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.

Bilateral Prefrontal Cortex Blood Flow Dynamics during Silent and Oral Reading Using Near-Infrared Spectroscopy.

This study aimed to investigate blood flow dynamics in the bilateral prefrontal cortex during silent and oral reading using near-infrared spectroscopy (NIRS). The subjects were 40 right-handed university students (20.5±1.8 years old, 20 men and 20 women). After completing the NIRS measurements, the subjects were asked to rate their level of proficiency in silent and oral reading, using a 5-point Likert scale. During oral reading, the left lateral prefrontal cortex (Broca's area) was significantly more active than the right side. During silent reading, prefrontal cortex activity was lower than that during oral reading, and there was no significant difference between both sides of the brain. A significant negative correlation was found between the change in oxy-hemoglobin (oxy-Hb) concentration in the left and right lateral prefrontal cortex during silent reading and silent reading speed. In addition, students with lower self-reported reading proficiency had significantly greater changes in oxy-Hb concentrations in the left and right lateral prefrontal cortex during silent/oral reading than did students with higher self-reported reading proficiency. Reading task assessment using NIRS may be useful for identifying language lateralization and Broca's area. The results demonstrate that NIRS is useful for assessing effortful reading and may be used to diagnose developmental dyslexia in children. J. Med. Invest. 71 : 92-101, February, 2024.

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.

Activation and functional connectivity of cerebellum during reading and during arithmetic in children with combined reading and math disabilities.

Background: Reading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children's educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing. Methods: Here we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex. Results: The two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity). Conclusion: These results do not support theories that children's deficits in reading and math originate in the cerebellum.

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.

Efficacy of Learning Disorder Treatment for Reading or Mathematics Disorders: An Open Study.

Objectives: This study aimed to identify the effectiveness of treatment programs for children with reading (RD) or mathematics disorders (MD). Structured treatment programs were developed to improve phonological awareness and number sense among children and adolescents with RD or MD, respectively, and the effectiveness of the learning disorder treatment programs were evaluated. Methods: We used standardized, objective diagnostic, and evaluation tools not only to recruit participants with RD, MD, or comorbid attention deficit and hyperactivity disorder, but also to assess the effectiveness of the treatments regarding both improved core neurocognitive deficits of RD or MD and academic achievement. Forty children with RD or MD received one-on-one treatments from therapists. Results: In the RD group, treatment effects were observed in all subtests. In the word and paragraph reading tests, the accuracy rates and fluency improved. The results of the phonological working memory test, word-sound correspondence test, and rapid automatic naming tests also improved. In the MD group, the accuracy rate and fluency on the arithmetic test improved. An increase in the accuracy rate in the size and distance comparison tests and a decrease in the error rate in the estimation test were also observed. However, there were no improvements in reaction time in these subtests. Conclusion: Learning disorder treatment programs that focus on improving phonological awareness or number sense in children with RD or MD improved achievement, phonological awareness, and number sense.

Supporting neurodivergent nursing students in their practice placements.

Neurodivergent conditions such as autism, attention deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia, dyscalculia and Tourette's syndrome are common, and it is highly likely that practice assessors and supervisors will be asked to support neurodivergent nursing students in their practice learning environments. This article details the strengths that neurodivergent students can bring to nursing, as well as some of the challenges they may experience in practice settings. It outlines how practice assessors and supervisors can develop neuro-inclusive learning environments where neurodivergent students can thrive, as well as how to support them if they are not meeting their required proficiencies. The authors also discuss how appropriate reasonable adjustments can be implemented by using a collaborative approach with students.

Impaired Ability in Visual-Spatial Attention in Chinese Children With Developmental Dyslexia.

