No description available.

Autism Spectrum Disorder (ASD), previously known as Pervasive Development Disorder (PDD) is a developmental disorder present from early childhood. Children diagnosed with ASD commonly exhibit symptoms of ADHD resulting in increased severity of symptoms and impairment of functioning. This group of children is frequently treated with methylphenidate which has been recommended by some but criticised by others. This systematic review aims to explore the effect of methylphenidate treatment on symptoms of ASD, functioning and adverse effects  Six articles were extracted from five different databases (Medline, Psych INFO, PubMed, Scopus, and Web of Science) and chosen based on a pre-determined inclusion and exclusion criteria. The results show that MPH treatment may be successful as an intervention for some children with ASD showing ADHD symptoms while other children are very susceptible to adverse effects with some being unable to tolerate the treatment. The chosen studies provided limited acknowledgement of the effect on functioning making it an important focus for future research. It is important that professionals are aware of the negative effects MPH might cause to ensure a positive outcome and well-being for children with this disorder. There is a need for further understanding of the connection between ASD and ADHD with additional exploration of possible moderators such as IQ, dose size and level of functioning.

Neurodevelopmental disorders (NDD) is a collective name for diagnoses such as ADHD, ASD/Autism, Tourette’s syndrome and language disorders. A child with these diagnoses has different deficits that can be divided into the following problem areas; Social interaction, Learning difficulties, Memory and motor skills, and Concentration difficulties. In order for these children to cope with their everyday lives, they need support in the form of assistive aid products or human care. This investigative work has been done in collaboration with Komikapp AB and focused on developing a product within the assistive technology industry. The goal was to design an assistive aid for children with NDD diagnoses that offers increased school performance. The work was planned through the design processes Double Diamond process and Design Thinking process and is placed within the framework of Eco Design. The project was initiated with literature studies on the different diagnoses together with what products were available on the current market. From the background research, conclusions could be drawn that the products were often considered to be large and bulky, stationary, non-discreet and had a childish appearance. It could also be stated that appreciated products were fidget toys that stimulate the user through tactile senses, such as stress balls. In addition, the product aid market for older children, those in their adolescence, was small. The decision was made to narrow down the target group for children in the higher stages of Swedish comprehensive school and that the problem area for the work should be focused on Concentration difficulties. The investigation was followed by a questionnaire sent to people who work or have worked within the teaching profession. Moreover, in-depth interviews were conducted with a principal at an NDD-adapted higher-stage school, an occupational therapist at Stockholm’s ADHD centre and five teaching assistants. After all the information was gathered, brainstorming methods were used to break down the chosen problem area, Concentration difficulties. A smaller subgroup to the problem area was observed and assumed to benefit the work from a course goal perspective. The new niche problem area was Time perception. Based on this choice, further market research was carried out on aids in the category of time perception. This was followed by ideation, which produced five concepts. Three of these were taken for further development after an evaluation. Common to all concepts was that the product would help the user perceive time by showing time, date and day as well as having features to set alarms and timers with a visual explanation of the remaining time. After workshops with three people in professions that deal with NDD diagnoses on a daily basis, and two design engineering students, the Flexitime concept was chosen. This concept was the watch that offered a discreet design and an option to also include a fidget function. The detailed design of the Flexitime watch began and further market research was done on today’s range of smartwatches. A survey was also sent out to young people between the ages of 12-16 to gain an understanding of what kind of design attracts the target group. The survey received 39 respondents and a 50/50 gender split which laid the foundation for the design methods used to achieve the exterior design. The watch’s inner design and user scenarios were designed for a final design proposal. The fidget feature and the navigation to set timers or to turn on/off the sound of the watch were determined. The final design proposal for the assistive product Flexitime was a discreet, user-friendly, simple watch designed for teenagers to use into adulthood. The watch had not only features to help the user understand and perceive time, but a fidget feature to tame restless fingers. The dial for navigating the watch’s menu also offered the ability to rotate freely and generate tactile stimulation through its structure. This investigative work and the final design proposal for Flexitime form a basis for further work. / Neuropsykiatriska funktionsnedsättningar (NPF) är ett samlingsnamn för diagnoser som ADHD, AST/Autism, Tourettes syndrom och språksvårigheter. Ett barn med dessa diagnoser har olika svårigheter som kan delas in efter följande problemområden; Social interaktion, Inlärningssvårigheter, Minne och motorik samt Koncentrationssvårigheter. För att dessa barn ska klara av sin vardag behöver de stöd i form av hjälpmedelsprodukter eller mänsklig vård. Detta utredningsarbete har gjorts i samarbete med Komikapp AB och fokuserats på framtagning av en produkt inom hjälpmedelsbranschen. Målet var att designa ett hjälpmedel för barn med NPF diagnoser som erbjuder en ökad prestation i skolan. Arbetet projekterades genom designprocesserna Double Diamond processen samt Design Thinking processen och placerar sig inom ramen för Eco Design. Projektet inleddes med litteraturundersökningar för de olika diagnoserna samt vilka produkter som finns för dessa på marknaden idag. Från bakgrundsinsamlingen kunde slutsatser dras om att produkterna ansågs ofta vara stora och klumpiga, stationära, ha ett barnsligt utseende och icke-diskreta. Det kunde också konstateras att produkter som uppskattades var pillerillprodukter som stimulerar användaren genom taktila sinnen som exempelvis stressbollar. Dessutom var utbudet för äldre barn, tonåringar, litet. Beslutet togs att målgruppen skulle avsmalnas till barn i högstadieåldern och att problemområdet för arbetet ska fokuseras på Koncentrationssvårigheter. Utredningen fortsatte genom utskick av frågeformulär till personer som jobbar eller tidigare har jobbat inom läraryrket samt djupa intervjuer med en rektor på en NPF anpassad högstadieskola, en terapeut på Stockholms ADHD-center och 5 lärarassistenter. Efter all informationsinsamling användes brainstorm metoder för att bryta ner det valda problemområdet, Koncentrationssvårigheter. En mindre subgrupp under problemområdet observerades och antogs gynna arbetet utifrån ett kursmål-perspektiv. Det nya nischade problemområdet var Tidsuppfattning. Utifrån detta val gjordes ytterligare marknadsundersökningar på hjälpmedel i kategorin tidsuppfattning. Därefter följde en idegenerering som frambringade fem koncept. Tre av dessa togs till vidareutveckling efter en utvärdering. Gemensamt för alla koncept var att produkten skulle hjälpa användaren uppfatta tiden genom att ange tid, datum och dag samt ha funktionerna att ställa alarm och timers med bildlig förklaring av kvarstående tid. Efter workshops med tre personer inom yrken som dagligen handskas med NPF diagnoser, och två designingenjörs-studenter valdes konceptet Flexitime. Detta koncept var armbandsuret som erbjöd en diskret design och möjlighet till att även inkludera en pillerillfunktion. Den detaljerade designen av klockan Flexitime påbörjades och ytterligare marknadsundersökningar gjordes på dagens utbud av smartwatches. Även en enkät skickades ut ungdommar mellan 12-16 år för att få en förståelse av vad för design som attraherar målgruppen. Enkäten fick 39 respondenter och en 50/50 könsfördelninng vilket la grunden för de designmetoder som användes för att nå den utvändiga designen. Klockans inre funktioner och användarscenarion designades för ett slutgiltigt designförslag. Pillerillfunktionen samt navigeringen, för att stänga av/sätta på klockans ljud och ställa timers, bestämdes. Det slutgiltiga designförslaget på hjälpmedelsprodukten Flexitime var en diskret, användarvänlig, simpel klocka designad för tonåringar att använda upp till vuxenåldern. Klockan hade inte bara funktioner för att hjälpa användaren förstå och uppfatta tiden, utan även en pillerillfunktion för att tämja rastlösa fingrar. Ratten för att navigera i klockans meny erbjöd även möjligheten att rotera fritt och generera taktil stimulering genom dess struktur. Detta utredningsarbete och det slutgiltiga designförslaget på Flexitime utgör en god grund till fortsatt arbete.

