Dataset Information

White Matter Alterations in Infants at Risk for Developmental Dyslexia.

ABSTRACT: Developmental dyslexia (DD) is a heritable condition characterized by persistent difficulties in learning to read. White matter alterations in left-lateralized language areas, particularly in the arcuate fasciculus (AF), have been observed in DD, and diffusion properties within the AF correlate with (pre-)reading skills as early as kindergarten. However, it is unclear how early these alterations can be observed. We investigated white matter structure in 14 infants with (FHD+; ages 6.6-17.6 months) and 18 without (FHD-; ages 5.1-17.6 months) familial risk for DD. Diffusion scans were acquired during natural sleep, and early language skills were assessed. Tractography for bilateral AF was reconstructed using manual and automated methods, allowing for independent validation of results. Fractional anisotropy (FA) was calculated at multiple nodes along the tracts for more precise localization of group differences. The analyses revealed significantly lower FA in the left AF for FHD+ compared with FHD- infants, particularly in the central portion of the tract. Moreover, expressive language positively correlated with FA across groups. Our results demonstrate that atypical brain development associated with DD is already present within the first 18 months of life, suggesting that the deficits associated with DD may result from altered structural connectivity in left-hemispheric regions.

SUBMITTER: Langer N

PROVIDER: S-EPMC6074795 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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White Matter Alterations in Infants at Risk for Developmental Dyslexia.

Langer Nicolas N Peysakhovich Barbara B Zuk Jennifer J Drottar Marie M Sliva Danielle D DD Smith Sara S Becker Bryce L C BL Grant P Ellen PE Gaab Nadine N

Cerebral cortex (New York, N.Y. : 1991) 20170201 2

Developmental dyslexia (DD) is a heritable condition characterized by persistent difficulties in learning to read. White matter alterations in left-lateralized language areas, particularly in the arcuate fasciculus (AF), have been observed in DD, and diffusion properties within the AF correlate with (pre-)reading skills as early as kindergarten. However, it is unclear how early these alterations can be observed. We investigated white matter structure in 14 infants with (FHD+; ages 6.6-17.6 month ...[more]

PMID: 26643353

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Project description:The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains.Based on a full-factorial analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores.We found that FA was reduced in the left arcuate fasciculus and splenium of the corpus callosum in subjects with versus without DCDC2d, irrespective of dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left hemisphere and in the corpus callosum; their counterpart without DCDC2d showed similar FA alterations. Noteworthy, a conjunction analysis in impaired readers revealed common regions with lower FA mainly in the left hemisphere. When we compared subjects with dyslexia with versus without DCDC2d, we found lower FA in the inferior longitudinal fasciculus and genu of the corpus callosum, bilaterally. Normal readers with versus without DCDC2d had FA increases and decreases in both the right and left hemisphere.The major contribution of our study was to provide evidence relating genes, brain and behaviour. Overall, our findings support the hypothesis that DCDC2d is associated with altered FA. In normal readers, DCDC2-related anatomical patterns may mark some developmental cognitive vulnerability to learning disabilities. In subjects with dyslexia, DCDC2d accounted for both common - mainly located in the left hemisphere - and unique - a more severe and extended pattern - alterations of white matter fibre tracts.

Project description:ImportanceMethamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development.ObjectiveTo investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences.Design, setting, and participantsA prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community.ExposuresPrenatal methamphetamine and/or tobacco exposure.Main outcomes and measuresQuantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method.ResultsOf the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02).Conclusions and relevancePrenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Dataset Information

White Matter Alterations in Infants at Risk for Developmental Dyslexia.

Publications

White Matter Alterations in Infants at Risk for Developmental Dyslexia.

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