1. Adebayo OL, Dewenter I, Rinne L, Golubiani G, Solomonia R, Müller M. {{Intensified mitochondrial hydrogen peroxide release occurs in all brain regions, affects male as well as female Rett mice, and constitutes a life-long burden}}. {Archives of biochemistry and biophysics}. 2020; 696: 108666.
The neurodevelopmental disorder Rett syndrome (RTT) affects mostly females. Upon an apparently normal initial development, cognitive impairment, irregular breathing, motor dysfunction, and epilepsy occur. The complex pathogenesis includes, among others, mitochondrial impairment, redox imbalance, and oxidative damage. As these arise already in neonatal Rett mice, they were proposed contributors of disease progression. Several mitochondrial studies in RTT used either full brains or selected brain regions only. Here, we mapped mitochondria-related ROS generation brain wide. Using sophisticated multi-sample spectrofluorimetry, H(2)O(2) release by isolated mitochondria was quantified in a coupled reaction of Amplex UltraRed and horseradish peroxidase. All brain regions and the entire lifespan were characterized in male and female mice. In WT mice, mitochondrial H(2)O(2) release was usually highest in cortex and lowest in hippocampus. Maximum rates occurred at postnatal day (PD) 10 and they slightly declined with further maturation. Already at PD 10, male and female Rett mice showed exaggerated mitochondrial H(2)O(2) releases in first brain regions and persistent brain-wide increases from PD 50 on. Interestingly, female Rett mice were more intensely affected than male Rett mice, with their brainstem, midbrain and hippocampus being most severely struck. In conclusion, we used a reliable multi-sample cuvette-based assay on mitochondrial ROS release to perform brain-wide analyzes along the entire lifespan. Mitochondrial H(2)O(2) release in Rett mice is intensified in all brain regions, affects hemizygous males and heterozygous females, and involves all maturational stages. Therefore, intensified mitochondrial H(2)O(2) release seriously needs to be considered throughout RTT pathogenesis and may constitute a potential therapeutic target.
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2. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Al-Ayadhi LY, Alsaad AMS, Assiri MA, Al-Mazroua HA, Attia SM. {{Upregulation of interleukin (IL)-31, a cytokine producing CXCR1 peripheral immune cells, contributes to the immune abnormalities of autism spectrum disorder}}. {J Neuroimmunol}. 2020; 349: 577430.
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by communication deficits, impaired social interactions, and restricted stereotypical behaviors. Several immune cells are associated with immune dysfunction in ASD; however, IL-31 has not been explored in ASD. This study aims to investigate the role of inflammatory cytokines and transcription factors of the CXCR1 cells in children with ASD. In the current study, we investigated the cytokines and transcription factors produced by CXCR1(+) cells (IL-31, IL-9, IL-21R, IL-21, NF-κB p65, RORγT, STAT1, and FoxP3) in peripheral blood mononuclear cells (PBMCs), from children with ASD and typically developing (TD) control children, using flow cytometric analysis. In addition, we measured mRNA and protein expression levels of IL-31 using quantitative real-time PCR and western blot analyses in PBMCs. In our study, children with ASD had increased CXCR1(+)IL-31(+), CXCR1(+)IL-9(+), CXCR1(+)IL-21R(+), CXCR1(+)IL-21(+), CXCR1(+)NF-κB(+) p65, CXCR1(+)RORγT(+), and CXCR1(+)STAT1(+), and decreased CXCR1(+)FoxP3(+) cells as compared with cells from the TD control samples. Similarly, children with ASD showed increased IL-31 mRNA and protein expression levels as compared to those of TD control samples. Our results suggest that upregulated production of inflammatory cytokines and transcription factors in CXCR1(+) cells cause immunological imbalance in children with ASD. Therefore, attenuation of inflammatory cytokines/mediators and transcription factors could have a therapeutic potential in the treatment of ASD.
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3. Alaerts K, Steyaert J, Vanaudenaerde B, Wenderoth N, Bernaerts S. {{Changes in endogenous oxytocin levels after intranasal oxytocin treatment in adult men with autism: An exploratory study with long-term follow-up}}. {Eur Neuropsychopharmacol}. 2020.
Intranasal administration of the neuropeptide oxytocin (OT) is increasingly explored as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD). Previously, interactions of exogenously administered OT with its endogenous production have been demonstrated following single-dose administrations. However, the impact of repeated, long-term OT use on endogenous salivary OT levels is unknown. In this double-blind, randomized, placebo-controlled study with between-subject design, 34 adult men with ASD were either assigned to a four-week treatment of once-daily intranasal OT administrations (24 IU) or placebo. Salivary OT samples were obtained before and after the treatment period as well as at two follow-up sessions, four weeks and one year after cessation of the treatment. Receiving OT intranasally but not placebo reliably increased endogenous salivary levels of OT immediately post-treatment and at the follow-up session four weeks post treatment, indicating an interaction between exogenously administered OT and its endogenous production. Notably, increases in salivary OT at the four-week follow-up session were most pronounced in individuals with larger behavioral improvements in ASD social symptoms. These results suggest that OT’s positive effects on social behaviors may lead to a self-perpetuating elevation of OT levels through a feed-forward triggering of its own release. Together, the current investigation provides initial evidence that repeated intranasal administration of OT can induce long-lasting changes in endogenous salivary OT levels, presumably through a positive spiral of OT release.
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4. Alfieri P, Scibelli F, Digilio MC, Novello RL, Caciolo C, Valeri G, Vicari S. {{Comparison of Adaptive Functioning in Children with Williams Beuren Syndrome and Autism Spectrum Disorder: A Cross-Syndrome Study}}. {Autism Res}. 2020.
