The purpose of this study is to examine the experiences some teachers in preschool have of how the social interaction looks like in play of children with autism spectrum disorder. The study relied on the following questions:   • How do teachers describe their experiences of children within the autism spectrum disorder? • How do teachers describe these children's social interaction in play? • How do teachers talk about how play is designed in preschool to promote social interaction among children with autism spectrum disorder?   To be able to answer the questions above, qualitative semi-structured interviews have been used. Four interviews have been conducted with active teachers in preschool who all have experience with children with autism spectrum disorder.   Results from this study shows that teachers' have experience of that social interaction in play is difficult for children with autism spectrum disorder. In play they do not seem to experience self-comfort in comparison with other children. They often play next to each other rather then together. At the same time teachers' experiences shows that play can work if the right support is given.   Keywords Autism spectrum disorder, social interaction, play, preschool, preschool teacher.

Cette thèse a eu pour objectif de contribuer à la compréhension de deux troubles du langage: ceux associés aux troubles du spectre autistique et la dyslexie. Les récentes avancées sur les mécanismes neuraux de segmentation acoustique du signal de parole indiquent le rôle majeur des oscillations qui offrent des fenêtres d'intégration temporelle à l'échelle de la syllabe et du phonème, unités linguistiques ayant un sens. À l'aide d'enregistrements simultanés d'EEG et d'IRM fonctionnelle durant la visualisation d'un film et au repos, nous avons étudié les rythmes corticaux auditifs et leur topographie chez des sujets sains, autistes et dyslexiques. Nous avons montré que les sujets dyslexiques et les sujets autistes montrent une sensibilité atypique à la structure syllabique et à la structure phonémique. L'activité gamma et l'activité thêta ne s'engagent pas de façon synergique dans l'autisme. L'activité thêta dans le cortex auditif gauche échoue à suivre les modulations de l'enveloppe temporelle du signal de parole dans l'autisme et à potentialiser l'activité gamma qui encode les détails acoustiques. Les troubles du langage dans l'autisme résultent d'une altération du couplage des oscillations lentes et rapides, perturbant le décodage neural du signal de parole. Dans la dyslexie, l'activité corticale auditive thêta n'est pas altérée, et l'activité de modulation de l'activité gamma par l'activité thêta préservée, rendant possible le décodage phonémique, bien qu'atypique. Dans les deux pathologies, ces altérations de l'activité oscillatoire dans le cortex auditif entraînent une altération de la connectivité fonctionnelle entre le cortex auditif et les autres aires du langage. / This research aimed to better understand two language disorders : those associated with autism spectrum disorder and dyslexia. Recent advances indicate how cortical collective neural behaviour intervene in speech segmentation and decoding. Cortical oscillations allow integration temporal windows at syllabic (4-7 Hz) and phonemic (25-35 Hz) time scale, resulting in chunking continuous speech signal into linguistically relevant units. We measured slow fluctuations of rhythmic cortical activity and their topography in healthy subjects, in subjects with autism spectrum disorder and in dyslexic subjects using combined fMRI and EEG. We showed that the sensitivity to syllabic and phonemic density is atypical in dyslexia and in autism. In autism gamma and theta activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations and to down-regulate gamma oscillations that encode speech acoustic details. The language disorder in autism results from an altered coupling of slow and fast oscillations that disrupts the temporal organization of the speech neural code. In dyslexia, theta activity is not altered and theta-paced readout of gamma activity is preserved, enabling the phonemic decoding, even atypical (faster). In both pathologies, auditory oscillatory anomalies lead to atypical oscillation-based connectivity between auditory and other language cortices.

La neurohormone ocytocine (OT) est de plus en plus étudiée pour son potentiel thérapeutique dans les troubles du comportement social, comme l'autisme, qui sont associés à une dérégulation de plusieurs systèmes de neurotransmission, notamment l'OT et la sérotonine (5-HT). Dans ce cadre, une étape importante afin de développer des médicaments basés sur des mécanismes biologiques est de caractériser les interactions entre l'OT et les autres neurotransmetteurs. La littérature sur les rongeurs montre que la relation entre OT et 5-HT est fortement impliquée dans plusieurs aspects du comportement social. Par ailleurs, nous avons récemment montré chez le sujet sain que le fonctionnement du récepteur 5-HT 1A (5-HT1AR) est modifié suite à l'administration d'OT.neuroJ'ai donc réalisé une première expérience chez des patients autistes en utilisant le scanner TEP avec le radiotraceur [18F]MPPF (spécifique du 5-HT1AR). Aucune différence n'est apparue, à l'état basal, entre 18 patients autistes et 24 sujets contrôles. Par ailleurs, l'OT n'a pas modifié le système 5-HT1AR. Enfin, alors qu'une corrélation entre la densité de 5-HT1AR et le volume de matière grise du striatum a été observé dans le groupe contrôle, cette relation était absente dans le groupe de patients. Ces résultats suggèrent une altération subtile du 5-HT1AR, ne pouvant être détectée qu'au niveau fonctionnel.Parce que le scanner TEP ne permet pas de dire si les changements observés sont dus à une libération de sérotonine ou à une modification directe du récepteur, j'ai réalisé une deuxième expérience chez 3 macaques rhésus, avec le [18F]MPPF et le [11C]DASB (marquant le transporteur de la 5-HT). Par rapport au placebo, l'OT injectée dans le ventricule latéral a significativement augmenté la liaison du [18F]MPPF dans l'amygdale et l'insula tandis que la liaison du [11C]DASB diminuait dans ces mêmes régions. Ainsi, nous pouvons dire que l'OT a provoqué la libération de 5-HT ainsi qu'une modification du 5-HT1AR dans ces régions importantes pour les comportements socio-émotionnels. Une étude par autoradiographie a confirmé cette interprétation.Ces expériences montrent qu'il existe une action régulatrice de l'OT sur la 5-HT chez le primate, mais que ce mécanisme est dérégulé chez les patients avec autisme. Cela ouvre donc la voie à l'investigation de traitements combinés exerçant un effet sur ces deux neurotransmetteurs / The neurohormone oxytocin (OT) is increasingly studied for its therapeutic potential in social disorders, like autism, which are associated with the deregulation of several neurotransmission systems, including OT and serotonin (5-HT). Hence investigating OT’s interactions with other neurotransmitters is a relevant step towards mechanism-based treatments. Studies in rodents demonstrated that the interaction between OT and 5-HT, is critical for several aspects of social behaviour. Moreover, using PET-scan in humans we have recently found that 5-HT 1A receptor (5-HT1AR) function is modified after intra-nasal oxytocin intake. Thus I performed a first experiment in which intra-nasal OT was administered to patients with autism undergoing a [18F]MPPF (a 5-HT1AR radiotracer) PET scanner, in order to study their basal serotonergic system and to look if the oxytocin modulates the 5-HT1AR system. I found no differences of baseline 5-HT1AR concentration between 18 autistic subjects and 24 controls. Critically, in patients, OT did not induce changes on the 5-HT1AR system. Moreover, in controls, there was a correlation between 5-HT1AR and grey matter volume in the striatum, that was not observed in patients. These results suggest a subtle disruption of patients’ serotonergic system, that can only be seen at the functional level. Because PET scan does not tell us if the observed modification is due to a change in 5-HT1AR or 5-HT concentration, I performed a second PET scan experiment on 3 macaque monkeys, using [18F]MPPF and [11C]DASB, that marks the serotonin transporter. Compared to placebo, OT injections in the lateral ventricle significantly reduced [11C]DASB binding potential in right amygdala, insula and hippocampus whereas [18F]MPPF binding potential increased in right amygdala and insula. Thus we reproduced results obtained in healthy humans and extended it by suggesting that OT provokes the release of 5-HT in key limbic regions involved in socio-emotional processing. These results were confirmed with autoradiography.Taken together, these experiments indicate that OT modulates 5-HT release in primates, but this mechanism is disrupted in patients with autism. This opens ways to investigate combined OT/5-HT treatments, especially since FDA approved drugs targeting the two systems are already available for use in patients with autism

In this thesis, we propose a Serious Game (SG) for children with the Autism Spectrum Disorder (ASD) that builds on the concept of LEGO®-Based Therapy that is aimed at improving social and cognitive skills. The proposed SG is composed of building blocks augmented with electronic modules that connect to a computing device that provides visual feedback. We investigate the effects of using the proposed computer SG by comparing it to a non-computer block-game during two empirical studies, one following an unstructured play approach and a second one with structured play by assigning roles to the players. For the first study, the proposed system showed an improvement in social interaction, collaborative play and exercise performance, as well as a decrease in solitary play. For the second study, the proposed system showed an improvement in social interaction, positive vocalizations and exploratory behavior. There was also a marked preference towards the proposed game. Furthermore, we perceived a decrease on the assistance needed when using the proposed system during both studies. Our results suggest that the proposed system can be a useful play therapy tool aimed for young children with ASD.

O transtorno do espectro autista (ASD) é uma doença clinica e geneticamente heterogênea, com mecanismo etiológico ainda pouco conhecido. Assim, os principais objetivos deste trabalho foram descrever as características clínicas e genéticas de pacientes brasileiros com ASD, bem como determinar o risco de recorrência e a herdabilidade. Verificamos que a maioria das comorbidades avaliadas tem prevalência similar àquelas anteriormente descritas. A hipotonia exibiu maior prevalência no sexo feminino. A ausência de fala apresentou prevalência significativamente maior no grupo de pacientes com comorbidades, sendo que a gravidade da fala foi positivamente correlacionada com a presença das crises convulsivas. A herdabilidade estimada foi de 76% e o risco de recorrência ~5%. As alterações citogenéticas e os casos positivos para a Síndrome do X-Frágil explicaram cerca de 8% dos casos de ASD da nossa amostra. As CNVs nas regiões estudadas foram detectadas em 2,7% da amostra. Nós verificamos que há penetrância incompleta do ASD para as regiões. O estudo mais detalhado dos dois casos de duplicação da região 15q13.3, envolvendo somente o gene CHRNA7, mostrou que um dos pacientes (F5240) exibiu uma segunda CNV, possivelmente patogênica. A análise in silico sugeriu que genes que interagem diretamente com o CHRNA7 podem conter mutações patogênicas e, juntamente com a duplicação do 15q13.3, possivelmente estão envolvidos na etiologia do ASD. Este estudo mostrou que é necessário fazer uma ampla caracterização genética dos pacientes, para possibilitar o estudo dos possíveis mecanismos moleculares envolvidos na causa do ASD / Autism Spectrum Disorder (ASD) is a clinically and genetically heterogeneous disease and its etiological mechanisms are still poorly understood. The main objectives of this study were to describe the clinical and genetic features of Brazilian patients with ASD, and to determine the recurrence risk and heritability. Great part of the comorbidities assessed here had comparable prevalence to those of previous works. The hypotonia was significantly prevalent in the female sex. Absent speech was significantly more frequent in patients with comorbidities, and severity of speech problems was positively correlated with presence of seizures. Heritability was estimated as 76% and the recurrence risk as approximately 5%. Cytogenetic alterations and positive results for Fragile X Syndrome explain about 8% of the ASD etiology of our sample. The CNVs at the chromosomal regions 15q11-q13, 16p11.2 and 22q13 were present in 2.7% of the sample. Incomplete penetrance of ASD was observed for the 16p and 15q regions. Further investigation of the two cases with duplication of the region 15q13.3, involving only the CHRNA7 gene, revealed that one of them (F5240) exhibited a second possible pathogenic CNV. In silico analysis suggested that genes interacting directly with the CHRNA7 could harbor pathogenic mutations and, together with the duplication at 15q13.3, could be involved in the ASD etiology. This study showed the necessity of a broad genetic characterization of patients with ASD, to enable the elucidation of possible molecular mechanisms related to ASD etiology

Since the start of 2019 a new law has been introduced in Sweden, it serves to regulate web accessibility conformity for all publicly funded organisations. At the same time, many services and businesses move their physical fronts to the web. With more digitalization comes a greater need for web accessibility and there might be a risk that users with cognitive disabilities are neglected or forgotten when new and advanced tools and technologies are developed. Accessibility often receives low or no priority in the private sector due to the lack of time and resources. Cognitive disabilities do not always show and there is a risk that the difficulties are not taken into account when services or webpages are developed. These disabilities can affect areas such as the ability to learn new things, memory and the ability to plan one's actions. The purpose of this study is to investigate if there is any knowledge and experience among Swedish developers concerning accessibility, cognitive disabilities and the needs those individuals might have. To perform this study the needs had to be identified and connected to the standard that acts as a base for the new Swedish law. For this purpose, theory was gathered through a literature study as a foundation for a qualitative study consisting of a series of interviews with developers from six different organisations in the Swedish private sector. The interview subjects were selected from different organisations so that their views and opinions would not be affected by one and other for the purpose of increasing the studies generalizability. The interviews were held at locations selected by the interviewees by two different interviewers. The result from the literature study showed that there was no direct support for cognitive disabilities in the standard, but there are guidelines that could be applied to some of the needs identified in the study. Furthermore, the results of the interviews showed that the general knowledge and experience concerning accessibility and specifically cognitive accessibility is very low among Swedish developers. This study is aimed towards people working with development but is also suitable for students and teachers who wish to know more about accessibility and cognitive accessibility.

Autism Disorder and related disorders such as Asperger's Syndrome and Pervasive Developmental Disorder, Not Otherwise Specified, are collectively known as Autism Spectrum Disorders (ASD). These disorders are currently the fastest growing diagnosed disorders among children and have been found in 110 in 10,000 individuals. Individuals with ASD are delayed in social development according to diagnostic criteria. To address the social development delays of students with ASD, two research-based interventions have been developed: Social StoriesTM and video modeling. Social StoriesTM uses a specific combination of sentences to describe a social situation or a social skill in story form. Video modeling is an isolation of social skill steps delivered through a video medium to model the social skill. The purpose of this study was to combine Social StoriesTM and video modeling (combined intervention) and investigate the perceptions of educational multidisciplinary team members (school counselors, parents, teachers) regarding the combination intervention for the development of social behavior in students with ASD. School counselors participating in this study delivered the combination Social StoriesTM and video modeling intervention to student participants with ASD. Then, the perceptions of the school-based multidisciplinary team members of this combination intervention were collected through qualitative surveys and analyzed to develop the Qualitative Criticism. This Qualitative Criticism describes, interprets, and evaluates the pragmatic use of the combination of the Social StoriesTM and video modeling intervention with students with ASD in schools from the perspectives of the school counselors, teachers, and parents of these students. Organized by case, team members of each of the student participants reflected on the strengths and weaknesses of these interventions for that student. Across cases, comments were analyzed by role (i.e., parent, teacher, school counselor). Then, these roles were combined into a cross-case analysis of multidisciplinary team perspectives of the usefulness of these interventions for students with ASD. Pre-test and post-test data were collected using teachers' responses to the Vineland II Teacher Rating Form (V-II TRF) and the Summary of Observations section on the V-II TRF to triangulate findings grounded in the qualitative data. Findings suggested that parents, teachers, and school counselors supported the use of these interventions for several reasons. The combination intervention increased opportunities for repetition of the target skills; for visual learning through written words in stories, cartoons, and videos; and for individualization to meet the varying needs and interests of students with ASD. The intervention was also developmentally appropriate, engaging, and fun for students. In addition, when the school counselor collaborated with parents and teachers through the intervention, the parents and teachers seemed to be more knowledgeable about the intervention, and supported these students to use the intervention and generalize the target skills. While V-II TRF scores did not show statistically significant gains to confirm the multidisciplinary team members' support for the combination intervention, clinical significance was found in the domain scores of Communication and Daily Living, and in the Composite score measuring overall adaptive functioning.

