Made available in DSpace on 2016-03-15T19:40:52Z (GMT). No. of bitstreams: 1 Jael Breitschwerdt.pdf: 952030 bytes, checksum: 787f5cd0ef86094489b72b510635ffc9 (MD5) Previous issue date: 2010-06-08 / Fundo Mackenzie de Pesquisa / The aim of this study was to evaluate early signs of Autism Spectrum Disorders, using retrospective video analysis. The participants were eight children later diagnosed with ASD and eight children with typical development. Home videos of the participants were collected from families, at the ages 12, 24 and 36 months. Videos were edited and then analysed by two ASD specialists. The behaviors: Eye Contact; Facial Expression; Play behavior/ Imitation; Communication; Joint Attention and Repetitive Behaviors, were analysed. The results suggest that early signs such as, deficits in Communication, Play behavior, Imitation and Repetitive behaviors, can be detected in infants at 24 months. Most importantly, findings indicate that deficit in Joint Attention was the most discriminating sign of children with ASD, as early as 12 months. / O objetivo desta pesquisa foi avaliar sinais precoces dos Transtornos do Espectro Autista, por meio da observação de vídeos. Os participantes foram oito crianças diagnosticadas com TEA e oito crianças com desenvolvimento típico, nas idades 12, 24 e 36 meses. Os comportamentos: Contato Visual; Expressão Facial/Sorriso Social; Brincadeiras/Imitação; Comunicação; Atenção Compartilhada; Comportamentos Estereotipados, foram analisados e classificados por dois especialistas. Os resultados sugerem que sinais como disfunções na Brincadeira/Imitação, Comunicação e Comportamentos Estereotipados podem ser detectados a partir de 24 meses de idade. Déficits na Atenção Compartilhada foi o sinal que mais discriminou as crianças com TEA das crianças com desenvolvimento típico, já aos 12 meses de idade.

Objectives: Within the last decade there has been growing emphasis on early diagnosis of autism. It has been proved, that early diagnosis of autism followed by an appropriate intensive intervention lead to the reduction of autistic psychopathology and significant improvement of the child's prognosis. Efforts to identify children at risk of autism as early as possible resulted in the development of many screening tools and some new diagnostic methods that could be used even before the age of two years. Despite many attempts of the researchers worldwide, we still lack general agreement on the optimal screening method. Abnormal sensory symptoms have a specific position among the early signs of autism. Difficulties with sensory processing have been associated with autism since it was first defined as a diagnosis; nevertheless evaluation of sensory symptoms is under-represented in autism screening tools. There has been a long lasting debate whether sensory symptoms are a component of core autistic deficits or a co-morbid phenomenon, however, new version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has already included sensory dysfunction among the diagnostic criteria of Autism Spectrum Disorder. Methods: Over 90% of children with autism have sensory abnormalities and present with...

La perception de notre environnement repose sur les informations sensorielles reçues, mais aussi sur nos a priori. Dans le cadre Bayésien, ces a priori capturent les régularités de notre environnement et sont essentiels pour inférer les causes de nos sensations. Récemment, les théories du cerveau Bayésien ont été appliquées à l'autisme pour tenter d'en expliquer les symptômes. Les troubles du spectre de l'autisme (TSA) sont caractérisés par des difficultés de compréhension des interactions sociales, par des comportements restreints et répétitifs, et par une perception sensorielle atypique.Cette thèse vise à caractériser l'inférence et l'apprentissage perceptifs dans les TSA, en étudiant la sensorialité et la construction d'a priori. Nous avons utilisé des tests comportementaux, des modèles computationnels, des questionnaires, de l'imagerie fonctionnelle et de la spectroscopie par résonnance magnétique chez des adultes avec ou sans TSA. La définition des profils sensoriels de personnes avec des hauts quotients autistiques a été affinée grâce à un questionnaire dont nous avons validé la traduction française. En explorant les stratégies d'apprentissage perceptif, nous avons ensuite montré que les personnes avec TSA étaient moins enclines à spontanément utiliser une mode d'apprentissage permettant de généraliser. L'étude de la construction implicite des a priori a montré que les personnes avec TSA étaient capables d'apprendre un a priori, mais l'ajustaient difficilement suite à un changement de contexte. Enfin, l'étude des corrélats neurophysiologiques de l'inférence perceptive a révélé un réseau cérébral et une neuromodulation différents dans les TSA.L'ensemble de ces résultats met en lumière une perception atypique dans les TSA, marquée par un apprentissage et une pondération anormale des a priori. Une approche Bayésienne des TSA pourrait améliorer leur caractérisation, diagnostics et prises en charge / How we perceive our environment relies both on sensory information and on our priors or expectations. Within the Baysian framework, these priors capture the underlying statistical regularities of our environment and allow inferring sensation causes. Recently, Bayesian brain theories suggested that autistic symptoms could arise from an atypical weighting of sensory information and priors. Autism spectrum disorders (ASD) is characterized defined by difficulties in social interactions, by restricted and repetitive patterns of behaviors, and by an atypical sensory perception.This thesis aims at characterizing perceptual inference and learning in ASD, and studies sensory sensitivity and prior learning. This was investigated using behavioral tasks, computational models, questionnaires, functional magnetic resonance imaging and magnetic resonance spectroscopy in adults with or without ASD. Sensory profiles in people with high autism spectrum quotients were first refined, using a questionnaire that we validated in French. The study of perceptual learning strategies then revealed that subjects with ASD were less inclined to spontaneously use a learning style enabling generalization. The implicit learning of priors was explored and showed that subjects with ASD were able to build up a prior but had difficulties adjusting it in changing contexts. Finally, the investigation of the neurophysiological correlates and molecular underpinnings of a similar task showed that perceptual decisions biased by priors relied on a distinct neural network in ASD, and was not related to the same modulation by the glutamate/GABA ratio.The overall results shed light on an atypical learning and weighting of priors in ASD, resulting in an abnormal perceptual inference. A Bayesian approach could help characterizing ASD and could contribute to ASD diagnosis and care

Recent genome-wide sequencing projects revealed the pervasive transcription of intergenic long noncoding RNAs (lincRNAs) in eukaryotic genomes (reviewed in Ponting et al. 2009). For the vast majority of lincRNAs, their mechanisms of function remain largely unrecognized. However, the genome-wide signatures of functionality associated with many lincRNAs, including apparent evolutionary sequence conservation, spatial and temporal-restricted expression patterns, strong associations with epigenetic marks, and reported molecular and cellular functions, reinforce their biological relevance. My work investigates lincRNAs that post-transcriptionally regulate gene abundance by competing for the binding of common microRNAs (miRNAs) with protein-coding transcripts, termed competitive endogenous RNAs (ceRNAs) acting lincRNAs (lnceRNAs). First, I examine the biological relevance of this post-transcriptional regulation of gene abundance by ceRNAs. Next, I estimate the genome-wide prevalence of lnceRNAs in mouse embryonic stem cells (mESCs) and characterize their properties. Finally, using two specific examples of lnceRNAs, I show the contributions of lnceRNAs to human monogenic and complex trait diseases. Collectively, these results illustrate that lnceRNAs provide a novel layer of post-transcriptional regulation via a miRNA-mediated mechanism that contributes to organismal and cellular biology.

