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High angular resolution diffusion imaging in a child with autism spectrum disorder and comparison with his unaffected identical twin.

ABSTRACT: In recent years, the use of brain diffusion MRI has led to the hypothesis that children with autism spectrum disorder (ASD) show abnormally connected brains. We used the model of disease-discordant identical twins to test the hypothesis that higher-order diffusion MRI protocols are able to detect abnormal connectivity in a single subject. We studied the structural connectivity of the brain of a child with ASD, and of that of his unaffected identical twin, using high angular resolution diffusion imaging (HARDI) probabilistic tractography. Cortical regions were automatically parcellated from high-resolution structural images, and HARDI-based connection matrices were produced for statistical comparison. Differences in diffusion indexes between subjects were tested by Wilcoxon signed rank test. Tracts were defined as discordant when they showed a between-subject difference of 10 percent or more. Around 11 percent of the discordant intra-hemispheric tracts showed lower fractional anisotropy (FA) values in the ASD twin, while only 1 percent showed higher values. This difference was significant. Our findings in a disease-discordant identical twin pair confirm previous literature consistently reporting lower FA values in children with ASD.

SUBMITTER: Conti E

PROVIDER: S-EPMC4610756 | biostudies-literature | 2015 Jul-Sep

REPOSITORIES: biostudies-literature

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High angular resolution diffusion imaging in a child with autism spectrum disorder and comparison with his unaffected identical twin.

Conti Eugenia E Pannek Kerstin K Calderoni Sara S Gaglianese Anna A Fiori Simona S Brovedani Paola P Scelfo Danilo D Rose Stephen S Tosetti Michela M Cioni Giovanni G Guzzetta Andrea A

Functional neurology 20150701 3

In recent years, the use of brain diffusion MRI has led to the hypothesis that children with autism spectrum disorder (ASD) show abnormally connected brains. We used the model of disease-discordant identical twins to test the hypothesis that higher-order diffusion MRI protocols are able to detect abnormal connectivity in a single subject. We studied the structural connectivity of the brain of a child with ASD, and of that of his unaffected identical twin, using high angular resolution diffusion ...[more]

PMID: 26446271

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Project description:BackgroundThe etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.MethodsA PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins.ResultsThe meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability.ConclusionsWe demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.

Project description:Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs).Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis.On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.

Project description:Magnetic Resonance Imaging (MRI) of the rodent brain at ultra-high magnetic fields (> 9.4 Tesla) offers a higher signal-to-noise ratio that can be exploited to reduce image acquisition time or provide higher spatial resolution. However, significant challenges are presented due to a combination of longer T1 and shorter T2/T2* relaxation times and increased sensitivity to magnetic susceptibility resulting in severe local-field inhomogeneity artefacts from air pockets and bone/brain interfaces. The Stejskal-Tanner spin echo diffusion-weighted imaging (DWI) sequence is often used in high-field rodent brain MRI due to its immunity to these artefacts. To accurately determine diffusion-tensor or fibre-orientation distribution, high angular resolution diffusion imaging (HARDI) with strong diffusion weighting (b >3000 s/mm2) and at least 30 diffusion-encoding directions are required. However, this results in long image acquisition times unsuitable for live animal imaging. In this study, we describe the optimization of HARDI acquisition parameters at 16.4T using a Stejskal-Tanner sequence with echo-planar imaging (EPI) readout. EPI segmentation and partial Fourier encoding acceleration were applied to reduce the echo time (TE), thereby minimizing signal decay and distortion artefacts while maintaining a reasonably short acquisition time. The final HARDI acquisition protocol was achieved with the following parameters: 4 shot EPI, b = 3000 s/mm2, 64 diffusion-encoding directions, 125×150 ?m2 in-plane resolution, 0.6 mm slice thickness, and 2h acquisition time. This protocol was used to image a cohort of adult C57BL/6 male mice, whereby the quality of the acquired data was assessed and diffusion tensor imaging (DTI) derived parameters were measured. High-quality images with high spatial and angular resolution, low distortion and low variability in DTI-derived parameters were obtained, indicating that EPI-DWI is feasible at 16.4T to study animal models of white matter (WM) diseases.

Dataset Information

High angular resolution diffusion imaging in a child with autism spectrum disorder and comparison with his unaffected identical twin.

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High angular resolution diffusion imaging in a child with autism spectrum disorder and comparison with his unaffected identical twin.

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