1. Alfaro Arenas R, Rosell Andreo J, Heine Suner D. {{Fragile X syndrome screening in pregnant women and women planning pregnancy shows a remarkably high FMR1 premutation prevalence in the Balearic Islands}}. {Am J Med Genet B Neuropsychiatr Genet}. 2016.
There are no reported studies to determine incidence of Fragile X Syndrome (FXS) in women within the Spanish population. For this reason, together with the high incidence of FXS in the general population, the exclusively maternal expansion, the familial and social impact of the syndrome, and the ease of use and level of detection of current PCR-based techniques, we have conducted a population-based screening pilot program of which we present here the molecular results. We typed prospectively 3,413 pregnant and 318 non-pregnant women and found a prevalence of premutation (PM) carriers of 1 in 106, which is the highest described to date in any population. We also found 230 different alleles of which the most frequent are 10A9A9 (38.4%), 9A9A9 (15.1%), and 10A9 (10.5%). Furthermore, alleles with 0 AGG interruptions or with a pure (uninterrupted) CGG repeat run larger than 34 (presumably more unstable), were more frequent among PM alleles compared to normal alleles. Thea unexpected high frequency of expanded PM alleles in females in the general population makes a very compelling argument for the need for prenatal or preconceptional FXS screening in our community. Furthermore, we find FMR1 triplet primed PCR (TP-PCR) confidently and precisely determines sizes for both alleles of the CGG repeat in women and offers AGG information which greatly improves CGG expansion risk estimations for genetic counselling. Thus, TP-PCR is an informative, efficient and robust method for FXS screening in the female population. (c) 2016 Wiley Periodicals, Inc.
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2. Bennett M, Goodall E. {{Towards an Agenda for Research for Lesbian, Gay, Bisexual, Transgendered and/or Intersexed People with an Autism Spectrum Diagnosis}}. {J Autism Dev Disord}. 2016.
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3. Capriola NN, Maddox BB, White SW. {{No Offense Intended: Fear of Negative Evaluation in Adolescents and Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
Social anxiety disorder (SAD) is a common comorbidity for individuals with autism spectrum disorder (ASD). The present study examined the cardinal cognitive component of SAD, fear of negative evaluation (FNE), in adolescents and adults with ASD (n = 44; 59 % with social anxiety) and those without ASD (n = 69; 49 % with social anxiety). Group (ASD or non-ASD) significantly moderated the relationship between social disability, as well as social motivation impairment, and FNE, such that there was a stronger positive relationship for the adolescents and adults without ASD. Few differences emerged between those with and without ASD, with respect to specific indicators of FNE. Clinical implications are discussed, including the importance of assessing FNE among individuals with ASD.
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4. Chambers NJ, Wetherby AM, Stronach ST, Njongwe N, Kauchali S, Grinker RR. {{Early detection of autism spectrum disorder in young isiZulu-speaking children in South Africa}}. {Autism}. 2016.
Culturally appropriate tools are needed for detecting symptoms of autism spectrum disorder in young South African children. The objectives of this study were to (1) adapt and translate into isiZulu existing measures for detecting early signs of autism spectrum disorder, (2) use the measures to characterize and compare behavioural profiles of young isiZulu-speaking children with and without autism spectrum disorder and (3) compare symptom profiles across sampling procedures. Measures were translated and adapted into isiZulu and used to evaluate 26 isiZulu-speaking children, 15 children with no reported developmental concerns and 11 referred for suspected autism spectrum disorder. A video-recorded observation of children and caregivers in their home environment was also made. Based on best-estimate diagnoses, 10 children were classified as autism spectrum disorder and 16 as non-autism spectrum disorder. The children with autism spectrum disorder presented with significantly more autism spectrum disorder red flags than the non-autism spectrum disorder group according to parent report and systematic ratings of red flags. Significant correlations between parent report and observational measures of red flags were observed. More red flags were observed during structured evaluations than home observations in the autism spectrum disorder group. Findings provide a foundation for tool translation and adaptation in South Africa and identifying social communication markers to detect autism spectrum disorder in young isiZulu-speaking children.
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5. Chan JS, Langer A, Kaiser J. {{Temporal integration of multisensory stimuli in autism spectrum disorder: a predictive coding perspective}}. {J Neural Transm (Vienna)}. 2016.
Recently, a growing number of studies have examined the role of multisensory temporal integration in people with autism spectrum disorder (ASD). Some studies have used temporal order judgments or simultaneity judgments to examine the temporal binding window, while others have employed multisensory illusions, such as the sound-induced flash illusion (SiFi). The SiFi is an illusion created by presenting two beeps along with one flash. Participants perceive two flashes if the stimulus-onset asynchrony (SOA) between the two flashes is brief. The temporal binding window can be measured by modulating the SOA between the beeps. Each of these tasks has been used to compare the temporal binding window in people with ASD and typically developing individuals; however, the results have been mixed. While temporal order and simultaneity judgment tasks have shown little temporal binding window differences between groups, studies using the SiFi have found a wider temporal binding window in ASD compared to controls. In this paper, we discuss these seemingly contradictory findings and suggest that predictive coding may be able to explain the differences between these tasks.
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6. Doenyas C. {{The Social Living Complex: A New, All Day, Yearlong Intervention Model for Individuals with Autism Spectrum Disorder and Their Parents}}. {J Autism Dev Disord}. 2016.
We propose an unprecedented intervention for individuals with autism spectrum disorder (ASD) and their parents: the social living complex. Unlike existing social skills interventions, peer-mediated interventions here are not limited to the school/experiment duration and setting. Whereas other supported living services house adults with ASD only, here children with ASD and their families live and interact with typically developing (TD) individuals. Another novelty is support groups for parents of children with ASD, who report feeling higher levels of stress than parents of TD children and children with other disabilities, feeling isolated, and not receiving social support. This complex will enable the practice and generalization of schooled skills in the lives of children with ASD and foster an accepting, autism-friendly community.
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7. Dong T, He J, Wang S, Wang L, Cheng Y, Zhong Y. {{Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes}}. {Proc Natl Acad Sci U S A}. 2016.
The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes.
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8. Egilson ST, Jakobsdottir G, Olafsson K, Leosdottir T. {{Community participation and environment of children with and without autism spectrum disorder: parent perspectives}}. {Scand J Occup Ther}. 2016: 1-10.
AIM: This study explored parent perspectives of participation patterns and environmental supports and barriers for high-functioning children with autism spectrum disorder (ASD) within their communities compared with a group of children without ASD. METHOD: The Participation and Environment Measure for Children and Youth was used to gather online data from parents of 99 children with ASD and 241 children without ASD. Mann-Whitney U test and chi-square tests were used to explore differences between groups and partial eta squared was calculated to examine effect sizes. RESULTS: Significant differences between children with and without ASD were observed for all participation and environment summary scores. Children with ASD participated less frequently, were less involved, and their parents were less satisfied with their child’s participation in community-based activities. Parents of children with ASD also identified fewer supports for their child’s participation and more environmental barriers than other parents. CONCLUSION: Children with ASD participated less in community-related activities than children without ASD as perceived by their parents. Barriers limiting community participation included features of the social and physical environment and limited resources. SIGNIFICANCE: Occupational therapists should focus on decreasing environmental challenges in their efforts to facilitate participation of children with ASD in the community.
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9. Grainger C, Williams DM, Lind SE. {{Recognition memory and source memory in autism spectrum disorder: A study of the intention superiority and enactment effects}}. {Autism}. 2016.
It is well established that neurotypical individuals generally show better memory for actions they have performed than actions they have observed others perform or merely read about, a so-called ‘enactment effect’. Strikingly, research has also shown that neurotypical individuals demonstrate superior memory for actions they intend to perform in the future (but have not yet performed), an effect commonly known as the ‘intention superiority effect’. Although the enactment effect has been studied among people with autism spectrum disorder, this study is the first to investigate the intention superiority effect in this disorder. This is surprising given the potential importance this issue has for general theory development, as well as for clinical practice. As such, this study aimed to assess the intention superiority and enactment effects in 22 children with autism spectrum disorder, and 20 intelligence quotient/age-matched neurotypical children. The results showed that children with autism spectrum disorder demonstrated not only undiminished enactment effects in recognition and source memory, but also (surprisingly for some theories) typical intention superiority effects. The implications of these results for theory, as well as clinical practice, are discussed.