Bien que reconnue comme critique pour le devenir socio-professionnel desenfants avec Troubles du Spectre Autistique (TSA), l’inclusion scolaire en classeordinaire demeure en France peu acces- sible pour ce public. En effet, lefonctionnement cognitif atypique associé aux limitations des comportements socioadaptatifs(communication, socialisation, autonomie etc.), se heurte bien souvent auxconditions normées des milieux ordinaires tels que l’école. Les nouvelles technologiessont aujourd’hui pressenties comme leviers prometteurs pour surmonter ces barrières àl’inclusion scolaire. Cependant, malgré un marché pléthorique de technologies ciblantles TSA, les études scientifiques manquent pour statuer sur leur efficacité mais aussisur les fondements mêmes de leur conception.Ce travail présente la conception et la validation d’applications mobiles pourl’inclusion scolaire d’enfants avec TSA en classe ordinaire au travers de trois études.Dans une approche centrée- utilisateur, l’Étude 1 présente des principes de conceptiond’applications d’assistance aux activités de classe et activités communicationnelles desenfants avec TSA pour une utilisation in situ. Dans une approche centrée utilisateur etde recherche clinique pilote, l’Étude 2 présente les principes de conception et lavalidation expérimentale d’une application d’assistance à la régulation émotionnelledes enfants TSA en classe ordinaire. Les résultats indiquent des bénéfices sur lescomportements d’auto-régulation ainsi que sur les processus sociocognitifs sousjacents.Enfin, dans une approche cross-syndromes, l’Étude 3 présente les résultatsd’une intervention globale reposant sur des ap- plications d’assistance et deremédiation cognitives (dispositif Collège+) déployées auprès de 48 enfants et visant àsoutenir la primo-inclusion en classe ordinaire d’enfants avec TSA et d’enfants nonTSA (avec Déficiences intellectuelles ou troubles globaux de l’apprentissage). Desbénéfices sont rapportés pour tous les enfants équipés en termes de comportementssocio-adaptatifs, de réponse sociale et de fonctionnement sociocognitif. Aussi, de pluslarges bénéfices sont observés pour les enfants TSA révélant ainsi la pertinence del’intervention Collège+ pour le public avec TSA.En conclusion, un approche systémique dans la conception et l’expérimentationd’applications mobiles a permis des améliorations dans l’adaptation descomportements et du fonctionnement socio-cognitif, cruciaux dans la réussite d’uneinclusion scolaire en classe ordinaire. Cette approche semble donc prometteuse poursoutenir l’inclusion scolaire en milieu ordinaire des enfants avec TSA, et offre delarges perspectives de travail, tant sur l’enrichissement des contenus, la conception denouvelles applications que des méthodes de validation expérimentale. / School inclusion of children with Autism Spectrum Disorders (ASD) inmainstream classrooms remains dramatically limited in France, even though it hasbeen recognized as critical for socio- professional perspectives. In fact, the atypicalcognitive functioning, associated with socio-adaptive behavior difficulties(communication, social skills, autonomy, etc.), are usually confronted to nor- malizedexpectations in these mainstream environments, such as schools. New technologiescan be seen as promising levers to overcome the barriers of school inclusion.However, despite a plethoric offer of technologies for children with ASD, scientificstudies are lacking to establish their efficacy, as well as the relevance of their design.This work presents the design and validation of mobile applications to support schoolinclusion of children with ASD in mainstream classrooms through three studies. Thefirst study presents design principles for assistive applications addressing schoolroutines and verbal communication activities of children with ASD; these applicationsare to be used in situ. Combining a user-centered approach and pilot clinical research,the second study presents design principles and experimental validation of an emotionregulation application targeting children with ASD in mainstream classroom. Theresults reveal benefits on self-regulation behaviors, as well as underpinning sociocognitiveprocesses. Finally, in across-syndrome approach, the third study presents theresults of a global intervention, based on cognitive assistive and rehabilitationapplications, involving 48 children and supporting the first inclusion in mainstreamclassrooms of children with ASD and children without ASD (with IntellectualDisabilities or learning disabilities). Benefits are reported for both equipped groups interms of socio-adaptive behaviors, social response and socio-cognitive functioning.Larger benefits have been observed for equipped children with ASD, revealing therelevance of Collège+ intervention for this population.A systemic approach to designing and experimenting mobile applications allowed forimprove- ments in socio-adaptive behaviors and socio-cognitive functioning, crucialfor the success of main- stream school inclusion. Such approach seems promising tosupport school inclusion of children with ASD in mainstream classrooms, and offersbroad perspectives by enriching contents, designing new applications as well asexperimenting validation methodologies for mainstream environments.

O Distúrbio do Espectro do Autismo caracteriza-se como uma síndrome comportamental complexa, que compromete o processo do desenvolvimento ao longo da vida, ocorrendo uma grande variabilidade na intensidade e forma de expressão da sintomatologia, nas áreas que definem o seu diagnóstico. Pessoas com autismo necessitam de atenção especial durante toda a vida e é necessário voltar a atenção também para cuidador. O estresse parental da família de uma criança com autismo é significantemente maior do que o observado em famílias de crianças com desenvolvimento típico ou outras deficiências. A comunicação é um aspecto especialmente afetado nos quadros de autismo e pode ser potencializadora do estresse, sendo uma das primeiras preocupações dos pais. Assim foi indagado se, com relação à comunicação, o fato do filho com autismo não usar alguma fala para se comunicar teria relação com o aumento do nível de estresse dos pais. O Objetivo deste estudo foi investigar o nível de estresse de pais de crianças com autismo, verificando sua associação com a ausência de oralidade na comunicação de seus filhos. Participaram dessa pesquisa os pais de 75 crianças com autismo e pais de 100 crianças sem nenhuma queixa quanto ao desenvolvimento, que foram divididos em três grupos, sendo o grupo 1 formado por pais de crianças autistas que não apresentam comunicação oral; o grupo 2 por pais de crianças autistas que apresentam comunicação oral e o grupo 3, por pais de crianças sem nenhuma queixa. Todos os participantes responderam ao questionário sócio-demográfico, ao questionário de nível de estresse (formulado pela própria autora) e ao questionário de qualidade de vida. Os resultados mostraram que a maioria dos pais dos três grupos apresentaram médio nível de estresse e que não houve diferença significativa entre os pais de crianças com autismo, com e sem comunicação verbal. Quando os pais de crianças com autismo foram comparados aos pais do grupo controle, foi verificada diferença significativa, sendo que mais pais de crianças com autismo apresentaram alto nível de estresse. Foi constatada existência de associações entre o nível de estresse identificado e a qualidade de vida relatada pelos pais, mostrando que quanto maior o estresse apresentado pelos pais, menor é a qualidade de vida. Conclui-se, portanto, que o nível de estresse de pais de crianças com autismo não é influenciado pela ausência de oralidade na comunicação de seus filhos / Autism spectrum disorders are described as a complex behavioral syndrome. It impairs the development throughout life and has great variability in symptoms and intensity in the various areas that define the diagnosis. Persons with autism need special care during all life and therefore the caretakers need attention too. Parental stress in families with children with autism is significantly higher than the observed in families with children with other disorders or with typical development. Communication is specially affected in autism, is one of parent\'s first concerns and may increase stress. This study asked if parents of non-verbal children with autism have higher levels of stress than parents of verbal children with autism. The purpose of this study was to assess the stress levels of parents of children with autism and to verify its association with the abscess of verbal communication. Participants were parents of 75 children with autism and 100 parents with no complaints about their children development. They were divided in 3 groups: Group 1 comprised by parents by children with autism and no verbal communication; Group 2 comprised by parents by verbal children with autism and Group 3 with parents with no complaints about their children development. All participants responded to a socio-demographic questionnaire, to a stress level questionnaire (proposed by the author) and the questionnaire about quality of life. Results show that most parents from the three groups presented medium level of stress and that there was no significant difference between parents of children with autism with and without verbal communication. When parents of children with autism were compared with parents from the control group a significant difference was observed, with more parents of children with autism with high levels of stress. Associations between the stress level and the quality of life were also observed, showing that when higher stress levels were reported, lower quality of life was verified. It can be concluded that the stress level of parents of children with autism not influenced by their lack of verbal communication

