Autism Spectrum Disorder (ASD) is a pervasive developmental disorder characterized by two distinct features; the social, including impairments in communication and social functioning (empathizing), and the non-social, including preoccupation with restricted interests and repetitive behaviours (systemizing). This thesis investigated non-social cognition in the autism spectrum by undertaking six studies, three with neurotypical participants from the general population and three with an ASD group and matched neurotypical controls. These studies measured autonomic arousal to social and non-social stimuli and stimuli associated with the participant's own special interest or hobby, and change blindness tasks that utilized both social and non-social changes, along with measures of attention to detail and anxiety in an attempt to understand some of the cognitive and affective mechanisms that underlie non-social cognition in ASD and in the wider autism spectrum. A further study assessed 'drive to systemize' along with an objective behavioural assessment of logical thinking ability and a measure of preference for deliberative or intuitive thinking style, to try to further elucidate connections between drive to systemize and ability to systemize, and the modes of cognition that relate to systemizing. Findings included the relationship between autistic traits and stronger physiological responses to non-social stimuli in the neurotypical sample, and a significantly stronger response in the ASD group to non-social stimuli related to personal special interest than in controls. Participants with a larger number of autistic traits showed enhanced change blindness when changes were social in nature. Self-reported high systemizers report that they prefer slow, deliberative styles of thinking and provide more accurate responses to questions that should involve logical thinking-yet they are less able to provide sound logical reasoning for their correct answers than those who are low systemizers. Together, the results suggest that non-social cognition, or systemizing, in autism is motivated by bottom up perceptual and affective processes that share features with conventional social and emotional cognition, or empathizing.

Little is known about the experience of families of children with autism spectrum disorder (ASD) in community settings. The purpose of this research is to learn about the family experience when visiting a science museum, focusing on the motivations of the family, environmental features of the museum, strategies used by family members, and definitions of a successful visit to the museum. Data were collected through semistructured interviews and observations of four families that included a child with ASD. The families in this study appear to want the same community experiences for their children as families with typically developing children. Both the motivations for the visit and features of the environment appeared to influence the family’s approach and strategies they employed for a successful visit. Strategies included those completed before the visit (visitor planning strategies), as well as during the visit (strategies at the museum). The strategies enabled families to enjoy and experience success within the museum environment. The information learned in this study may help families with a child with ASD prepare for and use features of the museum to enjoy successful museum visits. Recommendations are provided for museums seeking to create inclusive opportunities for all families.

The first part of this thesis discusses developmental influences on the human connectome in relation to autism and attention deficit hyperactivity disorder (ADHD), conditions associated with alterations in brain connectivity and marked by social impairments. It reports an experiment investigating whether the connectomes of individuals with autism or ADHD differ from the connectome of neurotypical individuals, and what the underlying genetic basis could be for any differences in neural architecture. Chapter 2 reports an analysis of networks in children with autism or ADHD, using structural covariance magnetic resonance imaging (scMRI). We found overlapping as well as distinct network features across both conditions. Chapter 3 reports an analysis of how gene expression might be associated with the basic building blocs of these structural covariance networks. We found that synaptic and transcriptionally downregulated genes were replicably associated with cortical thickness differences in children with autism, but not in children with ADHD. In addition, the first part also aims to elucidate the potential modulation effects of sex on autism neurobiology. Chapter 4 reports an analysis of structural covariance networks in male and female adults with and without autism. We found that biological sex is a modulator of neurobiological heterogeneity in autism. Chapter 5 reports pilot data aiming to identify an electrophysiological signature of these network properties using electroencephalography (EEG). We find little evidence for theories about network asymmetry, but indications of altered frontal network integration. The second part of the thesis examines the acute effects of hormones on brain connectomics. Hormones are an integral part of the mechanism of social behaviour. In a series of hormone administration studies, we report experiments to test the acute effects of steroid and peptide hormones on brain functional connectivity (Chapters 6 and 7). Chapter 6 reports an oxytocin administration study that used a novel data-driven approach to assess resting-state fMRI connectivity in women. Although the number of fMRI studies on oxytocin have increased over past years, little is known about its effect on women. We found that oxytocin robustly enhances cortico-subcortical connectivity, and that this effect positively correlates with autistic traits. This is interesting given that oxytocin has been proposed as a potential therapeutic in autism. Chapter 7 reports an experiment testing if testosterone modulates connectivity in a specific social environment (a fear response). This was confirmed during the social task, but not during baseline resting-state, highlighting the role of testosterone in functional connectivity in this specific context. Chapter 8 is the concluding chapter that integrates all the empirical findings in the thesis. We discuss their implications for our understanding of autism and ADHD, and of the role of steroid and peptide hormones in the typically and atypically developing connectome. Chapter 8 also reflects on the limitations of the experiments reported, and sets out future directions for research in this area.

