Quantitative multidimensional phenotypes improve genetic analysis of laterality traits.

Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h2, n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2 for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h2 reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.

Electroencephalography decoding of Chinese characters in primary school children and its prediction for word reading performance and development.

Research on what neural mechanisms facilitate word reading development in non-alphabetic scripts is relatively rare. The present study was among the first to adopt a multivariate pattern classification analysis to decode electroencephalographic signals recorded for primary school children (N = 236) while performing a Chinese character decision task. Chinese is an ideal script for studying the relationship between neural discriminability (i.e., decodability) of the orthography and behavioral word reading skills since the mapping from orthography to phonology is relatively arbitrary in Chinese. This was also among the first empirical attempts to examine the extent to which decoding performance can predict current and subsequent word reading skills using a longitudinal design. Results showed that neural activation patterns of real characters can be distinguished from activation patterns for pseudo-characters, non-characters, and random stroke combinations in both younger and older children. Topography of the transformed classifier weights revealed two distinct cognitive sub-processes underlying single character recognition, but temporal generalization analysis suggested common neural mechanisms between the distinct cognitive sub-processes. Suggestive evidence from correlational and hierarchical regression analyses showed that decoding performance, assessed on average 2 months before the year 2 behavioral testing, predicted both year 1 word reading performance and the development of word reading fluency over the year. Results demonstrate that decoding performance, one indicator of how the neural system is functionally organized in processing characters and character-like stimuli, can serve as a useful neural marker in predicting current word reading skills and the capacity to learn to read.

Study of Genetic Association With DCDC2 and Developmental Dyslexia in Hong Kong Chinese Children.

BACKGROUND: Doublecortin domain-containing 2 (DCDC2) is a doublecortin domain-containing gene family member and the doublecortin domain has been demonstrated to bind to tubulin and enhance microtubule polymerization. It has been associated with developmental dyslexia and this protein family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. OBJECTIVES: The objective of the study is to find out if there is any association of genetic variants of DCDC2 with developmental dyslexia in Chinese children from Hong Kong. METHODS: The dyslexic children were diagnosed as developmental dyslexia (DD) using the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD) by the Department of Health, Hong Kong. Saliva specimens were collected and their genotypes of DCDC2 were studied by DNA sequencing or TaqMan Real Time PCR Assays. RESULTS: The most significant marker is rs6940827 which is associated with DD with nominal p-value (0.011). However, this marker did not remain significant after multiple testing corrections and the adjusted p-value from permutation test was 0.1329. Using sliding window haplotype analysis, several haplotypes were found to be nominally associated with DD. The smallest nominal p values was 0.0036 (rs2996452-rs1318700, C-A). However, none of the p values could withstand the multiple testing corrections. CONCLUSION: Despite early findings that DCDC2 is a strong candidate for developmental dyslexia and that some of the genetic variants have been linked to brain structure and functions, our findings showed that DCDC2 is not strongly associated with dyslexia.

Defective Number Sense or Impaired Access? Differential Impairments in Different Subgroups of Children With Mathematics Difficulties.

Developmental dyscalculia (DD) is a specific learning disability in mathematics that affects around 6% of the population. Currently, the core deficit of DD remains unknown. While the number sense deficit hypothesis suggests that the core deficit of DD lies in the inability to represent nonsymbolic numerosity, the access deficit hypothesis suggests that the origin of this disability lies in the inability to associate numbers with the underlying magnitude representation. The present study compared the performance of DDs with their low-achieving (LA) and normally achieving peers in nonsymbolic numerosity processing and number-magnitude mapping over 1 year (from kindergarten to 1st grade). The results demonstrated differential impairments in different subgroups of children with mathematics difficulties. While DDs showed deficits in both nonsymbolic numerosity processing and number-magnitude mapping, LAs showed deficit only in the number-magnitude mapping. Furthermore, the deficit in number-magnitude mapping among the DD group was partially explained by their number sense deficit. The number sense deficit hypothesis is supported. Theoretical and practical implications are discussed.

Auditory perception and word recognition in Cantonese-Chinese speaking children with and without Specific Language Impairment.

Auditory processing and spoken word recognition difficulties have been observed in Specific Language Impairment (SLI), raising the possibility that auditory perceptual deficits disrupt word recognition and, in turn, phonological processing and oral language. In this study, fifty-seven kindergarten children with SLI and fifty-three language-typical age-matched controls were assessed with a speech-gating task to measure spoken word recognition, psychophysical tasks to measure auditory Frequency Modulation (FM) detection and Frequency Discrimination (FD), and standardized psychometric tests of phonological processing and oral language. As a group, children with SLI took significantly longer than language-typical controls to recognize words with high neighborhood density, perhaps reflecting subpar phonological representations. FM, but not FD, was significantly worse in SLI. However, while both poorer speech-gating performance and poorer auditory thresholds (FM) were evident in SLI, spoken word recognition did not mediate any relation between auditory perception and either phonological processing or oral language.