Les Troubles du Spectre Autistique (TSA) forment un groupe hétérogène de troubles neurodéveloppementaux caractérisés par des déficits de l’interaction sociale et de la communication ainsi que la présence de comportements répétitifs et d’intérêts restreints. Les TSA affectent environ un individu sur 68. Ils se manifestent généralement durant les trois premières années de vie mais, pour certains cas, les symptômes sont reconnus plus tard, quand les exigences sociales augmentent. Les études de jumeaux et la récurrence des troubles dans certaines familles démontrent l’importance des facteurs génétiques dans la vulnérabilité aux TSA. Cependant, l’architecture génétique des TSA reste difficile à caractériser car elle est extrêmement hétérogène et il est très compliqué d’identifier, pour chacun des patients, la combinaison d’allèles à risque. Notre laboratoire a identifié la première voie génétique associée aux TSA – la voie NLGN-NRXN-SHANK- qui joue un rôle clé dans la plasticité synaptique. Il existe un nombre de plus en plus grand de gènes associés aux TSA mais peu d’études ont été réalisées sur des cohortes épidémiologiques et dans des populations isolées. L'analyse des données de génotypage et de séquençage d’exome de 357 individus issus des îles Féroé (36 patients, 136 apparentés des patients, 185 témoins) nous a permis de mettre en évidence un nombre plus important de Variations du Nombre de Copies (CNVs), un coefficient de consanguinité supérieur, un plus grand nombre de mutations homozygotes et délétères ainsi qu’un Polygenic Risk Score (ASD-PRS) supérieur chez les patients TSA comparés aux individus témoins. Notre analyse confirme le rôle de plusieurs loci associés aux TSA (NRXN1, ADNP, délétion 22q11) et a permis d’identifier de nouvelles mutations tronquant la protéine (GRIK2, ROBO1, NINL et IMMP2L) ou récessives (KIRREL3 et CNTNAP2) affectant des gènes déjà associés aux TSA. Nous avons également mis en évidence trois nouveaux gènes candidats jouant un rôle important dans la plasticité synaptique (RIMS4, KALRN et PLA2G4A) à travers la présence de mutations de novo délétères chez des patients sans déficience intellectuelle. Au total, nous avons pu identifier une cause génétique expliquant les TSA pour 11% des patients et au moins une mutation fortement délétère dans des gènes candidats chez 39% des patients. Aucune cause génétique n'a pu être trouvée chez 50% des patients. En résumé, notre étude permet de mieux comprendre l’architecture génétique des TSA dans les populations isolées en soulignant à la fois l'impact des variants communs et des variants rares mais également en révélant le rôle de nouveaux gènes pour les TSA. Ces gènes codent pour des protéines essentielles pour le neurodéveloppement et l’identification de ces facteurs impliqués dans la formation et l'entretien des synapses pourrait ainsi fournir de nouvelles pistes afin de mieux comprendre les bases biologiques des TSA et de découvrir de nouvelles stratégies thérapeutiques. Il est cependant nécessaire de comprendre plus avant l'impact de la combinaison de différentes mutations sur la fonction neuronale afin de mieux caractériser l’architecture génétique des TSA. / Autism Spectrum Disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as the presence of repetitive behaviors and restricted interests. ASD affects approximately one in 68 individuals. They usually occur during the first three years of life but, in some cases, symptoms are recognized later, when social demands increase. There is a strong genetic component to ASD, as indicated by the recurrence risk in families and twin studies. However, the genetic architecture of ASD remains largely unknown because of its extreme heterogeneity. It is very challenging to identify, for each patient, the combination of risk alleles. Our laboratory identified the first genetic pathway associated with ASD – the NLGN-NRXN-SHANK pathway – playing a key role in synaptogenesis during development. There are an increasing number of genes associated with ASDs but few studies have been conducted on epidemiological cohorts and isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 patients with ASD, 136 of their relatives and 185 non-ASD controls. Data from SNP array and whole exome sequencing revealed that patients had a higher burden of copy-number variants, higher inbreeding status, higher load of homozygous deleterious mutations, and a higher ASD polygenic risk score compared to controls. We confirmed the role of several ASD-associated loci (NRXN1, ADNP, 22q11 deletion) and identified new truncating (GRIK2, ROBO1, NINL and IMMP2L) or recessive variants (KIRREL3 and CNTNAP2) affecting genes already associated with ASD. We have also identified three novel candidate genes playing key roles in synaptic plasticity (RIMS4, KALRN and PLA2G4A) carrying deleterious de novo mutations in patients without intellectual disability. Overall, for 11% of individuals with ASD, a known genetic cause was identified, for 39% at least one strongly deleterious mutation was identified in a compelling candidate gene and for 50% no obvious genetic cause was detected. In summary, our study provides a better understanding of the genetic architecture of ASD in isolated populations by highlighting both the impact of common and rare variants but also by revealing the role of new genes for ASD. These genes code for proteins that are essential for neurodevelopment. The identification of these factors involved in synapse formation and maintenance could provide new leads to better understand the biological basis of ASD and find novel therapeutic strategies. However, it is necessary to further understand the combined impact of different mutations on neuronal function in order to better characterize the genetic architecture of ASD.

The aim of this master’s thesis is to study how a group of people diagnosed with autism spectrum disorder experience a visit to the library. By interviewing them I hoped to hear their thoughts on noise, lighting and the over all library environment. Did the informants get a fair treament by the library staff or did they feel stigmatized? The thesis is also aiming to expose how accessible the libraries’ websites are. Two librarians shared their insights about accessibility from the library in which they work. The interview showed there are still many aspects that need to improve until the library is autism friendly. The study shows that the informants prefer a silent library compared to a noisy one. They did not experience any stigmatization in the library. The informants use the digital services offered by the library in order to renew their books and to request new ones. However, the websites are not customized for people with Austism spectrum disorder. The informants main concern when visiting the library are loud noise and insufficient signs. This study is a two years master’s thesis in Library and Information Science.

Despite the growing interest for autistic users within the field of Human-Computer Interaction (HCI), the research is mostly limited to assistive technology and often neglects autistic users' own perspectives. Exploring autistic users’ experiences of different mainstream technologies that they use may give valuable knowledge. Using Instagram as a case for a qualitative study with 30 autistic adults, this paper contributes with such knowledge and in the process, it challenges preconceptions about autism that are common in HCI-research. Data from interviews and a survey (N=30) is analysed in the context of previous research and design concepts, discussing the implications for design and future research. Findings show that autistic users' needs are often similar to those of users in general, but may be more pronounced, and that if design recommendations are to be useful, researchers need to take the diversity within the autistic population into account more than is currently done.