Autism Spectrum Disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that affects about 1% of the worldwide population and has a strong genetic component. Stereotyped behavior and restricted interests, as well as problems of social interaction and communication characterize ASD. Moreover, in 10% of cases, ASD occurs as a secondary condition in addition to a syndrome, such as Phelan-McDermid syndrome (PMS), which is associated with a great clinical variability. Among genetic factors, copy number variations (CNVs) are one of the most important. However, the clinical significance of many CNVs remains nuclear and there is an underrepresentation of small CNVs associated with ASD in the literature. In this context, this project aimed to 1) characterize large and small CNVs in Brazilian patients with ASD using an array-CGH previously customized in our laboratory. 2) Clinically and genetically describe a cohort of Brazilian patients with PMS, as well as to determine the frequency of this syndrome among Brazilian patients with ASD and other neurodevelopmental disorders. In result, we 1) further validated the customized array-CGH, 2) provided additional evidence of association with ASD for 27 candidate genes, 3) described 15 CNVs never reported in the literature in association with this disorder, 4) presented evidence that around 70% of CNVs found in our cohort are not polymorphism of our population and 5) reinforced the idea of shared molecular pathways among different neurodevelopmental disorders. In addition, we described for the first time a Brazilian cohort of patients with PMS and contributed to the molecular and clinical characterization of this syndrome. We also provided additional evidence of genotype-phenotype association with regard to the presence of renal problems and speech status in patients with PMS and estimated the frequency of this syndrome among Brazilian patients with ASD and intellectual disability (syndromic or not). With these results, we hope to contribute to better understand the ASD and PMS etiology, especially in our population / O Transtorno do Espectro Autista (TEA) corresponde ao um grupo heterogêneo de alterações no neurodesenvolvimento que afeta cerca de 1% da população mundial e apresenta um forte componente genético. O TEA é caracterizado pela presença de comportamento estereotipado e interesses restritos, além de problemas de interação social e comunicação. Além disso, em 10% dos casos, o TEA ocorre como uma condição secundária somada a uma síndrome. Um exemplo é a síndrome de Phelan-McDermid (PMS), associada a uma grande variabilidade clínica. Dentre os fatores genéticos, as variações no número de cópias (CNVs) são um dos mais importantes. No entanto, o significado clínico de muitas CNVs permanece incerto, além de haver juma sub-representação de CNVs pequenas associadas ao TEA na literatura. Dentro deste contexto, este projeto teve como objetivos 1) caracterizar CNVs grandes e pequenas em pacientes brasileiros com TEA utilizando uma lâmina de array-CGH previamente customizada no Laboratório de Genética do Desenvolvimento - USP. 2) descrever clínica e geneticamente uma casuística de pacientes brasileiros com PMS, bem como determinar a frequência desta síndrome em pacientes com TEA e com outras alterações de neurodesenvolvimento. Como resultados, nós 1) validamos a lâmina customizada, 2) fornecemos evidencia adicional de associação com o TEA para 27 genes, 3) descrevemos 15 CNVs nunca reportadas em associação com o transtorno 4) apresentamos evidências de que cerca de 70% das CNVs encontradas em nossa coorte não são polimorfismo de nossa população e 5) reforçamos a ideia de vias moleculares compartilhadas entre diferentes alterações do neurodesenvolvimento. Além disso, descrevemos pela primeira vez uma casuística brasileira de pacientes com PMS e contribuímos para a síndrome. Fornecemos evidência adicional de associação genótipo-fenótipo no que diz respeito à presença de problemas renais e status de fala em pacientes com PMS e estimamos a frequência da síndrome entre pacientes brasileiros com TEA e com deficiência intelectual (sindrômica ou não). Com estes resultados, esperamos ter contribuído para o entendimento da etiologia tanto do TEA, quanto da PMS, sobretudo na nossa população

Autism Spectrum Disorder (ASD) is part of the developmental disabilities. There are numerous symptoms for ASD patients, including lack of abilities in social interaction, communication obstacle and repeatable behaviors. Meanwhile, the rate of ASD prevalence has kept rising by the past 20 years from 1 out of 150 in 2000 to 1 out of 54 in 2016. In addition, the ASD population is quite large. Specifically, 3.5 million Americans live with ASD in the year of 2014, which will cost U.S. citizens $236-$262 billion dollars annually for autism services. So, it is critical to make an accurate diagnosis for preschool age children with ASD, in order to give them a better life. Instead of using traditional ASD behavioral tests, such as ADI-R, ADOS, and DSM-IV, we applied brain MRI images as input to make diagnosis. We revised 3D-ResNet structure to fit 110 preschool children's brain MRI data, along with Convolution 3D and VGG model. The prediction accuracy with raw data is 65.22%. The accuracy is significantly improved to 82.61% by removing the noise around the brain. We also showed the speed of ML prediction is 308 times faster than behavior tests.

Several studies show that physical activity has positive effects for children with autism. Therefore, I chose to investigate the form of adaptions student in autism spectrum in the subject of sports and health and what conditions the physical education teachers have to create a favorable environment for student with autism. Through a qualitative research method with teachers in physical education and health, the material has been collected with semi structured interviews. The results show how teachers adapt teaching to student with autism spectrumdisorders. Physical education and health teachers work in different ways. The adaption can consist of preparation, the student’s special interests, structure, participation/involvement, andclarity in the teaching. Based on the discussion, all students are different and the teachers need to adapt the student’s needs. / Flertal studier visar att fysisk aktivitet har positiva effekter för barn med autism. Därför valde jag att undersöka vilken form av anpassningar elever inom autismspektrumet i ämnet idrott och hälsa och vilka förutsättningar idrottslärarna har för att skapa en gynnsam miljö för elever med autism. Genom en kvalitativ forskningsmetod med lärare inom idrott och hälsa har materialet samlats in via semistrukturerade intervjuer. I resultatet framkommer det hur lärarna anpassar undervisningen till elever med autismspektra. Idrott och hälsa lärarna arbetar på olika sätt för att anpassa undervisningen. Anpassningen kan bestå av förberedelser, elevensspecialintressen, struktur, delaktighet/involvering samt tydlighet i undervisningen. Utifrån diskussionen är alla elever olika och lärarna behöver anpassa elevens behov.

Philosophiae Doctor - PhD / This thesis examined the difficulties experienced by Grade 6 isiXhosa-speaking learners in learning Natural Science through English as the medium of instruction at a primary school in the Western Cape. In 1994, South Africa became a democratic country where people were given the right to choose the language of learning and communication (Constitution of the Republic of South Africa, 1996). The assumption made in relation to the right to language was that this would provide equal opportunities and equal access to education for all learners. All learners would then be able to attain academic success. The study was pursued against the backdrop of the serious academic underachievement of African learners at schools around the country (often culminating in high matric failure rates), particularly in mathematics, science and technology (Probyn, 2005; Cleghorn, 2005; Taylor & Vinjevold, 1999). Following a mixed-method approach (involving both qualitative and quantitative research methods), within the constructivist paradigm, the study examined the various factors which act as barriers to learning and contribute to difficulties in learning Natural Science by Grade 6 isiXhosa-speaking learners in one school in the Western Cape. It also examined the coping strategies used in dealing with the barriers by both the learners and educators in order to address the learning difficulties. The study was conducted over a period of four months, spread over two years (2008 and 2009), in the Metropole Central Education District (MCED) of the Western Cape. The following participants were involved in the study: 205 Grade 6 learners (103 learners in 2008 and 102learners in 2009), 4 Natural Science educators (including 2 HODs), 1 principal, and 4 parents. The focus of the study was, however, on 26 isiXhosa-speaking learners (13 learners from each year in 2008 and 2009). The data were collected using the following research methods: questionnaires, classroom observation, document analysis, and interviews. The data were analysed through content analysis and (analysis of) language usage (including sentence construction), and were interpreted with respect to the study's research questions. The findings of the research revealed that language (including both the English language of learning and teaching or LOLT, and the language of science) was a major barrier to the learning of Natural Science by Grade 6 isiXhosa-speaking learners. The language barrier was exacerbated by factors within the teaching and learning context, the school environment, as well as by social factors in the learners' own home backgrounds. On the basis of the findings of the research and the related literature, the study makes recommendations regarding what could be done to address the difficulties, as well as proposals for future research. The key recommendations include: • Introducing a more flexible bilingual education policy to enable additive bilingualism to be practised by both learners and educators; • Compiling a list or glossary of words, concepts and terms that matter in Natural Science and ensuring that the learners fully understand their meaning and use them appropriately; • Educators constantly reflecting on their own teaching styles and practices in relation to their effectiveness and impact on their learners; • Educators constantly considering 'different and creative ways' of assessing learners for whom the English LOLT is not a home language; and • District Offices providing systemic support for schools and creating an enabling learning environment.

