1. Ashbaugh K, Koegel R, Koegel L. {{Increasing Social Integration for College Students with Autism Spectrum Disorder}}. {Behav Dev Bull}. 2017; 22(1): 183-96.
Increasing numbers of individuals with Autism Spectrum Disorder (ASD) are entering postsecondary education; however, many report feeling lonely and isolated. These difficulties with socialization have been found to impact students’ academic success, involvement within the university, and overall well being. Therefore, the purpose of this study was to assess, within the context of a multiple-baseline across participants design, whether a structured social planning intervention would increase social integration for college students with ASD. The intervention consisted of weekly meetings to plan social activities around the student with ASD’s interests, improve organizational skills, and target specific social skills. Additionally, each participant had a peer mentor for support during the social activities. The results showed that following intervention all participants increased their number of community-based social events, extracurricular activities, and peer interactions. Furthermore, participants improved in their academic performance and satisfaction with their college experience. Results are discussed in regards to developing specialized programs to assist college students with ASD.
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2. Baghdadli A, Russet F, Mottron L. {{Measurement properties of screening and diagnostic tools for autism spectrum adults of mean normal intelligence: A systematic review}}. {Eur Psychiatry}. 2017; 44: 104-24.
BACKGROUND: The autism spectrum (AS) is a multifaceted neurodevelopmental variant associated with lifelong challenges. Despite the relevant importance of identifying AS in adults for epidemiological, public health, and quality of life issues, the measurement properties of the tools currently used to screen and diagnose adults without intellectual disabilities (ID) have not been assessed. OBJECTIVES: This systematic review addresses the accuracy, reliability, and validity of the reported AS screening and diagnostic tools used in adults without ID. METHODS: Electronic databases and bibliographies were searched, and identified papers evaluated against inclusion criteria. The PRISMA statement was used for reporting the review. We evaluated the quality of the papers using the COSMIN Checklist for psychometric data, and QUADAS-2 for diagnostic data. For the COSMIN assessment, evidence was considered to be strong when several methodologically good articles, or one excellent article, reported consistent evidence for or against a measurement property. For the QUADAS ratings, evidence was considered to be « satisfactory » if at least one study was rated with a low risk of bias and low concern about applicability. RESULTS: We included 38 articles comprising 32 studies, five reviews, and one book chapter and assessed nine tools (three diagnostic and six screening, including eight of their short versions). Among screening tools, only AQ-50, AQ-S, and RAADS-R and RAADS-14 were found to provide satisfactory or intermediate values for their psychometric properties, supported by strong or moderate evidence. Nevertheless, risks of bias and concerns on the applicability of these tools limit the evidence on their diagnostic properties. We found that none of the gold standard diagnostic tools used for children had satisfactory measurement properties. CONCLUSION: There is limited evidence for the measurement properties of the screening and diagnostic tools used for AS adults with a mean normal range of measured intelligence. This may lessen the validity of conclusions and public health decisions on an important fraction of the adult autistic population. This not only justifies further validation studies of screening and diagnostic tools for autistic adults, but also supports the parallel use of self-reported information and clinical expertise with these instruments during the diagnostic process.
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3. Beelen C, Cuypers K, van Schuerbeeck L, Braeken M, Ross V, Jongen E, Meesen R, Vanvuchelen M. {{Preserved imitation in contrast to limited free application of comfortable hand actions in intellectually able young adults with an autism spectrum disorder}}. {Autism}. 2017: 1362361317698454.
Imitation problems are commonly reported in children with an autism spectrum disorder. However, it has not yet been determined whether imitation problems persist into young adulthood. In this study, we investigated imitation skills of 20 intellectually able young adults with autism spectrum disorder relative to 19 age-matched neurotypical adults. For this purpose, we used a bar-transport task, which evokes the application of the end-state comfort principle. Specifically, we examined whether young adults with autism spectrum disorder imitated the means-end structure of a demonstrator’s bar-transport action with and without application of the end-state comfort principle (imitation task). In addition, we examined whether participants spontaneously applied the end-state comfort principle during a similar bar-transport task (free execution task). Results revealed that young adults with autism spectrum disorder imitated the means-end structure of observed actions to the same degree as neurotypical adults ( p = 0.428). In contrast, they applied the end-state comfort principle less often during free executed actions ( p = 0.035). Moreover, during these actions, they were slower to place the bar into the penholder ( p = 0.023), which contributed to the reduced efficiency of their performance. Findings suggest that imitation abilities of young adults with autism spectrum disorder are preserved and that observing others’ actions might promote more efficient action planning in this population.
