Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disease caused by loss of the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) genes. Neurologic symptoms are common and varied in TSC and include epilepsy and behavioral conditions like autism spectrum disorders (ASD). Between 17 and 61% of children with TSC exhibit symptoms of ASD. The purpose of this study was to investigate a potential correlate of poor neurological outcome in TSC by assessing the integrity of brain language pathways and the relationship to ASD. 42 patients with TSC and 42 age-matched control subjects were scanned with advanced diffusion-weighted MRI. White matter language pathways were identified with a validated automatic method and analyzed for microstructural characteristics, including fractional anisotropy (FA) and mean diffusivity (MD). Well-defined white matter pathways in the brain are characterized by high FA and low MD. During normal development, brain white matter pathways increase in FA and decrease in MD. Out of 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD showed a small decrease in FA of the arcuate fasciculus compared to control subjects, and TSC patients with ASD had much lower FA than both control subjects and TSC patients without ASD. Similarly, while TSC patients without ASD had only a small increase in MD compared to control subjects in the arcuate fasciculus, TSC patients with ASD had much higher MD than control subjects and TSC patients without ASD. A new method for assessing the microstructure of young patients showed similar results with decreased compactness in language pathways of TSC patients with ASD. Another new method designed to better analyze regions with crossing pathways showed modifications in language pathway microstructure that correlated with ASD diagnosis in the TSC patients. Preliminary analysis of neuropsychiatric data also showed a trend toward an association of arcuate fasciculus MD with verbal IQ, although the result was not significant after multiple comparisons correction. It remains unclear why some patients with TSC develop ASD, while others have better language outcomes. Our results suggest that aberrant development of language pathways may act as a marker for poor neurological outcome in TSC patients. The impaired microstructure in language pathways of TSC patients may be responsible for the development of ASD, although prospective studies examining the development of language pathways and subsequent ASD diagnosis in this patient population remain essential. It is also possible that a primary problem with language leads to decreased use and subsequent poor development of language pathways. Early diagnosis of ASD is crucial for improving the outcomes of affected children.

Mirror neurons are very specific nerve cells that are both motor and sensory in nature. Mirror neurons are a relatively new discovery first identified by a team of neurophysiologists at the University of Parma. These neurons were first observed in primates, and then later in humans in several regions of the cerebral cortex. A large amount of research on mirror neurons have shown that they play an important role in imitation, language acquisition and empathy. The theoretical part of this work summarizes what is currently known about mirror neurons. It emphasizes the relationship between mirror neurons, autism, empathy, and its training. This theoretical framework is followed by pilot research, which consists of two components: the quantitative part consisted of a questionnaire survey to ascertain the level of empathy of the participants using the Index of Interpersonal Reactivity. The participants were the parents of autistic children who were compared with a control group. A statistically significant difference in empathy levels between the two groups was not observed but there was a tendency for higher scoring in some questionnaire scales in experimental group The second part of this work is an analysis of observations of the interactions between parents and autistic children. Additionally, two...

Infants 5-34 weeks of age were observed in their homes playing with their mothers as part of a longitudinal study. Two mother-infant dyads were observed once per week for twelve weeks, during a ten-minute play session. The purpose of the observation system is to describe contingencies leading to the development of attention-seeking behaviors in typically developing infants. Observations were coded using a type-based format (person engagement, object engagement, supported joint engagement, coordinated joint engagement, and unengaged). Child eye gaze, reaching, and grabbing were coded as well as all child and adult vocalizations. It is suggested that the data from the observation system will help inform and assess the effectiveness of infant and toddler social interventions in autism spectrum disorders and advance our understanding of attention seeking behaviors.

The purpose of this study was to teach preschool children with autism spectrum disorders to make requests with a speech generating device using a naturalistic time delay prompting procedure. The participants in this study were two males, enrolled in a public preschool program, between four and five years old. Both participants showed significant delays in expressive communication requiring alternative and augmented communication. The study utilized a multiple probe design across behaviors. Results showed utilizing naturalistic time delay increases independent requests using a speech generating device.

Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice we have found that alcohol-induced cortical neuroapoptosis is closely correlated in space and time with the appearance of activated microglia near dead cells. Microglia found in close proximity to dying neurons selectively engulfed those that were in later stages of apoptosis. Remarkably, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, in the 5 g/kg alcohol model, there was a transient but substantial increase in pro-inflammatory factor (PIFs) expression. Work in BAX-null mice demonstrated that microglial activation and PIF expression were linked to BAX-dependent neuroapoptosis. As such, the level of microglial activation scaled with alcohol-induced cell death. Therefore, acute alcohol exposure in the developing cortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain. Given that alcohol exposure on either P7 or P8 induced comparable levels of neuroapoptosis and microglial activation, we hypothesized that alcohol exposure on two sequential days (P7 and P8) would exacerbate neuroapoptosis and extend microglial activation. Instead, we found that the period of neuroapoptosis and microglial activation was similar after one day of alcohol exposure on P7 or after two days of exposure on P7 and P8. This was true for both the moderate and severe alcohol paradigms. Potentially, the low levels of cell death produced by the second day of injection may be due to neuroprotective mechanisms elicited by the first day of alcohol injection. In support of this idea, a preliminary microarray analysis of cortical gene expression 12 and 24 h after 5 g/kg alcohol exposure shows a decrease in expression of several pro-apoptotic factors and an increase in the expression of pro-survival factors, including neurotrophins. Of particular interest, BDNF, which has previously been shown to inhibit alcohol-induced neuroapoptosis, showed an eight-fold increase in expression at 24 h following 5 g/kg alcohol exposure and in situ hybridization showed strong BDNF expression near cortical regions with high levels of cell death. Future studies will be needed to extend the analysis of microglial activation states in this two-day injection model and to further explore the possibility that BDNF expression by microglia enacts neuroprotective mechanisms against a second insult. Finally, work in cell culture has suggested that chronic alcohol exposure may potentiate or inhibit microglial phagocytosis of dead cells. These studies raise the possibility that alcohol may directly affect microglial mobility which is important for their surveillance and synaptic remodeling functions. Therefore, we measured the effect of increasing doses of alcohol (0, 0.25, 0.5 and 1%) on microglial migration, branch motility, and morphology in dissociated BV-2 cell cultures and in acutely isolated neonatal (P5-6) brain slices. The results indicate that alcohol dose-dependently inhibits microglial migration and ruffling in cell culture, but in brain slices even high alcohol concentrations (0.5%) only reduce microglial branch motility by ~2%. When combined with our evidence for efficient microglial phagocytic clearance of dead cells in the neonatal cortex, these data suggest that while there is a measurable effect of acute alcohol exposure on microglial mobility, it does not impede microglia from performing their surveillance and phagocytic functions in vivo.

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This session will provide PE teachers with specific strategies for modifying both formal and informal assessments for students with autism spectrum disorder (ASD). With an increased emphasis on assessment, and a rise in the prevalence of ASD, it is critical that teachers can adapt assessments to meet the needs of students with ASD. Session participants will learn practical strategies for modifying assessment specific to motor skill performance, FitnessGram, rubrics, checking for understanding, and peer assessments.

Identifying disease risk genes is a central topic of human genetics. Cost-effective exome and whole genome sequencing enabled large-scale discovery of genetic variations. However, the statistical power of finding new risk genes through rare genetic variation is fundamentally limited by sample sizes. As a result, we have an incomplete understanding of genetic architecture and molecular etiology of most of human conditions and diseases. In this thesis, I developed new computational methods that integrate functional genomics data sets, such as epigenomic profiles and single-cell transcriptomics, to improve power for identifying genetic risks and gain more insights on etiology of developmental disorders. The overall hypothesis that disease risk genes contributing to developmental disorders are bottleneck genes under normal development and subject to precise transcriptional regulations to maintain spatiotemporal specific expression during development. In this thesis I describe two major research projects. The first project, Episcore, predicts haploinsufficient genes based on a large integrated epigenomic profiles from multiple tissues and cell lines by supervised machine learning methods. The second one, A-risk, predicts plausibility of being risk genes of autism spectrum disorder based on single-cell RNA-seq data collected in human fetal midbrain and prefrontal cortex. Both methods were shown to be able to improve gene discovery in analysis of de novo mutations in developmental disorders. Overall, my thesis represents an effort to integrate functional genomics data by machine learning to facilitate both discovery and interpretation of genetic studies of human diseases. We believe that such integrative analysis can help us better understand genetic variants and disease etiology.

Aim. The aim of the present work is to examine and compare brain abnormalities found on magnetic resonance imaging (MRI) in children diagnosed with autism spectrum disorders (ASD) and in children without this diagnosis. In terms of psychopathology, the aim is to evaluate a possible relationship between the MRI findings and the severity of autistic symptomatology. Methods. The research study is based on a retrospective analysis of a sample of patients who attended a diagnostic examination focused on ASD and at the same time underwent brain MRI at the Department of Child Psychiatry of the Second Faculty of Medicine at Charles University and University Hospital Motol between the years 1998 and 2015. For clinical diagnosis of ASD, the International Classification of Diseases, 10th revision (ICD-10), was used. Between 1998 and 1999, the assessment of patients was supported by the Childhood Autism Rating Scale. Starting in 2000, the third version of the Autism Diagnostic Interview - Revised was used for assessments; and from 2012 onwards, the Autism Diagnostic Observation Schedule - Generic was added to the diagnostic procedures. From 1998 to 2015, a total of 489 children were diagnosed with pervasive developmental disorder (404 boys, 85 girls). The mean age in the group was 8.0 ± 4.2 years (range...

Title: Specifics of swimming teaching children with autism spectrum disorder. Objectives: Application of the structured learning by the concept of common preparatory and basic swimming lessons for children with autism spectrum disorder. Presentation and evaluation of nine case studies and subsequent implementation of policy for teaching swimming to children with autism spectrum disorder. Methods: Analysis of specialized literature, case studies, surveys, interviews, scaling observation and statistics method. Results of the work: Methods of the structured learning support and facilitate the implementation of standard swimming lessons for children with autism spectrum disorder. The case studies confirm the effectiveness of our taught realized swimming lessons. The principles for swimming education of children with autism spectrum disorder are designed based on the above-mentioned examples of swimming lessons. Keywords: Autism Spectrum Disorders, structured teaching swimming lessons