POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells.

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON-OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2-/- mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

Functional connectivity is linked to working memory differences in children with reading learning disability.

Reading learning disability (RLD) is characterized by a specific difficulty in learning to read that is not better explained by an intellectual disability, lack of instruction, psychosocial adversity, or a neurological disorder. According to the domain-general hypothesis, a working memory deficit is the primary problem. Working memory in this population has recently been linked to altered resting-state functional connectivity within the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) compared to that in typically developing individuals. The main purpose of the present study was to compare the within-network functional connectivity of the DMN, SN, FPN, and reading network in two groups of children with RLD: a group with lower-than-average working memory (LWM) and a group with average working memory (AWM). All subjects underwent resting-state functional magnetic resonance imaging (fMRI), and data were analyzed from a network perspective using the network brain statistics framework. The results showed that the LWM group had significantly weaker connectivity in a network that involved brain regions in the DMN, SN, and FPN than the AWM group. Although there was no significant difference between groups in reading network in the present study, other studies have shown relationship of the connectivity of the angular gyrus, supramarginal gyrus, and inferior parietal lobe with the phonological process of reading. The results suggest that although there are significant differences in functional connectivity in the associated networks between children with LWM and AWM, the distinctive cognitive profile has no specific effect on the reading network.

Rapid online assessment of reading and phonological awareness (ROAR-PA).

Phonological awareness (PA) is at the foundation of reading development: PA is introduced before formal reading instruction, predicts reading development, is a target for early intervention, and is a core mechanism in dyslexia. Conventional approaches to assessing PA are time-consuming and resource intensive: assessments are individually administered and scoring verbal responses is challenging and subjective. Therefore, we introduce a rapid, automated, online measure of PA-The Rapid Online Assessment of Reading-Phonological Awareness-that can be implemented at scale without a test administrator. We explored whether this gamified, online task is an accurate and reliable measure of PA and predicts reading development. We found high correlations with standardized measures of PA (CTOPP-2, r = .80) for children from Pre-K through fourth grade and exceptional reliability (α = .96). Validation in 50 first and second grade classrooms showed reliable implementation in a public school setting with predictive value of future reading development.

Human-specific insights into candidate genes and boosted discoveries of novel loci illuminate roles of neuroglia in reading disorders.

Reading disorders (RD) are human-specific neuropsychological conditions associated with decoding printed words and/or reading comprehension. So far only a handful of candidate genes segregated in families and 42 loci from genome-wide association study (GWAS) have been identified that jointly provided little clues of pathophysiology. Leveraging human-specific genomic information, we critically assessed the RD candidates for the first time and found substantial human-specific features within. The GWAS candidates (i.e., population signals) were distinct from the familial counterparts and were more likely pleiotropic in neuropsychiatric traits and to harbor human-specific regulatory elements (HSREs). Candidate genes associated with human cortical morphology indeed showed human-specific expression in adult brain cortices, particularly in neuroglia likely regulated by HSREs. Expression levels of candidate genes across human brain developmental stages showed a clear pattern of uplifted expression in early brain development crucial to RD development. Following the new insights and loci pleiotropic in cognitive traits, we identified four novel genes from the GWAS sub-significant associations (i.e., FOXO3, MAPT, KMT2E and HTT) and the Semaphorin gene family with functional priors (i.e., SEMA3A, SEMA3E and SEMA5B). These novel genes were related to neuronal plasticity and disorders, mostly conserved the pattern of uplifted expression in early brain development and had evident expression in cortical neuroglial cells. Our findings jointly illuminated the association of RD with neuroglia regulation-an emerging hotspot in studying neurodevelopmental disorders, and highlighted the need of improving RD phenotyping to avoid jeopardizing future genetic studies of RD.

A systematic review of factors that impact reading comprehension in children with developmental language disorders.

Children with developmental language disorder (DLD) have a high rate of co-occurring reading difficulties. The current study aims to (i) examine which factors within the Active View of Reading (AVR; Duke & Cartwright, 2021) apply to individuals with DLD and (ii) investigate other possible factors that relate to reading comprehension ability in individuals with DLD, outside the components in the AVR. Electronic database search and journal hand-search yielded 5058 studies published before March 2022 related to reading comprehension in children with DLD. 4802 articles were excluded during abstract screening, yielding 256 studies eligible for full-text review. Following full-text review, 44 studies were included and further coded for demographics, language of assessment, description of reported disabilities, behavioral assessment, and reading comprehension assessment. While the results aligned with the AVR model, three additional factors were identified as significantly relating to reading comprehension abilities in children with DLD: expressive language (oral and written), question types of reading assessment, and language disorder history. Specifically, expressive language was positively associated with reading comprehension ability, while resolved DLD showed higher reading comprehension abilities than persistent DLD. Furthermore, children with DLD may face additional difficulties in comprehending inference-based questions. This study provides factors for researchers, educators, and clinical professionals to consider when evaluating the reading comprehension of individuals with DLD. Future research should further explore the relative importance of factors of the AVR to reading comprehension outcomes throughout development.