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10. Lodhi SK, Thaver D, Akhtar IN, Javaid H, Masoor M, Bano S, Malik FN, Iqbal MR, Hashmi HR, Siddiqullah S, Saleem S. {{ASSESSING THE KNOWLEDGE, ATTITUDES AND PRACTICES OF SCHOOL TEACHERS REGARDING DYSLEXIA, ATTENTION-DEFICIT/ HYPERACTIVITY AND AUTISTIC SPECTRUM DISORDERS IN KARACHI, PAKISTAN}}. {J Ayub Med Coll Abbottabad}. 2016; 28(1): 99-104.
BACKGROUND: Learning impairments in children consist of a spectrum of disorders that are under diagnosed in Pakistan. Most learning disorders have long term consequences for a child and early detection is thus imperative. Teachers may be able to play a key role in such identification. The objective of our study was to survey knowledge, attitudes and practices of school teachers regarding dyslexia, Attention-deficit/hyperactivity disorder (ADHD) and autistic spectrum disorder, and assess their ability to identify learning disabilities. METHODS: A cross-sectional study was conducted with 233 primary school teachers from Karachi using a self-administered questionnaire. RESULTS: Mean scores for the knowledge test and the ability to identify learning- impaired children were 58.8% and 53.3%, respectively. Better qualified teachers scored significantly more on the knowledge and ability to identify learning impairments sections. Most teachers believed that these students should study in mainstream schools with special educators. Majority of the teachers belonged to schools where children with learning disabilities were detected using teachers’ judgment. Most teachers manage these children by involving them in discussions, seating them at the front of the class, and giving them extra time. CONCLUSION: Knowledge about learning disabilities is very low amongst school teachers, which may limit their ability to identify learning impairments.
11. Lozano R, Saito N, Reed D, Eldeeb M, Schneider A, Hessl D, Tassone F, Beckett L, Hagerman R. {{Aging in Fragile X Premutation Carriers}}. {Cerebellum}. 2016.
It is now recognized that FMR1 premutation carriers (PC) are at risk to develop a range of neurological, psychiatric, and immune-mediated disorders during adulthood. There are conflicting findings regarding the incidence of hypertension, hypothyroidism, diabetes, and cancer in these patients that warrant further study. A retrospective controlled study was performed in a convenience sample of 248 controls (130 men, 118 women) and 397 FMR1 PC with and without fragile X-associated tremor ataxia syndrome (FXTAS) (176 men, 221 women); all participants were at least 45 years old (men: mean 62.4, SD 9.5; women: mean 62.8, SD 9.9; p = 0.63). Memory and cognitive assessments (Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III)) and molecular testing (CGG repeats and FMR1-mRNA levels) were performed. Additional data included body mass index (BMI), cholesterol levels, blood pressure, hemoglobin A1c (HbA1c) levels, and medical history. A higher percentage of PC subjects self-reported having a diagnosis of hypertension (50.0 vs. 35.0 %, p = 0.006) and thyroid problems (20.4 vs. 10.0 %, p = 0.012) than control subjects. When comparing controls versus PC with FXTAS, the association was higher for diabetes (p = 0.043); however, the effect was not significant after adjusting for demographic predictors. Blood pressure, blood glucose levels, HbA1c, and BMI values were not significantly different between the two groups. The PC with FXTAS group performed consistently lower in neuropsychological testing compared with the PC without FXTAS group, but the differences were very small for all but the WAIS full-scale IQ. Based on these findings, it appears that the risk for hypertension, thyroid problems, and diabetes may be more frequent in PC with FXTAS, which will require verification in future studies.
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12. Martinez-Cayuelas E, Ibanez-Mico S, Cean-Cabrera L, Domingo-Jimenez R, Alarcon-Martinez H, Martinez-Salcedo E. {{[Level of training in autistic spectrum disorders among hospital paediatricians]}}. {An Pediatr (Barc)}. 2016.
BACKGROUND: Training in autistic spectrum disorders is crucial in order to achieve an early diagnosis. However, the number of papers describing this training is limited. This study describes this level of knowledge among paediatricians from tertiary care hospitals in different regions of Spain and detects areas that need improvement. MATERIAL AND METHOD: A total of one hundred and fifty-seven (157) paediatricians working in tertiary healthcare hospitals located in three different regions in Spain consented to complete an online questionnaire divided in three sections (socio-demographic, knowledge about childhood autism, and opinion). Data were analysed using SPSS version 15. RESULTS: The total mean score of participating paediatricians in the questionnaire was 20.34 (+/- 2.43 SD) out of a total possible score of 23. Approximately two-thirds (65%) of paediatricians scored more or equal to the mean score. The knowledge gap was found to be higher with symptoms of repetitive behaviour patterns, concept of autism, and comorbidity, with no statistical significance. There were no differences in paediatrician scores within different socio-demographic groups. Just under two-thirds (64%) of paediatricians subscribed to the opinion that their own knowledge about autism is limited, and there is a significant lack of knowledge about facilities in every region. CONCLUSIONS: There is a sufficient level of knowledge about autism among paediatricians in tertiary healthcare, although a lack of awareness about the management of these patients, with poor coordination between the different specialists that are involved in their treatment. Efforts should focus on achieving a better coordination between these specialists, and update the knowledge gaps identified.
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13. Meng X, Wang W, Lu H, He LJ, Chen W, Chao E, Fiorotto ML, Tang B, Herrera JA, Seymour ML, Neul JL, Pereira FA, Tang J, Xue M, Zoghbi HY. {{Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders}}. {Elife}. 2016; 5.
Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.
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14. Nelson AT, Lopata C, Volker MA, Thomeer ML, Toomey JA, Dua E. {{Exploratory Factor Analysis of SRS-2 Teacher Ratings for Youth with ASD}}. {J Autism Dev Disord}. 2016.
This study examined the factor structure and internal consistency of special education teaching staff ratings on the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), as well as the percentage of ratings falling above pre-established cut scores, for a sample of lower-functioning youth with autism spectrum disorder (ASD; n = 264). Results of the exploratory factor analysis yielded a four-factor correlated solution. The individual factors and total score demonstrated satisfactory internal consistency reliability for screening purposes. When applying the lowest pre-established cut score (T >/= 60; minimum indication of clinically significant symptoms/impairments), 85 % of the sample had ratings in that range or higher (more severe). Implications for assessment and future research are provided.
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15. Notwell JH, Heavner WE, Fazel Darbandi S, Katzman S, McKenna WL, Ortiz-Londono CF, Tastad D, Eckler MJ, Rubenstein JL, McConnell SK, Chen B, Bejerano G. {{TBR1 regulates autism risk genes in the developing neocortex}}. {Genome Res}. 2016.
Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the 9 ASD genes examined, 7 were misexpressed in the cortices of Tbr1 knockout mice, including 6 with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.
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16. Patriquin MA, DeRamus T, Libero LE, Laird A, Kana RK. {{Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder}}. {Hum Brain Mapp}. 2016.
Social impairments in autism spectrum disorder (ASD), a hallmark feature of its diagnosis, may underlie specific neural signatures that can aid in differentiating between those with and without ASD. To assess common and consistent patterns of differences in brain responses underlying social cognition in ASD, this study applied an activation likelihood estimation (ALE) meta-analysis to results from 50 neuroimaging studies of social cognition in children and adults with ASD. In addition, the group ALE clusters of activation obtained from this was used as a social brain mask to perform surface-based cortical morphometry (SBM) in an empirical structural MRI dataset collected from 55 ASD and 60 typically developing (TD) control participants. Overall, the ALE meta-analysis revealed consistent differences in activation in the posterior superior temporal sulcus at the temporoparietal junction, middle frontal gyrus, fusiform face area (FFA), inferior frontal gyrus (IFG), amygdala, insula, and cingulate cortex between ASD and TD individuals. SBM analysis showed alterations in the thickness, volume, and surface area in individuals with ASD in STS, insula, and FFA. Increased cortical thickness was found in individuals with ASD, the IFG. The results of this study provide functional and anatomical bases of social cognition abnormalities in ASD by identifying common signatures from a large pool of neuroimaging studies. These findings provide new insights into the quest for a neuroimaging-based marker for ASD. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.
