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. 2015 Aug 1;9:50-7.
doi: 10.1016/j.nicl.2015.07.006. eCollection 2015.

Abnormal Auditory and Language Pathways in Children With 16p11.2 Deletion

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Free PMC article

Abnormal Auditory and Language Pathways in Children With 16p11.2 Deletion

Jeffrey I Berman et al. Neuroimage Clin. .
Free PMC article

Abstract

Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD). This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4-BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.

Keywords: 16p11.2 deletion; AD, axial diffusivity; ASD, autism spectrum disorder; Arcuate fasciculus; Auditory system; Autism; CELF, clinical evaluation of language fundamentals; CNV, copy number variation; DTI, diffusion tensor imaging; Diffusion MR; FA, fractional anisotropy; GFA, generalized fractional anisotropy; HARDI, high angular resolution diffusion imaging; Language; MD, mean diffusivity; RD, radial diffusivity.

Figures

Fig. 1
Fig. 1
Fiber tractography of the arcuate fasciculus from a 16p11.2 deletion carrier (panels A and C) and the auditory radiation from a control subject (panels B and D) are shown. The arcuate fasciculus images are sagittal and coronal projections of a 3D rendering. The auditory radiation images are axial and coronal slices through the delineated pathway.
Fig. 2
Fig. 2
Developmental trajectory of the arcuate fasciculus. Mean diffusivity decreases with age in both hemispheres. Deletion carriers exhibit higher mean diffusivity than controls (p < 0.005). The shaded regions represent the 95th percentile confidence interval of the lines. The slopes of the lines were not significantly different between groups. Deletion carriers with an ASD diagnosis are indicated with asterisk markers.
Fig. 3
Fig. 3
Developmental trajectory of the auditory radiation. Mean diffusivity significantly decreases with age in both hemispheres. Deletion carriers exhibit higher mean diffusivity than controls (p < 0.05). The shaded regions represent the 95th percentile confidence interval of the lines. The rate of maturation was not significantly different between groups. Deletion carriers with an ASD diagnosis are indicated with asterisk markers.
Fig. 4
Fig. 4
Correlation of diffusion metrics and language ability in the left hemisphere arcuate fasciculus. Deletion carriers with an ASD diagnosis are indicated with asterisk markers. Scatter plots include variance from covariates which are controlled for in the multivariate regression.

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