While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample ...sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well as 337 controls. We show that the frequency of large CNVs (>1 Mbp) is significantly greater for ID-associated phenotypes compared to autism (p = 9.58 × 10(-11), odds ratio = 4.59), dyslexia (p = 3.81 × 10(-18), odds ratio = 14.45), or controls (p = 2.75 × 10(-17), odds ratio = 13.71). There is a striking difference in the frequency of rare CNVs (>50 kbp) in autism (10%, p = 2.4 × 10(-6), odds ratio = 6) or ID (16%, p = 3.55 × 10(-12), odds ratio = 10) compared to dyslexia (2%) with essentially no difference in large CNV burden among dyslexia patients compared to controls. Rare CNVs were more likely to arise de novo (64%) in ID when compared to autism (40%) or dyslexia (0%). We observed a significantly increased large CNV burden in individuals with ID and multiple congenital anomalies (MCA) compared to ID alone (p = 0.001, odds ratio = 2.54). Our data suggest that large CNV burden positively correlates with the severity of childhood disability: ID with MCA being most severely affected and dyslexics being indistinguishable from controls. When autism without ID was considered separately, the increase in CNV burden was modest compared to controls (p = 0.07, odds ratio = 2.33).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet ...few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Reading and phonological processing deficits have been the primary focus of neuroimaging studies addressing the neurologic basis of developmental dyslexia, but to date there has been no objective ...assessment of the consistency of these findings. To address this issue, spatial coordinates reported in the literature were submitted to two parallel activation likelihood estimate (ALE) meta‐analyses. First, a meta‐analysis including 96 foci from nine publications identified regions where typical readers are likely to show greater activation than dyslexics: two left extrastriate areas within BA 37, precuneus, inferior parietal cortex, superior temporal gyrus, thalamus, and left inferior frontal gyrus. Right hemisphere ALE foci representing hypoactivity in dyslexia were found in the fusiform, postcentral, and superior temporal gyri. To identify regions in which dyslexic subjects reliably show greater activation than controls, 75 foci from six papers were entered into a second meta‐analysis. Here ALE results revealed hyperactivity associated with dyslexia in right thalamus and anterior insula. These findings suggest that during the performance of a variety of reading tasks, normal readers activate left‐sided brain areas more than dyslexic readers do, whereas dyslexia is associated with greater right‐sided brain activity. The most robust result was in left extrastriate cortex, where hypoactivity associated with dyslexia was found. However, the ALE maps provided no support for cerebellar dysfunction, nor for hyperactivity in left frontal cortex in dyslexia, suggesting that these findings, unlike those described above, are likely to be more varied in terms of their reproducibility or spatial location.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The co-occurrence of reading disorder (RD) and attention-deficit/hyperactivity disorder (ADHD) has received increasing attention. This review summarizes the epidemiology, treatment strategies, ...psychosocial impact, and economic burden associated with the co-occurrence of these conditions. Common genetic and neuropsychological deficits may partially explain the high degree of overlap between RD and ADHD. Children who face the additive problems of both disorders are at greater risk for academic failure, psychosocial consequences, and poor long-term outcomes that persist into adulthood. However, few studies have evaluated interventions targeted to this patient population, underscoring the importance of identifying effective multimodal treatments that address the neuropsychological deficits of RD and ADHD through carefully planned clinical research.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Consistently lateralized reading errors are commonly understood as side-effects of visuospatial neglect impairment. There is however a qualitative difference between systematically omitting full ...words presented on one side of passages (egocentric neglect dyslexia) and lateralized errors when reading single words (allocentric neglect dyslexia). This study aims to investigate the relationship between egocentric and allocentric neglect dyslexia and visuospatial neglect.
