1. Barakova E, Gillessen J, Feijs L. {{Social training of autistic children with interactive intelligent agents}}. {J Integr Neurosci};2009 (Mar);8(1):23-34.
The ability of autistic children to learn by applying logical rules has been used widely in behavioral therapies for social training. We propose to teach social skills to autistic children through games that simultaneously stimulate social behavior and include recognition of elements of social interaction. For this purpose we created a multi-agent platform of interactive blocks, and we created appropriate games that require shared activities leading to a common goal. The games included perceiving and understanding elements of social behavior that non-autistic children can recognize. We argue that the importance of elements of social interaction such as perceiving interaction behaviors and assigning metaphoric meanings has been overlooked, and that they are very important in the social training of autistic children. Two games were compared by testing them with users. The first game focused only on the interaction between the agents and the other combined interaction between the agents and metaphoric meanings that are assigned to them. The results show that most of the children recognized the patterns of interaction as well as the metaphors when they were demonstrated through embodied agents and were included within games having features that engage the interest of this user group. The results also show the potential of the platform and the games to influence the social behavior of the children positively.
2. Freitag CM, Luders E, Hulst HE, Narr KL, Thompson PM, Toga AW, Krick C, Konrad C. {{Total Brain Volume and Corpus Callosum Size in Medication-Naive Adolescents and Young Adults with Autism Spectrum Disorder}}. {Biol Psychiatry};2009 (Apr 30)
BACKGROUND: Increased total brain volume (TBV) has been reported for children with autism spectrum disorder (ASD) but studies in older ASD subjects have been contradictory. Similarly, studies of corpus callosum (CC) area in ASD differ with regard to inclusion criteria, age, and IQ. METHODS: In the present study, TBV, gray matter (GM), and white matter (WM) volume as well as midsagittal CC area were compared between 15 medication-naive, high-functioning adolescent and young adult ASD subjects and 15 healthy control individuals, and correlations with visuomotor coordination and imitation abilities were explored. In addition, computational surface-based methods were implemented to encode callosal thickness at high spatial resolution. RESULTS: Total brain volume, GM, and WM were increased and CC area was decreased in ASD subjects, a finding that was predominantly due to ASD subjects with lower IQ. Positive correlations of IQ with volume measures were observed only in control subjects. Autism spectrum disorder subjects showed reduced thickness in the posterior part of the CC. White matter volume showed a trend for negative correlation with dynamic balance and imitation abilities across groups. CONCLUSIONS: This study replicates previous structural magnetic resonance imaging (MRI) findings in ASD, emphasizes the role of IQ differences, and adds some evidence for functional implications of structural findings.
3. Hu VW, Sarachana T, Kim KS, Nguyen A, Kulkarni S, Steinberg ME, Luu T, Lai Y, Lee NH. {{Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism}}. {Autism Res};2009 (May 5)
Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males.
4. Luyster R, Gotham K, Guthrie W, Coffing M, Petrak R, Pierce K, Bishop S, Esler A, Hus V, Oti R, Richler J, Risi S, Lord C. {{The Autism Diagnostic Observation Schedule-Toddler Module: A New Module of a Standardized Diagnostic Measure for Autism Spectrum Disorders}}. {J Autism Dev Disord};2009 (May 5)
The Autism Diagnostic Observation Schedule (ADOS; Lord et al., J Autism Dev Disord, 30(3):205-223, 2000) is widely accepted as a « gold standard » diagnostic instrument, but it is of restricted utility with very young children. The purpose of the current project was to modify the ADOS for use in children under 30 months of age. A modified ADOS, the ADOS Toddler Module (or Module T), was used in 360 evaluations. Participants included 182 children with best estimate diagnoses of ASD, non-spectrum developmental delay or typical development. A final set of protocol and algorithm items was selected based on their ability to discriminate the diagnostic groups. The traditional algorithm « cutoffs » approach yielded high sensitivity and specificity, and a new range of concern approach was proposed.
5. Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C. {{Abnormalities of intrinsic functional connectivity in autism spectrum disorders}}. {Neuroimage};2009 (Apr 28)
Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
6. Solomon M, Ozonoff S, Ursu S, Ravizza S, Cummings N, Ly S, Carter C. {{The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders}}. {Neuropsychologia};2009 (Apr 30)
Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control -the ability to maintain task context online to support adaptive functioning in the face of response competition-in 22 adolescents aged 12-18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. (226 words).