Background: Children and youths with neurodevelopmental disorders are less physically active and have inferior physical fitness levels than their typically developed peers. Organized activities, especially team sports, can be challenging to this group due to common socio-behavioral, linguistic, and personality characteristics and limitations in motor proficiency. Physical activity and team sports may benefit this group by improving cognition, attention, socio-emotional functioning, and motor skills. Aim: Explore the conditions for including children and youths with neurodevelopmental disorders in team sports in Sweden. Methods: A mixed-methods approach was applied. Semi-structured interviews investigated the structural and organizational practices surrounding barriers and enablers to inclusion and coach education. A nationwide web survey described the coaching population and assessed perceived knowledge and conditions for inclusion in team sports. Soccer, ice hockey, floorball, handball, and group gymnastics represented the team sports. A qualitative content analysis was applied to interview data, followed by descriptive and bivariate (chi-square and simple multinomial logistic regression) analyses and multiple multinomial logistic regressions. Results: This neurodiverse group was described as difficult to target due to its heterogeneity. Sports associations described going through an identity introspection and working on inclusion issues at large but had different ways of addressing neurodevelopmental disorders, and varying strategies to educate coaches. Most coaches reported receiving education outside of sports. 40% of coaches claimed to have knowledge of neurodevelopmental disorders, associated with personal experiences, female gender, and coaching older junior teams. 71.6% of coaches felt comfortable accommodating this group, also related to personal experience, coaching under 8 teams, knowing whom to turn to for support, and coaching older junior teams. Conclusion: While most coaches felt capable of accommodating children with neurodevelopmental disorders, coach knowledge was based on personal experiences and interests. Sports associations addressed the inclusion issue but need to develop their educational opportunities for coaches. Increased knowledge could make team sports more accessible to children with invisible disabilities. / Bakgrund: Barn och unga med neuropsykiatriska funktionsnedsättningar är mindre fysiskt aktiva och har sämre fysisk kondition än sina neurotypiska jämlikar. Organiserade aktiviteter, särskilt lagidrott, kan utgöra en utmaning för denna grupp på grund av vanliga sociala, språkliga och personliga egenskaper och beteenden, samt motoriska begränsningar. Fysisk aktivitet och lagidrott kan gagna denna grupp genom att förbättra kognition, uppmärksamhet, socio-emotionella och motoriska färdigheter. Syfte: Att utforska förutsättningarna för att inkludera barn och unga med neuropsykiatriska funktionsnedsättningar inom lagidrotten i Sverige. Metod: En blandad metod tillämpades. Semistrukturerade intervjuer användes för att undersöka strukturell och organisatorisk praxis kring hinder och möjliggörare för inkludering och ledarutbildningar. En nationell webb-baserad tvärsnittsundersökning beskrev gruppen med ledare och undersökte ledares självskattade kunskap och förutsättningar för inkludering inom lagidrotten. Fotboll, ishockey, innebandy, handboll och truppgymnastik representerade lagidrotten. En kvalitativ innehållsanalys applicerades på intervjumaterialet, följt av deskriptiva och bivariata (chi2 samt enkel multinomial logistisk regression) analyser samt multivariata logistiska regressioner. Resultat: Denna neurodiversa grupp beskrevs som en svår målgrupp på grund av sin heterogenitet. Idrottsförbunden beskrev hur de analyserar sig själva och arbetar med inkludering i bred bemärkelse men har olika sätt att adressera neuropsykiatriska funktionsnedsättningar, samt varierande strategier för att utbilda ledare. De flesta ledare rapporterade att de genomgått sin utbildning utanför idrotten. 40% av ledarna ansåg sig ha kunskap om neuropsykiatriska funktionsnedsättningar, vilket kunde associeras med personlig erfarenhet, kvinnligt kön och att träna äldre juniorer. 71,6% av ledare kände sig bekväma i att bemöta denna grupp, vilket också kunde associeras med personlig erfarenhet, att träna under 8-åringar, veta vem man kan vända sig till för hjälp, samt att träna äldre juniorer. Slutsats: Medan de flesta ledare kände sig kapabla att bemöta barn med neuropsykiatriska funktionsnedsättningar, baserades ledares kunskap på personlig erfarenhet och intresse. Idrottsförbunden adresserade inkluderingsfrågan men behöver utveckla utbildningsmöjligheterna för ledare. Ökad kunskap skulle kunna göra lagidrott mer tillgänglig för barn med osynliga funktionsnedsättningar.

Plusieurs insertions/délétions (indels) génétiques ont été identifiées en lien avec des troubles du neurodéveloppement, notamment le trouble du spectre de l’autisme (TSA) et la déficience intellectuelle (DI). Bien que ce soit le deuxième type de variant le plus courant, la détection et l’identification des indels demeure difficile à ce jour, et on y retrouve un grand nombre de faux positifs. Ce projet vise à trouver une méthode pour détecter des indels de haute qualité ayant une forte probabilité d’être des vrais positifs. Un « ensemble de vérité » a été construit à partir d’indels provenant de deux cohortes familiales basé sur un diagnostic d’autisme. Ces indels ont été filtrés selon un ensemble de paramètres prédéterminés et ils ont été appelés par plusieurs outils d’appel de variants. Cet ensemble a été utilisé pour entraîner trois modèles d’apprentissage automatique pour identifier des indels de haute qualité. Par la suite, nous avons utilisé ces modèles pour prédire des indels de haute qualité dans une cohorte de population générale, ayant été appelé par une technologie d’appel de variant. Les modèles ont pu identifier des indels de meilleure qualité qui ont une association avec le QI, malgré que cet effet soit petit. De plus, les indels prédits par les modèles affectent un plus petit nombre de gènes par individu que ceux ayant été filtrés par un seuil de rejet fixe. Les modèles ont tendance à améliorer la qualité des indels, mais nécessiteront davantage de travail pour déterminer si ce serait possible de prédire les indels qui ont un effet non-négligeable sur le QI. / Genetic insertions/deletions (indels) have been linked to many neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). However, although they are the second most common type of genetic variant, they remain to this day difficult to identify and verify, presenting a high number of false positives. We sought to find a method that would appropriately identify high-quality indels that are likely to be true positives. We built an indel “truth set” using indels from two diagnosis-based family cohorts that were filtered according to a set of threshold values and called by several variant calling tools in order to train three machine learning models to identify the highest quality indels. The two best performing models were then used to identify high quality indels in a general population cohort that was called using only one variant calling technology. The machine learning models were able to identify higher quality indels that showed a association with IQ, although the effect size was small. The indels predicted by the models also affected a much smaller number of genes per individual than those predicted through using minimum thresholds alone. The models tend to show an overall improvement in the quality of the indels but would require further work to see if it could a noticeable and significant effect on IQ.

No description available.

This research delves into idiopathic autism spectrum disorder (ASD), investigating the role of TrkB signaling pathways and BDNF regulation in the cortex. Additionally, it explores offering insights into maternal influences on mouse models. / Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by challenges in social interactions and repetitive behaviors. Prevalence of ASD is estimated to be 1 in 54 globally and is rising recently in many countries including Canada. ASD affects individuals differently, making diagnosis challenging. At present, no molecular diagnosis of ASD is available. Further, available medications only manage some symptoms of the disease and have adverse side effects in children. Therefore, there is a need for accurate molecular diagnostic tools to aid in molecular detection and treatment of ASD. To this end, a better understanding of the underlying molecular mechanisms that link ASD etiology to ASD-related behavior is crucial. While genetic factors contribute to syndromic ASD, most cases of ASD are idiopathic with unknown causes, influenced by a combination of epigenetic and environmental factors. TrkB and its downstream signaling pathways, such as Akt and Erk, are hyper-activated in syndromic ASD and hypo-activated in idiopathic cases. Therefore, drugs like rapamycin that inhibit the mTOR pathway downstream of TrkB are beneficial for syndromic ASD but not idiopathic cases. Additionally, insulin-like growth factor 1 (IGF-1), which mitigates ASD-related synaptic disruptions via Akt and Erk signaling, shows unchanged mRNA and protein levels along with its receptor in the idiopathic ASD fusiform gyrus. In ASD with either genetic or epigenetic/environmental causes, disruptions in synaptic connectivity are observed. Synaptic function is regulated by signaling pathways involving brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), as well as their downstream signaling cascades such as MAPK and Akt. The existing literature suggests that there is an association between BDNF and TrkB signaling pathways and ASD. However, a serious gap in knowledge about the precise molecular role of TrkB in ASD pathology is that our current understanding is correlational in nature and based on observational studies that lack causal experiments. This underscores the importance of further research to understand the causative role of TrkB