L’objectif de ce travail est d’évaluer le développement des compétences sociales chez les enfants avec TSA d’âge préscolaire. 19 enfants (âge moyen au début de l’étude = 52,44 mois ; écart-type = 10,07) scolarisés en Unités d’Enseignement en Maternelle ont été suivis pendant 10 mois. En référence au modèle de Yeates et collaborateurs (2007), les compétences sociales sont appréhendées selon 2 composantes parmi 3, le traitement de l’information sociale et les comportements d’interaction sociale. Le traitement de l’information sociale est évalué au moyen de l’exploration visuelle de scènes sociales dans un paradigme d’eye-tracking. Les comportements d’interaction sociale sont observés en situation écologique, en milieu scolaire. De façon attendue, les principaux résultats montrent que la sévérité des troubles et le niveau socio-communicatif au début de l’étude des enfants influencent le développement de leurs compétences sociales dans ces deux composantes. Toutefois, ceci est à moduler en fonction du contexte. Les patterns d’exploration des scènes sociales sont relativement stables au cours de l’année scolaire. En revanche, des progrès sont notables au niveau des comportements sociaux en classe. De plus, des liens peuvent être faits entre le développement du traitement de l’information sociale et des comportements d’interaction sociale en classe. L’analyse des profils individuels démontre une variété de trajectoires individuelles de développement des compétences sociales pouvant être mise en lien avec les profils cliniques des enfants. / The purpose of this work is to assess the development of social skills in preschool childrenwith ASD. 19 children (mean age at baseline = 52.44 months, SD = 10.07) enrolled in Kindergarten special schools were followed for 10 months. Based on the model of Yeates et al. (2007), social skills are apprehended according to two of three components, the social information processing and the social interaction behaviors. The social information processing is evaluated by the visual exploration of social scenes in an eye-tracking paradigm. The social interaction behaviors are observed in ecological situation at school. Expectedly, the main results show that the severity of the disorders and the socio-communicative level at the beginning of the study influence the development of children’s social skills in these two components. However, this need to be modulated according to the context. Patterns of social scenes exploration are relatively stable during the school year. On the other hand, a progress is notable in terms of social behavior in the classroom. In addition, links can be made between the development of social information processing and social interaction behaviors in the classroom. The analysis of individual profiles demonstrates a variety of individual social skills development trajectories that can be linked to the clinical profiles of children.

Les Troubles du Spectre de l’Autisme (TSA) représentent la deuxième pathologie neuro-développementale la plus fréquente chez l’enfant. Le handicap est présent tout au long de la vie et a des conséquences majeures sur le fonctionnement de la personne mais aussi sur l’entourage familial et notamment les parents. Comme souligné par le dernier Plan Autisme, il est urgent de développer les offres d’accompagnement des aidants familiaux. L’objectif de cette recherche est d’étudier l’ajustement et les besoins parentaux dans les Troubles du Spectre de l’Autisme en vue de développer un programme d’éducation thérapeutique et d’en mesurer son impact. Trois études ont été réalisées successivement à partir d’une méthodologie soit qualitative (Etude 1) soit quantitative (Etudes 2 et 3). Notre première étude a permis d’identifier les besoins des parents d’enfant avec un TSA par rapport à des parents tout-venants (N=162). Des cibles d’accompagnement ont été formulées à partir des besoins matériel, d’information, de guidance parentale et de soutien émotionnel rapportés majoritairement par les parents d’enfant avec un TSA. Notre seconde étude visait à étudier les déterminants de l’ajustement parental dans les TSA (N=115). Les variables liées au contexte étaient davantage associées à l’ajustement parental que les variables individuelles. Du point de vue contextuel, les caractéristiques de l’environnement familial et l’accès de l’enfant à une scolarisation semblent être des déterminants importants de l’ajustement. Du point de vue individuel la présence de comorbidités chez l’enfant et d’un phénotype autistique élargie chez le parent étaient associés à un moins bon ajustement parental. Enfin, notre troisième étude a permis de développer et d’évaluer l’impact du programme d’éducation thérapeutique ETAP auprès de parents d’enfant avec un TSA (N=40). Le programme comporte 7 séances collectives structurées. Une bonne acceptabilité ainsi que des améliorations significatives de la qualité de vie et de la symptomatologie dépressive ont été notées. En conclusion, les besoins et les difficultés d’ajustement relevés chez les parents confirment la nécessité d’accompagner, de façon plus systématique, les pères et les mères d’enfant avec un TSA. Dans une logique de prévention, il est primordial d’évaluer, de manière précoce et continue, les besoins d’accompagnement et la qualité de l’ajustement parental. Cette évaluation doit s’appuyer sur une vision globale de la situation parentale et intégrer des aspects individuels et contextuels. On retrouve ces éléments au sein du programme ETAP qui apparaît comme un dispositif prometteur pour accompagner les parents d’enfant avec un TSA. La proposition d’un modèle de compréhension de l’ajustement parental dans les TSA permet d’articuler les résultats des trois volets de cette recherche. / Autism Spectrum Disorders (ASD) are the second most common childhood neurodevelopmental disorder. Disability is present throughout life and has major implications for the individual functioning but also on the family environment, especially on parents. As highlighted by the last French Autism Plan, it is crucial to develop support programs for parents. The goal of this research is to study the adjustment and parental needs in ASD in order to develop and evaluate a therapeutic education program. Three studies were carried out successively using a qualitative method (Study 1) or quantitative method (Studies 2 and 3). The first study aimed at identifying needs in two groups: parents of children with ASD compared to parents of typically developing children (N = 162). Support targets were formulated from reported needs by parents with ASD child in the following areas: material, information, parental guidance and emotional support. Our second study considered the determinants of parental adjustment in ASD (N = 115). The contextual variables were more involved in parental adjustment than individual measures. From a contextual perspective, the characteristics of the family environment and children school access are important determinants of adjustment. From an individual perspective, comorbidities in children and a broader autism phenotype in parents were associated with lower parental adjustment. Finally, the last study developed and evaluated the impact of therapeutic education program to parents of children with ASD (N = 40). The program consists in seven group-structured sessions. Good acceptability as well as significant improvements in quality of life and depressive symptoms was noted. In conclusion, the parents’ needs and adjustment difficulties confirm the relevance to support fathers and mothers of children with ASD. From a prevention way, it is important to early and continually assess support needs and parental adjustment. This assessment should be based on a global vision of parental status and to consider individual and contextual aspects. These elements are present in the ETAP program, which appears as a promising device to support parents of children with ASD. A theoretical model of parental adjustment in ASD is proposed from the results of the three components of this research.