No description available.

Every second throughout life, cortical circuitry efficiently compresses and interprets huge volumes of incoming sensory information. This high fidelity sensory processing guides normal brain development and is essential for animals’ successful interaction with the environment. Low-level sensory perceptual disturbance is nearly ubiquitous in Autism Spectrum Disorder (ASD), but despite the potential to offer crucial insight into the abnormal development of higher brain function is poorly understood. Fragile X Syndrome (FXS) is the most common heritable cause of ASD. Previous studies in the Fmr1-KO mouse model of FXS report cell-intrinsic, synaptic and local connectivity abnormalities in the neuronal physiology of primary sensory cortices. This suggests that sensory perceptual dysfunction could emerge from interacting circuit-wide pathophysiology to impair neural adaptations that support high fidelity sensory information processing. However, there is little mechanistic consensus about how this might occur. To address this, in this thesis I use brain slice electrophysiology and computer modelling to provide a bottom-up description of how thalamocortical (TC) responses, the principal cortical input for ascending sensory information, are mis-interpreted in the somatosensory Layer 4 (L4) circuit in Fmr1-KOs at a crucial developmental transition to active sensory processing. Recruitment of intracortical L4 network activity could be atypically evoked by lower frequency thalamic stimulation in Fmr1-KO slices. Furthermore, profound alterations to single-cell and network response dynamics were observed, in particular loss of spike timing precision considered critical for sensory circuit performance. These network phenomena were supported by interacting single-cell and local circuitry pathophysiology, including hyperexcitable cortical neurons and temporally distorted feed forward and feedback inhibition. Together, these data demonstrate cortical hypersensitivity to TC inputs and abnormal recruitment of network activity in critical period Fmr1-KO somatosensory cortical circuits. The hyperresponsiveness of intracortical circuitry may underlie tactile hyperexcitability and distorted sensory perception in FXS patients. Interestingly, modelling suggests that many of the alterations of synaptic and neuronal function are compensatory, thus minimizing the impact of the genetic lesion. Thus, this study shows for the first time that circuit level dysfunction emerges in the Fmr1-KO mouse from an accumulation of effects at the synaptic and cellular level; however, it also highlights the challenge of understanding which of these changes are pathological and which are compensatory.

Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental disorders characterized by complex genetic etiology. Mutations in human APBA2, which encodes for the neuronal adaptor protein Mint2, have been genetically linked to ASD patients. APBA2 maps to the distal portion of chromosome 15q13.1, a region commonly deleted in Prader-Willi and Angelman neurodevelopmental disorders and duplicated in cases of autism, making APBA2 an attractive candidate gene associated with autism. Seven novel nonsynonymous coding variants in APBA2 in ASD subjects have been identified, five of which were predicted to affect protein function; however, they have not been examined functionally. Mint2 belongs to a family of neuronal adaptor proteins that are important for synaptic function. Mint2 interacts directly with the cell adhesion protein neurexin-1α, as part of a multi-protein complex that acts as a facilitator of neurotransmitter release. Together, these data suggest that Mint2 plays an important role in neuronal function, and sequence variations in Mint2 may alter neuronal dysfunction associated with ASD. This thesis examines a point mutation in Mint2, which changes a conserved asparagine residue to a serine (N723S) in the second PDZ domain of Mint2, which binds to neurexin-1α. We found the Mint2 N723S mutation did not affect the binding to neurexin-1α; however, it dramatically altered neurexin-1α stabilization and trafficking in HEK293T cells. While Mint2 wild type greatly increased neurexin-1α at the membrane, Mint2 N723S showed a decreased membrane level of neurexin-1α, indicating the steady-state surface expression of neurexin is affected by the Mint2 N723S mutation. Also, we found that Mint2 N723S decreased neurexin localization in axons and the presynaptic terminal in neurons, which correlated with a decrease in synaptogenesis and miniature event frequency in excitatory synapses in neurons. Together, these results suggest that Mint2 N723S leads to dysfunction in neuronal development, in part due to alterations in intracellular neurexin trafficking and altered synaptic function of Mint2, as potential mechanisms that contribute to ASD pathogenesis. / 2018-11-01T00:00:00Z

