Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | INTRODUCTION <s> We review current knowledge about reading development and the origins of difficulties in learning to read. We distinguish between the processes involved in learning to decode print, and the processes involved in reading for meaning (reading comprehension). At a cognitive level, difficulties in learning to read appear to be predominantly caused by deficits in underlying oral language skills. The development of decoding skills appears to depend critically upon phonological language skills, and variations in phoneme awareness, letter-sound knowledge and rapid automatized naming each appear to be causally related to problems in learning to read. Reading comprehension difficulties in contrast appear to be critically dependent on a range of oral language comprehension skills (including vocabulary knowledge and grammatical, morphological and pragmatic skills). <s> BIB001 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | INTRODUCTION <s> Reading and language disorders are common childhood conditions that often co-occur with each other and with other neurodevelopmental impairments. There is strong evidence that disorders, such as dyslexia and Specific Language Impairment (SLI), have a genetic basis, but we expect the contributing genetic factors to be complex in nature. To date, only a few genes have been implicated in these traits. Their functional characterization has provided novel insight into the biology of neurodevelopmental disorders. However, the lack of biological markers and clear diagnostic criteria have prevented the collection of the large sample sizes required for well-powered genome-wide screens. One of the main challenges of the field will be to combine careful clinical assessment with high throughput genetic technologies within multidisciplinary collaborations. <s> BIB002 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | INTRODUCTION <s> Aim ::: The neurobiological contributions of childhood language disorder are not well understood. Yet there is increasing evidence that language disorder is associated with differences in brain structure and/or function in core language regions. A key hypothesis has been that children with language disorder do not show the same degree of leftward asymmetry of these regions as observed in typically developing children. We aimed to systematically review structural and functional magnetic resonance imaging (fMRI) studies to examine brain commonalities and differences between children with language disorder and typically developing controls; and differences in leftward asymmetry between these groups. ::: ::: Method ::: A systematic review was conducted using MeSH terms synonymous with childhood language disorder and brain MRI methods. The search identified 1443 papers, and 18 articles met the criteria and were appraised for level and quality of evidence. ::: ::: Results ::: Atypical brain structure and function was reported within traditionally recognized language regions across studies, including the inferior frontal gyrus, posterior superior temporal gyrus, and caudate nucleus. The direction of difference (e.g. increased/decreased) was variable, however, likely because of differences in language disorder groups examined and magnetic resonance data acquisition and analysis approaches. As regards asymmetry, there was some evidence of reduction of the anticipated structural and functional leftward asymmetry in frontal language regions in language disorder groups. ::: ::: Interpretation ::: Mounting evidence suggests that children with language disorder have atypical brain structure and function within neural regions integral to language. There is limited support for the hypothesis that children with language disorder show a reduction of leftward structural and/or functional asymmetry in frontal language regions. Interpretation is limited, however, by a high degree of variability in language disorder assessment and phenotype, and in magnetic resonance methodologies. A large-scale magnetic resonance study of brain structure and function is required in a well-defined language disorder population cohort, with replication, to provide confirmatory data on the neural correlates of childhood language disorder. <s> BIB003 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | INTRODUCTION <s> Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences before formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia. <s> BIB004
Developmental disorders of spoken and written language are characterized by deficits in various linguistic domains such as reading, phonological processing, vocabulary, and grammatical skills BIB001 , as well as atypical neural structure and function BIB003 BIB004 . A growing number of genes have been implicated in the etiology of these disorders, many of which play a role in neurodevelopmental processes such as neuronal migration, neurite outgrowth, cortical morphogenesis, and ciliary structure and function BIB002 . The developmental function of such genes is a likely source of neural anomalies, and the emerging field of neuroimaging genetics seeks to better understand the relationships among genetic and behavioral markers of disorders by establishing intermediate phenotypes at the neural level. Findings to date provide some compelling evidence for links among specific genes, brain structure and/or function, and reading-and language-associated phenotypes. Here, we review research employing a neuroimaging genetics approach to study specific reading disability (SRD) and developmental language disorder (DLD). 1 These disorders are of interest to study in parallel due to overlap in characteristic deficits, such as phonological processing, as well as shared neural and genetic underpinnings. We provide a brief introduction on genetic approaches to the study of complex disorders (please see Appendix A for explanation of technical concepts), along with an overview of each disorder and the related neuroimaging genetic findings reported thus far. Given the complex polygenic underpinnings of SRD and DLD, we have organized our discussion of the relevant imaging genetic findings by gene, beginning with coverage of well-established candidate genes for SRD and DLD and followed by those more recently associated with reading and/or language (genes investigated in relation to SRD and DLD using a neuroimaging genetic approach are listed in Table 1 , and findings are summarized in Table 2 ). In addition, we only include genes that have been studied using a neuroimaging genetics approach. In order to present a clear account within the scope of neurodevelopmental disorders of spoken and written language, we have limited our review to studies including typically developing populations and populations with SRD or DLD and no additional neurological or psychiatric diagnosis.