and its related molecular events in idiopathic ASD. The present work aims to provide a deeper understanding about the causative role of molecular mechanisms underlying TrkB signaling in ASD. ASD mouse models exhibit behaviors and molecular features resembling those observed in human ASD. Therefore, these mouse models are helpful tools for studying ASD. However, understudied physiological confounding factors, such as maternal age and parity, can introduce biases and add to data variability, thus negatively impacting the reproducibility and translational value of ASD mouse models. To achieve a reliable mouse model of ASD, we conducted our first study that examines the impact of maternal age and parity on pregnancy complications, neurodevelopment, and social behavior in mice. Results demonstrate that older maternal age and prior motherhood interact to ensure a normal, steady developmental rate and provide protective effects against anxiety, social impairment, and olfactory deficits. Given the current lack of clarity regarding the causative impact of TrkB on ASD pathology, our subsequent investigation sought to establish a causal relationship between TrkB signaling and ASD. We used the TrkB agonist, LM22A-4 treatment in a validated ASD mouse model. Our results demonstrate that treatment with LM22A-4 effectively rescues the core symptoms associated with ASD (social impairment and repetitive behavior). These findings indicate that impaired TrkB signaling is responsible for ASD-like behavior of valproic acid (VPA)-exposed mice. However, unlike TrkB-related molecular events occurring in the fusiform gyrus of idiopathic ASD, TrkB isoform protein levels, BDNF species, Akt, and Erk total protein levels and activation remained unchanged in VPA-exposed cortices compared to healthy control mice. Since our VPA mouse model does not replicate human idiopathic ASD, our study cannot draw a conclusion on how disruptions in these signaling pathways may contribute to the development and manifestation of ASD symptoms. Cortex is responsible for various aspects of social behavior that are impaired in ASD. However, regulatory mechanisms that are involved in ASD upstream of cortical TrkB and BDNF are not well known. BDNF expression is highly cell-and tissue-specific and is regulated by different sets of transcription factors in specific tissues. While NURR1, the BDNF regulator in midbrain neurons, is associated with ASD pathology, its specific role in regulation of cortical BDNF is not yet well-established. Our third study aimed to understand the role of NURR1 in regulating BDNF specifically in the cortex. We showed that in resting and depolarized neurons, when NURR1 is knocked down, BDNF mRNA levels remained unchanged, suggesting that NURR1 does not regulate BDNF in cortical neurons and highlighting the tissue-specificity of BDNF regulation. In summary, we address the understudied effects of maternal factors on mouse models, which enhances the reliability of ASD research. Further, our studies significantly enhance the understanding of ASD by elucidating the role of TrkB and its downstream signaling pathways in the behavioral aspects of the disorder. We also contribute to the knowledge of BDNF regulation in the cortex, a brain tissue with crucial roles in various aspects of social behavior. In a forward-looking approach, the results of our studies provide valuable insights into mouse modeling of idiopathic ASD and the potential role of TrkB in ASD behavioral symptoms. / Thesis / Candidate in Philosophy / Autism spectrum disorder (ASD) is a condition that is accompanied by challenges in social interaction and repetitive behaviors. ASD is a complicated condition because we do not fully understand all the details of how it works in the body. Studying ASD is important as it is the most challenging condition in children and it is becoming more common, especially in the last two decades. While scientists are developing molecular tools to improve ASD diagnosis and understand its biology, these tools are not widely used in clinics for ASD diagnosis yet. Also, the approved medications available can only help with managing some of the behavioral symptoms like self-harming behavior. Despite the pressing need to find a solution, our recent advancements have not yet brought us closer to a cure for ASD, mainly because of the complexity of the disorder. Therefore, identifying the specific ASD-related mechanisms at the molecular level that contribute to ASD-related behaviors is crucial for gaining a deeper understanding of the disease. In ASD, there are problems with how brain cells communicate with each other. This communication is controlled by certain molecules in the brain, such as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), along with other molecules. There is evidence suggesting a link between these molecules and ASD, but we have not fully understood their precise roles because most of the current knowledge is based on observations and correlations, rather than on establishing cause-and-effect relationships. To bridge this gap, our research focused on understanding TrkB's role in ASD. We required reliable mouse models. Since we aimed to induce ASD-like behaviors in mice using an ASD-causing chemical, it was crucial to ensure they were healthy beforehand. We