Williams Beuren syndrome (WBS) and autism spectrum disorder (ASD) have been long considered as « polar opposite » disorders. Although children with WBS appears to be hypersociable, recent researches have revealed difficulties in socio-communicative skills such as shared attention, showing or giving objects, social relationships comprehension, pragmatic use of language, and emotion’s recognition. The aim of this cross-syndrome study is to compare clinician-report adaptive profiles of two wide developmental range children by means of Vineland Adaptive Behavior Scales-Interview Edition, Survey Form. Eighty individuals, 40 with WBS and 40 with ASD (31 preschoolers and 49 scholars) with ASD and WBS matched for chronological age and developmental/cognitive level were recruited. Analysis of domains and subdomains have been reported. Results showed no significant difference in global adaptive level between WBS and ASD in both preschooler and scholar children. Communication domain significantly differ in preschoolers (higher in WBS children), but not in scholars. Expressive subdomain significantly differ in both preschoolers and scholars (higher in WBS children). Play and Leisure subdomain significantly differ in scholars (higher in WBS children), but not in preschoolers. Our results support hypothesis on a shared global adaptive impairment in children with WBS and ASD, by extending this findings to scholar-age children. Analysis of domains and subdomains differences highlight the need for interventions targeting social-pragmatic skills since first years of life. Differences in preschoolers and scholars adaptive profiles could be explained through a developmental perspective. LAY SUMMARY: Little is known about differences in adaptive profiles between Williams Beuren syndrome and autism spectrum disorder. Our results show similarities in global adaptive level and difference in communication level. Furthermore, expressive skills seem to be higher in Williams Beuren Syndrome.
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5. Baba Y, Otani K, Sakai K, Kawaguchi R. {{Sustained compression leading to liner pressure ulcers following improper surgical mask use in autism spectrum disorder}}. {Acute medicine & surgery}. 2020; 7(1): e604.
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6. Brkić D, Ng-Cordell E, O’Brien S, Scerif G, Astle D, Baker K. {{Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study}}. {Mol Autism}. 2020; 11(1): 98.
BACKGROUND: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. METHODS: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n = 29) or chromatin regulation (n = 23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components-Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. RESULTS: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. LIMITATIONS: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. CONCLUSION: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful.
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7. Chan JS, Deng K, Yan JH. {{The effectiveness of physical activity interventions on communication and social functioning in autistic children and adolescents: A meta-analysis of controlled trials}}. {Autism}. 2020: 1362361320977645.
Difficulty with communication and social functioning are two outstanding core symptoms of autism spectrum disorder, while there is no efficacious pharmacologic treatment available to deal with them. Traditional behavioral therapies usually require specialist therapist and be conducted in specific settings, increasing burdens on families and individuals with autism. Physical activity has long been found to promote physical and mental well-beings, and it is more affordable and versatile than traditional therapies. There is preliminary support for the use of physical activity interventions to improve communication and social functioning in individuals with autism. In this study, we quantitatively aggregate data from existing controlled trials to provide an up-to-date inquiry into the effectiveness of physical activity interventions on communication and social functioning in autistic children and adolescents. We included 12 trials involving 350 participants (8 trials reported communication outcomes and 11 trials reported social functioning outcomes) and found small to moderate benefits on communication and social functioning. Further analyses showed that the benefit of physical activity interventions is greater in younger participants. Results of this study suggest that physical activity interventions are effective to improve communication and social functioning in autistic children and adolescents, and early participation in the interventions can be more beneficial. Given their affordability, versatility, and efficacy, physical activity interventions could be considered a cost-effective option for autism spectrum disorder management in the future.
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8. Charman T. {{Editorial: One Good Thing (Sometimes) Leads to Another: Demonstrating Mechanistic Connections Between Parent and Child Outcomes in a Community Implementation Autism Trial}}. {J Am Acad Child Adolesc Psychiatry}. 2020.
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9. Cheffer A, Flitsch LJ, Krutenko T, Röderer P, Sokhranyaeva L, Iefremova V, Hajo M, Peitz M, Schwarz MK, Brüstle O. {{Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction}}. {Mol Autism}. 2020; 11(1): 99.
The controlled differentiation of pluripotent stem cells (PSCs) into neurons and glia offers a unique opportunity to study early stages of human central nervous system development under controlled conditions in vitro. With the advent of cell reprogramming and the possibility to generate induced pluripotent stem cells (iPSCs) from any individual in a scalable manner, these studies can be extended to a disease- and patient-specific level. Autism spectrum disorder (ASD) is considered a neurodevelopmental disorder, with substantial evidence pointing to early alterations in neurogenesis and network formation as key pathogenic drivers. For that reason, ASD represents an ideal candidate for stem cell-based disease modeling. Here, we provide a concise review on recent advances in the field of human iPSC-based modeling of syndromic and non-syndromic forms of ASD, with a particular focus on studies addressing neuronal dysfunction and altered connectivity. We further discuss recent efforts to translate stem cell-based disease modeling to 3D via brain organoid and cell transplantation approaches, which enable the investigation of disease mechanisms in a tissue-like context. Finally, we describe advanced tools facilitating the assessment of altered neuronal function, comment on the relevance of iPSC-based models for the assessment of pharmaceutical therapies and outline potential future routes in stem cell-based ASD research.
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10. Cicaloni V, Pecorelli A, Cordone V, Tinti L, Rossi M, Hayek J, Salvini L, Tinti C, Valacchi G. {{A proteomics approach to further highlight the altered inflammatory condition in Rett syndrome}}. {Archives of biochemistry and biophysics}. 2020; 696: 108660.
Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with perturbed redox homeostasis and inflammation, which appear as possible key factors in RTT pathogenesis. In this study, using primary dermal fibroblasts from control and RTT subjects, we performed a proteomic analysis that, together with data mining approaches, allowed us to carry out a comprehensive characterization of RTT cellular proteome. Functional and pathway enrichment analyses showed that differentially expressed proteins in RTT were mainly enriched in biological processes related to immune/inflammatory responses. Overall, by using proteomic data mining as supportive approach, our results provide a detailed insight into the molecular pathways involved in RTT immune dysfunction that, causing tissue and organ damage, can increase the vulnerability of affected patients to unknown endogenous factors or infections.
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11. Crasta JE, Gavin WJ, Davies PL. {{Expanding our understanding of sensory gating in children with autism spectrum disorders}}. {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}. 2020; 132(1): 180-90.
OBJECTIVE: This study examined sensory gating in children with autism spectrum disorders (ASD). Gating is usually examined at the P50 component and rarely at mid- and late-latency components. METHODS: Electroencephalography data were recorded during a paired-click paradigm, from 18 children with ASD (5-12 years), and 18 typically-developing (TD) children. Gating was assessed at the P50, N1, P2, and N2 event-related potential components. Parents of all participants completed the Short Sensory Profile (SSP). RESULTS: TD children showed gating at all components while children with ASD showed gating only at P2 and N2. Compared to TD children, the ASD group showed significantly reduced gating at P50, N1, and P2. No group differences were found at N2, suggesting typical N2 gating in the ASD group. Time-frequency analyses showed reduced orientation and neural synchronization of auditory stimuli. P50 and N1 gating significantly correlated with the SSP. CONCLUSION: Although children with ASD have impaired early orientation and filtering of auditory stimuli, they exhibited gating at P2 and N2 components suggesting use of different gating mechanisms compared to TD children. Sensory deficits in ASD may relate to gating. SIGNIFICANCE: The data provide novel evidence for impaired neural orientation, filtering, and synchronization in children with ASD.
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12. Deserno MK, Borsboom D, Begeer S, van Bork R, Hinne M, Geurts HM. {{Highways to happiness for autistic adults? Perceived causal relations among clinicians}}. {PLoS One}. 2020; 15(12): e0243298.
The network approach to psychological phenomena advances our understanding of the interrelations between autism and well-being. We use the Perceived Causal Relations methodology in order to (i) identify perceived causal pathways in the well-being system, (ii) validate networks based on self-report data, and (iii) quantify and integrate clinical expertise in autism research. Trained clinicians served as raters (N = 29) completing 374 cause-effects ratings of 34 variables on well-being and symptomatology. A subgroup (N = 16) of raters chose intervention targets in the resulting network which we found to match the respective centrality of nodes. Clinicians’ perception of causal relations was similar to the interrelatedness found in self-reported client data (N = 323). We present a useful tool for translating clinical expertise into quantitative information enabling future research to integrate this in scientific studies.
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13. Donskoy I, Loghmanee D. {{Iron and Insomnia in Autism Spectrum Disorder}}. {Pediatric neurology briefs}. 2020; 34: 17.
Investigators from four major Universities studied the impact of iron supplementation on insomnia symptoms in children with Autism Spectrum Disorder (ASD) and ferritin levels not indicative of iron deficiency anemia.
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14. Emberti Gialloreti L, Enea R, Di Micco V, Di Giovanni D, Curatolo P. {{Clustering Analysis Supports the Detection of Biological Processes Related to Autism Spectrum Disorder}}. {Genes}. 2020; 11(12).
Genome sequencing has identified a large number of putative autism spectrum disorder (ASD) risk genes, revealing possible disrupted biological pathways; however, the genetic and environmental underpinnings of ASD remain mostly unanswered. The presented methodology aimed to identify genetically related clusters of ASD individuals. By using the VariCarta dataset, which contains data retrieved from 13,069 people with ASD, we compared patients pairwise to build « patient similarity matrices ». Hierarchical-agglomerative-clustering and heatmapping were performed, followed by enrichment analysis (EA). We analyzed whole-genome sequencing retrieved from 2062 individuals, and isolated 11,609 genetic variants shared by at least two people. The analysis yielded three clusters, composed, respectively, by 574 (27.8%), 507 (24.6%), and 650 (31.5%) individuals. Overall, 4187 variants (36.1%) were common to the three clusters. The EA revealed that the biological processes related to the shared genetic variants were mainly involved in neuron projection guidance and morphogenesis, cell junctions, synapse assembly, and in observational, imitative, and vocal learning. The study highlighted genetic networks, which were more frequent in a sample of people with ASD, compared to the overall population. We suggest that itemizing not only single variants, but also gene networks, might support ASD etiopathology research. Future work on larger databases will have to ascertain the reproducibility of this methodology.
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15. Gecz J, Berry JG. {{Cerebral palsy with autism and ADHD: time to pay attention}}. {Dev Med Child Neurol}. 2020.
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16. Hamama L, Gaber S. {{Seeing the siblings: Gender differences in emerging-adult siblings of individuals with autism spectrum disorder}}. {Res Dev Disabil}. 2020; 108: 103829.
