1. Bean Jaworski JL, Flynn T, Burnham N, Chittams JL, Sammarco T, Gerdes M, Bernbaum JC, Clancy RR, Solot CB, Zackai EH, McDonald-McGinn DM, Gaynor JW. {{Rates of autism and potential risk factors in children with congenital heart defects}}. {Congenit Heart Dis};2017 (Mar 16)
OBJECTIVE: Atypical development, behavioral difficulties, and academic underachievement are common morbidities in children with a history of congenital heart defects and impact quality of life. Language and social-cognitive deficits have been described, which are associated with autism spectrum disorders. The current study aimed to assess the rates of autism spectrum disorders in a large sample of children with a history of congenital heart defects and to assess medical, behavioral, and individual factors that may be associated with the risk of autism spectrum disorders. DESIGN: Participants included 195 children with a history of congenital heart defects, who are followed in a large-scale longitudinal study. Measures included behavioral data from 4-year-old neurodevelopmental evaluations and parent-report data from a later annual follow-up. RESULTS: Using established cutoffs on an autism spectrum disorder screener, children with congenital heart defects showed higher rates of « possible » autism spectrum disorders than national rates, (Chi-square Test of Equal Proportions), all Ps < .05. A stepwise variable selection method was used to create a "best prediction model" and multivariable logistic regression was used to identify variables predicting diagnostic status. Factors associated with diagnostic risk included medical (delayed sternal closure, prematurity, positive genetic findings), behavioral (cognitive, language, attention issues), and individual (socioeconomic, cultural/racial) variables. ROC analyses identified a cutoff of 7 to maximize sensitivity/specificity based on parent-reported diagnosis. CONCLUSIONS: Risk of autism spectrum disorder screening status in children with congenital heart defects was higher than expected from population rates. Findings highlight the need for referral to a specialist to assess the presence and severity of social-communication issues and congenital heart defects population-specific screening thresholds for children with concern for autism spectrum disorders. Lien vers le texte intégral (Open Access ou abonnement)
2. Dekker LP, van der Vegt EJ, van der Ende J, Tick N, Louwerse A, Maras A, Verhulst FC, Greaves-Lord K. {{Psychosexual Functioning of Cognitively-able Adolescents with Autism Spectrum Disorder Compared to Typically Developing Peers: The Development and Testing of the Teen Transition Inventory- a Self- and Parent Report Questionnaire on Psychosexual Functioning}}. {J Autism Dev Disord};2017 (Mar 16)
To gain further insight into psychosexual functioning, including behaviors, intrapersonal and interpersonal aspects, in adolescents with Autism Spectrum Disorder (ASD), comprehensive, multi-informant measures are needed. This study describes (1) the development of a new measure of psychosexual functioning in both parent- and self-reports (Teen Transition Inventory; TTI) covering all three domains of psychosexual functioning (i.e. psychosexual socialization, psychosexual selfhood, and sexual/intimate behavior). And (2) the initial testing of this instrument, comparing adolescents with ASD (n = 79 parent-report; n = 58 self-report) to Typically Developing (TD) adolescents (n = 131 parent-report; n = 91 self-report) while taking into account gender as a covariate. Results from both informants indicate more difficulties regarding psychosexual socialization and psychosexual selfhood in the ASD group. With regard to sexual/intimate behavior, only parents reported significantly more problems in adolescents with ASD.
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3. Ferreira C, Bevilacqua M, Ishihara M, Fiori A, Armonia A, Perissinoto J, Tamanaha AC. {{Selection of words for implementation of the Picture Exchange Communication System – PECS in non-verbal autistic children}}. {Codas};2017 (Mar 09);29(1):e20150285.
Purpose: It is known that some autistic individuals are considered non-verbal, since they are unable to use verbal language and barely use gestures to compensate for the absence of speech. Therefore, these individuals’ ability to communicate may benefit from the use of the Picture Exchange Communication System – PECS. The objective of this study was to verify the most frequently used words in the implementation of PECS in autistic children, and on a complementary basis, to analyze the correlation between the frequency of these words and the rate of maladaptive behaviors. Methods: This is a cross-sectional study. The sample was composed of 31 autistic children, twenty-five boys and six girls, aged between 5 and 10 years old. To identify the most frequently used words in the initial period of implementation of PECS, the Vocabulary Selection Worksheet was used. And to measure the rate of maladaptive behaviors, we applied the Autism Behavior Checklist (ABC). Results: There was a significant prevalence of items in the category « food », followed by « activities » and « beverages ». There was no correlation between the total amount of items identified by the families and the rate of maladaptive behaviors. Conclusion: The categories of words most mentioned by the families could be identified, and it was confirmed that the level of maladaptive behaviors did not interfere directly in the preparation of the vocabulary selection worksheet for the children studied.
