Dataset Information

BOLD signal variability and complexity in children and adolescents with and without autism spectrum disorder.

ABSTRACT: Variability of neural signaling is an important index of healthy brain functioning, as is signal complexity, which relates to information processing capacity. Alterations in variability and complexity may underlie certain brain dysfunctions. Here, resting-state fMRI was used to examine variability and complexity in children and adolescents with and without autism spectrum disorder (ASD). Variability was measured using the mean square successive difference (MSSD) of the time series, and complexity was assessed using sample entropy. A categorical approach was implemented to determine if the brain measures differed between diagnostic groups (ASD and controls). A dimensional approach was used to examine the continuum of relationships between each brain measure and behavioral severity, age, IQ, and the global efficiency (GE) of each participant's structural connectome, which reflects the structural capacity for information processing. Using the categorical approach, no significant group differences were found for neither MSSD nor entropy. The dimensional approach revealed significant positive correlations between each brain measure, GE, and age. Negative correlations were observed between each brain measure and the severity of ASD behaviors across all participants. These results reveal the nature of variability and complexity of BOLD signals in children and adolescents with and without ASD.

SUBMITTER: Easson AK

PROVIDER: S-EPMC6969202 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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BOLD signal variability and complexity in children and adolescents with and without autism spectrum disorder.

Easson Amanda K AK McIntosh Anthony R AR

Developmental cognitive neuroscience 20190305

Variability of neural signaling is an important index of healthy brain functioning, as is signal complexity, which relates to information processing capacity. Alterations in variability and complexity may underlie certain brain dysfunctions. Here, resting-state fMRI was used to examine variability and complexity in children and adolescents with and without autism spectrum disorder (ASD). Variability was measured using the mean square successive difference (MSSD) of the time series, and complexit ...[more]

PMID: 30878549

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Project description:BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Project description:Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase (GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase (GAMT gene), and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher's exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum disorder (ASD) in children.

Dataset Information

BOLD signal variability and complexity in children and adolescents with and without autism spectrum disorder.

Publications

BOLD signal variability and complexity in children and adolescents with and without autism spectrum disorder.

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