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4. Bottema-Beutel K. {{Glimpses into the blind spot: Social interaction and autism}}. {J Commun Disord}. 2017; 68: 24-34.
A primary feature of autism spectrum disorder (ASD) is marked difficulty in social interactions. Despite the centrality of social interaction differences to the clinical presentation of ASD, only a small portion of research in this field characterizes interaction in everyday social contexts. This theoretical paper reviews the growing corpus of interactional research on ASD, including discourse analysis (DA) and conversation analysis (CA) approaches. DA and CA are micro-analytic methods aimed at understanding the organizational structure of, and actions pursued within, social encounters. These methods are aligned with enactive theories of social interaction. The bulk of current ASD research construes social interaction as involving isolated individuals who represent and/or theorize about the minds of an interlocutor. Enactive approaches posit that achieving intersubjectivity does not require theories of other minds, but instead a propensity for coordinating social actions with others. Through the complementary lenses of enactivism and interactional research, I offer an account of autistic social interaction as involving differences in interactional coordination, interactional priorities, and the enactment of meaning across conversational turns. This characterization challenges the explanatory role of cognitive processes such as Theory of Mind, and points to new avenues for conceptualizing, measuring, and supporting social interaction.
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5. Chan W, Smith LE, Hong J, Greenberg JS, Mailick MR. {{Validating the social responsiveness scale for adults with autism}}. {Autism Res}. 2017.
The Social Responsiveness Scale [SRS; Constantino & Gruber, 2005] is a widely-used measure of autism symptoms, but its application for the study of adults with autism spectrum disorders has not been fully evaluated. Using a factor structure consistent with The Diagnostic and Statistical Manual of Mental Disorders (5th ed., DSM-V) criteria for autism spectrum disorder [Frazier et al., 2014], the primary purpose of the current study was to establish the validity of the SRS with a sample of adults with autism spectrum disorder (N = 237). Correlational analyses indicated that SRS factors were highly associated with autism symptoms and behavioral measures, indicating concurrent and predictive validity. Multiple regression results demonstrated that SRS factors were differentially related to measures specific to social or behavioral domains, indicating convergent and discriminant validity. Implications for future research are discussed. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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6. Dhamne SC, Silverman JL, Super CE, Lammers SHT, Hameed MQ, Modi ME, Copping NA, Pride MC, Smith DG, Rotenberg A, Crawley JN, Sahin M. {{Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism}}. {Mol Autism}. 2017; 8: 26.
BACKGROUND: Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. METHODS: In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant (Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each behavioral domain, including social, repetitive, cognitive, anxiety-related, sensory, and motor categories of assays. RESULTS: Relative to WT mice, Shank3B KO mice displayed a dramatic resistance to PTZ seizure induction and an enhancement of gamma band oscillatory EEG activity indicative of enhanced inhibitory tone. These findings replicated in two separate cohorts. Behaviorally, Shank3B KO mice exhibited repetitive grooming, deficits in aspects of reciprocal social interactions and vocalizations, and reduced open field activity, as well as variable deficits in sensory responses, anxiety-related behaviors, learning and memory. CONCLUSIONS: Robust animal models and quantitative, replicable biomarkers of neural dysfunction are needed to decrease risk and enable successful drug discovery and development for ASD and other neurodevelopmental disorders. Complementary to the replicated behavioral phenotypes of the Shank3B mutant mouse is the new identification of a robust, translational in vivo neurophysiological phenotype. Our findings provide strong evidence for robustness and replicability of key translational phenotypes in Shank3B mutant mice and support the usefulness of this mouse model of ASD for therapeutic discovery.
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7. Filippini A, Bonini D, Lacoux C, Pacini L, Zingariello M, Sancillo L, Bosisio D, Salvi V, Mingardi J, La Via L, Zalfa F, Bagni C, Barbon A. {{Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse}}. {RNA Biol}. 2017: 0.