BACKGROUND: The present study focused on typically developing siblings (TDS) in emerging adulthood of individuals with autism spectrum disorder (ASD) and sought insight into how gender may interact with positive and negative affects in this population. In addition, we aimed to explore the gender differences as a moderator in the link between personal resources (i.e., family cohesion and flexibility coping strategy) and positive and negative affects among such TDS. An understanding of gender differences in this population should prove relevant to the development of potential interventions. METHOD: A total of 116 emerging adult (age 18-29) TDS of younger siblings with ASD (the latter were under the age of 18 at the time of data collection), 80 females and 36 males, participated in the study. All participants completed self-report measures. RESULTS: Female TDS reported higher negative affect than male TDS, while no differences emerged regarding positive affect. Female siblings reported higher family cohesion and higher flexibility in the forward-focused subscale of flexibility coping strategy, but not in its trauma-focused subscale, compared to male siblings. Additionally, gender moderates the links between family cohesion and positive affect but not negative affect. Gender also moderates the association between flexibility and negative affect, but not positive affect. CONCLUSIONS: This study highlights the gender differences among TDS in emerging adulthood of individuals with ASD in relation to negative affect, family cohesion, and flexibility coping strategy. Understanding the gender-specific internal and external experiences of TDS as interplaying with their resources, at the unique developmental stage of emerging adulthood, may afford to identify TDS in need and to suggest potential interventions.
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17. Hollowood-Jones K, Adams JB, Coleman DM, Ramamoorthy S, Melnyk S, James SJ, Woodruff BK, Pollard EL, Snozek CL, Kruger U, Chuah J, Hahn J. {{Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study}}. {BMC pediatrics}. 2020; 20(1): 557.
BACKGROUND: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism. METHODS: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods. RESULTS: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. CONCLUSIONS: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
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18. Jones-Jang SM, Noland C. {{The Politicization of Health and Science: Role of Political Cues in Shaping the Beliefs of the Vaccine-Autism Link}}. {Health Commun}. 2020: 1-9.
One critical lesson learned from public opinion research about climate change is that the cost of politicization is disastrous. Although the literature has shown the dire consequences of politicized science issues, few have examined how such politicization is possibly triggered by political leaders in a seemingly nonpartisan science topic. Using two experiments (total n = 1,249), this article demonstrates how political cues over scientific expertise shape individuals’ beliefs in the vaccine and autism debate. The results indicate that Republicans tend to follow President Trump compared to scientists in the subject matter. On the other hand, Democrats follow scientists but are not influenced by Trump. The implications of political encroachment into health and science are discussed.
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19. Kalavai SV, Ikezu S. {{Neuritogenic function of microglia in maternal immune activation and autism spectrum disorders}}. {Neural regeneration research}. 2021; 16(7): 1436-7.
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20. Kanney ML, Durmer JS, Trotti LM, Leu R. {{Rethinking bedtime resistance in children with autism: is restless legs syndrome to blame?}}. {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}. 2020; 16(12): 2029-35.
STUDY OBJECTIVES: In this study we investigated the clinical correlates of restless legs syndrome in children with autism and report on our experiences with response to treatment. METHODS: A retrospective chart review of children seen in our sleep center from 2016-2019 was performed to identify children with autism and chronic insomnia. Patients underwent clinical assessments for restless legs symptomatology. Overnight polysomnogram, serum ferritin testing, and response to clinical treatment data were collected. RESULTS: A total of 103 children with autism and chronic insomnia were identified (age range 2-19 years). Of these, 41 children (39%) were diagnosed with restless legs syndrome. The diagnosis of restless legs syndrome was associated with significantly lower serum ferritin levels (mean 29 ± 18.62 ng/mL vs non-restless legs syndrome 56.7 ± 17.59, P < .001) and higher periodic limb movements of sleep on polysomnogram (8.12 ± 6.6 vs non-restless legs syndrome 0.06 ± 0.17). The presence of leg kicking, body rocking, or any symptoms involving the legs was highly correlated with the diagnosis of restless legs syndrome. Positive treatment response was noted in nearly all treated patients, including those treated with oral iron supplementation alone (25 children, 23 responders), gabapentin alone (12 children, all responders), and combination therapy (3 children, all responders). CONCLUSIONS: Our findings suggest restless legs syndrome may represent an under-recognized cause of insomnia in children with autism. Initial assessment should include a thorough query of behaviors related to nocturnal motor complaints, because restless legs syndrome may be a treatable cause of sleep disruption. Lien vers le texte intégral (Open Access ou abonnement)
21. Khusaifan SJ, El Keshky MES. {{Social support as a protective factor for the well-being of parents of children with autism in Saudi Arabia}}. {Journal of pediatric nursing}. 2020.
PURPOSE: Parents of children with autism spectrum disorder (ASD) experience higher levels of stress and impaired life satisfaction as a result of their children’s behavior. The well-acknowledged protective role of social support against stress has not been studied in detail with regard to parents of children with ASD in the Kingdom of Saudi Arabia (KSA). Therefore, the purpose of this study is to assess the impact of social support as a mediator and/or a moderator between parental stress and life satisfaction among parents of children with ASD in KSA. DESIGN AND METHOD: A cross-sectional survey was conducted among centers that care for children with autism in KSA. The survey encompassed four dimensions: demographic data, family stress and coping, parenting life satisfaction, and perceived social support. Multiple linear regression analyses were conducted to assess the moderating and/or mediating effect of social support. RESULTS: The analysis of 131 parents indicated that perceived family and parental stress was associated with life satisfaction levels, and this relationship was approximately 0.19 points lower when mediated by social support (β = -0.19, 95% CI [-0.34, -0.05], p = .02). Social support moderated the relationship between family stress and life satisfaction, which was significant at low (p = .002) and average levels of stress (p = .017) but not at high levels of stress. CONCLUSION: Social support is protective for parents of children with ASD. PRACTICE IMPLICATIONS: Social support, including the use of social media groups, should be considered in supporting stressed parents of children with ASD. Therefore, the protective role of social support should be highlighted to healthcare professionals.
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22. Kilroy E, Harrison L, Butera C, Jayashankar A, Cermak S, Kaplan J, Williams M, Haranin E, Bookheimer S, Dapretto M, Aziz-Zadeh L. {{Unique deficit in embodied simulation in autism: An fMRI study comparing autism and developmental coordination disorder}}. {Hum Brain Mapp}. 2020.
A deficit in pre-cognitively mirroring other people’s actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people’s actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks.
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23. Landes SD, Turk MA, Wong A. {{COVID-19 outcomes among people with intellectual and developmental disability in California: The importance of type of residence and skilled nursing care needs}}. {Disability and health journal}. 2020: 101051.
BACKGROUND: People with intellectual and developmental disabilities (IDD) appear to be at greater risk for severe outcomes from COVID-19. The roles of congregate living and skilled nursing care needs in this disparity are unclear. OBJECTIVE: To determine the impact of residential setting and level of skilled nursing care on COVID-19 outcomes for people receiving IDD services, compared to those not receiving IDD services. METHODS: Utilizing publicly available California data on COVID-19 outcomes for people receiving IDD services (early May through October 2, 2020), we report outcomes based on seven types of residence, differentiated by number of residents and level of skilled nursing care provided. We compared these results to the larger California published outcomes. RESULTS: Compared to Californians not receiving IDD services, in general, those receiving IDD services had a 60% lower case rate, but 2.8 times higher case-fatality rate. COVID-19 outcomes varied significantly among Californians receiving IDD services by type of residence and skilled nursing care needs: higher rates of diagnosis in settings with larger number of residents, higher case-fatality and mortality rates in settings that provided 24-h skilled nursing care. CONCLUSIONS: Diagnosis with COVID-19 among Californians receiving IDD services appears to be related to the number of individuals within the residence, while adverse COVID-19 outcomes were associated with level of skilled nursing care. When data is available, future research should examine whether these relationships persist even when controlling for age and pre-existing conditions.
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24. Minami K, Horikawa E. {{Social anxiety tendency and autism spectrum disorder in Japanese Adolescence}}. {Pediatrics international : official journal of the Japan Pediatric Society}. 2020.
BACKGROUND: In Japanese high schools, the understanding of school non-attendance and students with developmental disabilities, including autism spectrum disorder (ASD), is gradually improving. On the other hand, few people recognize social anxiety disorder (SAD), which onsets during youth. SAD and ASD share various overlapping characteristics, but have different diagnostic criteria. Also, the anxiety caused by these disorders sometimes appears as school non-attendance. This study examined the relationship between SAD tendency, ASD trait, and history of school non-attendance in high school students. METHODS: 158 students at one Japanese high school that accepts school non- attendance students were investigated. To understand the features of ASD and how it relates to SAD tendencies, Liebowitz Social Anxiety Scale-Japanese (LSAS-J) and Autism-Spectrum Quotient-Japanese (AQ-J) was used. Based on the LSAS-J cutoff point, participants were divided into high and low anxiety groups, and then data were compared between the two groups. Potential factors associated with a high-SAD trend were evaluated using multivariate logistic regression. RESULTS: The results showed that students with high ASD scores were more likely to have SAD and that a lack of « social skill », a subscale of ASD, was closely associated with a trend of social anxiety. However, the relationship between school non-attendance and social anxiety could not be confirmed. CONCLUSIONS: Focusing on the lack of social skills in ASD may provide an opportunity to identify students with High SAD tendencies.
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25. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Ayadhi LY, Attia SM, Alasmari AF, As Sobeai HM, Bakheet SA. {{Ubiquitous plasticizer, Di-(2-ethylhexyl) phthalate enhances existing inflammatory profile in monocytes of children with autism}}. {Toxicology}. 2020; 446: 152597.
Genetic as well as environmental factors are believed to play a significant role in the pathogenesis and progression of autism spectrum disorder (ASD). Phthalates are ubiquitous environmental contaminants as they are used plasticizers in several household/industrial products such as vinyl flooring, plastic toys, and cosmetic products. One of the plasticizers that is quite prevalent in these products is di-2-ethylhexyl phthalate (DEHP) which can cause human exposure via dermal/inhalation/ingestion routes. DEHP and its metabolites are associated with behavioral dysregulations and reported to be increased in systemic circulation of ASD children. DEHP is reported to cause upregulation of several inflammatory cytokines in different cells/tissues, however its role in inflammatory signaling of ASD monocytes has not been investigated earlier. Therefore, this study evaluated the effects of DEHP (at 5 μM final concentration for 24 h) on inflammatory profile (NFkB, STAT3, IL-6, TNF-α, IL-1β) in monocytes of ASD subjects and typically developing control (TDC) children. Our data show that DEHP upregulates NFkB/STAT3 expression which is associated with increased inflammatory profile in monocytes of ASD and TDC subjects, however its effect is much greater in magnitude in the former group. This was confirmed by utilization of NFkB inhibitor, PDTC and STAT3 inhibitor, Stattic which caused reduction in inflammatory cytokines from DEHP-treated monocytes in ASD group. In short, DEHP causes further elevation in inflammatory signaling in ASD monocytes which could be due to existing inflammation in this group. These data suggest that use of plasticizers such as DEHP should be minimized in order to avoid their potential effects on immune dysfunction associated with ASD.