Syftet med föreliggande examensarbetet är att genom en litteraturstudie försöka generera teori för hur den specialpedagogiska verksamheten kan dra nytta av forskningsresultaten gällande hur hjärnans funktioner fungerar i samband med inlärning vid ADHD (attention deficit hyperactivity disorder) och/eller autismspektrumtillstånd (AST). Metoden som valts för denna studie är en kvalitativ litteraturstudie, där resultatet analyserats efter Grounded Theory. Vi har tagit del av relevant forskning och litteratur gällande hjärnans funktioner och det pedagogiska fältet för individer med ADHD samt AST i åldern 6–16 år. Resultatet gällande hjärnans funktioner visar att grunden till ADHD samt AST är biologisk betingad. Resultatet gällande de pedagogiska implikationerna visar på flera möjliga sätt att anpassa undervisningen och inlärningen för att stödja och hjälpa dessa elever. Litteraturen beskriver bitvis hur de ser länkar mellan hjärnans funktioner och de svårigheter som elever med ADHD och AST kan ställas inför i skolmiljön. I litteraturen kring vilka implikationer som föreslås för elever med ADHD och AST framkommer många likheter och att de gynnas av liknande insatser, men på olika vis. De slutsatser vi drar av resultatet är att individer med ADHD och AST har avvikelser i hjärnans funktioner samt dess nervsystem vilket beror på biologiska orsaker. Slutsatserna av de pedagogiska implikationerna gör sig gällande för övergripande områdena inom miljö, visuella hjälpmedel, struktur, bemötande samt uppgifters upplägg. Vi ser genom analysen även ett samband mellan de annorlunda funktionerna i hjärnan hos elever med ADHD och AST och vilka metoder som föreslås vara mest gynnsamma för kunskapsinhämtning. / The purpose of this literature study is an attempt to generate theory for how the special education can benefit from the research results regarding how the brain's functions work in connection with learning in ADHD (attention deficit hyperactivity disorder) and/or autism spectrum disorder (AST). The method chosen for this study is a qualitative literature study, where the results have been analyzed according to Grounded Theory. We have taken part of relevant research and literature regarding brain functions and the educational field for individuals with ADHD and ASD aged 6-16 years. The result regarding brain functions shows that the basis for ADHD and ASD is biologically determined, but the diagnoses should still not be defined as a disease but as a functional variation. The result regarding the pedagogical implications shows in several possible ways how to adapt the teaching and learning to support and help these students. The literature describes in part how they detect links between brain functions and the difficulties that students with ADHD and ASD may face in the school environment. Many similarities emerge in the literature regarding the implications proposed for students with ADHD and ASD and they benefit from similar efforts, but in different ways. The conclusions of the results regarding brain function of individuals with ADHD and ASD reveal that they have abnormalities in the brain's functions and its nervous system and are due to biological causes. The conclusions of the pedagogical implications apply to the overall areas within the environment, visual aids, structure, teacher’s response, and tasks. Through the analysis, we also see a connection between the different functions in the brain of students with ADHD and ASD and which methods are proposed to be most favorable for acquiring knowledge.