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. In order to evaluate the ADAR2-FMRP interaction in mammals we analysed several RNA editing re-coding sites in the fmr1 knockout (KO) mice. Ex vivo and in vitro analysis revealed that absence of FMRP lead to an increase in the editing levels of brain specific mRNAs, indicating that FMRP might act as an inhibitor of editing activity. Proximity Ligation Assay (PLA) in mouse primary cortical neurons and in non-neuronal cells revealed that ADAR2 and FMRP co-localize in the nucleus. The ADAR2-FMRP co-localization was further observed by double-immunogold Electron Microscopy (EM) in the hippocampus. Moreover, ADAR2-FMRP interaction appeared to be RNA independent. Because changes in the editing pattern are associated with neuropsychiatric and neurodevelopmental disorders, we propose that the increased editing observed in the fmr1-KO mice might contribute to the FXS molecular phenotypes.
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8. Guo W, Samuels JF, Wang Y, Cao H, Ritter M, Nestadt PS, Krasnow J, Greenberg BD, Fyer AJ, McCracken JT, Geller DA, Murphy DL, Knowles JA, Grados MA, Riddle MA, Rasmussen SA, McLaughlin NC, Nurmi EL, Askland KD, Cullen BA, Piacentini J, Pauls DL, Bienvenu OJ, Stewart SE, Goes FS, Maher B, Pulver AE, Valle D, Mattheisen M, Qian J, Nestadt G, Shugart YY. {{Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD}}. {Eur Neuropsychopharmacol}. 2017; 27(7): 657-66.
Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10-7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.
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9. Havdahl KA, Bishop SL, Suren P, Oyen AS, Lord C, Pickles A, von Tetzchner S, Schjolberg S, Gunnes N, Hornig M, Lipkin WI, Susser E, Bresnahan M, Magnus P, Stenberg N, Reichborn-Kjennerud T, Stoltenberg C. {{The influence of parental concern on the utility of autism diagnostic instruments}}. {Autism Res}. 2017.
The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35-47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve >/= 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Jones RM, Pickles A, Lord C. {{Evaluating the quality of peer interactions in children and adolescents with autism with the Penn Interactive Peer Play Scale (PIPPS)}}. {Mol Autism}. 2017; 8: 28.
BACKGROUND: A core difficulty for individuals with autism is making friends and successfully engaging and interacting with peers. The majority of measures to assess peer interactions are observations in a school setting or self-report. The present study examined the convergent validity of using a teacher rating scale, the Penn Interactive Peer Play Scale (PIPPS), for collecting information about the quality of peer interactions at school. METHODS: Teachers completed the PIPPS for 107 children with ASD when the child was 9 and 13 years of age. Clinicians completed diagnostic and cognitive assessments and caregivers completed the Autism Diagnostic Interview-Revised (ADI-R) when the child was 9. RESULTS: Parent report of reciprocal friendships from the ADI-R was associated with teacher report about how socially connected the child was at school on the PIPPS, indicating strong convergence between teachers and parents. Children with more severe restricted and repetitive behaviors and lower verbal abilities were less connected with peers. Children with access to typical peers had more connections with peers compared to those who were in a special education classroom. CONCLUSIONS: The findings suggest that teacher ratings from the PIPPS can accurately capture the quality of peer interactions in children and adolescents with ASD and may be useful for clinicians and researchers to evaluate peer engagement in the classroom.
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11. Livingston LA, Happe F. {{Conceptualising Compensation in Neurodevelopmental Disorders: Reflections from Autism Spectrum Disorder}}. {Neurosci Biobehav Rev}. 2017.
Within research into neurodevelopmental disorders, little is known about the mechanisms underpinning changes in symptom severity across development. When the behavioural presentation of a condition improves/symptoms lessen, this may be because core underlying atypicalities in cognition/neural function have ameliorated. An alternative possibility is ‘compensation’; that the behavioural presentation appears improved, despite persisting deficits at cognitive and neurobiological levels. There is, however, currently no agreed technical definition of compensation or its behavioural, cognitive and neural characteristics. Furthermore, its workings in neurodevelopmental disorders have not been studied directly. Here, we review current evidence for compensation in neurodevelopmental disorders, using Autism Spectrum Disorder as an example, in order to move towards a better conceptualisation of the construct. We propose a transdiagnostic framework, where compensation represents the processes responsible for an observed mismatch between behaviour and underlying cognition across development. Further, we explore potential cognitive and neural mechanisms underlying compensation and discuss the broader relevance of the concept within research and clinical settings.