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4. Gauducheau M, Lemaire-Mayo V, D’Amato FR, Oddi D, Crusio WE, Pietropaolo S. {{Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice}}. {Autism Res};2017 (Mar 16)
Fragile X syndrome (FXS) is a major developmental disorder and the most frequent monogenic cause of autism. Surprisingly, most existing studies on the Fmr1-KO mouse model for FXS have focused on males, although FX women, who are mostly heterozygous for the Fmr1 mutation, are known to exhibit several behavioral deficits, including autistic-like features. Furthermore, most animal research has been carried out on adults only; so that little is known about the age progression of the behavioral phenotype of Fmr1 mutants, which is a crucial issue to optimize the impact of therapeutic interventions. Here, we performed an extensive analysis of autistic-like social behaviors in heterozygous (HET) Fmr1-KO females and their WT littermates at different ages. No behavioral difference between HET and WT mice was observed at infancy, but some abnormalities in social interaction and communication were first detected at juvenile age. At adulthood some of these alterations disappeared, but avoidance of social novelty appeared, together with other FXS-relevant behavioral deficits, such as hyperactivity and reduced contextual fear response. Our data provide for the first time evidence for the presence of autistic-relevant behavioral abnormalities in Fmr1-HET female mice, demonstrating the utility of this mouse line to model autistic-like behaviors in both sexes. These results also highlight the importance of taking into account age differences when using the Fmr1-KO mouse model, suggesting that the early post-natal phases are the most promising target for preventive interventions and the adult age is the most appropriate to investigate the behavioral impact of potential therapies. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Howsmon DP, Kruger U, Melnyk S, James SJ, Hahn J. {{Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation}}. {PLoS Comput Biol};2017 (Mar);13(3):e1005385.
The number of diagnosed cases of Autism Spectrum Disorders (ASD) has increased dramatically over the last four decades; however, there is still considerable debate regarding the underlying pathophysiology of ASD. This lack of biological knowledge restricts diagnoses to be made based on behavioral observations and psychometric tools. However, physiological measurements should support these behavioral diagnoses in the future in order to enable earlier and more accurate diagnoses. Stepping towards this goal of incorporating biochemical data into ASD diagnosis, this paper analyzes measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transulfuration pathways taken from blood samples of 83 participants with ASD and 76 age-matched neurotypical peers. Fisher Discriminant Analysis enables multivariate classification of the participants as on the spectrum or neurotypical which results in 96.1% of all neurotypical participants being correctly identified as such while still correctly identifying 97.6% of the ASD cohort. Furthermore, kernel partial least squares is used to predict adaptive behavior, as measured by the Vineland Adaptive Behavior Composite score, where measurement of five metabolites of the pathways was sufficient to predict the Vineland score with an R2 of 0.45 after cross-validation. This level of accuracy for classification as well as severity prediction far exceeds any other approach in this field and is a strong indicator that the metabolites under consideration are strongly correlated with an ASD diagnosis but also that the statistical analysis used here offers tremendous potential for extracting important information from complex biochemical data sets.
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6. Karaminis T, Lunghi C, Neil L, Burr D, Pellicano E. {{Binocular rivalry in children on the autism spectrum}}. {Autism Res};2017 (Mar 16)
When different images are presented to the eyes, the brain is faced with ambiguity, causing perceptual bistability: visual perception continuously alternates between the monocular images, a phenomenon called binocular rivalry. Many models of rivalry suggest that its temporal dynamics depend on mutual inhibition among neurons representing competing images. These models predict that rivalry should be different in autism, which has been proposed to present an atypical ratio of excitation and inhibition [the E/I imbalance hypothesis; Rubenstein & Merzenich, 2003]. In line with this prediction, some recent studies have provided evidence for atypical binocular rivalry dynamics in autistic adults. In this study, we examined if these findings generalize to autistic children. We developed a child-friendly binocular rivalry paradigm, which included two types of stimuli, low- and high-complexity, and compared rivalry dynamics in groups of autistic and age- and intellectual ability-matched typical children. Unexpectedly, the two groups of children presented the same number of perceptual transitions and the same mean phase durations (times perceiving one of the two stimuli). Yet autistic children