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26. Nunes AS, Mamashli F, Kozhemiako N, Khan S, McGuiggan NM, Losh A, Joseph RM, Ahveninen J, Doesburg SM, Hämäläinen MS, Kenet T. {{Classification of evoked responses to inverted faces reveals both spatial and temporal cortical response abnormalities in Autism spectrum disorder}}. {Neuroimage Clin}. 2020; 29: 102501.
The neurophysiology of face processing has been studied extensively in the context of social impairments associated with autism spectrum disorder (ASD), but the existing studies have concentrated mainly on univariate analyses of responses to upright faces, and, less frequently, inverted faces. The small number of existing studies on neurophysiological responses to inverted face in ASD have used univariate approaches, with divergent results. Here, we used a data-driven, classification-based, multivariate machine learning decoding approach to investigate the temporal and spatial properties of the neurophysiological evoked response for upright and inverted faces, relative to the neurophysiological evoked response for houses, a neutral stimulus. 21 (2 females) ASD and 29 (4 females) TD participants ages 7 to 19 took part in this study. Group level classification accuracies were obtained for each condition, using first the temporal domain of the evoked responses, and then the spatial distribution of the evoked responses on the cortical surface, each separately. We found that classification of responses to inverted neutral faces vs. houses was less accurate in ASD compared to TD, in both the temporal and spatial domains. In contrast, there were no group differences in the classification of evoked responses to upright neutral faces relative to houses. Using the classification in the temporal domain, lower decoding accuracies in ASD were found around 120 ms and 170 ms, corresponding the known components of the evoked responses to faces. Using the classification in the spatial domain, lower decoding accuracies in ASD were found in the right superior marginal gyrus (SMG), intra-parietal sulcus (IPS) and posterior superior temporal sulcus (pSTS), but not in core face processing areas. Importantly, individual classification accuracies from both the temporal and spatial classifiers correlated with ASD severity, confirming the relevance of the results to the ASD phenotype.
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27. Rojas-Torres LP, Alonso-Esteban Y, Alcantud-Marín F. {{Early Intervention with Parents of Children with Autism Spectrum Disorders: A Review of Programs}}. {Children (Basel, Switzerland)}. 2020; 7(12).
The aim of this article was to analyze the evidence regarding the effectiveness of intervention programs for children with autism based on the participation of their parents. To obtain the data, a systematic search was carried out in four databases (PsycARTICLES (ProQuest), ERIC (ProQuest), PubMed (ProQuest), and Scopus). The retrieved documents were refined under the inclusion/exclusion criteria, and a total of 51 empirical studies were selected. These studies were first classified according to the function of the intervention objective and, later, by the methodology applied (19 studies were based on comprehensive interventions, 11 focused on the nuclear symptoms of autism spectrum disorder (ASD), 12 focused on the promotion of positive parenting, and nine interactions focused on child play). Once all of the documents had been analyzed, the evidence indicated scientific efficacy in most studies, mainly in those based on child development and the application of behavioral analysis principles. Moreover, the positive influence of parent participation in such programs was demonstrated.
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28. Rybczynski S, Flanders XC, Murphy C, Hughes D, Reber P. {{Case Report: Ventilator weaning, tracheostomy decannulation and noninvasive ventilation in an adolescent with autism spectrum disorder and new onset spinal cord injury}}. {Spinal cord series and cases}. 2019; 5(1): 102.
INTRODUCTION: Spinal cord injury (SCI) is a cause of significant psychosocial stress not only to the individual with SCI but also to their family. This is compounded when an individual with a new SCI has premorbid behavioral and medical conditions. For individuals requiring long term positive pressure ventilation, transition to noninvasive ventilation (NIV) can improve the long term outcome and improve quality of life. CASE PRESENTATION: This case report describes a teenage boy with premorbid autism spectrum disorder who incurred an acute SCI and developed chronic respiratory failure. He was admitted to acute inpatient rehabilitation with tracheostomy and ventilator dependence. Using an interdisciplinary team approach with in vivo desensitization behavioral interventions, he was successfully weaned off mechanical ventilation, his tracheostomy tube was removed, and he was transitioned to NIV. DISCUSSION: This case describes a medically complex adolescent who was successfully transitioned to NIV through behavioral desensitization using a team approach. This is noteworthy given the magnitude of behaviors demonstrated prior to his desensitization protocol. This case demonstrates how serious behavioral barriers to NIV can be overcome using desensitization and strategic behavioral reinforcement techniques.
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29. Schafer EC, Mathews L, Gopal K, Canale E, Creech A, Manning J, Kaiser K. {{Behavioral Auditory Processing in Children and Young Adults with Autism Spectrum Disorder}}. {Journal of the American Academy of Audiology}. 2020.