Le cerveau contient environ cent milliards de cellules nerveuses, ou neurones. Ces neurones communiquent entre eux par des structures fonctionnellement distinctes – l’axone et la dendrite – capables d’émettre et recevoir des signaux électriques ou chimiques à partir d’un compartiment présynaptique vers un compartiment, dit post-synaptique. Nous avons focalisé notre étude sur les synapses des neurones hippocampiques, qu’on estime responsables de fonctions cérébrales dites supérieures, comme la mémoire et l’apprentissage. Plus particulièrement, on s’est intéressé au développement et au maintien des épines dendritiques, dont les changements morphologiques sont intimement liés à la plasticité synaptique, autrement dit, capacité de réponse à l’activité synaptique. Les épines dendritiques ont pour origine les filopodes qui évoluent en épines lors du contact axonal. La transition entre filopode et épine implique une myriade de molécules, dont des récepteurs glutamatergiques, des protéines d’échafaudage et du cytosquelette d’actine capables de recevoir, transmettre et intégrer le signal présynaptique. Cependant, la coordination spatiale et temporelle de tous ces composants moléculaires au long de la formation et maturation d’une synapse reste largement méconnue.Scribble1 (Scrib1) est une protéine de polarité cellulaire (PCP) classiquement impliquée dans l’homéostasie de tissues épithéliaux ainsi que dans la croissance et progression des tumeurs. Scrib1 est aussi une protéine d’échafaudage critique pour le développement et le bon fonctionnement du cerveau. L’objectif de cette étude a donc été d’étudier les mécanismes moléculaires sous-jacents à un rôle potentiel de Scrib1 dans la formation et le maintien des synapses. Dans un premier temps, on a décrit l’importance d’interactions dépendantes des domaines PDZ sur le trafic des récepteurs glutamatergiques ainsi que sur la voie de signalisation de plasticité synaptique sous-jacente à la mémoire spatiale. Dans un second temps, nous avons évalué les conséquences fonctionnelles d’une mutation de Scrib1 récemment identifiée chez un patient humain atteint des troubles du spectre autistique (TSA) dans la morphologie et fonction des neurones. On a démontré que Scrib1 régule l’arborisation dendritique ainsi que la formation et le maintien fonctionnel des épines dendritiques via un mécanisme dépendent du cytosquelette d’actine. Le dérèglement de ces mécanismes pourrait être à l’origine du phénotype TSA. L’ensemble de ce travail met en évidence que Scrib1, protéine d’échafaudage clé dans le développement et la fonction du cerveau, joue une multitude de rôle du niveau subcellulaire au niveau cognitif. / The brain is made up of billions of nerve cells, or neurons. Neurons communicate with each other through functionally distinct structures - the axon and the dendrite - which are able to release and receive an electrical or chemical signal from a pre- to a post-synaptic compartment, respectively. We focused our study on hippocampal neurons synapses, which ultimately underlie high-order brain functions, such as learning and memory. In particular, we studied the development and maintenance of dendritic spines, whose changes in morphology are intimately correlated with synaptic plasticity, or the ability to respond to synaptic activity. Dendritic spines originate from motile dendritic filopodia, which mature into spines following axonal contact. The filopodia-to-spine transition involves a plethora of molecular actors, including glutamate receptors, scaffold proteins and the actin cytoskeleton, able to receive, transmit and integrate the pre-synaptic signal. The spatial and temporal coordination of all these molecular components throughout the formation and maturation of a synapse remains, however, unclear. Scribble1 (Scrib1) is planar cell polarity protein (PCP) classically implicated in the homeostasis of epithelial tissues and tumour growth. In the mammalian brain, Scrib1 is a critical scaffold protein in brain development and function. The main goal of this work was, therefore, to investigate the molecular mechanisms underlying Scrib1 role in synapse formation and maintenance. In a first part, we depict the importance of Scrib1 PDZ-dependent interactions on glutamate receptors trafficking as well as bidirectional plasticity signalling pathway underying spatial memory. In a second part, we focus on the functional consequences of a recently identified autism spectrum disorder (ASD) mutation of Scrib1 on neuronal morpholgy and function. We demonstrated that Scrib1 regulates dendritic arborization as well as spine formation and functional maintenance via an actin-dependent mechanism, whose disruption might underlie the ASD phenotype. Taken altogether, this thesis highlights the PCP protein Scrib1 as key scaffold protein in brain development and function, playing a plethora of roles from the subcelular to the cognitive level.

Information processing in the brain relies on a functional balance between excitation and inhibition, the disruption of which leads to network destabilization and many neurodevelopmental disorders, such as autism spectrum disorders. One of the homeostatic mechanisms that maintains the excitatory and inhibitory balance is called synaptic scaling: Neurons dynamically modulate postsynaptic receptor abundance through activity-dependent gene transcription and protein synthesis. In the first part of my thesis work, I discuss our findings that a chromatin reader protein L3mbtl1 is involved in synaptic scaling. We observed that knockout and knockdown of L3mbtl1 cause a lack of synaptic downscaling of glutamate receptors in hippocampal primary neurons and organotypic slice cultures. Genome-wide mapping of L3mbtl1 protein occupancies on chromatin identified Ctnnb1 and Gabra2 as downstream target genes of L3mbtl1-mediated transcriptional regulation. Importantly, partial knockdown of Ctnnb1 by itself prevents synaptic downscaling. Another aspect of maintaining E/I balance centers on GABAergic inhibitory neurons. In the next part of my thesis work, we address the role of the scaffold protein Shank1 in excitatory synapses onto inhibitory interneurons. We showed that parvalbumin-expressing interneurons lacking Shank1 display reduced excitatory synaptic inputs and decreased levels of inhibitory outputs to pyramidal neurons. As a consequence, pyramidal neurons in Shank1 mutant mice exhibit increased E/I ratio. This is accompanied by a reduced expression of an inhibitory synapse scaffolding protein gephyrin. These results provide novel insights into the roles of chromatin reader molecules and synaptic scaffold molecules in synaptic functions and neuronal homeostasis.

Les Troubles du Spectre de l'Autisme (TSA) sont devenus une priorité nationale et internationale en matière de santé publique. À ce titre, de nombreux outils et différents types de prises en charge sont proposés avec plus ou moins de résultats pour les personnes qui en sont atteintes. C'est pourquoi, les dernières recommandations de la Haute Autorité de Santé (HAS, 2012) ainsi que le plan gouvernemental autisme 2013-2017 insistent sur l'importance de mener des études objectives concernant l'évolution et les prises en charge des personnes porteuses de TSA. Cette recherche qui comprend 2 études distinctes, vise à (1) objectiver l'efficacité d'un dispositif innovant d'intervention développementale en milieu ordinaire pour les personnes porteuses de TSA (le programme IDDEES : Intervention - Développement - Domicile - Ecole - Entreprise - Supervision) et à (2) démontrer le bénéfice de l'utilisation de nouvelles technologies (applications LearnEnjoy) associées à ce programme sur la dysrégulation fonctionnelle et les comportements restreints et répétitifs. Les participants de l'étude 1 sont des enfants âgés de 1 à 9 ans, ayant un TSA et bénéficiant tous du programme IDDEES (N = 51 enfants). Le diagnostic a été établi sur la base des critères du DSM-5 (APA, 2013) et de l'échelle d'évaluation quantitative, la CARS (Schopler, Reichler & Renner, 1988). Les enfants sont évalués à 3 temps différents (10 mois d'intervalle) sur le plan développemental (PEP-3, Schopler, Lansing, & Reichler, 2010 ; EDEI-R, Perron-Borelli, 1996 ; etc.) et comportemental (CARS, Schopler, et al., 1988). La population de l'étude 2 est constituée de 31 enfants et adolescents âgés de 3 ans à 17 ans et de 9 adultes âgés de 17 à 38 ans, bénéficiant du programme IDDEES et de l'utilisation des applications LearnEnjoy dans leur programme de remédiation. Tous les 3 mois durant 2 ans, les accompagnants de ces personnes cotent des échelles permettant d'analyser l'évolution de leur dysrégulation (GRAM, Adrien, 1996) et de leurs comportements répétitifs et restreints (EC2R, Bourreau, Gomot, Roux et Barthélémy, 2009). Les résultats de la 1ère étude mettent en évidence une évolution des âges de développement et une diminution de la symptomatologie autistique des personnes bénéficiant du programme IDDEES, indépendamment de l'âge réel et de l'intensité du trouble autistique au début de l'étude. Les résultats de la seconde, montrent que les personnes bénéficiant à la fois du programme IDDEES et des applications LearnEnjoy, après un temps d'adaptation nécessaire, parviennent à se réguler de mieux en mieux au fil des mois. De plus, leur comportements restreints et répétitifs et leur résistance au changement diminuent au profit d'une plus grande souplesse cognitive. Le programme IDDEES qui tient compte du développement atypique et du fonctionnement dysrégulé et si particulier des personnes avec TSA, constitue ainsi une bonne méthode pour favoriser leur développement et leur adaptation à l'environnement physique et