1209 stroke survivors completed standardized reading and cancellation tests. Stringent criteria identified unambiguous cases of allocentric neglect dyslexia (N = 17) and egocentric neglect dyslexia (N = 35). These conditions were found to be doubly dissociated with all cases of egocentric and allocentric neglect dyslexia occurring independently. Allocentric neglect dyslexia was dissociated from both egocentric and allocentric visuospatial neglect. Additionally, two cases of allocentric neglect dyslexia which co-occurred with oppositely lateralized domain-general visuospatial neglect were identified. Conversely, all cases of egocentric neglect dyslexia were found in the presence of domain-general visuospatial neglect. These findings suggest that allocentric neglect dyslexia cannot be fully understood as a consequence of visuospatial neglect. In contrast, we found no evidence for a dissociation between egocentric neglect dyslexia and visuospatial neglect. These findings highlight the need for new, neglect dyslexia specific rehabilitation strategies to be designed and tested.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dyslexia is a neurobiological disorder impairing learning to read. Brain responses of infants at genetic risk for dyslexia are abnormal already at birth, and associations from infant speech ...perception to preschool cognitive skills and reading in early school years have been documented, but there are no studies showing predicting power until adolescence. Here we show that in at-risk infants, brain activation to pseudowords at left hemisphere predicts 44% of reading speed at 14 years, and even improves the prediction after taking into account neurocognitive preschool measures of letter naming, phonology, and verbal short-term memory. The association between infant brain responses and reading speed is mediated by preschool rapid automatized naming ability. Therefore, we suggest that rapid naming and reading speed could share a similar cognitive process of automatized access to lexicon via phonological representations, and brain activation to speech sounds in infancy probably acts as an index of deficient development of the same process.
•Associations of infant ERPs to speech and reading speed in 14 years were studied.•ERPs of infants at-risk for dyslexia predicted 44% of reading speed at 14 years.•The prediction was mediated via preschool-age rapid naming (RAN).•This suggests that poor automatization of lexical access hinders reading and RAN.•Atypical infant ERPs index a deficient development of representations on background.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Reading disabilities (RD) and attention‐deficit/hyperactivity disorder (ADHD) are two of the most common developmental disorders. RD and ADHD frequently co‐occur, which raises questions about how the ...disorders interact and to what extent they can be differentiated. To date, the underlying neural mechanisms leading to RD–ADHD comorbidity (COM) are not understood. In this study, structural and functional magnetic resonance imaging (fMRI) were combined with comprehensive behavioral testing in order to characterize the behavior, brain structure, and neural correlates of executive function, phonological processing and reading fluency in 60 children with clinical diagnoses of RD, ADHD, or COM, and controls. Whole‐brain analyses of variance were performed on cortical thickness values and on the data of the three fMRI tasks to investigate overall group differences. To validate these findings, a region of interest analysis was performed in regions that have previously been shown to exhibit group differences in children with RD or ADHD using the same paradigms. The neuroimaging results demonstrated structural and functional atypicalities for COM in regions that are frequently associated with deficits in children with isolated ADHD or RD. A combination of shared and distinctive brain alterations between the clinical groups was identified, supporting the multiple deficit model for ADHD, RD, and its comorbidity.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Written for dyslexic adults or anyone who thinks they might be dyslexic, this bold and imaginative book is deliberately concise and easy to dip into.User-friendly, essential guide to the world of ...study and work for anyone with dyslexia;Identifies the key needs of adults and young people who are dyslexic;Encourages them to put together their own package of ideas and strategies for success;Offers practical activities, examples and support covering reading, memory, organization, self-esteem, IT and dyslexia in the workplace;Over 100 topics from this book are expanded on our online resource.This unique guide to overcoming the day-to-day difficulties associated with dyslexia will also be of great interest to employers, colleagues, teachers, friends and family of those with dyslexia.
This paper provides a selective review of data on phonology, audition, vision, and learning abilities in developmental dyslexia, with a specific focus on patterns of normal alongside poor ...performance. Indeed we highlight the difficulties of interpreting poor performance, and we criticize theories of dyslexia that are exclusively suited to explaining poor performance, at the risk of overgeneralizing and predicting deficits in many more situations than are observed. We highlight a number of tasks and conditions where individuals with dyslexia seem to show perfectly normal performance, and we discuss the value of taking such data seriously into account and the difficulties of current theories to explain them. Finally, we discuss the experimental challenges for tasks investigating the nature of cognitive deficits in dyslexia and in other developmental disorders and the challenges for any proper theory of dyslexia aiming to explain cases of normal as well as poor performance.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential ...predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Based on standardised and age-normed reading and spelling tests administered at school age, children were classified as 16 dyslexic participants and 16 controls. This longitudinal design allowed us to disentangle possible neurobiological predispositions for developing dyslexia from effects of individual differences in literacy experience. In our sample, the disorder can be predicted already before literacy learning from auditory cortex gyrification and aberrant downstream connectivity within the speech processing system. These results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction.
•Longitudinal MRI study following preliterate children developing dyslexia.•Auditory cortex folding was more variable in dyslexic children.•Altered speech network connectivity in dyslexia predates literacy instruction.•Combination of neural and behavioural data reliably predicted dyslexia before school.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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