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17. Pruett JR, Jr., Povinelli DJ. {{Commentary – Autism Spectrum Disorder: Spectrum or Cluster?}}. {Autism Res}. 2016.
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18. Ruzich E, Allison C, Smith P, Ring H, Auyeung B, Baron-Cohen S. {{The Autism-Spectrum Quotient in Siblings of People With Autism}}. {Autism Res}. 2016.
This study measures the distribution of autistic traits, using the autism-spectrum quotient (AQ), in siblings of individuals with autism spectrum conditions (ASC). Total AQ scores, along with AQ subscales, were collected from child, adolescent and adult controls, siblings, and volunteers with ASC using one of the three age-appropriate versions of the instrument: the AQ (adult self-report), the AQ-adolescent and AQ-child (both parent-reports). We examined the effect of Group (case, sibling and control) and AQ version (adult, adolescent and adult) on total and subscale scores. In addition, we tested for sex differences in all groups and on all versions. We found that in male and female adults, AQ scores in siblings fell between cases and controls (cases > siblings > controls). In children and adolescents, female siblings also scored higher than control females (female cases > female siblings > female controls), but there was no difference between male siblings and controls (male cases > male siblings = male controls). An investigation of subscale scores revealed that male siblings only differed from controls on the « Communication » subscale (male cases > male siblings > male controls), while female siblings differed from controls on all subscales except « Imagination » (female cases > female siblings > female controls). This study confirms the broader autism phenotype in siblings, and reveals this is modulated by sex and AQ version. Autism Res 2016. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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19. Ure K, Lu H, Wang W, Ito-Ishida A, Wu Z, He LJ, Sztainberg Y, Chen W, Tang J, Zoghbi HY. {{Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett Syndrome}}. {Elife}. 2016; 5.
The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.
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20. Van der Hallen R, Evers K, Boets B, Steyaert J, Noens I, Wagemans J. {{Visual Search in ASD: Instructed Versus Spontaneous Local and Global Processing}}. {J Autism Dev Disord}. 2016.
Visual search has been used extensively to investigate differences in mid-level visual processing between individuals with ASD and TD individuals. The current study employed two visual search paradigms with Gaborized stimuli to assess the impact of task distractors (Experiment 1) and task instruction (Experiment 2) on local-global visual processing in ASD versus TD children. Experiment 1 revealed both groups to be equally sensitive to the absence or presence of a distractor, regardless of the type of target or type of distractor. Experiment 2 revealed a differential effect of task instruction for ASD compared to TD, regardless of the type of target. Taken together, these results stress the importance of task factors in the study of local-global visual processing in ASD.
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21. Venker CE. {{Spoken word recognition in children with autism spectrum disorder: The role of visual disengagement}}. {Autism}. 2016.
Deficits in visual disengagement are one of the earliest emerging differences in infants who are later diagnosed with autism spectrum disorder. Although researchers have speculated that deficits in visual disengagement could have negative effects on the development of children with autism spectrum disorder, we do not know which skills are disrupted or how this disruption takes place. As a first step in understanding this issue, this study investigated the relationship between visual disengagement and a critical skill in early language development: spoken word recognition. Participants were 18 children with autism spectrum disorder (aged 4-7 years). Consistent with our predictions, children with poorer visual disengagement were slower and less accurate to process familiar words; disengagement explained over half of the variance in spoken word recognition. Visual disengagement remained uniquely associated with spoken word recognition after accounting for children’s vocabulary size and age. These findings align with a recently proposed developmental model in which poor visual disengagement decreases the speed and accuracy of real-time spoken word recognition in children with autism spectrum disorder-which, in turn, may negatively affect their language development.
