Vocabulary is important for some, but not all reading skills

Although there is evidence for a close link between the development of oral vocabulary and reading comprehension, less clear is whether oral vocabulary skills relate to the development of word-level reading skills. This study investigated vocabulary and literacy in 81 children of 8-10 years. In regression analyses, vocabulary accounted for unique variance in exception word reading and reading comprehension, but not text reading accuracy, decoding and regular word reading. Consistent with these data, children with poor reading comprehension exhibited oral vocabulary weaknesses and read fewer exception words correctly. These findings demonstrate that oral vocabulary is associated with some, but not all reading skills. Results are discussed in terms of current models of reading development

Investigating orthographic and semantic aspects of word learning in poor comprehenders

This study compared orthographic and semantic aspects of word learning in children who differed in reading comprehension skill. Poor comprehenders and controls matched for age (9-10 years), nonverbal ability and decoding skill were trained to pronounce 20 visually presented nonwords, 10 in a consistent way and 10 in an inconsistent way. They then had an opportunity to infer the meanings of the new words from story context. Orthographic learning was measured in three ways: the number of trials taken to learn to pronounce nonwords correctly, orthographic choice and spelling. Across all measures, consistent items were easier than inconsistent items and poor comprehenders did not differ from control children. Semantic learning was assessed on three occasions, using a nonword-picture matching task. While poor comprehenders showed equivalent semantic learning to controls immediately after exposure to nonword meaning, this knowledge was not well-retained over time. Results are discussed in terms of the language and reading skills of poor comprehenders and in relation to current models of reading development

Measurement of language laterality using functional transcranial Doppler ultrasound: a comparison of different tasks [version 2; referees: 2 approved]

Background: Relative blood flow in the two middle cerebral arteries can be measured using functional transcranial Doppler sonography (fTCD) to give an index of lateralisation as participants perform a specific task. Language laterality has mostly been studied with fTCD using a word generation task, but it is not clear whether this is optimal. Methods: Using fTCD, we evaluated a sentence generation task that has shown good reliability and strong left lateralisation in fMRI. We interleaved trials of word generation, sentence generation and list generation and assessed agreement of these tasks in 31 participants (29 right-handers). Results: Although word generation and sentence generation both gave robust left-lateralisation, Bland-Altman analysis showed that these two methods were not equivalent. The comparison list generation task was not systematically lateralised, but nevertheless laterality indices (LIs) from this task were significantly correlated with the other two tasks. Subtracting list generation LI from sentence generation LI did not affect the strength of the laterality index. Conclusions: This was a pre-registered methodological study designed to explore novel approaches to optimising measurement of language lateralisation using fTCD. It confirmed that sentence generation gives robust left lateralisation in most people, but is not equivalent to the classic word generation task. Although list generation does not show left-lateralisation at the group level, the LI on this task was correlated with left-lateralised tasks. This suggests that word and sentence generation involve adding a constant directional bias to an underlying continuum of laterality that is reliable in individuals but not biased in either direction. In future research we suggest that consistency of laterality across tasks might have more functional significance than strength or direction of laterality on any one task

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis [version 1; referees: 2 approved]

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions.  Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.

The neuronal migration hypothesis of dyslexia : a critical evaluation 30 years on

This work was supported by the Wellcome Trust (092071/Z/10/Z to A.P.M., Z.M. and A.V.-B., and 082498/Z/07/Z to D.V.M.B.); L.G.G. receive a Doctoral Training Award from the Medical Research Council; S.P. is a Royal Society University Research Fellow.The capacity for language is one of the key features underlying the complexity of human cognition and its evolution. However, little is known about the neurobiological mechanisms that mediate normal or impaired linguistic ability. For developmental dyslexia, early postmortem studies conducted in the 1980s linked the disorder to subtle defects in the migration of neurons in the developing neocortex. These early studies were reinforced by human genetic analyses that identified dyslexia susceptibility genes and subsequent evidence of their involvement in neuronal migration. In this review, we examine recent experimental evidence that does not support the link between dyslexia and neuronal migration. We critically evaluate gene function studies conducted in rodent models and draw attention to the lack of robust evidence from histopathological and imaging studies in humans. Our review suggests that the neuronal migration hypothesis of dyslexia should be reconsidered, and the neurobiological basis of dyslexia should be approached with a fresh start.PreprintPublisher PDFPeer reviewe

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome

Generalized Structured Component Analysis in candidate gene association studies: applications and limitations

Background: Generalized Structured Component Analysis (GSCA) is a component-based alternative to traditional covariance-based structural equation modelling. This method has previously been applied to test for association between candidate genes and clinical phenotypes, contrasting with traditional genetic association analyses that adopt univariate testing of many individual single nucleotide polymorphisms (SNPs) with correction for multiple testing. Methods: We first evaluate the ability of the GSCA method to replicate two previous findings from a genetics association study of developmental language disorders. We then present the results of a simulation study to test the validity of the GSCA method under more restrictive data conditions, using smaller sample sizes and larger numbers of SNPs than have previously been investigated. Finally, we compare GSCA performance against univariate association analysis conducted using PLINK v1.9. Results: Results from simulations show that power to detect effects depends not just on sample size, but also on the ratio of SNPs with effect to number of SNPs tested within a gene. Inclusion of many SNPs in a model dilutes true effects. Conclusions: We propose that GSCA is a useful method for replication studies, when candidate SNPs have been identified, but should not be used for exploratory analysis

Stage 1 Registered Report: The relationship between handedness and language ability in children [version 1; referees: 2 approved]

Weak or inconsistent hand preference may be a risk factor for developmental language delay.  This study will test the extent to which variations in language skills are associated with the strength of hand preference. Data are drawn from a large sample (n = 569) of 6- to 7-year-old children unselected for ability, assessed at two time points, 6 months apart. Hand preference is assessed using the Quantitative Hand Preference task (QHP) and five uni-manual motor tasks. Language skills (expressive and receptive vocabulary, receptive grammar, and morphological awareness) are assessed with standardized measures. If weak cerebral lateralisation (as assessed by the QHP task) is a risk factor for language difficulties, it should be possible to detect such effects in the large representative sample of children examined here