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Abnormal auditory and language pathways in children with 16p11.2 deletion.

Berman JI, Chudnovskaya D, Blaskey L, Kuschner E, Mukherjee P, Buckner R, Nagarajan S, Chung WK, Spiro JE, Sherr EH, Roberts TP - Neuroimage Clin (2015)

Bottom Line: In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA ; Department of Radiology, Perelman School of Medicine University of Pennsylvania, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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f0005: 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.

Mentions: The left and right arcuate fasciculi were defined with deterministic DTI tractography using coronal starting and target regions of interest as previously described (Nagaeet al., 2012; Mori et al., 1999). Prior studies have indicated that a majority of left-handed individuals have left-hemispheric language dominance (Szaflarski et al., 2002; Pujol et al., 1999). Thus, left-hemispheric language dominance was assumed in all subjects. Probabilistic tractography using the solid angle q-ball HARDI reconstruction was used to delineate the auditory radiation from the thalamus to the auditory cortex (Berman et al., 2008). The starting and target regions of interest were generated with the white matter parcellation provided by Freesurfer applied to the structural imaging (Fischl et al., 1999). As previously shown, a HARDI tractography approach is necessary for traversing the crossing fibers within the auditory radiation (Berman et al., 2013). DTI (b = 1000 s/mm2) measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were made within the 3D region encompassed by the arcuate fasciculus and auditory radiation (Fig. 1). Radial diffusivity is the mean of the second and third eigenvalues of the diffusion tensor. In addition, the HARDI derived generalized fractional anisotropy (GFA) was measured within the auditory radiation.


Abnormal auditory and language pathways in children with 16p11.2 deletion.

Berman JI, Chudnovskaya D, Blaskey L, Kuschner E, Mukherjee P, Buckner R, Nagarajan S, Chung WK, Spiro JE, Sherr EH, Roberts TP - Neuroimage Clin (2015)

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.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543079&req=5

f0005: 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.
Mentions: The left and right arcuate fasciculi were defined with deterministic DTI tractography using coronal starting and target regions of interest as previously described (Nagaeet al., 2012; Mori et al., 1999). Prior studies have indicated that a majority of left-handed individuals have left-hemispheric language dominance (Szaflarski et al., 2002; Pujol et al., 1999). Thus, left-hemispheric language dominance was assumed in all subjects. Probabilistic tractography using the solid angle q-ball HARDI reconstruction was used to delineate the auditory radiation from the thalamus to the auditory cortex (Berman et al., 2008). The starting and target regions of interest were generated with the white matter parcellation provided by Freesurfer applied to the structural imaging (Fischl et al., 1999). As previously shown, a HARDI tractography approach is necessary for traversing the crossing fibers within the auditory radiation (Berman et al., 2013). DTI (b = 1000 s/mm2) measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were made within the 3D region encompassed by the arcuate fasciculus and auditory radiation (Fig. 1). Radial diffusivity is the mean of the second and third eigenvalues of the diffusion tensor. In addition, the HARDI derived generalized fractional anisotropy (GFA) was measured within the auditory radiation.

Bottom Line: In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA ; Department of Radiology, Perelman School of Medicine University of Pennsylvania, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.

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.

No MeSH data available.


Related in: MedlinePlus