needed to confirm that any social deficits or repetitive behaviors were not due to other factors, such as adverse infancy experiences or impaired interactions between mother and infant. We discovered that sexually mature dams aged between 3 to 6 months, with a history of previous pregnancies and motherhood, give birth to healthier litters. These litters can serve as a more dependable source for our animal behavioral studies. Many cases of ASD in humans are caused by non-genetic factors such as environmental influences like pesticides, air pollution, and the use of certain drugs during pregnancy. In cases of human ASD triggered by non-genetic factors, there is an increase in proBDNF, the precursor of BDNF. However, this proBDNF does not efficiently convert to BDNF. With insufficient BDNF and TrkB receptors, molecules like Akt (protein kinase B, also PKB) and Erk (Extracellular Signal-Regulated Kinase), which are crucial for neuron communication, are also less active downstream. This imbalance disrupts neuron connections, leading to ASD behaviors. In our research, the ASD-causing chemical which we used is valproic acid. It is originally an anti-seizure medication. When pregnant women took valproic acid, the chance of their child having ASD increased. Scientists used this information to inject pregnant mice with valproic acid, and as a result, all the offspring showed ASD-like behaviors. We anticipated that by isolating the brains of these offspring and measuring protein levels of BDNF, TrkB, Akt, and Erk, we would observe a similar pattern to that seen in humans with non-genetic ASD cases. We focused on studying the cortex, a region of the brain responsible for regulating social behaviors in both mice and humans. Since ASD is associated with challenges in social behaviors, we isolated the cortex from mouse brains to analyze protein levels. A chemical known as LM22A-4 with a structure resembling BDNF can bind to TrkB and activate it. We expected that the offspring of pregnant dams injected with valproic acid, which led to reduced TrkB axis activation in their brains, would show improvement in ASD behavior. This anticipation stems from the understanding that LM22A-4 activates the TrkB axis, thus compensating for its reduction, which is thought to be causing ASD-like behaviors. The offspring of mothers injected with valproic acid exhibited ASD-like behaviors, unlike the control mice. Control mice were offspring of pregnant dams injected with a solution containing only the substances used to dissolve valproic acid, typically water and salt (saline). Mice prenatally exposed to valproic acid (VPA) exhibited ASD-like behaviors, but treatment with LM22A-4 helped alleviate these behaviors, promoting more typical behavior patterns. LM22A-4, by activating TrkB receptors, helped to protect the brain from harm caused by exposure to valproic acid before birth. This could mean that valproic acid-induced changes in TrkB-related molecular mechanisms are involved in social behavior difficulties and increased repetitive behaviors seen in autism. Nevertheless, the levels of TrkB, BDNF, proBDNF, Akt, and Erk in the cortex of offspring from mothers injected with valproic acid were like those in the offspring from mothers injected with the saline solution. Therefore, the BDNF and TrkB signaling pathways remained unchanged in the cortex of our valproic acid model in this study, and they differ from those observed in human idiopathic ASD. We also speculated that a protein, called NURR1 acting upstream of BDNF and TrkB might be involved in the process. NURR1 acts as a regulatory protein that binds to the BDNF, increasing the production of copies from the BDNF. We also used a small RNA that targets a specific region in the Nurr1 and inhibits its protein production We anticipated a reduction in Nurr1 levels. As NURR1 acts as an upregulator of BDNF, lower levels of Nurr1 would result in decreased BDNF production. Activating NURR1 resulted in increased BDNF mRNA levels. However, when NURR1 was reduced, BDNF mRNA levels remained unaffected. This led us to conclude that if NURR1 levels decrease, other proteins may step in to maintain BDNF mRNA levels. Therefore, in the cortex, unlike in some other brain regions, the presence of NURR1 is not essential for regulating Bdnf. In summary, before inducing ASD-like behavior in mice using valproic acid, it is crucial to ensure the health of the mice. We used sexually mature mothers with prior pregnancy experience to provide a healthy baseline. We showed valproic acid induced ASD-like behaviors in mice offspring. We also observed that LM22A-4 treatment alleviated ASD-like behaviors of offspring. In our study, we demonstrated that the levels of BDNF, TrkB, Erk, and Akt proteins in the cortex of mice exposed to valproic acid were not affected. For this reason, our mouse model does not resemble human non-genetic ASD. Finally, NURR1's role in BDNF regulation varies by brain region. Lowering NURR1 did not affect BDNF mRNA levels, suggesting compensatory mechanisms. Our findings suggest new directions for further research to better understand the roles of TrkB and BDNF in non-genetic ASD. Overall, this study provides valuable knowledge that can contribute to advancing our understanding of idiopathic ASD-related molecular mechanisms.

Robot assisted therapy is becoming increasingly popular. Research has proven it can be of benefit to persons dealing with a variety of disorders, such as Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and it can also provide a source of emotional support e.g. to persons living in seniors’ residences. The advancement in technology and a decrease in cost of products related to consumer electronics, computing and communication has enabled the development of more advanced social robots at a lower cost. This brings us closer to developing such tools at a price that makes them affordable to lower income individuals and families. Currently, in several cases, intensive treatment for patients with certain disorders (to the level of becoming effective) is practically not possible through the public health system due to resource limitations and a large existing backlog. Pursuing treatment through the private sector is expensive and unattainable for those with a lower income, placing them at a disadvantage. Design and effective integration of technology, such as using social robots in treatment, reduces the cost considerably, potentially making it financially accessible to lower income individuals and families in need. The Objective of the research reported in this manuscript is to design and implement a social robot that meets the low-cost criteria, while also containing the required functions to support children with ASD. The design considered contains knowledge acquired in the past through research involving the use of various types of technology for the treatment of mental and/or emotional disabilities.

Certaines recherches ont investigué le traitement visuel de bas et de plus hauts niveaux chez des personnes neurotypiques et chez des personnes ayant un trouble du spectre de l’autisme (TSA). Cependant, l’interaction développementale entre chacun de ces niveaux du traitement visuel n’est toujours pas bien comprise. La présente thèse a donc deux objectifs principaux. Le premier objectif (Étude 1) est d’évaluer l’interaction développementale entre l’analyse visuelle de bas niveaux et de niveaux intermédiaires à travers différentes périodes développementales (âge scolaire, adolescence et âge adulte). Le second objectif (Étude 2) est d’évaluer la relation fonctionnelle entre le traitement visuel de bas niveaux et de niveaux intermédiaires chez des adolescents et des adultes ayant un TSA. Ces deux objectifs ont été évalué en utilisant les mêmes stimuli et procédures. Plus précisément, la sensibilité de formes circulaires complexes (Formes de Fréquences Radiales ou FFR), définies par de la luminance ou par de la texture, a été mesurée avec une procédure à choix forcés à deux alternatives. Les résultats de la première étude ont illustré que l’information locale des FFR sous-jacents aux processus visuels de niveaux intermédiaires, affecte différemment la sensibilité à travers des périodes développementales distinctes. Plus précisément, lorsque le contour est défini par de la luminance, la performance des enfants est plus faible comparativement à celle des adolescents et des adultes pour les FFR sollicitant la perception globale. Lorsque les FFR sont définies par la texture, la sensibilité des enfants est plus faible comparativement à celle des adolescents et des adultes pour les conditions locales et globales. Par conséquent, le type d’information locale, qui définit les éléments locaux de la forme globale, influence la période à laquelle la sensibilité visuelle atteint un niveau développemental similaire à celle identifiée chez les adultes. Il est possible qu’une faible intégration visuelle entre les mécanismes de bas et de niveaux intermédiaires explique la sensibilité réduite des FFR chez les enfants. Ceci peut être attribué à des connexions descendantes et horizontales immatures ainsi qu’au sous-développement de certaines aires cérébrales du système visuel. Les résultats de la deuxième étude ont démontré que la sensibilité visuelle en autisme est influencée par la manipulation de l’information locale. Plus précisément, en présence de luminance, la sensibilité est seulement affectée pour les conditions sollicitant un traitement local chez les personnes avec un TSA. Cependant, en présence de texture, la sensibilité est réduite pour le traitement visuel global et local. Ces résultats suggèrent que la perception de formes en autisme est reliée à l’efficacité à laquelle les éléments locaux (luminance versus texture) sont traités. Les connexions latérales et ascendantes / descendantes des aires visuelles primaires sont possiblement tributaires d’un déséquilibre entre les signaux excitateurs et inhibiteurs, influençant ainsi l’efficacité à laquelle l’information visuelle de luminance et de texture est traitée en autisme. Ces résultats supportent l’hypothèse selon laquelle les altérations de la perception visuelle de bas niveaux (local) sont à l’origine des atypies de plus hauts niveaux chez les personnes avec un TSA. / Most studies investigating visual perception in typically developing populations and in Autism Spectrum Disorder (ASD) have assessed lower- (local) and higher-levels (global) of processing in isolation. However, much less is known about the developmental interactions between mechanisms mediating early- and intermediate-level vision in both typically developing populations and in ASD. Based on such premise, the present thesis had two main objectives. The first objective (Study 1) was to evaluate the developmental interplay between low- and intermediate-levels of visual analysis at different periods of typical development (school-age, adolescence and adulthood). The second objective (Study 2) was to evaluate the functional relationship between low- and intermediate-levels of visual analysis in adolescents and adults diagnosed with ASD. Common methodologies were used to assess both objectives. Specifically, sensitivity to slightly curved circles (Radial Frequency Patterns or RFP), defined by luminance or texture information, was measured using a two alternative temporal forced choice procedure. Results obtained in Study 1 demonstrated that local information defining a RFP (mediated by intermediate visual mechanisms) differentially affected sensitivity at different periods of development. Specifically, when the contour was luminance-defined, children performed worse when compared to adolescents and adults only when RFPs targeted a global processing style (few deformations along the RFP’s contour). When RFPs were texture-defined, children’s sensitivity was worse compared to that of adolescents and adults for both local and global conditions. Therefore, timing of adult-like sensitivity to RFPs is dependent on the type of local physical elements defining its global shape. Poor visual integration between low and intermediate visual mechanisms, which could be attributed to immature feedback and horizontal connections as well as under-developed visual cortical areas, may account for such reduced sensitivity in children. Results obtained from Study 2 demonstrated that manipulating the local physical elements of RFPs impacts visual sensitivity in ASD. Specifically, sensitivity to RFPs is unaffected in ASD only when visual analysis is dependent on local deformations of luminance-defined contours. However, sensitivity is reduced for both local and global visual analysis when shapes are texture-defined. Such results suggest that intermediate-level, shape perception in ASD is functionally related to the efficacy with which local physical elements (luminance versus texture) are processed. It is possible that abnormal lateral or feed-forward / feedback connectivity within primary visual areas in ASD, which possibly arise from excitatory / inhibitory signalling imbalance, accounts for differential efficacy with which luminance and texture information is processed in ASD. These results support the hypothesis that atypical higher-level perception in ASD, when present, may have early (local) visual origins.

TITLE: Developing Communication Skills in Children with Autism Using Verbal Behavior - Applied Behavior Analysis AUTHOR: Bc. Kateřina Chrapková DEPARTMENT: The Department of Special Education SUPERVISOR: doc. PaedDr. Jiřina Klenková, Ph.D. ABSTRACT: This thesis deals with the development of communication skills in children with autism using Verbal Behavior - Applied Behavioral Analysis (VB-ABA). The aim of this work is to introduce VB-ABA approach as an effective intervention for people with Autism Spectrum Disorders (ASD). It is a monographic work with emphasis on a theory. The empirical part consist evaluative single-case study. The thesis is devided into six theoretical and one empirical chapter. The first theoretical chapter presents the issue of communication in a view of behaviorism and compares this approach with classical linguistics. The second chapter describes theories of language acquisition and language development from behavioral and linguistic perspective. The third chapter discusses the development of children's speech in the context of ontogeny and its functions. The fourth chapter deals with the issue of communication skills in the context of ASD. The fifth chapter introduces evidence based practice and provides information on current international research of interventions for persons...