<p>  </p> <p><em>Syngap1+/-</em> is a mouse mode for intellectual disability and autism spectrum disorder where haploinsufficiency of the <em>Syngap1</em> gene and therefore downregulation of SynGAP1 leads to early maturation of synapses within the brain within post-natal days fourteen and sixteen instead of at the normal developmental schedule of post-natal day thirty. This early-shifted timeline falls directly before the visual critical where binocular matching between inputs from the two eyes occurs, and during a period where neurons become selective to specific orientations. High-level visual and cognitive issues observed in autism spectrum disorder patients might follow from deficits in basic sensory processing development, but it is not yet understand how <em>Syngap1</em> haploinsufficiency affects visual development and visual processing. Therefore, to characterize visual processing within the <em>Syngap1+/-</em> mouse model of autism spectrum disorder, acute electrophysiological recordings were performed within the monocular and binocular regions of the mouse visual cortex (V1). Responses to a series of visual stimuli were analyzed to measure and compare receptive field size, orientation selectivity, and binocularity between <em>Syngap1+/-</em> mice and littermate controls. In order to understand how potential deficits in physiology could translate into visual perception, a behavioral training protocol was implemented which isolated visual acuity in mice. In accordance with known developmental timelines in the visual cortex, it was found that the receptive field sizes of V1 neurons in <em>Syngap1+/-</em> mice were unchanged from wild type controls. However, these same neurons had wider tuning curves and lower firing rates than neurons in littermate controls. Ocular dominance was unaltered between <em>Syngap1+/-</em> and wild type mice, but this was possibly due to low sample sizes of neurons from the binocular regions of V1. At the behavioral level, lower visual acuities were discovered in <em>Syngap1+/-</em> mice with a size degree difference compared to littermate controls – a minor but significant difference. These results indicate a reduction in SynGAP1 expression has a perceivable effect on V1 development and function at both physiological and behavioral levels.</p>

Autism has no cure, but early and appropriate diagnosis and intervention may increase outcomes for individuals affected. The level of awareness, acceptance, and support for autism spectrum disorder (ASD) in Nigeria is very low. There is a gap in the literature regarding a detailed account of the experiences of parents raising children with ASD within the Nigerian environment and culture. The purpose of this phenomenological study was to explore the perceptions and lived experiences of mothers raising children with ASD in Nigeria including the impact of Nigerian culture on their experiences. Bronfenbrenner’s ecological systems theory was the guiding conceptual framework for this study. Ten mothers of children with autism were recruited through purposeful sampling and interviewed using a semistructured interview format. Moustakas’s steps to phenomenological research analysis were used to analyze the data and report emergent themes. The 8 themes that emerged from the data were low societal awareness about ASD, cultural attitudes and acceptance about ASD, neglect and abuse, inadequate services, impact on parents and other family members, refusing to be isolated by society, nature of support, and the way forward. The findings of this study can contribute to ASD awareness in Nigeria through the experiences reported. Positive social change may result from this increased awareness including improved acceptance and treatment, and policy changes or service improvements to support families living with this disorder in Nigeria.

Young adults with Autism Spectrum Disorder (ASD) face unique social skills challenges as they transition into independent living environments and seek fulfilling relationships within their communities. Research has focused on social education and interventions for children with autism, while transitioning young adults with ASD have received insufficient attention. The purpose of this multisite case study was to explore perceptions of school personnel related to the use of visual support system (VSS) technology and enhancement of social skillsets for young adults with ASD. Information processing theory and social learning theory provided the research framework. Research questions addressed perceptions related to the utility of VSS technology and social skills teaching strategies. Interviews were conducted with 11 special education administrators, teachers, and intervention specialists from 3 different programs in the United States. Data from interviews and field notes were analyzed using open, axial, and selective coding; themes such as social skills, video-modeling, learning strategies, use of visual technology, and cognition emerged. Participants indicated that exploring cognitive learning strategies underpinned with VSS technology provided alternative methods to teach social skills in classroom settings. They identified the need for more funding for VSS technologies for all learners. Implications for social change include that social skills and critical thinking skills can be enhanced by learning through the use of VSS technology. Empowering young adults with ASD to participate with greater confidence in learning situations and in social situations will support their efforts to be more comfortable and to interact more appropriately in work and community interactions.