BACKGROUND: Auditory-processing deficits are common in children and adults who are diagnosed with autism spectrum disorder (ASD). These deficits are evident across multiple domains as exhibited by the results from subjective questionnaires from parents, teachers, and individuals with ASD and from behavioral auditory-processing testing. PURPOSE: Few studies compare subjective and behavioral performance of adults and children diagnosed with ASD using commercially available tests of auditory processing. The primary goal of the present study is to compare the performance of adults and children with ASD to age-matched, neurotypical peers. The secondary goal is to examine the effect of age on auditory-processing performance in individuals with ASD relative to age-matched peers. RESEARCH DESIGN: A four-group, quasi-experimental design with repeated measures was used in this study. STUDY SAMPLE: Forty-two adults and children were separated into four groups of participants: (1) 10 children with ASD ages 14 years or younger; (2) 10 age-matched, neurotypical children; (3) 11 adolescents and young adults with ASD ages 16 years and older; and (4) 11 age-matched, neurotypical adolescents or young adults. DATA COLLECTION AND ANALYSIS: Data from each participant were collected in one test session. Data were analyzed with analysis of variance (ANOVA), repeated measures ANOVA, or nonparametric analyses. Effect sizes were calculated to compare performance between those with ASD and those who were neurotypical within each age group. RESULTS: Across all the questionnaires and the majority of the behavioral test measures, participants with ASD had significantly poorer ratings or auditory-processing performance than age-matched, neurotypical peers. Adults had more favorable performance than children on several of the test measures. Medium to large effect sizes corroborated the significant results. CONCLUSION: Overall, the questionnaires and behavioral tests used in this study were sensitive to detecting auditory-processing differences between individuals diagnosed with ASD and those who are considered neurotypical. On most test measures, children performed more poorly than adults. The findings in this study support that both children and adults with ASD exhibit auditory-processing difficulties. Appropriate school and work accommodations will be necessary to ensure appropriate access to speech in challenging environments.
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30. Tárraga-Mínguez R, Gómez-Marí I, Sanz-Cervera P. {{What Motivates Internet Users to Search for Asperger Syndrome and Autism on Google?}}. {Int J Environ Res Public Health}. 2020; 17(24).
Social campaigns are carried out to promote autism spectrum disorder (ASD) awareness, normalization, and visibility. The internet helps to shape perceptions of Asperger syndrome and autism. In fact, these campaigns often coincide with the increase in searches for both diagnoses on Google. We have two study objectives: to use Google Trends to identify the annual time points from 2015 to 2019 with the highest Google search traffic in Spain for the terms « autism » and « Asperger », and to identify news and trending topics related to ASD that took place during the weeks with the highest number of Google searches for these terms. Google Trend, MyNews and Trendinalia were used to analyze the volume of searches and trending topics related to ASD. As a result, social marketing campaigns, social networks and the publication of news items act as powerful voices that can provide a realistic or sensationalist picture of the disorder. For this reason, we concluded that campaigns play an important role in the normalization of ASD, and that it is important for organizations concerned with the visibility and social inclusion of people with ASD to check the way ASD is portrayed through the internet, media, and social networks.
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31. Versaci TM, Mattie LJ, Imming LJ. {{Down Syndrome and Autism Spectrum Disorder Dual Diagnosis: Important Considerations for Speech-Language Pathologists}}. {American journal of speech-language pathology}. 2020: 1-13.
Purpose Individuals with Down syndrome (DS) often receive speech-language therapy services starting in infancy or toddlerhood. When providing speech-language therapy services for children with DS, speech-language pathologists (SLPs) need to consider the impact of other developmental and comorbid disorders that can affect language development, such as the presence of a dual diagnosis of DS and autism spectrum disorder (DS + ASD). The prevalence rate of ASD in DS is ~20%, which is higher than in the general population. Method This clinical focus article aims to provide SLPs with additional knowledge about DS + ASD to improve service delivery and support parents’ ability to advocate for their child with confirmed or suspected DS + ASD. This is accomplished by summarizing the current evidence base on the presence of ASD in DS and discussing implications of a DS + ASD diagnosis for clinical practice with SLPs. Conclusions SLPs play a key role in supporting families of those with DS + ASD by advocating and educating. By understanding the unique profiles of strengths and weaknesses of individuals with DS + ASD, SLPs can provide appropriate service delivery (i.e., treatment and intervention approaches) and advocacy for their clients and their families.
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32. Wiggs KK, Rickert ME, Sujan AC, Quinn PD, Larsson H, Lichtenstein P, Oberg AS, D’Onofrio BM. {{Antiseizure medication use during pregnancy and risk of ASD and ADHD in children}}. {Neurology}. 2020; 95(24): e3232-e40.
OBJECTIVE: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors. METHODS: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication. RESULTS: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HR(ASD) 0.86, 95% CI 0.67-1.53; HR(ADHD) 1.01, 95% CI 0.67-1.53). CONCLUSIONS: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.
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33. Williams NJ, Frederick L, Ching A, Mandell D, Kang-Yi C, Locke J. {{Embedding school cultures and climates that promote evidence-based practice implementation for youth with autism: A qualitative study}}. {Autism}. 2020: 1362361320974509.
Schools play a major role in providing services to youth with autism; however, not all schools use evidence-based practices, defined as interventions that are proven to improve youth well-being through rigorous research. School culture and climate are strong predictors of whether or not a school uses evidence-based practices; however, little is known about how principals can create school cultures and climates that support the use of these practices. This study interviewed 32 teachers in elementary schools that implemented three closely related evidence-based practices for youth with autism to better understand how principals create school cultures and climates that support effective services. Analysis of the teachers’ responses identified seven strategies principals can use to create school cultures and climates that support the implementation of effective practices for youth with autism. The strategies include the following: (a) support teachers to obtain professional development focused on autism, (b) align performance expectations and evaluations with the needs of students with autism and evidence-based practice delivery, (c) allocate resources to ensure adequate staff, materials, and training are available to implement evidence-based practices, (d) be open and flexible to allow teachers to use the building and resources as needed to meet students’ needs, (e) provide direct assistance, feedback, and coaching to troubleshoot challenges or involve outside experts to do so, (f) openly value the work of special education teachers and provide recognition to those who develop expertise in evidence-based practices, and (g) look for opportunities to integrate special and general education teachers and students to foster a truly inclusive climate.