The present study used a discounting task to evaluate how hypothetical treatment outcomes were discounter across successively greater probability values. Two discounting questionnaires were administered to thirty parents, half of which had a child with a disability. Delayed discounting of monetary rewards was assessed in relationship with probability discounting of hypothetical treatment outcomes. The questions on the probability discounting questionnaire consisted of asking participants to choose between a guaranteed percentage of symptom elimination or descending probability to eliminate all of their child’s symptoms. For example, “Which treatment outcome would you prefer for your child? (a) guaranteed elimination of 50% of symptoms or 30% chance to eliminate all symptoms.” Results showed a difference in the levels of discounting across the two groups of participants. Parents of children with disabilities discounted hypothetical monetary rewards more steeply while discounting hypothetical treatment outcomes less steeply compared to parents of children without disabilities. Exponential delay functions provided a strong fit for the monetary delayed function.

Ample research has examined the impact of autism for children and families, but less has addressed the effects of this condition for adults. The literature indicates that adults on the autism spectrum suffer from depression and have a heightened risk of suicidal ideation because of their social skills deficits. Research also shows that individuals with high-functioning autism (HFA) can benefit from participating in support groups. In addition, research indicates that use of the term "neurodiversity" rather than other diagnostic labels encourages increased self-esteem to persons on the autism spectrum. This grounded theory study sought to understand the belief of clinicians with regard to the incorporation of the concept of neurodiversity in support groups for adults with HFA. The population for this study comprised clinicians who led support groups for adults with HFA. The specific foundational theories used were Tuckman's stage model of group development and Salzer's peer support model. Data consisted of 3 pilot study interviews and 12 additional interviews. Participant recruitment occurred through LinkedIn, and interviews took place online through the chat modality GoToMeeting. Interview data were entered into NVivo and a Van Kaam coding procedure was used to decipher recurring themes. Key results indicated that clinicians believe that the incorporation of the concept of neurodiversity can help adults with autism to build self-esteem and change the way individuals with HFA consider the condition, which in turn can assist them to build social skills, and relationships with their peers. Positive social change that may result from this study includes encouragement for increased use of the concept of neurodiversity as a tool in support groups for people with HFA, and stimulation of further study of this concept for decreasing bias against those with HFA.

<p>Denna uppsats är en utvärdering av en befintlig introduktionsutbildning för föräldrar till barn med autismspektrumstörning som givits i tre varianter – en längre, en kortare respektive en intensiv – i regi av Autismcenter för små barn i Stockholms län. Utvärderingen inkluderar föräldrar till 70 barn och bygger på tidigare insamlade frågeformulär, samt kvalitativa intervjuer med föräldrarna till tio av barnen. Frågeformulären har analyserats statistiskt och intervjuerna tematiskt. Resultaten visar att föräldrarna huvudsakligen var nöjda med utbildningen och kände sig väl omhändertagna. Ibland upplevde de dock viss osäkerhet runt kursens syfte och därmed med vissa kursinslag. Sammanlagt visar resultaten att det fanns en tendens till att den längre kursen gav en bättre mognadsprocess än de övriga kursformaten. Avslutningsvis lämnas rekommendationer inför framtiden, både avseende kursens utformning och fortsatt utvärdering av den.</p>

<p>Idrottsundervisning för elever med diagnosen autism är en miljö som kräver</p><p>specialpedagogiska åtgärder. Struktur är en grundläggande del i undervisningen av dessa</p><p>elever. Detta är något som examensarbetet behandlar. Genom intervjuer och observationer har</p><p>denna undersökning resulterat i olika metoder och undervisningsstrategier för barn och</p><p>ungdomar med autism vad gäller motorik, kondition, bollspel, samarbete, tvångsmässiga</p><p>mönster och att fånga elevens intresse. Detta examensarbete kan fungera som ett underlag till</p><p>idrottslärare som arbetar med autistiska elever. Man bör ha i åtanke att detta examensarbete</p><p>och dess resultat inte fungerar för alla barn och ungdomar med autism, utan det är viktigt att</p><p>undervisningen individualiseras efter varje individ.</p>