reported mixed percepts for a shorter proportion of time (a difference which was in the opposite direction to previous adult studies), while elevated autistic symptomatology was associated with shorter mixed perception periods. Rivalry in the two groups was affected similarly by stimulus type, and consistent with previous findings. Our results suggest that rivalry dynamics are differentially affected in adults and developing autistic children and could be accounted for by hierarchical models of binocular rivalry, including both inhibition and top-down influences. Autism Res 2017. (c)2017 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Lintas C, Picinelli C, Piras IS, Sacco R, Brogna C, Persico AM. {{Copy number variation in 19 Italian multiplex families with autism spectrum disorder: Importance of synaptic and neurite elongation genes}}. {Am J Med Genet B Neuropsychiatr Genet};2017 (Mar 17)
Autism Spectrum Disorder (ASD) is endowed with impressive heritability estimates and high recurrence rates. Its genetic underpinnings are nonetheless very heterogeneous, with common, and rare contributing variants located in hundreds of different loci, each characterized by variable levels of penetrance. Multiplex families from single ethnic groups represent a useful means to reduce heterogeneity and enhance genetic load. We screened 19 Italian ASD multiplex families (3 triplets and 16 duplets, total N = 41 ASD subjects), using array-CGH (Agilent 180 K). Causal or ASD-relevant CNVs were detected in 36.6% (15/41) of ASD probands, corresponding to 36.8% (7/19) multiplex families with at least one affected sibling genetically positive. However, only in less than half (3/7) of positive families, affected siblings share the same causal or ASD-relevant CNV. Even in these three families, additional potentially relevant CNVs not shared by affected sib pairs were also detected. These results provide further evidence of genetic heterogeneity in ASD even within multiplex families belonging to a single ethnic group. Differences in CNV burden may likely contribute to the substantial clinical heterogeneity observed between affected siblings. In addition, Gene Ontology enrichment analysis indicates that most potentially causal or relevant ASD genes detected in our cohort belong to nervous system-specific categories, especially involved in neurite elongation and synaptic structure/function. These findings point toward the existence of genomic instability in these families, whose underlying genetic and epigenetic mechanisms deserve further scrutiny.
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8. Liu X, Li Z, Fan C, Zhang D, Chen J. {{Genetics implicate common mechanisms in autism and schizophrenia: synaptic activity and immunity}}. {J Med Genet};2017 (Mar 17)
The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk. The poor understanding of the genetics of ASD and SCHZ is a significant hurdle to developing effective treatments for these costly conditions. The recent implementation of next-generation sequencing technologies and the creation of large consortia have started to reveal the genetic bases of ASD and SCHZ. Alterations in gene expression regulation, synaptic architecture and activity and immunity seem to be the main cellular mechanisms contributing to both ASD and SCHZ, a surprising overlap given the distinct phenotypes and onset of these conditions. These diverse pathways seem to converge in aberrant synaptic plasticity and remodelling, which leads to altered connectivity between relevant brain regions. Continuous efforts to understand the genetic basis of ASD and SCHZ will soon lead to significant progress in the mechanistic understanding of these prominent psychiatric disorders and enable the development of disease-modifying therapies for these devastating conditions.
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9. Naigles LR, Johnson R, Mastergeorge A, Ozonoff S, Rogers SJ, Amaral DG, Nordahl CW. {{Neural correlates of language variability in preschool-aged boys with autism spectrum disorder}}. {Autism Res};2017 (Mar 16)
Children with autism vary widely in their language abilities, yet the neural correlates of this language variability remain unclear, especially early in development. Diffusion tensor imaging (DTI) was used to examine diffusivity measures along the length of 18 major fiber tracts in 104 preschool-aged boys with autism spectrum disorder (ASD). The boys were assigned to subgroups according to their level of language development (Low: no/low language, Middle: small vocabulary, High: large vocabulary and grammar), based on their raw scores on the expressive language (EL) and receptive language (RL) sections of the Mullen Scales of Early Learning (MSEL). Results indicate that the subgroups differed in fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) along the inferior longitudinal fasciculus (ILF) in both hemispheres. Moreover, FA correlated significantly with Mullen EL and RL raw scores, but not ADOS severity score, along the left and right ILF. Subgroups also differed in MD (but not FA) along the left superior longitudinal fasiculus and left corticospinal tract, but these differences were not correlated with language scores. These findings suggest that white matter microstructure in the left and right ILF varies in relation to lexical development in young males with ASD. The findings also support the use of raw scores on language-relevant standardized tests for assessing early language-brain relationships. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Northrup JB, Libertus K, Iverson JM. {{Response to changing contingencies in infants at high and low risk for autism spectrum disorder}}. {Autism Res};2017 (Mar 16)
One recently proposed theory of autism spectrum disorder (ASD) hypothesizes that individuals with the disorder may have difficulty using prior experiences to predict future events [Hellendoorn et al., 2015; Northrup, 2016; Sinha et al., 2014]. To date, this theory has not been tested in infancy. The current study analyzed how young infants at heightened (HR; older sibling with ASD) vs. low risk (LR; no first degree relatives with ASD) for ASD responded to changing contingencies when interacting with two visually identical rattles-one that produced sounds during shaking (Sound), and one that did not (Silent). Infants were given the rattles in a Sound-Silent-Sound order at 6 and 10 months, and shaking behavior was coded. Results indicated that LR and HR infants (regardless of ASD diagnosis) did not differ from each other in shaking behavior at 6 months. However, by 10 months, LR infants demonstrated high initial shaking with all three rattles, indicating expectations for rattle affordances, while HR infants did not. Significantly, HR infants, and particularly those with an eventual ASD diagnosis, did not demonstrate an « extinction burst »-or high level of shaking-in the first 10 sec with the « silent » rattle, indicating that they may have difficulty generalizing learning from one interaction to the next. Further, individual differences in the strength of this « extinction burst » predicted cognitive development in toddlerhood among HR infants. Difficulty forming expectations for new interactions based on previous experiences could impact learning and behavior in a number of domains. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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11. Oshodi YO, Olagunju AT, Oyelohunnu MA, Campbell EA, Umeh CS, Aina OF, Oyibo W, Lesi FE, Adeyemi JD. {{Autism Spectrum Disorder in a Community-based Sample with Neurodevelopmental Problems in Lagos, Nigeria}}. {J Public Health Afr};2016 (Dec 31);7(2):559.
Autism Spectrum Disorder (ASD) is a globally prevalent neurodevelopmental disorder for which early diagnosis and intervention is the mainstay of management. In the African continent, limited data is available regarding the non-clinic based samples. Lack of information available to caregivers and inadequate skilled manpower often limit early detection and access to the few available though under resourced services in the community. Community based screening can be an important drive to create awareness and improve information dissemination regarding services available for those living with this disorder. This is a descriptive cross-sectional study utilizing data obtained from participants of a community-based autism screening exercise. The surveillance exercise was part of the annual Orange Ribbon initiative for autism awareness and screening held in 2014. Data was obtained from 85 participants involved in the Autism Surveillance screening exercise within the Lagos community. Community public service radio announcements state wide and word of mouth were used to invite and enroll eligible participants to the screening and consultation exercise. A second stage screening and a brief sociodemographic questionnaire followed by a third stage clinical interview and evaluation using the Diagnostic and Statistical Manual of Mental Disorders – 5 Edition (DSM 5) were used. Appropriate consultation and referrals to services in the community were given. Participants had a mean age of 7.53 years (SD 4.35). Twenty-nine (34.5%) met the diagnosis of ASD. Other diagnosis included attention deficit hyperactivity disorder (ADHD), language and speech disorder, intellectual disability (8.3%) and learning disorders (9.5%). Main health concerns to caregivers were poor language development in all (100%), of which 11 (40.7%) were non-verbal; gaze avoidance was seen in 14 (48.3%) and challenging behavior in 12 (42.9%). Comorbidities included seizure disorders (3.4%) and ADHD (6.9%). Persons with autism had history of ASD behavior more often when compared to the other neurodevelopmental disorders and these findings were statistically significant. Referrals were given to caregivers to engage in services within the community. As seen in this study, community understanding of ASD is poor in such locations, in which many persons with other neurodevelopmental disorders are often presented as having autism. Caregivers in the study location are distressed by many symptoms associated with autism and their comorbid conditions. Currently there is an evident role for frequent large scale community based screening and autism awareness exercises possibly using inter-sectoral collaboration as a strategy.
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12. Uljarevic M, Hedley D, Alvares GA, Varcin KJ, Whitehouse AJ. {{Relationship between early motor milestones and severity of restricted and repetitive behaviors in children and adolescents with autism spectrum disorder}}. {Autism Res};2017 (Mar 16)
This study explored the relationships between the later age of achievement of early motor milestones, current motor atypicalities (toe walking), and the severity of restricted and repetitive behaviors (RRBs) in individuals with autism spectrum disorder (ASD). Parents of 147 children and adolescents with ASD (Mage = 8.09 years, SD = 4.28; 119 males) completed an early developmental milestones questionnaire and the Social Responsiveness Scale as a measure of Insistence on Sameness (IS) and Repetitive Mannerisms (RM). Two hierarchical regression analyses were conducted to test whether RM and IS behaviors were predicted by early motor milestones, or current toe walking. The final model predicting RM accounted for 15% of the variance (F = 3.02, p = .009), with toe walking as a unique and independent predictor of RM scores (t = 3.568, p = .001). The final model predicting IS accounted for 19.1% of variance in IS scores (F = 4.045, p = .001), with chronological age (CA) (t = 2.92, p = .004), age when first standing (t = 2.09, p = .038), and toe walking (t = 2.53, p = .013) as unique independent predictors. Toe walking (t = 2.4, p = .018) and age when first sitting (t = 2.08, p = .04) predicted the severity of RRBs on the Autism Diagnostic Observation Schedule (F = 2.334, p = .036). Our study replicates previous findings on the relationship between concurrent motor impairments and RRBs, and provides the first evidence for the association between RRBs and age of attainment of early motor milestones. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Veatch OJ, Sutcliffe JS, Warren ZE, Keenan BT, Potter MH, Malow BA. {{Shorter sleep duration is associated with social impairment and comorbidities in ASD}}. {Autism Res};2017 (Mar 16)
Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. To better understand the connection between sleep duration and ASD severity, we analyzed ASD-related symptoms using the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), IQ scores, and parent reports of the average amount of time slept per night that were available in the medical histories of 2,714 children with ASD in the Simons Simplex Collection (SSC). The mean (SD) sleep duration was 555 minutes. Sleep duration and severity of core ASD symptoms were negatively correlated, and sleep duration and IQ scores were positively correlated. Regression results indicated that more severe social impairment, primarily a failure to develop peer relationships, is the core symptom most strongly associated with short sleep duration. Furthermore, increased severity for numerous maladaptive behaviors assessed on the Child Behavior Checklist, as well as reports of attention deficit disorder, depressive disorder, and obsessive compulsive disorder were associated with short sleep duration. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep /=660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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14. Wang X, Liang S, Sun Y, Li H, Endo F, Nakao M, Saitoh N, Wu L. {{Analysis of estrogen receptor beta gene methylation in autistic males in a Chinese Han population}}. {Metab Brain Dis};2017 (Mar 16)
Autism spectrum disorder (ASD) is a neurodevelopment disorder with abnormalities of social interaction, communication and repetitive behaviors. The higher prevalence of ASD in men implies a potential relationship between sex hormones and ASD etiology. The ESR2 gene encodes estrogen receptor beta (ESR2) and plays an important role during brain development. A relationship between ESR2 and ASD has been suggested by studies on single nucleotide polymorphisms and mRNA and protein expression levels in ASD patients. Here, we explored the possible epigenetic regulation of the ESR2 gene in autism. We collected genomic DNA from the peripheral blood of Chinese Han males with autism and age-matched normal males and measured DNA methylation of CpG islands in the ESR2 gene, which consisted of 41 CpG sites among the proximal promoter region and an untranslated exon, by bisulfite sequencing. We also investigated a relationship between DNA methylation and phenotypic features of autism, as assessed by the Children Autism Rating Scale. We found little overall difference in the DNA methylation of the ESR2 5′-flanking region in individuals with autism compared with normal individuals. However, detailed analyses revealed that eight specific CpG sites were hypermethylated in autistic individuals and that four specific CpG sites were positively associated with the severity of autistic symptoms. Our study indicates that the epigenetic dysregulation of ESR2 may govern the development of autism.
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15. Wolff N, Chmielewski WX, Beste C, Roessner V. {{Working memory load affects repetitive behaviour but not cognitive flexibility in adolescent autism spectrum disorder}}. {World J Biol Psychiatry};2017 (Mar 16):1-12.
OBJECTIVES: Autism spectrum disorder (ASD) is associated with repetitive and stereotyped behaviour, suggesting that cognitive flexibility may be deficient in ASD. A central, yet not examined aspect to understand possible deficits in flexible behaviour in ASD relates (i) to the role of working memory and (ii) to neurophysiological mechanisms underlying behavioural modulations. METHODS: We analysed behavioural and neurophysiological (EEG) correlates of cognitive flexibility using a task-switching paradigm with and without working memory load in adolescents with ASD and typically developing controls (TD). RESULTS: Adolescents with ASD versus TD show similar performance in task switching with no memory load, indicating that ‘pure’ cognitive flexibility is not in deficit in adolescent ASD. However performance during task repetition decreases with increasing memory load. Neurophysiological data reflect the pattern of behavioural effects, showing modulations in P2 and P3 event-related potentials. CONCLUSIONS: Working memory demands affect repetitive behaviour while processes of cognitive flexibility are unaffected. Effects emerge due to deficits in preparatory attentional processes and deficits in task rule activation, organisation and implementation of task sets when repetitive behaviour is concerned. It may be speculated that the habitual response mode in ASD (i.e. repetitive behaviour) is particularly vulnerable to additional demands on executive control processes.