Action video games and posterior parietal cortex neuromodulation enhance both attention and reading in adults with developmental dyslexia.

The impact of action video games on reading performance has been already demonstrated in individuals with and without neurodevelopmental disorders. The combination of action video games and posterior parietal cortex neuromodulation by a transcranial random noise stimulation could enhance brain plasticity, improving attentional control and reading skills also in adults with developmental dyslexia. In a double blind randomized controlled trial, 20 young adult nonaction video game players with developmental dyslexia were trained for 15 h with action video games. Half of the participants were stimulated with bilateral transcranial random noise stimulation on the posterior parietal cortex during the action video game training, whereas the others were in the placebo (i.e. sham) condition. Word text reading, pseudowords decoding, and temporal attention (attentional blink), as well as electroencephalographic activity during the attentional blink, were measured before and after the training. The action video game + transcranial random noise stimulation group showed temporal attention, word text reading, and pseudoword decoding enhancements and P300 amplitude brain potential changes. The enhancement in temporal attention performance was related with the efficiency in pseudoword decoding improvement. Our results demonstrate that the combination of action video game training with parietal neuromodulation increases the efficiency of visual attention deployment, probably reshaping goal-directed and stimulus-driven fronto-parietal attentional networks interplay in young adults with neurodevelopmental conditions.

An executive-functions-based reading training enhances sensory-motor systems integration during reading fluency in children with dyslexia.

The Simple View of Reading model suggests that intact language processing and word decoding lead to proficient reading comprehension, with recent studies pointing at executive functions as an important component contributing to reading proficiency. Here, we aimed to determine the underlying mechanism(s) for these changes. Participants include 120 8- to 12-year-old children (n = 55 with dyslexia, n = 65 typical readers) trained on an executive functions-based reading program, including pre/postfunctional MRI and behavioral data collection. Across groups, improved word reading was related to stronger functional connections within executive functions and sensory networks. In children with dyslexia, faster and more accurate word reading was related to stronger functional connections within and between sensory networks. These results suggest greater synchronization of brain systems after the intervention, consistent with the "neural noise" hypothesis in children with dyslexia and support the consideration of including executive functions as part of the Simple View of Reading model.

The informant matters: Differences in bullying victim categorization rates assessed with self- and peer-reports in children with developmental language disorder and reading difficulties.

BACKGROUND: Children with Developmental Language Disorder (DLD) and Reading Difficulties (RD) can show more peer relation problems depending on the informant. AIMS: (1) To explore bullying victims' categorization, evaluated by self- and peer-reports, in children with DLD and RD; and (2) to assess agreement rates between informants. METHOD AND PROCEDURES: Victimization was assessed using a self-report (EBIP-Q) and a peer-report sociogram (CESC) in a sample of 83 participants (9-12 years; 10.5 ± 1.1 years), comprising of DLD (n = 19), RD (n = 32), and Control (n = 32) groups. OUTCOMES AND RESULTS: We found a higher frequency of the rejected sociometric profile in the DLD and RD groups, a higher peer-reported victimization in the DLD group, and more severe self-reported victimization in the DLD and RD groups. Odds of being classified as victimized were higher for self-report except in the DLD group. Informants' agreement was high using the most restrictive EBIP-Q criterion (7 points) for both the Control and the RD groups, being non-significant for the DLD group regardless of the criteria used. CONCLUSIONS AND IMPLICATIONS: We found a higher victimization risk in children with language difficulties, although self-assessment seems to under-detect children with DLD according to the agreement rates, pointing out the need to combine assessments and informants. WHAT DOES THIS PAPER ADD?: Several studies have shown that children with DLD or RD obtain higher scores of victimization and score lower on several scales of social skills with continuous data. Although continuous analyses are usual in research, professional decisions are usually based on cut-off criteria more than how high or low a score is in contrast to another group. This is one of the first works that analyses victimization following the cut-off criteria of self and peer assessments that professionals used in the school settings in children with DLD and RD. Our results will raise awareness among school professionals based on the evidence about the high risk of victimization, especially in children with DLD, and the implications of selecting between several measures of victimization, in this group of children. We think that our results would help to better detect and prevent bullying in schools for children with DLD.

Motor skills and capacities in developmental dyslexia: A systematic review and meta-analysis.

