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.

Identifying Dyslexia: Link between Maze Learning and Dyslexia Susceptibility Gene, DCDC2, in Young Children.

Dyslexia is a common learning disability that affects processing of written language despite adequate intelligence and educational background. If learning disabilities remain untreated, a child may experience long-term social and emotional problems, which influence future success in all aspects of their life. Dyslexia has a 60% heritability rate, and genetic studies have identified multiple dyslexia susceptibility genes (DSGs). DSGs, such as DCDC2, are consistently associated with the risk and severity of reading disability (RD). Altered neural connectivity within temporoparietal regions of the brain is associated with specific variants of DSGs in individuals with RD. Genetically altering DSG expression in mice results in visual and auditory processing deficits as well as neurophysiological and neuroanatomical disruptions. Previously, we demonstrated that learning deficits associated with RD can be translated across species using virtual environments. In this 2-year longitudinal study, we demonstrate that performance on a virtual Hebb-Williams maze in pre-readers is able to predict future reading impairment, and the genetic risk strengthens, but is not dependent on, this relationship. Due to the lack of oral reporting and use of letters, this easy-to-use tool may be particularly valuable in a remote working environment as well as working with vulnerable populations such as English language learners.

Training of vertical versus horizontal reading in patients with hemianopia - a randomized and controlled study.

HYPOTHESIS: Patients with hemianopic field defects (HFD) might benefit from reading text in vertical orientation if they place the text in the seeing hemifield along the vertical midline. METHODS: We assigned 21 patients with HFD randomly to either vertical or horizontal reading training. They trained reading single lines of texts from a computer screen at home for 2 × 30 min/day, 5 days/week, for 4 weeks. The main outcome variable was reading speed (RS) during reading standardized paragraphs of printed text (IReST) aloud. RS was assessed before training (T1), directly after training (T2) and 4 weeks later (T3). Quality of life (QoL) was assessed by Impact of Visual Impairment (IVI) questionnaire. RESULTS: Vertical training improved RS in the vertical direction significantly. Only patients with right HFD benefited. Horizontal training improved RS in horizontal diection significantly, but much more in patients with left than in those with right HFD. Both effects remained stable at T3. RS during training at the computer improved highly significantly and correlated strongly with RS of printed text (Pearson r= > 0.9). QoL: Vertical training showed a statistically significant improvement in the complete IVI-score, patients with right HFD in the emotional IVI-score. CONCLUSIONS: The improvements of RS were specific for the training. The stable effect indicates that the patients can apply the newly learned strategies to everyday life. The side of the HFD plays an essential role: Left-HFD patients benefitted from horizontal training, right-HFD patients from vertical training. However, the vertical RS did not reach the level of horizontal RS. The study was registered in the German Clinical Trials register (DRKS-ID: DRKS00018843).

Language difficulties are a shared risk factor for both reading disorder and mathematics disorder.

Disorders of reading and mathematics co-occur at greater than chance rates, but they are often studied separately. This article reports the reading and arithmetic outcomes at 9 years of age from a longitudinal study of 224 children at high risk for dyslexia. Using a cutoff at the 10th centile, groups of children with reading disorder (RD), mathematics disorder (MD), and comorbid reading disorder and math disorder (RD&MD) were identified. The risk of these disorders was elevated in children selected in preschool with language difficulties or at family risk for dyslexia. There was a high degree of comorbidity between RD and MD, and many cases-particularly in the comorbid group-also reached the diagnostic threshold for developmental language disorder (DLD). On measures of language, phoneme awareness, rapid automatized naming (RAN) digits, and rated inattention, there was a stepwise pattern: RD > MD > RD&MD. Poor language was associated with each disorder and appears to be a cognitive risk factor for RD, MD, and RD&MD. These findings suggest that there are shared genetic risk factors operating for both RD and MD.

The association between anxiety and academic performance in children with reading disorder: A longitudinal cohort study.

The purpose of this study was to examine the association between anxiety and overall academic performance (AP) in children with reading disorder (RD). This two-year longitudinal cohort study included 128 participants (aged 7-14 years) with RD. Anxiety symptoms were evaluated using the School Anxiety Scale - Teacher Report for the first year and the eight-item Spence Children's Anxiety Scale for the second year. AP was assessed by teacher ratings of progress in academic content areas, including reading, writing and math. Teachers completed evaluations every 3 months. We standardized all scores (to z scores). Multivariate linear regression models (adjusting for age, sex and Attention-Deficit/Hyperactivity Disorder symptoms) assessed the association cross-sectionally at each timepoint of survey completion. Repeated measures analysis using mixed models assessed the relationship longitudinally. Results from both univariate and multivariate analyses showed anxiety being significantly negatively associated with AP in children with RD, both cross-sectionally and longitudinally. Importantly, increased anxiety was significantly associated with reduced AP over time within an individual (adjusted ß = -0.22, p = .002). This lends support to screening for anxiety disorders in children with RD. Future research should examine the directionality of this relationship, potential mediators in the pathway and whether interventions to reduce anxiety increase AP.

