion criteria and enable future interpretation of treatment outcome results in the field.

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8. Peisch V, DePillis R, Hanson E, Brewster SJ, Sideridis G, Barbaresi WJ, Harstad E. The Impact of Face Mask Use on Research Evaluations of 5-7 Year-Old Children With Autism Spectrum Disorder. J Autism Dev Disord. 2024.

The COVID-19 pandemic changed the nature of clinical research assessments. Little is known about the impact of face mask use on research assessments for autism spectrum disorder (ASD). This study reports on tolerability of face mask use, child characteristics associated with tolerability, and the impact of face mask use on researcher ASD diagnostic certainty ratings. This paper describes results from a larger study of children who were clinically diagnosed with ASD in early childhood and were re-evaluated at age 5-7 years. Research diagnostic evaluations were conducted from 2018 to 2022 and included cognitive, language, and social-communication assessment. A research psychologist completed a rating scale on the potential impact of face mask use on research assessment diagnostic certainty for a subset of participants (n = 60) who were evaluated during the COVID-19 pandemic. The mean age of study participants was 6.2 years. Face masks were tolerated throughout the assessment for 40 children (66.7%); part-time for 13 (21.6%); and not tolerated for 7 (11.6%). Analysis of Variance (ANOVA) suggested that children who did not tolerate a face mask had significantly lower cognitive [F(2, 59) = 13.241, p < 0.001] and communication [F(2, 59) = 13.639, p < 0.001] scores compared to children who wore their mask for all or part of the visit. For 88% of research assessments, research staff indicated that face mask use had "no impact" on overall assessment results. Face mask use during clinical research assessment was not reported by research staff to significantly impact their ability to complete ASD evaluations.

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9. Quezada-Ugalde AM, Benavides AA, Murata C, Villegas SS, García Hernández AM. Findings in Child Development in Children Who Grew Up During the COVID-19 Pandemic in Two Countries. Infancy. 2025; 30(1): e12634.

The COVID-19 pandemic created an unprecedented situation for families worldwide, with its potential impact on child development remaining uncertain, particularly within Latin American communities. This study aimed to analyze child development in children from Costa Rica and Mexico who grew up during COVID-19 pandemic. A cross-sectional study was conducted using a convenience sample of 183 children; a historical control group of Costa Rican children (n = 171) was also included. Child development was assessed using the EDIN-II in Costa Rica and the EDI in Mexico, along with a parental questionnaire. Descriptive statistics, chi-square tests, and logistic regression analysis were performed, with a significance level of 0.05. Significant differences were found when comparing the risk of development delay, particularly in the overall score and the fine motor domain score. The probability of overall delay was associated with the child’s sex, age, maternal education level and whether the primary caregiver role was shared by both parents or fulfilled by a single parent. In Costa Rica, the development of children assessed post-pandemic was lower than that of children assessed pre-pandemic. The probability of these delays was associated with growing up during the pandemic, child’s sex, and families’ Socioeconomic Development Index. These results contribute to understanding child development during the COVID-19 context and provide a foundation for future research.

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10. Ran R, Liang W, Deng S, Fan X, Shi K, Wang T, Dong S, Hu Q, Liu C. Risk assessment and automatic identification of autistic children based on appearance. Sci Rep. 2024; 14(1): 29074.

The diagnosis of Autism Spectrum Disorder (ASD) is mainly based on some diagnostic scales and evaluations by professional doctors, which may have limitations such as subjectivity, time, and cost. This research introduces a novel assessment and auto-identification approach for autistic children based on the appearance of children, which is a relatively objective, fast, and cost-effective approach. Initially, a custom social interaction scenario was developed, followed by a facial data set (ACFD) that contained 187 children, including 92 ASD and 95 children typically developing (TD). Using computer vision techniques, some appearance features of children including facial appearing time, eye concentration analysis, response time to name calls, and emotional expression ability were extracted. Subsequently, these features were combined and machine learning methods were used for the classification of children. Notably, the Bayes classifier achieved a remarkable accuracy of 94.1%. The experimental results show that the extracted visual appearance features can reflect the typical symptoms of children, and the automatic recognition method can provide an auxiliary diagnosis or data support for doctors.

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11. Russell AS, McFayden TC, McAllister M, Liles K, Bittner S, Strang JF, Harrop C. Who, when, where, and why: A systematic review of « late diagnosis » in autism. Autism Res. 2024.

An autism diagnosis can be a critical milestone toward effective and affirming support. Despite the sharp increase in the number of studies focused on late diagnosis over the last 15 years, there remains no consensus as to what constitutes a late diagnosis of autism, with cutoffs ranging from infancy to middle adulthood. This preregistered systematic review evaluated (a) the field’s current quantification of late diagnosis in autism, (b) how the threshold for late diagnosis varies as a function of demographic and population factors, and (c) trends over time. Of the 11,697 records retrieved, N = 420 articles met inclusion criteria and were extracted. Articles spanned 35 years (1989-2024) and included participants from every continent except Antarctica. Only 34.7% of included studies provided a clear threshold for « late diagnosis » (n = 146/420). Late diagnosis cutoffs averaged 11.53 years (range = 2-55 years; median = 6.5 years) with a bimodal distribution (3 and 18 years). The threshold for late diagnosis varied by participant location, F(5,140) = 10.4, p < 0.0001, and sample age, F(5,140) = 20.1, p < 0.0001. Several key rationales for age determinations emerged, including access to services, considerations for adult diagnoses, and data driven approaches. What authors consider to be a "late" diagnosis of autism varies greatly according to research context. Justifications for a specific late-diagnosis age cutoff varied, underscoring the need for authors to contextualize their conceptualizations.

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12. Subramanian D, Eisenberg C, Huang A, Baek J, Naveed H, Komatireddy S, Shiflett MW, Tran TS, Santhakumar V. Dysregulation of neuropilin-2 expression in inhibitory neurons impairs hippocampal circuit development and enhances risk for autism-related behaviors and seizures. Mol Psychiatry. 2024.

Dysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated. We tested the hypothesis that the lack of Nrp2 in MGE-derived interneuron precursors disrupts the excitation/inhibition balance in hippocampal circuits, thus predisposing the network to seizures and behavioral patterns associated with ASD. Embryonic deletion of Nrp2 during the developmental period for migration of MGE derived interneuron precursors (iCKO) significantly reduced parvalbumin, neuropeptide Y, and somatostatin positive neurons in the hippocampal CA1. Consequently, when compared to controls, the frequency of inhibitory synaptic currents in CA1 pyramidal cells was reduced while frequency of excitatory synaptic currents was increased in iCKO mice. Although passive and active membrane properties of CA1 pyramidal cells were unchanged, iCKO mice showed enhanced susceptibility to chemically evoked seizures. Moreover, iCKO mice exhibited selective behavioral deficits in both preference for social novelty and goal-directed learning, which are consistent with ASD-like phenotype. Together, our findings show that disruption of developmental Nrp2 regulation of interneuron circuit establishment, produces ASD-like behaviors and enhanced risk for epilepsy. These results support the developmental interneuronopathy hypothesis of ASD epilepsy comorbidity.

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13. Timothy KW, Bauer R, Larkin KA, Walsh EP, Abrams DJ, Gonzalez Corcia C, Valsamakis A, Pitt GS, Dick IE, Golden A. A Natural History Study of Timothy Syndrome. Orphanet J Rare Dis. 2024; 19(1): 433.

BACKGROUND: Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C. Initially, Timothy syndrome was characterized by a cardiac presentation of long QT syndrome and syndactyly of the fingers and/or toes, all associated with the CACNA1C variant, Gly406Arg. However, subsequent identification of diverse variants in CACNA1C has expanded the clinical spectrum, revealing various cardiac and extra-cardiac manifestations. It remains underexplored whether individuals with the canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) exhibit overlapping symptoms. Moreover, case reports have indicated that some CACNA1C variants may produce a cardiac-selective form of Timothy syndrome often referred to as non-syndromic long QT type 8 or cardiac-only Timothy syndrome, however few reports follow up on these patients to confirm the cardiac selectivity of the phenotype over time. METHODS: A survey was administered to the parents of patients with Timothy syndrome, querying a broad range of symptoms and clinical features. Study participants were organized into 5 separate categories based on genotype and initial diagnosis, enabling comparison between groups of patients which have been described differentially in the literature. RESULTS: Our findings reveal that Timothy syndrome patients commonly exhibit both cardiac and extra-cardiac features, with long QT syndrome, neurodevelopmental impairments, hypoglycemia, and respiratory issues being frequently reported. Notably, the incidence of these features was similar across all patient categories, including those diagnosed with non-syndromic long QT type 8, suggesting that the ‘non-syndromic’ classification may be incomplete. CONCLUSIONS: This study represents the first Natural History Study of Timothy syndrome, offering a comprehensive overview of the disease’s clinical manifestations. We demonstrate that both cardiac and extra-cardiac features are prevalent across all patient groups, underscoring the syndromic nature of CACNA1C variants. While the critical role of long QT syndrome and cardiac arrhythmias in Timothy syndrome has been well recognized, our findings indicate that hypoglycemia and respiratory dysfunction also pose significant life-threatening risks, emphasizing the need for comprehensive therapeutic management of affected individuals.

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14. Wang Y, Liu Y, Wang X, Kendrick KM, Feng T. The Effects of Hearing One’s Own Name on Subsequent Attention to Visual Stimuli in Autistic and Neurotypical Children: An ERP Study. J Autism Dev Disord. 2024.

PURPOSE: Hearing one’s own name produces unique patterns of brain activation which triggers attention and orienting responses to the caller. Children with autism spectrum disorder (ASD) rarely orientate towards people calling their own name, but the extent to which it may facilitate processing of the following external stimuli are not yet clear. METHODS: The current study consisted of both auditory and visual stimuli. Electroencephalogram (EEG) was measured in 28 autistic and neurotypical children (aged 3-7 years) to investigate auditory event-related brain potentials (ERPs) while hearing either their own or an unfamiliar name, and subsequent visual ERPs when viewing objects after hearing them. RESULTS: The results demonstrated that, unlike neurotypical children, autistic children did not show enhanced P300 responses upon hearing their own name, but exhibited more negative N1 response in the left frontal region to hearing their own name than an unfamiliar name. However, both autistic and neurotypical children showed equivalent changes in N2, P3 and Late positive potential (LPP) visual ERPs when viewing objects after hearing their own name relative to an unfamiliar name. CONCLUSION: These findings suggest that autistic children who do not overtly respond to their own name (characterized by a head-turn), nevertheless exhibit increased attention to visual objects in their environment after hearing it. This implies that autistic children do recognize the sound of their name as important but may not understand the social meaning of it.

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