Syntactic and discourse skills in Chinese adolescent readers with dyslexia: a profiling study.

This study aims to investigate the relation of syntactic and discourse skills to morphological skills, rapid naming, and working memory in Chinese adolescent readers with dyslexia and to examine their cognitive-linguistic profiles. Fifty-two dyslexic readers (mean age, 13;42) from grade 7 to 9 in Hong Kong high schools were compared with 52 typically developing readers of the same chronological age (mean age, 13;30) in the measures of word reading, 1-min word reading, reading comprehension, morpheme discrimination, morpheme production, morphosyntactic knowledge, sentence order knowledge, digit rapid naming, letter rapid naming, backward digit span, and non-word repetition. Results showed that dyslexic readers performed significantly worse than their peers on all the cognitive-linguistic tasks. Analyses of individual performance also revealed that over half of the dyslexic readers exhibited deficits in syntactic and discourse skills. Moreover, syntactic skills, morphological skills, and rapid naming best distinguished dyslexic from non-dyslexic readers. Findings underscore the significance of syntactic and discourse skills for understanding reading impairment in Chinese adolescent readers.

Identification of children with mathematics learning disabilities (MLDs) using latent class growth analysis.

The traditional way of identifying children with mathematics learning disabilities (MLDs) using the low-achievement method with one-off assessment suffers from several limitations (e.g., arbitrary cutoff, measurement error, lacking consideration of growth). The present study attempted to identify children with MLD using the latent growth modelling approach, which minimizes the above potential problems. Two hundred and ten Chinese-speaking children were classified into five classes based on their arithmetic performance over 3 years. Their performance on various number-related cognitive measures was also assessed. A potential MLD class was identified, which demonstrated poor achievement over the 3 years and showed smaller improvement over time compared with the average-achieving class. This class had deficits in all number-related cognitive skills, hence supporting the number sense deficit hypothesis. On the other hand, another low-achieving class, which showed little improvement in arithmetic skills over time, was also identified. This class had an average cognitive profile but a low SES. Interventions should be provided to both low-achieving classes according to their needs.

Contrasting deficits on executive functions in Chinese delinquent adolescents with attention deficit and hyperactivity disorder symptoms and/or reading disability.

Many studies reported high prevalence of reading disability (RD) and attention deficit hyperactivity disorder (ADHD) among delinquent adolescents. Very few have examined their cognitive profile. The present study compared the executive functions (EFs) and severity of delinquency in delinquent adolescents with RD and/or ADHD symptoms (AS). Delinquents with AS (n=29), RD (n=24), comorbidity AS+RD (n=35) were recruited from juvenile institutions along with typically developing controls (n=29) from local schools; all completed EF assessments and self-report questionnaires on delinquency. Results showed that pure AS group exhibited impaired inhibition while the pure RD group was weak in processing speed and visual memory. The comorbidity group showed unique impairments in interference control and significantly higher delinquency severity. The present findings suggest that comorbidity AS+RD may influence delinquency severity. It also provides a more comprehensive picture of the unique EF deficits associated with different groups, allowing for better matching for future identification and intervention programme.

Contributions of syntactic awareness to reading in Chinese-speaking adolescent readers with and without dyslexia.

This study investigated the relative contribution of syntactic awareness to Chinese reading among Chinese-speaking adolescent readers with and without dyslexia. A total of 78 junior high school students in Hong Kong, 26 dyslexic adolescent readers, 26 average adolescent readers of the same age (chronological age control group) and 26 younger readers matched with the same reading level (reading-level group) participated and were administered measures of IQ, syntactic awareness, morphological awareness, vocabulary knowledge, working memory, word reading, and reading comprehension. Results showed that dyslexic readers scored significantly lower than chronological age but similarly to reading level control groups in most measures, especially in the areas of syntactic skills. Analyses of individual data also revealed that over half of the dyslexic readers exhibited certain aspects of deficits in syntactic skills. In regression analyses, syntactic skills were the strongest predictors of ability in word reading and reading comprehension measures. This study highlights the uniquely important correlates of syntactic skills in Chinese reading acquisition and impairment.

Cognitive skills and literacy performance of Chinese adolescents with and without dyslexia.

