Neural dissociation of visual attention span and phonological deficits in developmental dyslexia: A hub-based white matter network analysis.

It has been suggested that developmental dyslexia may have two dissociable causes-a phonological deficit and a visual attention span (VAS) deficit. Yet, neural evidence for such a dissociation is still lacking. This study adopted a data-driven approach to white matter network analysis to explore hubs and hub-related networks corresponding to VAS and phonological accuracy in a group of French dyslexic children aged from 9 to 14 years. A double dissociation in brain-behavior relations was observed. Structural connectivity of the occipital-parietal network surrounding the left superior occipital gyrus hub accounted for individual differences in dyslexic children's VAS, but not in phonological processing accuracy. In contrast, structural connectivity of two networks: the temporal-parietal-occipital network surrounding the left middle temporal gyrus hub and the frontal network surrounding the left medial orbital superior frontal gyrus hub, accounted for individual differences in dyslexic children's phonological processing accuracy, but not in VAS. Our findings provide evidence in favor of distinct neural circuits corresponding to VAS and phonological deficits in developmental dyslexia. The study points to connectivity-constrained white matter subnetwork dysfunction as a key principle for understanding individual differences of cognitive deficits in developmental dyslexia.

Neuroanatomy of dyslexia: An allometric approach.

Despite evidence for a difference in total brain volume between dyslexic and good readers, no previous neuroimaging study examined differences in allometric scaling (i.e. differences in the relationship between regional and total brain volumes) between dyslexic and good readers. The present study aims to fill this gap by testing differences in allometric scaling and regional brain volume differences in dyslexic and good readers. Object-based morphometry analysis was used to determine grey and white matter volumes of the four lobes, the cerebellum and limbic structures in 130 dyslexic and 106 good readers aged 8-14 years. Data were collected across three countries (France, Poland and Germany). Three methodological approaches were used as follows: principal component analysis (PCA), linear regression and multiple-group confirmatory factor analysis (MGCFA). Difference in total brain volume between good and dyslexic readers was Cohen's d = 0.39. We found no difference in allometric scaling, nor in regional brain volume between dyslexic and good readers. Results of our three methodological approaches (PCA, linear regression and MGCFA) were consistent. This study provides evidence for total brain volume differences between dyslexic and control children, but no evidence for differences in the volumes of the four lobes, the cerebellum or limbic structures, once allometry is taken into account. It also finds no evidence for a difference in allometric relationships between the groups. We highlight the methodological interest of the MGCFA approach to investigate such research issues.

Individual differences in the acquisition of non-linguistic audio-visual associations in 5 year olds.

Audio-visual associative learning - at least when linguistic stimuli are employed - is known to rely on core linguistic skills such as phonological awareness. Here we ask whether this would also be the case in a task that does not manipulate linguistic information. Another question of interest is whether executive skills, often found to support learning, may play a larger role in a non-linguistic audio-visual associative task compared to a linguistic one. We present a new task that measures learning when having to associate non-linguistic auditory signals with novel visual shapes. Importantly, our novel task shares with linguistic processes such as reading acquisition the need to associate sounds with arbitrary shapes. Yet, rather than phonemes or syllables, it uses novel environmental sounds - therefore limiting direct reliance on linguistic abilities. Five-year-old French-speaking children (N = 76, 39 girls) were assessed individually in our novel audio-visual associative task, as well as in a number of other cognitive tasks evaluating linguistic abilities and executive functions. We found phonological awareness and language comprehension to be related to scores in the audio-visual associative task, while no correlation with executive functions was observed. These results underscore a key relation between foundational language competencies and audio-visual associative learning, even in the absence of linguistic input in the associative task.

White matter network connectivity deficits in developmental dyslexia.

A number of studies have shown an abnormal connectivity of certain white matter pathways in developmental dyslexia, as well as correlations between these white matter pathways and behavioral deficits. However, whether developmental dyslexia presents broader white matter network connectivity disruption is currently unknown. The present study reconstructed white matter networks for 26 dyslexic children (11.61 ± 1.31 years) and 31 age-matched controls (11.49 ± 1.36 years) using constrained spherical deconvolution tractography. Network-based statistics (NBS) analysis was performed to identify network connectivity deficits in dyslexic individuals. Network topological features were measured based on graph theory to examine whether these parameters correlate with literacy skills, and whether they explain additional variance over previously established white matter connectivity abnormalities in dyslexic children. The NBS analysis identified a network connecting the left-occipital-temporal cortex and temporo-parietal cortex that had decreased streamlines in dyslexic children. Four network topological parameters (clustering coefficient, local efficiency, transitivity, and global efficiency) were positively correlated with literacy skills of dyslexic children, and explained a substantial proportion of additional variance in literacy skills beyond connectivity measures of white matter pathways. This study for the first time reports a disconnection in a local subnetwork in the left hemisphere in dyslexia and shows that the global white matter network topological properties contribute to reduced literacy skills in dyslexic children.

Atypical Structural Asymmetry of the Planum Temporale is Related to Family History of Dyslexia.

Research on the neural correlates of developmental dyslexia indicates atypical anatomical lateralization of the planum temporale, a higher-order cortical auditory region. Yet whether this atypical lateralization precedes reading acquisition and is related to a familial risk for dyslexia is not currently known. In this study, we address these questions in 2 separate cohorts of young children and adolescents with and without a familial risk for dyslexia. Planum temporale surface area was manually labeled bilaterally, on the T1-weighted MR brain images of 54 pre-readers (mean age: 6.2 years, SD: 3.2 months; 33 males) and 28 adolescents (mean age: 14.7 years, SD: 3.3 months; 11 males). Half of the pre-readers and adolescents had a familial risk for dyslexia. In both pre-readers and adolescents, group comparisons of left and right planum temporale surface area showed a significant interaction between hemisphere and family history of dyslexia, with participants who had no family risk for dyslexia showing greater leftward asymmetry of the planum temporale. This effect was confirmed when analyses were restricted to normal reading participants. Altered planum temporale asymmetry thus seems to be related to family history of dyslexia.

Multi-parameter machine learning approach to the neuroanatomical basis of developmental dyslexia.

Despite decades of research, the anatomical abnormalities associated with developmental dyslexia are still not fully described. Studies have focused on between-group comparisons in which different neuroanatomical measures were generally explored in isolation, disregarding potential interactions between regions and measures. Here, for the first time a multivariate classification approach was used to investigate grey matter disruptions in children with dyslexia in a large (N = 236) multisite sample. A variety of cortical morphological features, including volumetric (volume, thickness and area) and geometric (folding index and mean curvature) measures were taken into account and generalizability of classification was assessed with both 10-fold and leave-one-out cross validation (LOOCV) techniques. Classification into control vs. dyslexic subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of 10-fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature selection. Features that discriminated between dyslexic and control children were exclusively situated in the left hemisphere including superior and middle temporal gyri, subparietal sulcus and prefrontal areas. They were related to geometric properties of the cortex, with generally higher mean curvature and a greater folding index characterizing the dyslexic group. Our results support the hypothesis that an atypical curvature pattern with extra folds in left hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900-908, 2017. © 2016 Wiley Periodicals, Inc.

How reliable are gray matter disruptions in specific reading disability across multiple countries and languages? Insights from a large-scale voxel-based morphometry study.

The neural basis of specific reading disability (SRD) remains only partly understood. A dozen studies have used voxel-based morphometry (VBM) to investigate gray matter volume (GMV) differences between SRD and control children, however, recent meta-analyses suggest that few regions are consistent across studies. We used data collected across three countries (France, Poland, and Germany) with the aim of both increasing sample size (236 SRD and controls) to obtain a clearer picture of group differences, and of further assessing the consistency of the findings across languages. VBM analysis reveals a significant group difference in a single cluster in the left thalamus. Furthermore, we observe correlations between reading accuracy and GMV in the left supramarginal gyrus and in the left cerebellum, in controls only. Most strikingly, we fail to replicate all the group differences in GMV reported in previous studies, despite the superior statistical power. The main limitation of this study is the heterogeneity of the sample drawn from different countries (i.e., speaking languages with varying orthographic transparencies) and selected based on different assessment batteries. Nevertheless, analyses within each country support the conclusions of the cross-linguistic analysis. Explanations for the discrepancy between the present and previous studies may include: (1) the limited suitability of VBM to reveal the subtle brain disruptions underlying SRD; (2) insufficient correction for multiple statistical tests and flexibility in data analysis, and (3) publication bias in favor of positive results. Thus the study echoes widespread concerns about the risk of false-positive results inherent to small-scale VBM studies.

A functionally guided approach to the morphometry of occipitotemporal regions in developmental dyslexia: evidence for differential effects in boys and girls.

Developmental dyslexia is a learning disability that specifically affects reading acquisition. Cortical anomalies and gray matter volume differences in various temporal regions have been reported in dyslexic subjects compared with controls. However, consistency between studies is lacking. In the present experiments, we focused our structural analyses on the ventral occipitotemporal regions, defined by their functional response to visual categories. We applied a subject-by-subject functionally guided approach on a total of 76 participants (31 dyslexic children). Cortical thickness was estimated for each participant around his/her peak of specific functional activation to visual words, faces, or places. Results from two independent datasets showed a reduction in thickness in dyslexic children compared with controls in the region responsive to words, in the left hemisphere. Additionally, a gender-by-diagnosis interaction was observed at the same location, due to differences in girls only. To avoid the potential confound of reading level, we also contrasted dyslexic and control children matched for reading performance, and we observed a similar difference, although in a smaller extent of cortex. The present study thus provides the first account of a focal cortical thickness reduction in dyslexia in the subregion of ventral occipitotemporal cortex specifically responsive to visual words, when age, gender, and reading performance are taken into account.

Planum temporale asymmetry in developmental dyslexia: Revisiting an old question.

Among the various asymmetrical structures of the human brain, the planum temporale, an anatomical region associated with a variety of auditory and language-related processes, has received particular attention. While its surface area has been shown to be greater in the left hemisphere compared to the right in about two-thirds of the general population, altered patterns of asymmetry were revealed by post mortem analyses in individuals with developmental dyslexia. These findings have been inconsistently replicated in magnetic resonance imaging studies of this disorder. In this report, we attempt to resolve past inconsistencies by analyzing the T1-weighted MR images of 81 children (mean age: 11 years, sd: 17 months), including 46 control (25 boys) and 35 dyslexic children (20 boys). We manually outlined Heschl's gyri, the planum temporale and the posterior rami of the Sylvian fissure on participants' brain images, using the same anatomical criteria as in post mortem studies. Results revealed an altered pattern of asymmetry of the planum temporale surface area in dyslexic boys only, with a greater proportion of rightward asymmetrical cases among dyslexic boys compared to control boys. Additionally, analyses of cortical thickness showed no asymmetry differences between groups for any of the regions of interest. Finally, a greater number of Heschl's gyrus full duplications emerged for the right hemisphere of dyslexic boys compared to controls. The present findings confirm and extend early post mortem observations. They also stress the importance of taking gender into account in studies of developmental dyslexia.

A novel task and methods to evaluate inter-individual variation in audio-visual associative learning.

Learning audio-visual associations is foundational to a number of real-world skills, such as reading acquisition or social communication. Characterizing individual differences in such learning has therefore been of interest to researchers in the field. Here, we present a novel audio-visual associative learning task designed to efficiently capture inter-individual differences in learning, with the added feature of using non-linguistic stimuli, so as to unconfound language and reading proficiency of the learner from their more domain-general learning capability. By fitting trial-by-trial performance in our novel learning task using simple-to-use statistical tools, we demonstrate the expected inter-individual variability in learning rate as well as high precision in its estimation. We further demonstrate that such measured learning rate is linked to working memory performance in Italian-speaking (N = 58) and French-speaking (N = 51) adults. Finally, we investigate the extent to which learning rate in our task, which measures cross-modal audio-visual associations while mitigating familiarity confounds, predicts reading ability across participants with different linguistic backgrounds. The present work thus introduces a novel non-linguistic audio-visual associative learning task that can be used across languages. In doing so, it brings a new tool to researchers in the various domains that rely on multi-sensory integration from reading to social cognition or socio-emotional learning.

Adaptive compensation of arcuate fasciculus lateralization in developmental dyslexia.

Previous studies have reported anomalies in the arcuate fasciculus (AF) lateralization in developmental dyslexia (DD). Still, the relationship between AF lateralization and literacy skills in DD remains largely unknown. The purpose of our study is to investigate the relationship between lateralization of three segments of AF (AF anterior segment (AFAS), AF long segment (AFLS), and AF posterior segment (AFPS)) and literacy skills in DD. A total of 26 children with dyslexia and 31 age-matched control children were included in this study. High angular diffusion imaging, combined with spherical deconvolution tractography, was used to reconstruct the AF. Connectivity measures of hindrance-modulated orientational anisotropy (HMOA) were computed for each of the three segments of the AF. The lateralization index (LI) of each AF segment was calculated by (right HMOA - left HMOA)/(right HMOA + left HMOA). Results showed that the LIs of AFAS and AFLS were positively correlated with reading accuracy in children with dyslexia. Specifically, the LI of AFAS was positively correlated with nonword and meaningless text reading accuracy, while the LI of AFLS accounted for word reading accuracy. The results suggest adaptive compensation of arcuate fasciculus lateralization in developmental dyslexia and functional dissociation of the anterior segment and long segment in the compensation.

Enhancing reading skills through a video game mixing action mechanics and cognitive training.

In modern societies, training reading skills is fundamental since poor-reading children are at high risk of struggling both at school and in life. Reading relies not only on oral language abilities but also on several executive functions. Considering their importance for literacy, training executive functions-particularly, attentional control has been suggested as a promising way of improving reading skills. For this reason, we developed a video game-based cognitive intervention aimed at improving several facets of executive functions. This game is composed of mini-games that apply gamified versions of standard clinical exercises linked through a game environment with action video game dynamics. Here, in a study involving 151 typically reading children, we demonstrated that after this general-domain behavioural intervention reading abilities, as well as attentional and planning skills, were significantly improved. Our results showed that training attentional control can translate into better reading efficiency, maintained at a follow-up test 6 months later.

White matter connectivity in uncinate fasciculus accounts for visual attention span in developmental dyslexia.

The present study aimed to investigate the role of connectivity disruptions in two fiber pathways, the uncinate fasciculus (UF) and the frontal aslant tract (FAT), in developmental dyslexia and determine the relationship between the connectivity of these pathways and behavioral performance in children with dyslexia. A total of 26 French children with dyslexia and 31 age-matched control children were included. Spherical deconvolution tractography was used to reconstruct the two fiber pathways. Hindrance-modulated oriented anisotropy (HMOA) was used to measure the connectivity of each fiber pathway in both hemispheres. Only boys with dyslexia showed reduced HMOA in the UF compared to control boys. Furthermore, HMOA of the UF correlated with individual differences in the visual attention span in participants with dyslexia. All significant results found in HMOA of the UF were verified in fractional anisotropy (FA) of the UF using standard diffusion imaging model. This study suggests a differential sex effect on the connectivity disruption in the UF in developmental dyslexia. It also indicates that the UF may play an essential role in the visual attention span deficit in developmental dyslexia.

Maladaptive compensation of right fusiform gyrus in developmental dyslexia: A hub-based white matter network analysis.

Cognitive theories have been proposed to clarify the causes and symptoms of dyslexia. However, correlations between local network parameters of white matter connectivity and literacy skills remain poorly known. An unbiased hypothesis-free approach was adopted to examine the correlations between literacy symptoms (reading and spelling) and hub-based white matter networks' connectivity parameters [nodal degree fractional anisotropy (FA) values] of 90 brain regions based on Anatomical Atlas Labels (AAL) in a group of French children with dyslexia aged 9-14 years. Results revealed that the higher the right fusiform gyrus's (FFG) nodal degree FA values, the lower the reading accuracy for words and pseudowords in dyslexic children. The results indicate that the severity of word/pseudoword reading symptoms in dyslexia relates to a white matter network centered around the right FFG. The negative correlation between right FFG network connectivity and reading accuracy, in particular pseudoword reading accuracy, suggests that right FFG represents a maladaptive compensation towards a general orthography-to-phonology decoding ability in developmental dyslexia.

A universal reading network and its modulation by writing system and reading ability in French and Chinese children.

Are the brain mechanisms of reading acquisition similar across writing systems? And do similar brain anomalies underlie reading difficulties in alphabetic and ideographic reading systems? In a cross-cultural paradigm, we measured the fMRI responses to words, faces, and houses in 96 Chinese and French 10-year-old children, half of whom were struggling with reading. We observed a reading circuit which was strikingly similar across languages and consisting of the left fusiform gyrus, superior temporal gyrus/sulcus, precentral and middle frontal gyri. Activations in some of these areas were modulated either by language or by reading ability, but without interaction between those factors. In various regions previously associated with dyslexia, reading difficulty affected activation similarly in Chinese and French readers, including the middle frontal gyrus, a region previously described as specifically altered in Chinese. Our analyses reveal a large degree of cross-cultural invariance in the neural correlates of reading acquisition and reading impairment.

Neuroanatomy of developmental dyslexia: Pitfalls and promise.

Investigations into the neuroanatomical bases of developmental dyslexia have now spanned more than 40 years, starting with the post-mortem examination of a few individual brains in the 60s and 70s, and exploding in the 90s with the widespread use of MRI. The time is now ripe to reappraise the considerable amount of data gathered with MRI using different types of sequences (T1, diffusion, spectroscopy) and analysed using different methods (manual, voxel-based or surface-based morphometry, fractional anisotropy and tractography, multivariate analyses…). While selective reviews of mostly small-scale studies seem to provide a coherent view of the brain disruptions that are typical of dyslexia, involving left perisylvian and occipito-temporal regions, we argue that this view may be deceptive and that meta-analyses and large-scale studies rather highlight many inconsistencies and limitations. We discuss problems inherent to small sample size as well as methodological difficulties that still undermine the discovery of reliable neuroanatomical bases of dyslexia, and we outline some recommendations to further improve this research area.

Altered hemispheric lateralization of white matter pathways in developmental dyslexia: Evidence from spherical deconvolution tractography.

This study examines the structural integrity and the hemispheric lateralization patterns of four major association fiber pathways in a group of French dyslexic children and age-matched controls (from 9 to 14 years), using high angular diffusion imaging combined with spherical deconvolution tractography. Compared with age-matched controls, dyslexic children show increased hindrance-modulated oriented anisotropy (HMOA) in the right superior longitudinal fasciculus (SLF). They also show a reduced leftward asymmetry of the inferior fronto-occipital fasciculus (IFOF) and an increased rightward asymmetry of the second branch of the SLF (SLF II). The lateralization pattern of IFOF and SLF II also accounts for individual differences in dyslexic children's reading abilities. These data provide evidence for an abnormal lateralization of occipito-frontal and parieto-frontal pathways in developmental dyslexia.

Impaired functional differentiation for categories of objects in the ventral visual stream: A case of developmental visual impairment.

We report the case of a 14-year-old girl suffering from severe developmental visual impairment along with delayed language and cognitive development, and featuring a clear-cut dissociation between spared dorsal and impaired ventral visual pathways. Visual recognition of objects, including faces and printed words, was affected. In contrast, movement perception and visually guided motor control were preserved. Structural MRI was normal on inspection, but Voxel Based Morphometry (VBM) revealed reduced grey matter density in the mesial occipital and ventral occipito-temporal cortex. Functional MRI during the perception of line drawings uncovered impaired differentiation which is normally observed at even younger ages: no local category preferences could be identified within the occipito-temporal cortex for faces, houses, words or tools. In contrast, movement-related activations appeared to be normal. Finally, those abnormalities evolved on the background of chronic bilateral occipital epileptic activity, including continuous spike-wave discharges during sleep, which may be considered as the primary cause of non-specific intellectual disability and visual impairment.

Speech comprehension aided by multiple modalities: behavioural and neural interactions.

Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources - e.g. voice, face, gesture, linguistic context - to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with increased activation in left inferior frontal gyrus and left posterior STS. The current multimodal speech comprehension paradigm demonstrates recruitment of a wide comprehension network in the brain, in which posterior STS and fusiform gyrus form sites for convergence of auditory, visual and linguistic information, while left-dominant sites in temporal and frontal cortex support successful comprehension.