social. Pour les professionnels respectueux de l'éthique et soucieux d'améliorer la qualité de vie de ces personnes, il est indispensable de proposer des interventions de qualité et reconnues comme telles. / Autism Spectrum Disorders (ASD) became a national and international public health priority. As such, many tools and different types of care are offered with varying degrees of success for those affected. That's why the latest recommendations of the High Authority for Health (HAS, 2012) and the governmental plan for autism 2013-2017 stress the importance of conducting objective studies on the evolution and care of people Carriers. This research, which includes 2 separate studies, aims to (1) objectify the effectiveness of an innovative device for developmental intervention in a standard environment for persons with ASD (Program' IDHSFS : Intervention-Development-Home-School-Firm-Supervision) and (2) show the benefit of using of new technologies (LearnEnjoy' applications) associated to this program on functional dyregulation and their repetitive and restricted behaviours. Participants of study 1, are children aged 1-9 years with ASD and all with Program' IDHSFS  (N = 51 children). The diagnosis was based on DSM-5 criteria (APA, 2013) and the quantitative assessment scale, CARS (Schopler, Reichler & Renner, 1988). Children were assessed at 3 different times (10 months apart), developmental evaluation (PEP-3, Schopler, Lansing, & Reichler, 2010, EDEI-R, Perron-Borelli) and behavioral evaluation (CARS, Schopler, & al, 1988). The study 2 population is constituted of 31 children and teenagers aged 3 to 17 years and 9 adults aged 17 to 38 years, benefiting from the Program' IDHSFS and the use of LearnEnjoy' applications in their weekly socio-cognitive rehabilitation sessions. Every three months, for 2 years, expert in autism coaches of these people established some scales allowing to analyze the evolution of their activity's regulation (RAMG, Adrien, 1996) and their repetitive and restricted behaviours. (EC2R, Bourreau, Gomot, Roux and Barthélémy, 2009). The results of the first study shows an evolution of the developmental ages and a decrease in the autistic symptomatology of people benefiting from the IDDEES program, regardless of the real age and intensity of the autistic disorder at the start of the study. The results of the second, show that people benefiting from both the Program' IDHSFS and the LearnEnjoy' applications, after a necessary period of adaptation, manage to regulate better and better over the months. Moreover, their repetitive and restricted behaviours, and their resistance to change decreases in favor of greater mental flexibility. The IDDEES program, which takes into account the atypical development and the dysregulated functioning of people with ASD, is a good method for their development and adaptation to the physical and social environment. For professionals who respect ethical standards and are keen to improve the quality of life of these people, it is essential to offer high-quality and recognized interventions.

Many children with autism spectrum disorder (ASD) are included or mainstreamed in general education classrooms, yet general education teachers receive little, if any, formal training for working with children with ASD. The conceptual framework for this study was differentiated instruction, which is a best practice intended to improve educational experiences for children diagnosed with ASD. The purpose of this research study was to explore general education teachers' perceptions of providing differentiated instruction to these students. The research questions examined teachers' perceptions of barriers that can affect their ability to differentiate instruction in their classrooms and strategies teachers use to facilitate the process of providing differentiated instruction in their classrooms for their students diagnosed with ASD. Eight elementary and middle school teachers participated in this phenomenological study. Content analysis of interview data provided information regarding the barriers of outdated resources and the need for additional training of general education teachers to work with students diagnosed with ASD. In addition, the participants identified 2 models used as strategies to adapt instructional practices to promote students' social and academic outcomes. Professional development could assure that teachers and administrators are aware of the latest best practices needed to teach children with ASD in the general education classrooms. By providing teachers with effective strategies needed to work with students diagnosed with autism, social change can be realized, and students with ASD can receive educational services possibly leading to a better quality of life.