Cortical differences in preliterate children at familiar risk of dyslexia are similar to those observed in dyslexic readers

Kraft, Indra; Cafiero, Riccardo; Schaadt, Gesa; Bräuer, Jens; Neef, Nicole E.; Müller, Bent; Kirsten, Holger; Wilcke, Arndt; Boltze, Johannes; Friederici, Angela D.; Skeide, Michael

doi:10.1093/brain/awv036

Cited by 22 publications

(10 citation statements)

References 8 publications

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“…Furthermore, Darki, Peyrard-Janvid, Matsson, Kere, and Klingberg (2012) reported gray and white matter variation to be linked with variants within DYX1C1, DCDC2, and KIAA0319 dyslexia candidate genes, while Scerri et al (2012) showed white matter variation to be linked with variants within MRPL19/C2ORF3. These associations between dyslexia candidates and brain structure are in line with findings from MRI studies, where structural gray and white matter alterations were associated with dyslexia-relevant traits (Klingberg et al, 2000;Kraft et al, 2015).…”

Section: Introductionsupporting

confidence: 86%

“…(2012) showed white matter variation to be linked with variants within MRPL19/C2ORF3 . These associations between dyslexia candidates and brain structure are in line with findings from MRI studies, where structural gray and white matter alterations were associated with dyslexia‐relevant traits (Klingberg et al., 2000; Kraft et al., 2015). …”

Section: Introductionmentioning

confidence: 99%

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ATP2C2 and DYX1C1 are putative modulators of dyslexia‐related MMR

et al. 2017

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BackgroundDyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input.MethodsIn this study, we comprehensively analyzed associations of dyslexia‐specific late MMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.ResultsFirst, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia‐specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis and eQTLs.ConclusionOur findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNPs, the late component of MMR and dyslexia.

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Section: Introductionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

ATP2C2 and DYX1C1 are putative modulators of dyslexia‐related MMR

et al. 2017

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“…One study found no significant differences in left TP cortical thickness among pre-readers who later developed dyslexia versus those who did not; significant group differences were observed in other more sensory regions [17]. The number of pre-readers who later developed dyslexia in this study was small (N=7), however [43] Another study found that children with family history of dyslexia differed from controls in the organization of the left arcuate fasciculus; further, the trajectory of left arcuate development over time predicted their later reading ability [24]. In sum, though our meta-analysis identified left TP abnormalities in pre-readers at risk for dyslexia, future studies should further investigate the precise role of this region in reading development.…”

Section: Phonological Deficit Theorymentioning

confidence: 71%

Integrating MRI brain imaging studies of pre-reading children with current theories of developmental dyslexia: a review and quantitative meta-analysis

Vandermosten

Hoeft

Norton

2016

Current Opinion in Behavioral Sciences

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The neurobiological substrates that cause people with dyslexia to experience difficulty in acquiring accurate and fluent reading skills are still largely unknown. Although structural and functional brain anomalies associated with dyslexia have been reported in adults and school-age children, these anomalies may represent differences in reading experience rather than the etiology of dyslexia. Conducting MRI studies of pre-readers at risk for dyslexia is one approach that enables us to identify brain alterations that exist before differences in reading experience emerge. The current review summarizes MRI studies that examine brain differences associated with risk for dyslexia in children before reading instruction and meta-analyzes these studies. In order to link these findings with current etiological theories of dyslexia, we focus on studies that take a modular perspective rather than a network approach. Although some of the observed differences in pre-readers at risk for dyslexia may still be shaped by language experiences during the first years of life, such studies underscore the existence of reading-related brain anomalies prior to reading onset and could eventually lead to earlier and more precise diagnosis and treatment of dyslexia.

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“…The parietal operculum appears to be a target for tracking the effectiveness of interventions 46 , and may serve as an early marker of reading disability, if present in at-risk children before formal reading instruction 47, 48 . In contrast, the subcortical white matter findings within putative descending fiber tracts could be consistent with a procedural learning deficit hypothesis for language disabilities 49 and perhaps a cerebellar deficit hypothesis for dyslexia 50 .…”

Section: Resultsmentioning

confidence: 99%

Common Brain Structure Findings Across Children with Varied Reading Disability Profiles

Eckert

Vaden

Maxwell

et al. 2017

Sci Rep

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Dyslexia is a developmental disorder in reading that exhibits varied patterns of expression across children. Here we examined the degree to which different kinds of reading disabilities (defined as profiles or patterns of reading problems) contribute to brain morphology results in Jacobian determinant images that represent local brain shape and volume. A matched-pair brain morphometry approach was used to control for confounding from brain size and research site effects in this retrospective multi-site study of 134 children from eight different research sites. Parietal operculum, corona radiata, and internal capsule differences between cases and controls were consistently observed across children with evidence of classic dyslexia, specific comprehension deficit, and language learning disability. Thus, there can be common brain morphology findings across children with quite varied reading disability profiles that we hypothesize compound the developmental difficulties of children with unique reading disability profiles and reasons for their reading disability.

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Cortical differences in preliterate children at familiar risk of dyslexia are similar to those observed in dyslexic readers

Cited by 22 publications

References 8 publications

ATP2C2 and DYX1C1 are putative modulators of dyslexia‐related MMR

ATP2C2 and DYX1C1 are putative modulators of dyslexia‐related MMR

Integrating MRI brain imaging studies of pre-reading children with current theories of developmental dyslexia: a review and quantitative meta-analysis

Common Brain Structure Findings Across Children with Varied Reading Disability Profiles

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