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34. Zhang X, Ibi M, Haga R, Iwata K, Matsumoto M, Asaoka N, Liu J, Katsuyama M, Yabe-Nishimura C. {{NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model}}. {Biochemical and biophysical research communications}. 2020; 534: 59-66.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic and environmental factors. Among the environmental factors, maternal infection is known as one of the principal risk factors for ASD. On the other hand, postmortem studies suggested the relationship of oxidative stress with ASD etiology. However, the role of oxidative stress in the development of ASD remains unclear. Here, we report the involvement of NOX1/NADPH oxidase, an enzyme generating reactive oxygen species (ROS), in behavioral and anatomical abnormalities in a maternal immune activation (MIA) model. In the MIA model of gestational polyinosinic-polycytidylic acid (poly(I:C)) exposure, increased serum levels of IL-6 were observed in both wild-type (WT) and Nox1-deficient mice (Nox1KO). Following the comparable induction of MIA in the two genotypes, impairment of social preference and defects in motor coordination were observed in WT offspring but not in offspring deficient in Nox1. MIA up-regulated NOX1 mRNA in the cerebral cortex and cerebellum of the fetus but not in the adult offspring. Although the development of cortical neurons was unaffected by MIA in either genotype, the dropout of Purkinje cells in lobule VII of MIA-affected offspring was significantly ameliorated in Nox1KO. Taken together, these results suggested that NOX1/NADPH oxidase plays an essential role in some behavioral phenotypes observed in ASD, possibly by promoting the loss of Purkinje cells in the cerebellum.
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35. Zhao X, Zhang R, Yu S. {{Mutation screening of the UBE3A gene in Chinese Han population with autism}}. {BMC Psychiatry}. 2020; 20(1): 589.
BACKGROUND: 15q11-13 region is one of the most complex chromosomal regions in the human genome. UBE3A is an important candidate gene of autism spectrum disorder (ASD), which located at the 15q11-13 region and encodes ubiquitin-protein ligase E3A. Previous studies about UBE3A gene and ASD have shown inconsistent results and few studies were performed in Chinese population. This study aimed to detect the genetic mutations of UBE3A gene in Chinese Han population with ASD and analyze genetic association between these variants and ASD. METHODS: The samples consisted of 192 patients with autism according to the DSM-IV diagnostic criteria and 192 healthy controls. We searched for mutations at coding sequence (CDS) regions and their adjacent non-coding regions of UBE3A gene using the high resolution melting (HRM) and Sanger sequencing methods. We further increased sample size to validate the detected variants using HRM and conducted association analysis between case and control groups. RESULTS: A known single nucleotide polymorphism (T > C, rs150331504) located at the CDS4 and a known 5 bp insertion/deletion variation (AACTC+/-, rs71127053) located at the intron region of the upstream 288 bp of the CDS2 of UBE3A gene were detected using Sanger sequencing method. The ASD samples of case group were 391 for rs71127053, 384 for rs150331504 and 384 healthy controls, which were used to make an association analysis. The results of association analysis suggested that there were no significant difference about the allele and genotype frequencies of rs71127053 and rs150331504 between case and control groups after extending the sample size. Besides, rs150331504 is a synonymous mutation and we compared the secondary structure and minimum free energy (MFE) of mRNA harboring the allele T or C of rs150331504 using RNAfold software. We found that the centroid secondary structure apparently differs along with the polymorphisms of rs150331504 T > C, the results suggested that this variant might change the secondary structure of mRNA of UBE3A gene. We did not detect mutations in other coding regions of UBE3A gene. CONCLUSIONS: These findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.
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36. Zhou HY, Wang YM, Zhang RT, Cheung EFC, Pantelis C, Chan RCK. {{Neural Correlates of Audiovisual Temporal Binding Window in Individuals With Schizotypal and Autistic Traits: Evidence From Resting-State Functional Connectivity}}. {Autism Res}. 2020.
Temporal proximity is an important clue for multisensory integration. Previous evidence indicates that individuals with autism and schizophrenia are more likely to integrate multisensory inputs over a longer temporal binding window (TBW). However, whether such deficits in audiovisual temporal integration extend to subclinical populations with high schizotypal and autistic traits are unclear. Using audiovisual simultaneity judgment (SJ) tasks for nonspeech and speech stimuli, our results suggested that the width of the audiovisual TBW was not significantly correlated with self-reported schizotypal and autistic traits in a group of young adults. Functional magnetic resonance imaging (fMRI) resting-state activity was also acquired to explore the neural correlates underlying inter-individual variability of TBW width. Across the entire sample, stronger resting-state functional connectivity (rsFC) between the left superior temporal cortex and the left precuneus, and weaker rsFC between the left cerebellum and the right dorsal lateral prefrontal cortex were correlated with a narrower TBW for speech stimuli. Meanwhile, stronger rsFC between the left anterior superior temporal gyrus and the right inferior temporal gyrus was correlated with a wider audiovisual TBW for non-speech stimuli. The TBW-related rsFC was not affected by levels of subclinical traits. In conclusion, this study indicates that audiovisual temporal processing may not be affected by autistic and schizotypal traits and rsFC between brain regions responding to multisensory information and timing may account for the inter-individual difference in TBW width. LAY SUMMARY: Individuals with ASD and schizophrenia are more likely to perceive asynchronous auditory and visual events as occurring simultaneously even if they are well separated in time. We investigated whether similar difficulties in audiovisual temporal processing were present in subclinical populations with high autistic and schizotypal traits. We found that the ability to detect audiovisual asynchrony was not affected by different levels of autistic and schizotypal traits. We also found that connectivity of some brain regions engaging in multisensory and timing tasks might explain an individual’s tendency to bind multisensory information within a wide or narrow time window.