A growing body of evidence suggests that children with dyslexia in alphabetic languages exhibit visual-spatial attention deficits that can obstruct reading acquisition by impairing their phonological decoding skills. However, it remains an open question whether these visual-spatial attention deficits are present in children with dyslexia in non-alphabetic languages. Chinese, with its logographic writing system, offers a unique opportunity to explore this question. The presence of visual-spatial attention deficits in Chinese children with dyslexia remains insufficiently investigated. Therefore, this study aimed to explore whether such deficits exist, employing a visual search paradigm. Three visual search tasks were conducted, encompassing two singleton feature search tasks and a serial conjunction search task. The results indicated that Chinese children with dyslexia performed as well as chronological age-matched control children in color search tasks but less effectively in orientation search, suggesting a difficulty in the rapid visual processing of orientation: a deficit potentially specific to Chinese dyslexia. Crucially, Chinese children with dyslexia also exhibited lower accuracy, longer reaction times, and steeper slopes in the reaction times by set size function in the conjunction search task compared to control children, which is indicative of a visual-spatial attention deficit.

Analysis of reading-task-based brain connectivity in dyslexic children using EEG signals.

Developmental dyslexia, a neurodevelopment reading disorder, can impact even children with average intelligence. The present study examined the brain connectivity in dyslexic and control children during the reading task using graph theory. 19-channel electroencephalogram (EEG) signals were recorded from 15 dyslexic children and 15 control children. Functional connectivity was estimated by measuring the EEG coherence at 19 electrode locations, and graph measures were calculated using the graph theory method. Reading task results identified deprived task performance in dyslexic children against controls. Graph measures revealed longer path length, reduced clustering coefficient and reduced network efficiencies (in theta and alpha bands) of dyslexic group. At the nodal level, we found a significant increase in delta strength (T4 and T5 electrode locations) and reduced strength in theta (T6, P4, Fp1, F8 and F3) and alpha bands (T4, T3, P4 and F3) during the reading task in dyslexic group. In conclusion, the present study identified distinct graph measures between groups when performing a reading task and showed possible evidence for compromised brain networks in dyslexic group.

Leveraging brain science for impactful advocacy and policymaking: The synergistic partnership between developmental cognitive neuroscientists and a parent-led grassroots movement to drive dyslexia prevention policy and legislation.

Reading proficiency is crucial for academic, vocational, and economic success and has been closely linked to health outcomes. Unfortunately, in the United States, a concerning 63% of fourth-grade children are reading below grade level, with approximately 7%-10% exhibiting a disability in word reading, developmental dyslexia. Research in developmental cognitive neuroscience indicates that individuals with dyslexia show functional and structural brain alterations in regions processing reading and reading-related information, with some of these differences emerging as early as preschool and even infancy. This suggests that some children start schooling with less optimal brain architecture for learning to read, emphasizing the need for preventative education practices. This article reviews educational policies impacting children with dyslexia and highlights a decentralized parent-led grassroots movement, Decoding Dyslexia, which centers the voices of those directly impacted by dyslexia. It utilizes civic engagement practices, advocacy and lobbying on local, federal, and social media platforms, and strong partnerships with scientists to drive systems-level change in educational practices, leading to dyslexia prevention legislation across the U.S. The ongoing partnership continues to address the profound gaps between scientific findings and policymaking to drive systems-level change for contemporary challenges in educational practices within a learning disabilities framework.

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.

Reading and writing from right to left after anterior cerebral artery stroke.

This is the case report of a woman who started to write and read from right to left after anterior cerebral artery stroke, affecting the left supplementary motor area. No cases were found in the literature with exactly the same characteristics. She has been able to read and write faster after rehabilitation approach at Sarah Network of Rehabilitation Hospitals, in the Belo Horizonte city unit, Brazil, despite the maintenance of the inversion. She returned to her previous activities in an adaptive way. It was discussed how the dysfunction in this cerebral area and its connections may disturb the reading strategy and direction.

Relato do caso de uma mulher que passou a escrever e ler da direita para a esquerda após um acidente vascular encefálico isquêmico de artéria cerebral anterior, acometendo área motora suplementar esquerda. Não foram encontrados casos na literatura exatamente com as mesmas características. Durante a participação da paciente no programa de reabilitação neurológica da Rede Sarah de Hospitais de Reabilitação, unidade Belo Horizonte, foram observados ganhos na agilidade de leitura e escrita, ainda que mantendo a inversão, e retorno às suas atividades de forma adaptada. Realizou-se discussão de como o comprometimento dessa área e de suas conexões pode perturbar a estratégia de leitura e sua direção.

