Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Abstract Evidence from neuroimaging studies, including our own, suggest that skilled word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system appears to be functionally disrupted in developmental dyslexia. Relative to nonimpaired readers, reading-disabled individuals demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers, the dorsal circuit predominates at first, and in conjunction with premotor systems, is associated with analytic processing necessary for learning to integrate orthographic with phonological and lexical–semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word form system, which underlies fluency in word recognition. Learning outcomes: As a result of this activity, (1) the participant will learn about a model of lexical processing involving specific cortical regions. (2) The participant will learn about evidence which supports the theory that two dorsal LH systems may be disrupted in developmental dyslexia. (3) The participant will learn that individuals with reading impairment may rely on other regions of the brain to compensate for the disruption of posterior function. <s> BIB001 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> This paper elaborates on the components of a working definition of developmental dyslexia. It follows the general format of a paper by Lyon published in Annals of Dyslexia in 1995, which elaborated on a working definition proposed in 1994 (Lyon, 1995). The current definition agreed on by the work group updates and expands on the working definition from 1994. <s> BIB002 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (i) an age-matched group, and (ii) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (n = 19; mean 14.4 years), the dyslexic group (n = 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (n = 12; mean 9.8 years), the dyslexic group (n = 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia. <s> BIB003 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> 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. <s> BIB004 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Functional neuroimaging studies have consistently demonstrated less activation of the left occipitotemporal cortex in dyslexic readers. This region is considered critical for skilled reading and damage to it in adult readers leads to severe deficits in reading ability. In contrast to these findings, structural abnormalities in the occipitotemporal cortex were not consistently found to date. We used optimized Voxel Based Morphometry with T1 weighted MR images to investigate gray matter volume in 13 dyslexic and 15 nonimpaired reading adolescents (age 14-16). Less gray matter volume for dyslexic readers was found in the left and right fusiform gyrus, the bilateral anterior cerebellum and in the right supramarginal gyrus. Decreased gray matter volume in the left and right fusiform gyrus of dyslexic readers highlights the importance of this brain region for developmental dyslexia. The structural abnormalities in the right occipitotemporal cortex suggest that dyslexia may be such a persistent disorder because an occipitotemporal reading area, critical for skilled reading, cannot develop in any hemisphere. The extended areas of reduced gray matter volume in dyslexic readers in the cerebellum suggest that structural abnormalities in the cerebellum are also strongly associated with dyslexia and warrant further investigation. <s> BIB005 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> In the past 25 years, scientific understanding of dyslexia and other learning disabilities has seen rapid progress in domains involving definition and classification, neuropsychological correlates, neurobiological factors, and intervention. I discuss this progress, emphasizing the central organizing influence of research and theory on basic academic skills on identification and sampling issues. I also emphasize how neuropsychological approaches to dyslexia have evolved and the importance of an interdisciplinary perspective for understanding dyslexia. <s> BIB006 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> In this article, we critically review the evidence for overlap among three developmental disorders, namely speech sound disorder (SSD), language impairment (LI), and reading disability (RD), at three levels of analysis: diagnostic, cognitive, and etiological. We find that while overlap exists at all three levels, it varies by comorbidity subtype, and the relations among these three disorders are complex and not fully understood. We evaluate which comorbidity models can be rejected or supported as explanations for why and how these three disorders overlap and what new data are needed to better define their relations. <s> BIB007 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> This study used foci from 17 original studies on functional abnormalities in the dyslexic brain to identify brain regions with consistent under- or overactivation. Studies were included when reading or reading-related tasks were performed on visually presented stimuli and when results reported coordinates for group differences. Activation Likelihood Estimation (ALE) was used for quantification. Maxima of underactivation were found in inferior parietal, superior temporal, middle and inferior temporal and fusiform regions of the left hemisphere. With respect to left frontal abnormalities we found underactivation in the inferior frontal gyrus to be accompanied by overactivation in the primary motor cortex and the anterior insula. Tentative functional interpretations of the activation abnormalities are provided. <s> BIB008 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Using functional magnetic resonance imaging, we investigated multimodal (visual and auditory) semantic and unimodal (visual only) phonological processing in reading disabled (RD) adolescents and non-impaired (NI) control participants. We found reduced activation for RD relative to NI in a number of left-hemisphere reading-related areas across all processing tasks regardless of task type (semantic vs. phonological) or modality (auditory vs. visual modality). Moreover, activation differences in these regions, which included the inferior frontal gyrus, the superior temporal gyrus, and the occipitotemporal region, were largely independent of in-scanner performance in our auditory semantic task. That is, although RD participants and NI participants differed in performance in visually presented conditions, they did not differ significantly in the auditory condition, yet similar patterns of reduced activation were observed in these regions across conditions. These findings indicate a neurobiological marker in RD that is independent of task, modality, or performance. These findings are discussed in the context of current neurobiological models of RD. <s> BIB009 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills. <s> BIB010 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Abstract In this review paper we address whether deficits in reading (i.e. developmental dyslexia) are rooted in neurobiological anomalies in white matter tracts. Diffusion tensor imaging (DTI) offers an index of the connections between brain regions (via tractography) and of the white matter properties of these connections (via fractional anisotropy, FA). The reported studies generally show that lower FA values in left temporoparietal and frontal areas are indicative of poorer reading ability or dyslexia. Second, most studies have indicated that these regions coincide with the left arcuate fasciculus and corona radiata, with fewer studies suggesting a role for the posterior part of the corpus callosum or for more ventral tracts such as the inferior longitudinal fasciculus or the inferior fronto-occipital fasciculus. Finally, a quantitative activation likelihood estimation (ALE) meta-analysis on all reported studies that used a voxel-based approach reveals a cluster located close to the left temporoparietal region ( x = −29, y = −17, z = 26). Fibertracking through this cluster demonstrates that this region hosts both the left arcuate fasciculus and the left corona radiata. <s> BIB011 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> We used coordinate-based meta-analysis in order to objectively quantify gray matter abnormalities reported in nine Voxel-Based Morphometry studies of developmental dyslexia. Consistently across studies, reduced gray matter volume in dyslexic readers was found in the right superior temporal gyrus and left superior temporal sulcus. These results were related to findings from previous meta-analyses on functional brain abnormalities in dyslexic readers. Convergence of gray matter reduction and reading-related underactivation was found for the left superior temporal sulcus. Recent studies point to the presence of both functional and structural abnormalities in left temporal and occipito-temporal brain regions before reading onset. Hum Brain Mapp 34:3055–3065, 2013. © 2012 Wiley Periodicals, Inc. <s> BIB012 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Developmental dyslexia (DD) is highly heritable and previous studies observed reduced cortical volume, white matter integrity, and functional alterations in left posterior brain regions in individuals with DD. The primary sulcal pattern has been hypothesized to relate to optimal organization and connections of cortical functional areas. It is determined during prenatal development and may reflect early, genetically influenced, brain development. We characterize the sulcal pattern using graphbased pattern analysis and investigate whether sulcal patterns in parieto-temporal and occipito-temporal regions are atypical in elementary school-age children with DD and pre-readers/beginning readers (preschoolers/kindergarteners) with a familial risk(elementaryschool-agechildren:n[males/females],agerange = 17/11,84–155months;preschoolers/kindergarteners:16/15, 59–84 months). Thepatternofsulcalbasinareain leftparieto-temporaland occipito-temporal regionswassignificantlyatypical (more sulcalbasins of smaller size) in children with DD and furthercorrelated with reduced reading performanceon single- and nonword reading measures. A significantly atypical sulcal area pattern was also confirmed in younger preschoolers/ kindergarteners with a familial risk of DD. Our results provide further support for atypical early brain development in DD and suggest that DD may originate from altered organization or connections of cortical areas in the left posterior regions. <s> BIB013 </s> Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review <s> | SPECIFIC READING DISABILITY <s> Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. WIREs Cogn Sci 2016, 7:156–176. doi: 10.1002/wcs.1383 ::: ::: ::: ::: For further resources related to this article, please visit the WIREs website. <s> BIB014
Specific reading disability (SRD), or developmental dyslexia (DD), is a prevalent learning disability affecting around 7-16% of school-age children and is characterized by deficits in accurate and/or fluent word recognition, decoding and spelling which do not result from inadequate educational experiences BIB006 BIB002 BIB007 ). SRD is neurobiological in origin, and functional and structural magnetic resonance imaging (fMRI/MRI) reveal atypical brain characteristics (in both structure and function) associated with SRD in left temporo-parietal, occipito-temporal, and inferior frontal regions (e.g., BIB009 BIB004 BIB001 BIB008 . Specifically, individuals with SRD exhibit reduced activation during reading and phonological awareness tasks relative to controls in left temporo-parietal and occipito-temporal regions (e.g., BIB008 ). Mixed findings of over-and under-activation in the left inferior frontal cortex in SRD suggests that activation in this area may be task-specific and warrants further investigation (e.g., BIB008 ). Reports of anomalous cortical structure in SRD include reduced gray matter volume in bilateral superior temporal regions BIB003 BIB012 , bilateral temporo-parietal regions and insula BIB003 , bilateral occipito-temporal and right temporo-parietal regions BIB005 , and atypical sulcal pattern in left temporo-parietal and occipito-temporal regions BIB013 . Advances in the use of diffusion-weighted MRI (including diffusion tensor imaging, or DTI) allow examination of white matter microstructure, indexed by a measure of white matter integrity called fractional anisotropy (FA), and measures of diffusivity along white matter tracts: mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The application of diffusion-weighted MRI to the study of SRD has shown decreased white matter integrity (reduced FA) in left hemisphere tracts including the arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and corona radiata, which structurally link language-related cortical areas BIB011 BIB010 . Although some of the observed neurobiological alterations in SRD may be a result of reading difficulties, much of the altered brain function and structure characteristic of SRD is observed in pre-reading children and consequently has been proposed to be rooted in underlying genetic risk factors BIB014 . Neuroimaging genetics studies of specific reading disability   3.1.1 | SRD candidate genes: DCDC2, KIAA0319, THEM2, NRSN1, DYX1C1 , and ROBO1