White Matter Alterations in Infants at Risk for Developmental Dyslexia.
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ABSTRACT:
SUBMITTER: Langer N
PROVIDER: S-EPMC6074795 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chinese is a logographic language that is different from alphabetic languages in visual and semantic complexity. Thus far, it is still unclear whether Chinese children with dyslexia show similar disruption of white matter pathways as in alphabetic languages. The present study focused on the alteration of white matter pathways in Chinese children with dyslexia. Using diffusion tensor imaging tractography, the bilateral arcuate fasciculus (AF-anterior, AF-posterior and AF-direct segments), inferior fronto-occipital fasciculus (IFOF) and inferior longitudinal fasciculus (ILF) were delineated in each individual's native space. Compared with age-matched controls, Chinese children with dyslexia showed reduced fractional anisotropy in the left AF-direct and the left ILF. Further regression analyses revealed a functional dissociation between the left AF-direct and the left ILF. The AF-direct tract integrity was associated with phonological processing skill, an ability important for reading in all writing systems, while the ILF integrity was associated with morphological processing skill, an ability more strongly recruited for Chinese reading. In conclusion, the double disruption locus in Chinese children with dyslexia, and the functional dissociation between dorsal and ventral pathways reflect both universal and specific properties of reading in Chinese.
| S-EPMC6969203 | biostudies-literature
Project description:A number of studies have shown an abnormal connectivity of certain white matter pathways in developmental dyslexia, as well as correlations between these white matter pathways and behavioral deficits. However, whether developmental dyslexia presents broader white matter network connectivity disruption is currently unknown. The present study reconstructed white matter networks for 26 dyslexic children (11.61?±?1.31 years) and 31 age-matched controls (11.49?±?1.36 years) using constrained spherical deconvolution tractography. Network-based statistics (NBS) analysis was performed to identify network connectivity deficits in dyslexic individuals. Network topological features were measured based on graph theory to examine whether these parameters correlate with literacy skills, and whether they explain additional variance over previously established white matter connectivity abnormalities in dyslexic children. The NBS analysis identified a network connecting the left-occipital-temporal cortex and temporo-parietal cortex that had decreased streamlines in dyslexic children. Four network topological parameters (clustering coefficient, local efficiency, transitivity, and global efficiency) were positively correlated with literacy skills of dyslexic children, and explained a substantial proportion of additional variance in literacy skills beyond connectivity measures of white matter pathways. This study for the first time reports a disconnection in a local subnetwork in the left hemisphere in dyslexia and shows that the global white matter network topological properties contribute to reduced literacy skills in dyslexic children.
| S-EPMC6865529 | biostudies-literature
Project description:Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals.
| S-EPMC6867308 | biostudies-literature
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.
| S-EPMC6467201 | biostudies-literature
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.
| S-EPMC5975637 | biostudies-literature
Project description:The present study investigated whether children with a typical dyslexia profile and children with isolated spelling deficits show a distinct pattern of white matter alteration compared with typically developing peers. Relevant studies on the topic are scarce, rely on small samples, and often suffer from the limitations of conventional tensor-based methods. The present Constrained Spherical Deconvolution study includes 27 children with typical reading and spelling skills, 21 children with dyslexia and 21 children with isolated spelling deficits. Group differences along major white matter tracts were quantified utilizing the Automated Fiber Quantification software and a lateralization index was calculated in order to investigate the structural asymmetry of the tracts. The two deficit groups mostly displayed different patterns of white matter alterations, located in the bilateral inferior longitudinal fasciculi, right superior longitudinal fasciculus, and cingulum for the group with dyslexia and in the left arcuate fasciculus for the group with isolated spelling deficits. The two deficit groups differed also with respect to structural asymmetry. Children with dyslexia did not show the typical leftward asymmetry of the arcuate fasciculus, whereas the group with isolated spelling deficits showed absent rightward asymmetry of the inferior fronto-occipital fasciculus. This study adds evidence to the notion that different profiles of combined or isolated reading and spelling deficits are associated with different neural signatures.
| S-EPMC6492145 | biostudies-literature
Project description:The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions.
| S-EPMC3423424 | biostudies-literature
Project description:BackgroundSchizophrenia is considered a neurodevelopmental disorder with a pathophysiology that likely begins long before the onset of clinical symptoms. White matter abnormalities have been observed in schizophrenia and we hypothesized that the first 2 years of life is a period in which white matter abnormalities associated with schizophrenia risk may emerge.Methods38 infants at high risk for schizophrenia and 202 healthy controls underwent diffusion tensor MRIs after birth and at 1 and 2 years of age. Quantitative tractography was used to determine diffusion properties (fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD)) of 18 white matter tracts and a general linear model was used to analyze group differences at each age.ResultsAdjusting gestational age at birth, postnatal age at MRI, gender, MRI scanner type, and maternal education, neonates at high risk had significantly lower FA (p = 0.02) and AD (p = 0.03) in the superior segment of the left cingulate, and higher RD in the hippocampal segment of the left cingulate (p = 0.04). High risk one year olds had significantly lower FA (p < 0.01) and AD (p = 0.02) in the hippocampal segment of the left cingulate. High risk two year olds had significantly lower FA in the left prefrontal cortico-thalamic tract (p = 0.04) and higher RD in the right uncinate fasciculus (p = 0.04). None of the tract differences remained significant after correction for multiple comparisons.ConclusionsThere is evidence of abnormal white matter development in young children at risk for schizophrenia, especially in the hippocampal segment of left cingulum. These results support the neurodevelopmental theory of schizophrenia and indicate that impaired white matter may be present in early childhood.
| S-EPMC6689450 | biostudies-literature
Project description:BackgroundCausal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known.MethodsThe study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6 months (T1) at approximately annual intervals on tasks tapping cognitive, language, and executive-motor skills. The children were recruited to three groups: children at family risk of dyslexia, children with concerns regarding speech, and language development at 3;06 years and controls considered to be typically developing. At 8 years, children were classified as 'dyslexic' or not. Logistic regression models were used to predict the individual risk of dyslexia and to investigate how risk factors accumulate to predict poor literacy outcomes.ResultsFamily-risk status was a stronger predictor of dyslexia at 8 years than low language in preschool. Additional predictors in the preschool years include letter knowledge, phonological awareness, rapid automatized naming, and executive skills. At the time of school entry, language skills become significant predictors, and motor skills add a small but significant increase to the prediction probability. We present classification accuracy using different probability cutoffs for logistic regression models and ROC curves to highlight the accumulation of risk factors at the individual level.ConclusionsDyslexia is the outcome of multiple risk factors and children with language difficulties at school entry are at high risk. Family history of dyslexia is a predictor of literacy outcome from the preschool years. However, screening does not reach an acceptable clinical level until close to school entry when letter knowledge, phonological awareness, and RAN, rather than family risk, together provide good sensitivity and specificity as a screening battery.
| S-EPMC4672694 | biostudies-literature
Project description:Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes.Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30?wk gestation imaged up to four times from 26-42?wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ?2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age.FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle.This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.
| S-EPMC4724306 | biostudies-literature