Dataset Information

ROBO1 polymorphisms, callosal connectivity, and reading skills.

ABSTRACT: The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon-guidance-receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading-related ROBO1 polymorphisms were genotyped, and diffusion and structural MRI were acquired to measure the fiber microstructure of the corpus callosum (CC), the major white-matter tract that connects inter-hemispheric cortical regions. The results confirmed the significant influence of the ROBO1 polymorphisms on reading scores. The fiber microstructures of the midline-CC segments around the genu and splenium were also affected by the ROBO1 polymorphisms. Moreover, a mediation analysis further revealed that the genu could significantly mediate the effects of the ROBO1 polymorphisms on word-list reading performance, which suggests a ROBO1-to-genu-to-reading pathway. The genu-linked cortical morphology, however, was not associated with either the ROBO1 polymorphisms or reading performance. These findings offer direct evidence supporting ROBO1-callosum association in humans and also provide valuable insight into the functions of ROBO1 and the gene-to-brain mechanisms that underlie human reading. Hum Brain Mapp 38:2616-2626, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Sun X

PROVIDER: S-EPMC6866921 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ROBO1 polymorphisms, callosal connectivity, and reading skills.

Sun Xiaochen X Song Shuang S Liang Xinyu X Xie Yachao Y Zhao Chenxi C Zhang Yuping Y Shu Hua H Gong Gaolang G

Human brain mapping 20170227 5

The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon-guidance-receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading-related ROBO1 polymorphisms were genotyped, and dif ...[more]

PMID: 28240421

Similar Datasets

Project description:Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive. Here, we focused on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene. We found an increase in homotopic interhemispheric connectivity and functional hyperconnectivity across higher cognitive areas in adult male and female CDKL5-deficient mice by resting-state functional MRI (rs-fMRI) analysis. This was accompanied by an increase in the number of callosal synaptic inputs but decrease in local synaptic connectivity in the cingulate cortex of juvenile CDKL5-deficient mice, suggesting an impairment in excitatory synapse development and a differential role of CDKL5 across excitatory neuron subtypes. These deficits were associated with significant cognitive impairments in CDKL5 KO mice. Selective deletion of CDKL5 in the largest subtype of CPN likewise resulted in an increase of functional callosal inputs, without however significantly altering intracortical cingulate networks. Notably, such callosal-specific changes were sufficient to cause cognitive deficits. Finally, when CDKL5 was selectively re-expressed only in this CPN subtype, in otherwise CDKL5-deficient mice, it was sufficient to prevent the cognitive impairments of CDKL5 mutants. Together, these results reveal a novel role of CDKL5 by demonstrating that it is both necessary and sufficient for proper CPN connectivity and cognitive function and flexibility, and further validates a causal relationship between CPN dysfunction and cognitive impairment in a model of NDD.

Project description:BackgroundReading disability (RD) is characterized by slow and inaccurate word reading development, commonly reflecting underlying phonological problems. We have previously shown that exposure to white noise acutely improves cognitive performance in children with ADHD. The question addressed here is whether white noise exposure yields positive outcomes also for RD. There are theoretical reasons to expect such a possibility: a) RD and ADHD are two overlapping neurodevelopmental disorders and b) since prior research on white noise benefits has suggested that a central mechanism might be the phenomenon of stochastic resonance, then adding certain kinds of white noise might strengthen the signal-to-noise ratio during phonological processing and phoneme-grapheme mapping.MethodsThe study was conducted with a group of 30 children with RD and phonological decoding difficulties and two comparison groups: one consisting of skilled readers (n = 22) and another of children with mild orthographic reading problems and age adequate phonological decoding (n = 30). White noise was presented experimentally in visual and auditory modalities, while the children performed tests of single word reading, orthographic word recognition, nonword reading, and memory recall.ResultsFor the first time, we show that visual and auditory white noise exposure improves some reading and memory capacities "on the fly" in children with RD and phonological decoding difficulties. By contrast, the comparison groups displayed either no benefit or a gradual decrease in performance with increasing noise. In interviews, we also found that the white noise exposure was tolerable or even preferred by many children.ConclusionThese novel findings suggest that poor readers with phonological decoding difficulties may be immediately helped by white noise during reading. Future research is needed to determine the robustness, mechanisms, and long-term practical implications of the white noise benefits in children with reading disabilities.

Dataset Information

ROBO1 polymorphisms, callosal connectivity, and reading skills.

Publications

ROBO1 polymorphisms, callosal connectivity, and reading skills.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets