Orthographic Depth May Influence the Degree of Severity of Maze Learning Performance in Children at Risk for Reading Disorder.

Reading disability (RD), which affects between 5 and 17% of the population worldwide, is the most prevalent form of learning disability, and is associated with underactivation of a universal reading network in children. However, recent research suggests there are differences in learning rates on cognitive predictors of reading performance, as well as differences in activation patterns within the reading neural network, based on orthographic depth (i.e., transparent/shallow vs. deep/opaque orthographies) in children with RD. Recently, we showed that native English-speaking children with RD exhibit impaired performance on a maze learning task that taps into the same neural networks that are activated during reading. In addition, we demonstrated that genetic risk for RD strengthens the relationship between reading impairment and maze learning performance. However, it is unclear whether the results from these studies can be broadly applied to children from other language orthographies. In this study, we examined whether low reading skill was associated with poor maze learning performance in native English-speaking and native German-speaking children, and the influence of genetic risk for RD on cognition and behavior. In addition, we investigated the link between genetic risk and performance on this task in an orthographically diverse sample of children attending an English-speaking international school in Germany. The results from our data suggest that children with low reading skill, or with a genetic risk for reading impairment, exhibit impaired performance on the maze learning task, regardless of orthographic depth. However, these data also suggest that orthographic depth influences the degree of impairment on this task. The maze learning task requires the involvement of various cognitive processes and neural networks that underlie reading, but is not influenced by potential differences in reading experience due to lack of text or oral reporting. As a fully automated tool, it does not require specialized training to administer, and current results suggest it may be a practicable screening tool for early identification of reading impairment across orthographies.

Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development.

Dyslexia, also known as reading disability, is defined as difficulty processing written language in individuals with normal intellectual capacity and educational opportunity. The prevalence of dyslexia is between 5 and 17%, and the heritability ranges from 44 to 75%. Genetic linkage analysis and association studies have identified several genes and regulatory elements linked to dyslexia and reading ability. However, their functions and molecular mechanisms are not well understood. Prominent among these is KIAA0319, encoded in the DYX2 locus of human chromosome 6p22. The association of KIAA0319 with reading performance has been replicated in independent studies and different languages. Rodent models suggest that kiaa0319 is involved in neuronal migration, but its role throughout the cortical development is largely unknown. In order to define the function of KIAA0319 in human cortical development, we applied the neural developmental model of a human embryonic stem cell. We knocked down KIAA0319 expression in hESCs and performed the cortical neuroectodermal differentiation. We found that neuroepithelial cell differentiation is one of the first stages of hESC differentiation that are affected by KIAA0319 knocked down could affect radial migration and thus differentiation into diverse neural populations at the cortical layers.

Identifying Dyslexia: Link between Maze Learning and Dyslexia Susceptibility Gene, DCDC2, in Young Children.

Dyslexia is a common learning disability that affects processing of written language despite adequate intelligence and educational background. If learning disabilities remain untreated, a child may experience long-term social and emotional problems, which influence future success in all aspects of their life. Dyslexia has a 60% heritability rate, and genetic studies have identified multiple dyslexia susceptibility genes (DSGs). DSGs, such as DCDC2, are consistently associated with the risk and severity of reading disability (RD). Altered neural connectivity within temporoparietal regions of the brain is associated with specific variants of DSGs in individuals with RD. Genetically altering DSG expression in mice results in visual and auditory processing deficits as well as neurophysiological and neuroanatomical disruptions. Previously, we demonstrated that learning deficits associated with RD can be translated across species using virtual environments. In this 2-year longitudinal study, we demonstrate that performance on a virtual Hebb-Williams maze in pre-readers is able to predict future reading impairment, and the genetic risk strengthens, but is not dependent on, this relationship. Due to the lack of oral reporting and use of letters, this easy-to-use tool may be particularly valuable in a remote working environment as well as working with vulnerable populations such as English language learners.

Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African-American youth.

BACKGROUND: Rapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms. OBJECTIVE: To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach. METHODS: We conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African-American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted. RESULTS: Genome-wide significant effects were observed at rs1555839 (p=4.03×10-8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer-promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule. CONCLUSION: This study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene-brain-behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.