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12. Martzoukou M, Papadopoulou D, Kosmidis MH. {{The Comprehension of Syntactic and Affective Prosody by Adults with Autism Spectrum Disorder Without Accompanying Cognitive Deficits}}. {J Psycholinguist Res}. 2017.
The present study investigates the comprehension of syntactic and affective prosody in adults with autism spectrum disorder without accompanying cognitive deficits (ASD w/o cognitive deficits) as well as age-, education- and gender-matched unimpaired adults, while processing orally presented sentences. Two experiments were conducted: (a) an on-line sentence completion task containing local subject/object ambiguities and (b) an affective prosody task exploring the comprehension of six emotions. The syntactic prosody task revealed that the experimental group performed similar to the control group on the fillers and the object condition. On the other hand, the ASD w/o cognitive deficits group manifested lower accuracy compared to the unimpaired controls in the subject reading condition, as well as slower reaction times in all conditions. In the affective prosody task, the experimental group performed significantly worse than the controls in the recognition of the emotion of surprise, whereas no differences between the experimental and the control group were attested in the recognition of all other emotions. A positive correlation was found between the two tasks in the ASD w/o cognitive deficits group. Thus, individuals with ASD w/o cognitive deficits face slight difficulties with the decoding of prosody, both the syntactic and the affective one. More specifically, these difficulties are attested in the most difficult conditions, i.e. the subject reading and the emotion of surprise.
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13. McIntosh CE, Thomas CM, Wilczynski S, McIntosh DE. {{Increasing Nursing Students’ Knowledge of Autism Spectrum Disorder by Using a Standardized Patient}}. {Nurs Educ Perspect}. 2017.
Nursing students participated in a simulation using a standardized patient role-playing an adolescent with autism spectrum disorder (ASD). The researchers used student feedback to develop and improve a simulation aimed at increasing learner skills and knowledge for treating ASD patients. Students indicated that the standardized patient provided realism not obtained when using static manikins or high-fidelity simulators. Students strongly agreed or agreed that classroom instruction prior to the simulation was important to increasing their knowledge of ASD. Overall, the simulation provided students an opportunity to practice and develop their clinical skills in caring for patients with ASD.
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14. Nicholas DB, Zwaigenbaum L, Zwicker J, Clarke ME, Lamsal R, Stoddart KP, Carroll C, Muskat B, Spoelstra M, Lowe K. {{Evaluation of employment-support services for adults with autism spectrum disorder}}. {Autism}. 2017: 1362361317702507.
The employment rate among persons with autism spectrum disorder has been noted as unacceptably low. Employment-support services are increasingly linked to the potential for favorable job outcomes, yet little is known about employment-support practices and the outcome of these interventions. This mixed-methods study examined employment-support resources for persons with autism spectrum disorder. An online survey was completed by 137 senior clinicians or administrators in employment-support programs in Canada. Additionally, 122 follow-up interviews were conducted with individuals with autism spectrum disorder (n = 71) and their parents/caregivers (n = 51). Findings indicate that the quality and beneficial impact of employment-support services for adults with autism spectrum disorder may be more favorably perceived by employment-support personnel than by individuals with autism spectrum disorder and their families. Furthermore, employment-support personnel were more disparaging about autism spectrum disorder vocational support capacity within their community, compared to their own programs. Individuals with autism spectrum disorder and their families seek services that support both accessing and retaining employment. Capacity-building in employment support for youth and adults with autism spectrum disorder is recommended, based on a reported insufficiency of, and a lack of evidence guiding, existing services. Program recommendations and an emerging model for integrated vocational support in autism spectrum disorder are offered.
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15. Santosh P, Lievesley K, Fiori F, Singh J. {{Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire}}. {BMJ Open}. 2017; 7(6): e015342.
INTRODUCTION: Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT-methyl-CpG-binding protein 2 (MECP2) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT. As part of the HealthTracker-based Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database, the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire will be able to marry with the physiological aspects of the disease obtained using wearable sensor technology, along with genetic and psychosocial data to stratify patients. Taken together, the web-based TRIAL database will empower clinicians and researchers with the confidence to delineate between different aspects of disorder symptomatology to streamline care pathways for individuals or for those patients entering clinical trials. This protocol describes the anticipated development of the REST questionnaire and the TRIAL database which links with the outcomes of the wearable sensor technology, and will serve as a barometer for longitudinal patient monitoring in patients with RTT. METHODS AND ANALYSIS: The US Food and Drug Administration Guidance for Patient-Reported Outcome Measures will be used as a template to inform the methodology of the study. It will follow an iterative framework that will include item/concept identification, item/concept elicitation in parent/carer-mediated focus groups, expert clinician feedback, web-based presentation of questionnaires, initial scale development, instrument refinement and instrument validation. ETHICS AND DISSEMINATION: The study has received favourable opinion from the National Health Service (NHS) Research Ethics Committee (REC): NHS Research Ethics Committee (REC)-London, Bromley Research Ethics Committee (reference: 15/LO/1772).
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16. Vlaskamp C, Oranje B, Madsen GF, Mollegaard Jepsen JR, Durston S, Cantio C, Glenthoj B, Bilenberg N. {{Auditory processing in autism spectrum disorder: Mismatch negativity deficits}}. {Autism Res}. 2017.
Children with autism spectrum disorders (ASD) often show changes in (automatic) auditory processing. Electrophysiology provides a method to study auditory processing, by investigating event-related potentials such as mismatch negativity (MMN) and P3a-amplitude. However, findings on MMN in autism are highly inconsistent, partly due to small sample sizes in the studies and differences in MMN paradigms. Therefore, in the current study, MMN and P3a amplitude were assessed in a relatively large sample of children with ASD, using a more extensive MMN paradigm and compared with that of typically developing children (TDC). Thirty-five children (aged 8-12 years) with ASD and 38 age and gender matched TDC were assessed with a MMN paradigm with three types of deviants, i.e., frequency, duration and a combination of these two. MMN elicited by duration and frequency-duration deviants was significantly reduced in the ASD group. P3a-amplitude elicited by duration deviants was significantly increased in the ASD group. Reduced MMN in children with ASD suggests that children with ASD may be less responsive to environmentally deviant stimuli at an early (sensory) level. P3a-amplitude was increased in ASD, implying a hyper-responsivity at the attentional level. In addition, as similar MMN deficits are found in schizophrenia, these MMN results may explain some of the frequently reported increased risk of children with ASD to develop schizophrenia later in life. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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17. Yamaguchi H, Hara Y, Ago Y, Takano E, Hasebe S, Nakazawa T, Hashimoto H, Matsuda T, Takuma K. {{Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice}}. {Behav Brain Res}. 2017.
We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improve cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.
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18. Zheng Z, Fu Q, Zhao H, Swanson AR, Weitlauf AS, Warren ZE, Sarkar N. {{Design of an Autonomous Social Orienting Training System (ASOTS) for Young Children With Autism}}. {IEEE Trans Neural Syst Rehabil Eng}. 2017; 25(6): 668-78.
Social communication is among the core areas of impairment for children with Autism Spectrum Disorders (ASD). The training of social orientation is important for improving social communication of children with ASD. In recent years, technology-assisted ASD intervention had gained momentum due to its potential advantages in terms of precision, sustainability, flexibility and cost. In this paper, we propose a closed-loop autonomous computer system, named ASOTS, for training social orientation skills to young children with ASD. This system is designed to detect and track a child’s attention in response to social orientation bids and help the child towards appropriate social orientation when needed. Response to name, an important social orientation skill, was used to demonstrate the functionality of the proposed system. Ten toddlers with ASD participated in a pilot user study to show whether the system could be used on young children who have been diagnosed with ASD. Another pilot user study with 10 TD infants tested whether this system has a potential to be applied for early detection for infants who were younger than the age when ASD diagnoses can be done. This was done intentionally to separately demonstrate utility and functionality for the clinical population of interest and to demonstrate functionality beyond current clinical identification capacity (i.e., infants). The results showed that the proposed system and the protocol were well tolerated by both groups, successfully captured young children’s attention, and elicited the desired behavior.