The present study sought to identify cognitive abilities that might distinguish Hong Kong Chinese adolescents with dyslexia and to assess how these abilities were associated with Chinese word reading, word dictation, and reading comprehension. The cognitive skills of interest were morphological awareness, visual-orthographic knowledge, rapid naming, and verbal working memory. A total of 90 junior secondary school students, 30 dyslexic, 30 chronological age controls, and 30 reading level controls was tested on a range of cognitive and literacy tasks. Dyslexic students were less competent than the control students in all cognitive and literacy measures. The regression analyses also showed that verbal working memory, rapid naming, morphological awareness, and visual-orthographic knowledge were significantly associated with literacy performance. Findings underscore the importance of these cognitive skills for Chinese literacy acquisition. Overall, this study highlights the persistent difficulties of Chinese dyslexic adolescents who seem to have multiple causes for reading and spelling difficulties.

Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children.

BACKGROUND: Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. METHOD AND RESULTS: Eight single nucleotide polymorphisms (SNPs) were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (p(corrected) = 0.0072). This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. CONCLUSION: Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

The nature of the automatization deficit in Chinese children with dyslexia.

Clarifying whether automatization deficits constitute the primary causes or symptoms of developmental dyslexia, we focused on three critical issues of the dyslexic automatization deficit, namely universality, domain specificity, and severity. Thirty Chinese dyslexic children (mean age 10 years and 5 months), 30 chronological-age-, and 30 reading-level-matched children were tested in 4 areas of automaticity: motor, visual search, Stroop facilitation effects, and automatic word recognition. The results showed that the dyslexic children performed significantly worse than the CA-controls but not the RL-controls in all the tasks except for Stroop congruent-color words, on which they performed worse than children in both control groups. The deficits reflect a lag in reading experiences rather than a persistent cognitive deficit.

Perception of tone and aspiration contrasts in Chinese children with dyslexia.

BACKGROUND: Previous research has shown a relationship between speech perception and dyslexia in alphabetic writing. In these studies speech perception was measured using phonemes, a prominent feature of alphabetic languages. Given the primary importance of lexical tone in Chinese language processing, we tested the extent to which lexical tone and aspiration, two fundamental dimensions of Cantonese speech not represented in writing, would distinguish dyslexic from non-dyslexic 8-year-old Chinese children. Tone and aspiration were tested in addition to other phonological processing skills across groups to determine the importance of different aspects of phonological sensitivity in relation to reading disability. METHODS: Dyslexic children and age-matched and reading-level controls were tested on their categorical perception of minimal pairs contrasting in tone and aspiration, phonological awareness, rapid digit naming, and Chinese reading abilities. RESULTS: While performing similarly to reading-level controls, dyslexic children perceived tone and aspiration contrasts less categorically and accurately than age-matched controls. They also performed more poorly than the age-matched controls on rapid digit naming and a measure of phonological awareness testing children's sensitivity to different grain size units. CONCLUSIONS: Dyslexia in non-alphabetic Chinese correlates with the categorical organization and accuracy of Cantonese speech perception, along the tone and aspiration dimensions. This association with reading is mediated by its association with phonological awareness. Therefore, dyslexia is universally at least partly a function of basic speech and phonological processes independent of whether the speech dimensions in question are coded in writing.

The role of visual and auditory temporal processing for Chinese children with developmental dyslexia.

This study examined temporal processing in relation to Chinese reading acquisition and impairment. The performances of 26 Chinese primary school children with developmental dyslexia on tasks of visual and auditory temporal order judgement, rapid naming, visual-orthographic knowledge, morphological, and phonological awareness were compared with those of 26 reading level ability controls (RL) and 26 chronological age controls (CA). Dyslexic children performed worse than the CA group but similar to the RL group on measures of accurate processing of auditory and visual-order stimuli, rapid naming, morphological awareness, and phonological awareness and a minority performed worse on the two temporal processing tasks. However, hierarchical regression analyses revealed that visual but not auditory temporal processing contributed unique variance to Chinese character recognition even with other cognitive measures controlled, suggesting it may be as important a correlate of reading ability in Chinese as in alphabetic scripts.

In search of subtypes of Chinese developmental dyslexia.

The dual-route model offers a popular way to classify developmental dyslexia into phonological and surface subtypes. The current study examined whether this dual-route model could provide a framework for understanding the varieties of Chinese developmental dyslexia. Three groups of Chinese children (dyslexics, chronological-age controls, and reading-level controls) were tested on Chinese exception character reading, pseudocharacter reading (analogous to English nonword reading), novel word learning, and some phonological and orthographic skills. It was found that Chinese exception character reading and pseudocharacter reading were highly correlated and that orthographic skills was a better predictor of both Chinese exception character and pseudocharacter reading than was phonological skills. More than half (62%) of the children in the dyslexia sample were classified as belonging to the surface subtype, but no children were classified as belonging to the phonological subtype. These results suggested that the lexical and sublexical routes in Chinese are highly interdependent or that there may be only one route from print to speech as suggested by the connectionist models. Chinese dyslexic children generally are characterized as having delays in various phonological and orthographic skills, but some, such as those identified as surface dyslexics in the current study, are more severely impaired.