Autism is a severe childhood neuropsychiatric condition characterized by impairments in socialization and communication, and by restricted and repetitive behaviours. Autism spectrum disorder (ASD) is a complex and largely unknown disease with a strong genetic basis, multiple genes involved and environmental factors determining its phenotype. Interestingly, the DLX1/DLX2 and DLX5/DLX6 bigene clusters are located in autism susceptibility loci and Dlx genes are involved in GABAergic interneurons differentiation and migration to the cortex during forebrain development. Dlx gene expression is controlled by different cis-regulatory elements. Of these, 4 are active in the forebrain, URE2, I12b, I56ii and I56i. In order to determine the role of the DLX genes in ASD, variants were found in gene exons and in cis-regulatory elements in autistic individuals. A single nucleotide polymorphism (SNP), a change of an adenine for a guanine, was identified in I56i enhancer. Finding a SNP in I56i was very surprising considering that it is located in a Dlx binding motif highly conserved among >40 species. We showed, using in vitro approaches, that the presence of this SNP affects the affinity of Dlx for their binding site and reduces the transcriptional activation of the enhancer. The SNP also affects activity of the I56i enhancer in transgenic mice. In order to determine the real impact of the SNP in vivo, mutant mice harboring the SNP in their I56i enhancer were produced. That involved the insertion of the I56i enhancer with the SNP, using homologous recombination in mouse embryonic stem cells to replace the wild type version of the enhancer. With these mutant mice, we demonstrated that, in vivo, this SNP reduces Dlx5 and Dlx6 expression in the forebrain. Furthermore, this decrease in Dlx5/Dlx6 expression could affect the differentiation and/or migration of specific populations of inhibitory interneurons in the forebrain. No distinct iv behavioural phenotypes were observed between wild type mice and those carrying the SNP, during social interaction and anxiety tests. Therefore, these results suggest that even a subtle change in a regulatory element can have an impact in the development of the forebrain and may even contribute to disorders such as autism.

Despite the important benefits of physical activity, many people with autism spectrum disorder (ASD) have difficulty participating long enough to reap the rewards. Poor motor skills, difficulty planning movements, problems functioning in open environments, and low motivation combine to make sustained participation a challenge. This dissertation is a series of three studies designed to develop and assess intervention, based on self-determination theory, which promotes sustained physical activity for adolescents and young adults with ASD functioning at the low end of the spectrum. The studies were carried out at a high school for students with intellectual disabilities over three consecutive years. The results of studies and 2 were used to adapt the intervention to meet the needs of this population. Recent research has shown that when people act in a self-determined manner they become more engaged in what they are doing. The intervention for study I included one self-determination skill, self-monitoring. Goal-setting was added during study 2, this resulted in participants setting goals and self-monitoring as they walked and jogged. The intervention for the third study included 3 self-determination skills: goal-setting, self-monitoring, and self-reinforcement. The self-determination attitude of self-efficacy was measured during study 3 to better understand the relationship between self-efficacy and physical activity for individuals with ASD. Distance walked, jogged, or cycled, increased during studies 1 and 3. Visual methodologies were used during studies 2 and 3 to provide these participants with severe communication problems the opportunity to share their experiences during the physical activity with the researchers. Participants and teachers interpreted the facial expressions, which were captured with photographs, in terms of affect but their interpretations did not always match. The participants indicated that enjoyment of the activity increased over the duration of the physical activity program but this was not always obvious to the teachers. It was concluded that interventions which include self-determination skills increase engagement and enjoyment during physical activity for adolescents and young adults with ASD.