In recent decades, the connections between academic skills, such as reading, writing, and calculation, and motor skills/capacities have received increasing attention. Many studies provided evidence for motor difficulties in children and adolescents with dyslexia, prompting the need for a meta-analysis to combine these multiple findings. Therefore, we conducted a meta-analysis using PsycINFO, Pubmed, and SportDiscus as scientific databases. A total of 572 studies were analyzed following several stringent inclusion criteria, resulting in the inclusion of 23 peer-reviewed studies in the final analysis. Our results showed that children and adolescents with dyslexia displayed significant different performances in multiple motor tasks and these differences persisted also when the type of motor task was considered as moderator in the analysis. The present findings are in accordance with the literature that supports a close connection between reading disabilities and difficulties in motor skills/capacities.

Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Handwriting difficulties in children with dyslexia: Poorer legibility in dictation and alphabet tasks, slowness in the alphabet task.

Several studies have shown that children with dyslexia (DYS), in addition to their reading and spelling deficits, encounter handwriting difficulties that are still poorly understood in terms of their nature and origin. The present study aimed to better understand the handwriting difficulties of children with DYS by comparing their handwriting quality and speed in two tasks, a dictation task and an alphabet task, which required fewer spelling skills than the dictation task. Twenty-nine French-speaking children (Mage = 9.5 years) participated in the study, including 18 children with DYS and nine typically developing (TD) children matched on chronological age. The children performed control tasks, a dictation task with words varying in graphic and orthographic complexity and an alphabet writing task. Accuracy, handwriting quality (legibility), and fluency (speed, writing and pause time) were carefully measured using a digital tablet. GLMM analysis and t tests showed that children with DYS made more aesthetic errors (handwriting quality) in both the dictation and alphabet task than TD children. They also wrote more slowly than TD children in the alphabet task (speed, pause time). These findings suggest that children with DYS present handwriting difficulties, even in a simple alphabet task. In dictation, they seem to favour speed at the expense of handwriting quality.

Investigating low intelligence stereotype threat in adults with developmental dyslexia.

Stereotype threat (ST) is a phenomenon that leads to decreased test performance and occurs when one deals with added pressure of being judged on the basis of stereotyped group membership. The ST effect has been previously investigated in many contexts but not in individuals with dyslexia who are often stereotyped as less intelligent. Prevalent use of intelligence tests in job selection processes and employment gap between people with dyslexia and those without warrants this investigation. Sixty-three participants (30 with dyslexia and 33 without dyslexia; mean age = 33.7; SD = 13.7; 47 F, 13 M, three non-binary) were asked to complete intelligence test typically used in selection processes. All participants were randomly assigned to one of three test instruction conditions: (1) they were told the test was diagnostic of their intelligence (ST triggering instruction); (2) test was a measure of their problem-solving skills (reduced threat); (3) or they were simply asked to take the test (control). Results showed that participants with dyslexia in ST condition performed poorer than those in other conditions and those in the same condition who did not have dyslexia. This study provides preliminary evidence for diminishing effects of ST in individuals with dyslexia.

Developmental dyslexia susceptibility genes DNAAF4, DCDC2, and NRSN1 are associated with brain function in fluently reading adolescents and young adults.

Reading skills and developmental dyslexia, characterized by difficulties in developing reading skills, have been associated with brain anomalies within the language network. Genetic factors contribute to developmental dyslexia risk, but the mechanisms by which these genes influence reading skills remain unclear. In this preregistered study (https://osf.io/7sehx), we explored if developmental dyslexia susceptibility genes DNAAF4, DCDC2, NRSN1, and KIAA0319 are associated with brain function in fluently reading adolescents and young adults. Functional MRI and task performance data were collected during tasks involving written and spoken sentence processing, and DNA sequence variants of developmental dyslexia susceptibility genes previously associated with brain structure anomalies were genotyped. The results revealed that variation in DNAAF4, DCDC2, and NRSN1 is associated with brain activity in key language regions: the left inferior frontal gyrus, middle temporal gyrus, and intraparietal sulcus. Furthermore, NRSN1 was associated with task performance, but KIAA0319 did not yield any significant associations. Our findings suggest that individuals with a genetic predisposition to developmental dyslexia may partly employ compensatory neural and behavioral mechanisms to maintain typical task performance. Our study highlights the relevance of these developmental dyslexia susceptibility genes in language-related brain function, even in individuals without developmental dyslexia, providing valuable insights into the genetic factors influencing language processing.

Early life stress, literacy and dyslexia: an evolutionary perspective.

