Atypical functional connectivity during unfamiliar music listening in children with autism

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula.Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning.info:eu-repo/semantics/publishedVersio

Exploring the use of the verbal intelligence quotient as a proxy for language ability in autism spectrum disorder

Background: There is growing interest in understanding the brain and language associations in Autism Spectrum Disorder (ASD). A considerable number of studies investigating these associations have used the verbal intelligence quotient (VIQ) as their primary measure of language form and content. Given this current trend, we aimed to establish whether the VIQ could reliably be used as a measure of receptive and expressive language form and content in individuals with ASD and in typical development (TD). Method: We examined the VIQ standard scores derived from a Wechsler cognitive battery as well as receptive and expressive language standard scores from the Oral Written Language Scales – Second Edition (OWLS-II) of 714 participants aged 3–21 years: 488 with ASD and 226 with TD. Results: Regression analyses revealed that VIQ scores predicted greater variance in receptive and expressive language scores in males with ASD relative to males with TD, and predicted less variance in receptive and expressive language scores in females with ASD relative to females with TD. Overall, VIQ accounted for a small proportion of variance in receptive and expressive language scores. Conclusions: Our findings indicate that the VIQ does not accurately capture language form and content evaluated by language measures like the OWLS-II, but may perhaps be used as a proxy for language content only

A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting more than 1% of children. It is characterized by social communication deficits and repetitive behaviors/restricted interests. In the absence of any medications known to improve core symptom domains, parents often use complementary alternative treatments, including omega-3 fatty acid supplements. Methods We conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD. Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory (PDDBI) and the externalizing problems score of the Behavior Assessment System for Children (BASC-2). Secondary outcome measures included clinical global improvement (Clinical Global Impression-Improvement (CGI-I)), adaptive function (Vineland Adaptive Behavior Scale (VABS-II)), and language gains (Preschool Language Scale (PLS-4)), as well as safety. Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response. Results Thirty-eight participants were randomized in a 1:1 fashion. There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores (p = 0.5). There was a significant group by week interaction on the BASC-2 externalizing problem score, with participants randomized to the treatment group demonstrating worsening scores (p = 0.02). There was no statistically significant week by group effect on either adaptive function (p = 0.09) or language (p = 0.6). Omega-3s were relatively well tolerated. Changes in cytokines during the study did not significantly correlate with treatment response. Conclusions This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD. Trial registration Clinicaltrials.gov NCT01248728 . Registered 22 November 2010

Cross-Diagnosis Structural Correlates of Autistic-Like Social Communication Differences

Social communication differences are seen in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD), but the brain mechanisms contributing to these differences remain largely unknown. To address this gap, we used a data-driven and diagnosis-agnostic approach to discover brain correlates of social communication differences in ASD, ADHD, and OCD, and subgroups of individuals who share similar patterns of brain-behavior associations. A machine learning pipeline (regression clustering) was used to discover the pattern of association between structural brain measures (volume, surface area, and cortical thickness) and social communication abilities. Participants (n = 416) included children with a diagnosis of ASD (n = 192, age = 12.0[5.6], 19% female), ADHD (n = 109, age = 11.1[4.1], 18% female), or OCD (n = 50, age = 12.3[4.2], 42% female), and typically developing controls (n = 65, age = 11.6[7.1], 48% female). The analyses revealed (1) associations with social communication abilities in distributed cortical and subcortical networks implicated in social behaviors, language, attention, memory, and executive functions, and (2) three data-driven, diagnosis-agnostic subgroups based on the patterns of association in the above networks. Our results suggest that different brain networks may contribute to social communication differences in subgroups that are not diagnosis-specific

A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder

International audienceAutism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3 , a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention

Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic

Genomic architecture of autism from comprehensive whole-genome sequence annotation

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic. [Display omitted] •New MSSNG release contains WGS from 11,312 individuals from families with ASD•Extensive variant data available, including SNVs/indels, SVs, tandem repeats, and PRS•Annotation reveals 134 ASD-associated genes, plus SVs not detectable without WGS•Rare, dominant variation has a prominent role in multiplex ASD The latest release of the Autism Speaks MSSNG resource provides an expanded sample size and facilitates the comprehensive examination of the roles of many types of genetic variation in autism spectrum disorder

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD