Simple mindreading abilities predict complex theory of mind: developmental delay in autism spectrum disorders

Theory of Mind (ToM) is impaired in individuals with Autism Spectrum Disorders (ASD). The aims of this study were to: i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and ii) to assess if a ToM simple test known as Eyes-test could predict performance on the more advanced ToM task, i.e. Comic Strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry

Postural Hypo-Reactivity in Autism is Contingent on Development and Visual Environment: A Fully Immersive Virtual Reality Study

Although atypical motor behaviors have been associated with autism, investigations regarding their possible origins are scarce. This study assessed the visual and vestibular components involved in atypical postural reactivity in autism. Postural reactivity and stability were measured for younger (12–15 years) and older (16–33 years) autistic participants in response to a virtual tunnel oscillating at different frequencies. At the highest oscillation frequency, younger autistic participants showed significantly less instability compared to younger typically-developing participants; no such group differences were evidenced for older participants. Additionally, no significant differences in postural behavior were found between all 4 groups when presented with static or without visual information. Results confirm that postural hypo-reactivity to visual information is present in autism, but is contingent on both visual environment and development

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study

<p>Abstract</p> <p>Background</p> <p>The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact.</p> <p>Methods</p> <p>Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls.</p> <p>Results</p> <p>Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (<it>P </it>< 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz).</p> <p>Conclusions</p> <p>Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks.</p

The Latent Structure of Autistic Traits:A Taxometric, Latent Class and Latent Profile Analysis of the Adult Autism Spectrum Quotient

Autistic traits are widely thought to operate along a continuum. A taxometric analysis of Adult Autism Spectrum Quotient data was conducted to test this assumption, finding little support but identifying a high severity taxon. To understand this further, latent class and latent profile models were estimated that indicated the presence of six distinct subtypes: one with little probability of endorsing any autistic traits, one engaging in ‘systemising’ behaviours, three groups endorsing multiple components of Wing and Gould’s autistic triad, and a group similar in size and profile to the taxon previously identified. These analyses suggest the AQ (and potentially by extension autistic traits) have a categorical structure. These findings have important implications for the analysis and interpretation of AQ data

Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

International audienc

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

BackgroundTargeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing.ResultsAll panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden.ConclusionThis comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.Peer reviewe

The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes

Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype

Cognition and Behaviour in Sotos Syndrome: A Systematic Review

BACKGROUND:Research investigating cognition and behaviour in Sotos syndrome has been sporadic and to date, there is no published overview of study findings. METHOD:A systematic review of all published literature (1964-2015) presenting empirical data on cognition and behaviour in Sotos syndrome. Thirty four journal articles met inclusion criteria. Within this literature, data relating to cognition and/or behaviour in 247 individuals with a diagnosis of Sotos syndrome were reported. Ten papers reported group data on cognition and/or behaviour. The remaining papers employed a case study design. RESULTS:Intelligence quotient (IQ) scores were reported in twenty five studies. Intellectual disability (IQ < 70) or borderline intellectual functioning (IQ 70-84) was present in the vast majority of individuals with Sotos syndrome. Seven studies reported performance on subscales of intelligence tests. Data from these studies indicate that verbal IQ scores are consistently higher than performance IQ scores. Fourteen papers provided data on behavioural features of individuals with Sotos syndrome. Key themes that emerged in the behavioural literature were overlap with ASD, ADHD, anxiety and high prevalence of aggression/tantrums. CONCLUSION:Although a range of studies have provided insight into cognition and behaviour in Sotos syndrome, specific profiles have not yet been fully specified. Recommendations for future research are provided