Investigating Dyslexia through Diffusion Tensor Imaging across Ages: A Systematic Review.

Dyslexia is a neurodevelopmental disorder that presents a deficit in accuracy and/or fluency while reading or spelling that is not expected given the level of cognitive functioning. Research indicates brain structural changes mainly in the left hemisphere, comprising arcuate fasciculus (AF) and corona radiata (CR). The purpose of this systematic review is to better understand the possible methods for analyzing Diffusion Tensor Imaging (DTI) data while accounting for the characteristics of dyslexia in the last decade of the literature. Among 124 articles screened from PubMed and Scopus, 49 met inclusion criteria, focusing on dyslexia without neurological or psychiatric comorbidities. Article selection involved paired evaluation, with a third reviewer resolving discrepancies. The selected articles were analyzed using two topics: (1) a demographic and cognitive assessment of the sample and (2) DTI acquisition and analysis. Predominantly, studies centered on English-speaking children with reading difficulties, with preserved non-verbal intelligence, attention, and memory, and deficits in reading tests, rapid automatic naming, and phonological awareness. Structural differences were found mainly in the left AF in all ages and in the bilateral superior longitudinal fasciculus for readers-children and adults. A better understanding of structural brain changes of dyslexia and neuroadaptations can be a guide for future interventions.

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.

Do early musical impairments predict later reading difficulties? A longitudinal study of pre-readers with and without familial risk for dyslexia.

The present longitudinal study investigated the hypothesis that early musical skills (as measured by melodic and rhythmic perception and memory) predict later literacy development via a mediating effect of phonology. We examined 130 French-speaking children, 31 of whom with a familial risk for developmental dyslexia (DD). Their abilities in the three domains were assessed longitudinally with a comprehensive battery of behavioral tests in kindergarten, first grade, and second grade. Using a structural equation modeling approach, we examined potential longitudinal effects from music to literacy via phonology. We then investigated how familial risk for DD may influence these relationships by testing whether atypical music processing is a risk factor for DD. Results showed that children with a familial risk for DD consistently underperformed children without familial risk in music, phonology, and literacy. A small effect of musical ability on literacy via phonology was observed, but may have been induced by differences in stability across domains over time. Furthermore, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status. These findings are consistent with the idea that certain key auditory skills are shared between music and speech processing, and between DD and congenital amusia. However, they do not support the notion that music perception and memory skills can serve as a reliable early marker of DD, nor as a valuable target for reading remediation. RESEARCH HIGHLIGHTS: Music, phonology, and literacy skills of 130 children, 31 of whom with a familial risk for dyslexia, were examined longitudinally. Children with a familial risk for dyslexia consistently underperformed children without familial risk in musical, phonological, and literacy skills. Structural equation models showed a small effect of musical ability in kindergarten on literacy in second grade, via phonology in first grade. However, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status.

Scoping Review of Music Interventions Aimed at Improving Reading Skills in Children with Specific Learning Disorders in Reading.

An emerging body of research utilizes music in the treatment of children with specific learning disorders in reading. However, greater understanding of music interventions is necessary for efficient application of music to address children's specific reading needs. Therefore, this scoping review aimed to identify the key musical concepts used to improve reading skills. Intervention studies were identified through online searches of databases and hand searching of primary journals in music therapy, and 12 studies met the inclusion criteria. For the 12 studies, auditory processing, phonological processing, and temporal processing were the underlying mechanisms identified in the interventions. Most of the interventions presented rhythmic activities for the purpose of improving reading accuracy. The results of this study highlight the lack of specific descriptions for the musical elements used within music interventions targeting reading skills. In addition, due to the diversity of the terms used to describe the music interventions, it was difficult to compare the effectiveness of these interventions on reading accuracy, comprehension skills, and fluency. Therefore, future studies are needed to articulate clear rationales for how musical elements can be used in music interventions to treat specific reading disabilities in children.

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.

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.

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.