Younger siblings of children with autism (Sibs-ASD) are at risk for the development of an Autism Spectrum Disorder (ASD) or subclinical social and cognitive deficits better known as the Broader Autism Phenotype (BAP).The current study utilized a multi-level approach to examine executive attention and social competence in preschool-aged Sibs-ASD and a comparison group of age-, sex-, and Verbal IQ-matched younger siblings of children without autism (Sibs-COM). Forty-two participants (24 Sibs-ASD, 18 Sibs-COM) completed a modified version of the Children’s Attention Network Task (ANT), with electroencephalograph (EEG) collected simultaneously, and a peer interaction paradigm with an unfamiliar peer.Overall, Sibs-ASD and Sibs-COM displayed comparable performance on behavioral indices of the Children’s ANT, P3 amplitude and latency, and measures of observed social functioning. Surprisingly, Sibs-ASD displayed a reduced (less negative) N2 amplitude and shorter N2 latency, most evident at Fz compared to FCz, a finding not observed in Sibs-COM. Furthermore, on a parent-report index of social functioning,Sibs-ASD reportedly displayed greater social impairments than Sibs-COM. Interestingly, post-hoc analyses indicated that differences in N2 amplitude and social functioning were most apparent between affected Sibs-ASD and Sibs-COM. Therefore, results of this study provide support for social and cognitive deficits consistent with theories of the BAP.

本論文主旨在探討自閉症病患對於情緒節律(emotional prosody)在聽覺上的區辨(discrimination)、理解(comprehension)及在口語上的表達(production)能力。結果顯示，聽覺區辨並非自閉症患者在處理情緒語音上的問題所在。其在情緒語音的聽覺理解及口語表達上則呈現顯著障礙。經由聲學分析，自閉症患者情緒語音表達的平均基礎頻率(mean fundamental frequency)、基礎頻率範圍(fundamental frequency range)及時長(duration)除了在覆述生氣的情緒語音外，並未隨情緒情境的轉換而呈現顯著的起伏變化。一般聽眾亦難由自閉症患者的情緒語音表達中，判斷其情緒狀態。Baron-Cohen (1995)所提出的自閉症成因－"心智閱讀障" (mindblindness)和情緒理解及表達間的關連性在文中將進行檢視。此外，本文亦自語言發展(language development)及語言歷程(language processing)的觀點探討自閉症患者在超音段(suprasegmental)上理解與表達異常的徵結所在。 / This study investigated the autistic children's ability to discriminate, comprehend, and produce emotional (features of anger, happy, and sad) speech prosody based on tasks involving behavioral (linguistic/emotional) as well as structural (acoustic) features. The preliminary results indicate that the discrimination of acoustic features might not be the main problem of autistic deficiency in processing emotional prosody. Subjects' utterances were subjected to acoustic analysis to examine the variations of mean Fo, Fo range and duration under specific emotional condition. The results revealed that the autistic subjects tended to produce various emotional prosody with less Fo variations. The autistic subjects were also less reliable than normal subjects at transmitting emotional contrasts when judged from the listener's perspective. To understand the nature of this clinical deficiency, autistic patients' impairment in integrating relevant pragmatic information and their " mindblindness (deficiency in mindreading, Baron-Cohen, 1995)" have to be taken into consideration as well. These clinical cases pose fundamental questions in language development and models of language processing (comprehension and production).

Teaching children with autism to interact with their typically developing peers can be a challenge. Previous research has documented that there are many effective ways to teach social interaction; however, these interventions were implemented almost exclusively by trained professionals. The purpose of this study was to assess the effectiveness of parent-implemented contextually supported play dates. Specifically, two parents were taught to use mutual reinforcement and to design cooperative arrangements to help their child with autism to interact with a typical peer in their homes. Two independent reversal designs were used to demonstrate a functional relationship between parent-supported contextually supported play dates and an increase in synchronous reciprocal interactions for both participants. Social validity was also high for both parents; however, there was no consistent impact on participant, confederate, or parent affect. The results are discussed with reference to previous research, future directions, and implications for practice.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: Calvin Gidney. Submitted to the Dept. of Child Development. Includes bibliographical references (leaves 60-64). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (Ph. D.)--University of Nevada, Reno, 2006. / "December, 2006." Includes bibliographical references (leaves 74-84). Online version available on the World Wide Web. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2006]. 1 microfilm reel ; 35 mm.

Thesis (Ph.D.) -- McMaster University, 1998. / Includes bibliographical references (leaves 112-124). Also available via World Wide Web.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available in print.