Stress and learning co-evolved in parallel, with their interdependence critical to the survival of the species. Even today, the regulation of moderate levels of stress by the central autonomic network (CAN), especially during pre- and post-natal periods, facilitates biological adaptability and is an essential precursor for the cognitive requisites of learning to read. Reading is a remarkable evolutionary achievement of the human brain, mysteriously unusual, because it is not pre-wired with a genetic address to facilitate its acquisition. There is no gene for reading. The review suggests that reading co-opts a brain circuit centered in the left hemisphere ventral occipital cortex that evolved as a domain-general visual processor. Its adoption by reading depends on the CAN's coordination of the learning and emotional requirements of learning to read at the metabolic, cellular, synaptic, and network levels. By stabilizing a child's self-control and modulating the attention network's inhibitory controls over the reading circuit, the CAN plays a key role in school readiness and learning to read. In addition, the review revealed two beneficial CAN evolutionary adjustments to early-life stress "overloads" that come with incidental costs of school under-performance and dyslexia. A short-term adaptation involving methylation of the FKBP5 and NR3C1 genes is a liability for academic achievement in primary school. The adaptation leading to dyslexia induces alterations in BDNF trafficking, promoting long-term adaptive fitness by protecting against excessive glucocorticoid toxicity but risks reading difficulties by disruptive signaling from the CAN to the attention networks and the reading circuit.

Are Communication Skills, Emotion Regulation and Theory of Mind Skills Impaired in Adolescents with Developmental Dyslexia?

This study investigates pragmatic language impairment, Theory of Mind (ToM), and emotion regulation in adolescents with Developmental Dyslexia(DD). The Social Responsiveness Scale-2(SRS) and Children's Communication Checklist-2(CCC-2) scores were found to be statistically significantly higher in the DD group than in healthy controls. DD group had lower performance in ToM skills and they have more difficulties in emotion regulation. We also found that CCC-2 and ToM scores were significantly correlated in adolescents with DD. These results may be important in understanding the difficulties experienced in social functioning and interpersonal relationships in adolescents with DD.

A Systematic Review on Visual-Processing Deficits in Neurofibromatosis Type 1: What Possible Impact on Learning to Read?

This systematic review aimed to examine the possible implication of visual-perceptual, visuo-attentional and oculomotor processing in the reading deficits frequently experienced by children with Neurofibromatosis type 1 (NF1), as previously shown in dyslexia. Using PRISMA methodological guidelines, we examined 49 studies; most of these reported visual-processing deficits in this population, raising the importance of directly studying the visuo-perceptual and visuo-attentional processes and eye-movement control involved in the learning-to-read process in NF1. The discussion provides a reflection for a better understanding of how visual-processing skills interact with reading deficits in NF1, as well as new avenues for their screening and care.

Localized alterations in cortical thickness and sulcal depth of the cingulo-opercular network in relation to lower reading fluency skills in children with dyslexia.

The traditional models of reading development describe how language processing and word decoding contribute to reading comprehension and how impairments in word decoding, a defining feature of dyslexia, affect reading comprehension outcomes. However, these models do not include word and sentence reading (contextual reading) fluency, both of which engage executive functions, with notably decreased performance in children with dyslexia. In the current study, we compared cortical thickness and sulcal depth (CT/SD) in the cingulo-opercular (CO) executive functions brain network in children with dyslexia and typical readers and examined associations with word vs. contextual reading fluency. Overall, CT was lower in insular regions and higher in parietal and caudal anterior cingulate cortex regions in children with dyslexia. Children with dyslexia showed positive correlations between word reading fluency and CT/SD in insular regions, whereas no significant correlations were observed in typical readers. For sentence reading fluency, negative correlations with CT/SD were found in insular regions in children with dyslexia, while positive correlations with SD were found in insular regions in typical readers. These results demonstrate the differential relations between word and sentence reading fluency and anatomical circuitry supporting executive functions in children with dyslexia vs. typical readers. It also suggests that word and sentence reading fluency, relate to morphology of executive function-related regions in children with dyslexia, whereas in typical readers, only sentence reading fluency relates to morphology of executive function regions. The results also highlight the role of the insula within the CO network in reading fluency. Here we suggest that word and sentence reading fluency are distinct components of reading that should each be included in the Simple View of Reading traditional model.

Cognitive strengths in neurodevelopmental disorders, conditions and differences: A critical review.

Neurodevelopmental disorders are traditionally characterised by a range of associated cognitive impairments in, for example, sensory processing, facial recognition, visual imagery, attention, and coordination. In this critical review, we propose a major reframing, highlighting the variety of unique cognitive strengths that people with neurodevelopmental differences can exhibit. These include enhanced visual perception, strong spatial, auditory, and semantic memory, superior empathy and theory of mind, along with higher levels of divergent thinking. Whilst we acknowledge the heterogeneity of cognitive profiles in neurodevelopmental conditions, we present a more encouraging and affirmative perspective of these groups, contrasting with the predominant, deficit-based position prevalent throughout both cognitive and neuropsychological research. In addition, we provide a theoretical basis and rationale for these cognitive strengths, arguing for the critical role of hereditability, behavioural adaptation, neuronal-recycling, and we draw on psychopharmacological and social explanations. We present a table of potential strengths across conditions and invite researchers to systematically investigate these in their future work. This should help reduce the stigma around neurodiversity, instead promoting greater social inclusion and significant societal benefits.