[Missed opportunities: The new ICD-11 diagnostic guidelines for reading, spelling and calculation disorders]. / Verpasste Chancen: Die neuen diagnostischen Leitlinien zur Lese-, Rechtschreib- und Rechenstörung der ICD-11.

Missed opportunities: The new ICD-11 diagnostic guidelines for reading, spelling and calculation disorders Abstract. Abstract. The introduction of the ICD-11 caused changes to the concept of the disorder and in the diagnostic criteria of reading, spelling, and arithmetic disorders. ICD-10 had classified these disorders as specific development disorders of scholastic skills, whereas ICD-11 summarizes these disorders as developmental learning disorders in the groups of "neurodevelopmental disorders," together with ADHD, depression, autism, Tourette's syndrome, and schizophrenia. A major change is the classification of an isolated reading disorder and the expansion of the spelling disorder as a learning disorder with impairment in written expression. The diagnostic criteria still focus on the IQ discrepancy criterion, which is no longer supported in practice or by the research results.

Reading-writing disorder in children with idiopathic epilepsy.

Several studies have documented learning disabilities (LDs) in subjects with epilepsy, who have been shown to be at greater risk of mild neuropsychological damage, with the consequent risk of academic failure. This retrospective study aimed to investigate the peculiarities of reading and writing disorders in subjects with idiopathic epilepsy. The reading and writing performance of 35 children affected by reading and writing disorders and idiopathic epilepsy (R/WD + E group) has been compared with the performance of 37 children with only reading and writing disorders (R/WD group). A comparison group of 22 typical developing healthy children (TDC group) was also included in the study. As expected, the TDC group reached better performances in the reading and writing tests administered. Between R/WD + E and R/WD groups, there was a substantial analogy in reading and writing disabilities. The differences between the two clinical groups concern writing ability in sentences dictation and verbal and visuospatial short-term memory in digit span and memory-for-location (MFL) tests.

Assessment for familial pattern and association of polymorphisms in KIAA0319 gene with specific reading disorder in children from North India visiting a tertiary care centre: A case-control study.

Genetic association studies have identified KIAA0319 gene as a possible susceptibility locus for reading disorder; however, very few studies are available from India. The study was planned to investigate the familial pattern and association of KIAA0319 polymorphisms among children with reading disorder visiting a tertiary centre in North India. This is a case-control, familial, and genetic association study on 30 children diagnosed with reading disorder (ICD-10) and 30 matched healthy controls and their families. The Aggregate Neurobehavioral Student Health and Educational Review System was administered on parents of probands and controls for reading problems in their siblings, and Adult Reading Questionnaire was administered for parents of both groups. The blood sample was taken from probands, and DNA was isolated. Four KIAA0319 coding sequence single nucleotide polymorphisms (SNPs; rs4504469, rs6935076, rs2038137, and rs2179515) were genotyped using SNaPshot single nucleotide extension. The incidence of reading problem was significantly higher in families of probands as compared with families of controls. There were no significant differences in both groups regarding the frequency of alleles of four SNPs. The reading disorder showed a significant familial pattern, but KIAA0319 gene did not appear to be a susceptibility factor. Future replications with larger samples and whole genome studies are warranted.

Phonological memory problems are magnified in children from language minority homes when predicting reading disability.

Children from language minority (LM) environments speak a language at home that differs from that at school, are often from socioeconomically disadvantaged backgrounds, and are at risk for reading impairment. We evaluated the main effects and interaction of language status and phonological memory and awareness on reading disorder in 352 children from socioeconomically disadvantaged backgrounds. A significant phonological memory by language status interaction indicated that phonological memory problems were magnified in predicting reading impairment in children from LM versus English dominant (ED) homes. Among children without reading disorder, language minority status was unrelated to phonological processing.

Genetic association analysis with pedigrees: Direct inference using the composite likelihood ratio.

The likelihood function represents statistical evidence given data and a model. The evidential paradigm (EP), an alternative to Bayesian and Frequentist paradigms, provides considerable theory demonstrating evidence strength for different parameter values via the ratio of likelihoods at different parameter values; thus, enabling inference directly from the likelihood function. The likelihood function, however, can be difficult to compute; for example, in genetic association studies with a binary outcome in large pedigrees. Composite likelihood (CL) is an alternative when the real likelihood is intractable. We show CLs have the two large sample properties of the EP for reliable evidence interpretation: (1) CL supports the true value over a false value by an arbitrarily large factor; and (2) the probability of favouring a false value over the true value is small and bounded. Using simulation, and in a genetic association analysis of reading disability (RD) in large rolandic epilepsy pedigrees, we show that the CL approach yields valid statistical inference and identifies RD associated variants. When compared to analyses using generalized estimating equations, results show a similar prioritization of SNPs, although the CL approach provides additional complementary information, and more intuitive solutions to the multiple hypothesis testing problem.

Understanding comorbidity of learning disorders: task-dependent estimates of prevalence.

BACKGROUND: Reading disorder (RD) and mathematics disorder (MD) frequently co-occur. However, the exact comorbidity rates differ largely between studies. Given that MD is characterised by high heterogeneity on the symptom level, differences in comorbidity rates may result from different mathematical subskills used to define MD. Comorbidity rates with RD are likely to be higher when MD is measured by mathematical subskills that do not only build on number processing, but also require language (i.e. arithmetic fluency), than when measured by magnitude processing skills. METHODS: The association between literacy, arithmetic fluency and magnitude processing as well as the overlap between deficits in these domains were assessed in a representative sample of 1,454 third Graders. RESULTS: Associations were significantly higher between literacy and arithmetic, than between literacy and magnitude processing. This was also reflected in comorbidity rates: comorbidity rates between literacy and arithmetic deficits were four times higher than expected by chance, whereas comorbidity rates between literacy and magnitude processing deficits did not exceed chance rate. Deficits in the two mathematical subskills showed some overlap, but also revealed dissociations, corroborating the high heterogeneity of MD. Results are interpreted within a multiple-deficit framework and implications for diagnosis and intervention are discussed. CONCLUSIONS: The overlap between RD and MD depends on the subskills used to define MD. Due to shared domain-general factors mathematical subskills that draw on language skills are more strongly associated with literacy than those that do not require language. The findings further indicate that the same symptom, such as deficits in arithmetic, can be associated with different cognitive deficits, a deficit in language skills or a deficit in number processing.

WordDriver-1: evaluating the efficacy of an app-supported decoding intervention for children with reading impairment.

BACKGROUND: Fluent word reading is a key characteristic of skilled reading, yet most children with reading disorders have impaired word-reading skills. Previous research has demonstrated that multi-component interventions targeting phonemic awareness and the alphabetic principle are effective for children with reading disorders. However, about 25% of children fail to respond to these interventions. While it has been difficult to isolate the active ingredient, the findings of some studies suggest that tasks targeting phonological recoding and orthographic processing are essential elements in improving decoding. AIMS: To develop and evaluate an intervention that specifically targets phonological recoding and orthographic processing (a decoding intervention) for children with persistent word-reading impairment. METHODS & PROCEDURES: A single-subject crossover design with multiple treatments was used to examine the efficacy of the decoding intervention (15 × 20-min sessions) compared with a language intervention that controlled for individual therapy time. Eight children (aged 7:6-8:11 years) with persistent word-reading impairment were randomly assigned to one of two intervention sequences. The effect of the decoding intervention was evaluated by (1) changes in decoding accuracy measured by performance on researcher-developed non-word lists; and (2) generalization to other standardized measures of reading. OUTCOMES & RESULTS: The results showed that all participants demonstrated significant gains in non-word reading on researcher-developed non-word lists and standardized measures of non-word-reading accuracy and efficiency. Trends for improvement on standardized measures of word-reading efficiency, text-reading accuracy and reading comprehension were observed. CONCLUSIONS & IMPLICATIONS: This decoding intervention significantly improved non-word decoding skills in all participants who had not responded to previous reading interventions. As such, it may be an efficient adjunct to the first stage of reading interventions for this population. The relative lack of generalization to other word-reading skills may have been due to the nature of the outcome measures, the short intervention time and/or additional delays in participant orthographic processing skills.

Examining the double-deficit hypothesis in vowelized-transparent Arabic in a national representative sample of Grades 3 and 4.

We examined the double-deficit hypothesis in Arabic by investigating the reading and cognitive profiles of readers with selective deficits in naming speed, phonological awareness, or both. In a nationally representative sample of 486 children in the third and fourth grades, we identified 171 children with reading difficulties: 20 (12%) were classified as having a phonological deficit, 31 (18%) as having a naming speed deficit, and 41 (24%) as having a double deficit. Differences between the subgroups extended to reading, cognitive, and linguistic processes beyond phonological and naming abilities. Children with a double deficit performed worse than those with a naming speed deficit but similar to those with a phonological deficit. Numerous unconfirmed theories led to an in-depth analysis of the nature of rapid automatized naming and its relation to orthographic processing. Surprisingly, our findings revealed that orthographic processing may be considered a novel and separate core deficit, suggesting a triple deficit in Arabic rather than a double deficit. The findings are discussed in light of the uniqueness and complexity of Arabic orthography and orthographic transparency in the Arabic language.

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs.

Developmental evaluation of atypical auditory sampling in dyslexia: Functional and structural evidence.

Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information at either syllabic- or phonemic-rates is still under debate. In addition, whereas neuroanatomical alterations in auditory regions have been documented in dyslexic readers, whether and how these structural anomalies are linked to auditory sampling and reading deficits remains poorly understood. In this study, we measured auditory neural synchronization at different frequencies corresponding to relevant phonological spectral components of speech in children and adults with and without dyslexia, using magnetoencephalography. Furthermore, structural MRI was used to estimate cortical thickness of the auditory cortex of participants. Dyslexics showed atypical brain synchronization at both syllabic (slow) and phonemic (fast) rates. Interestingly, while a left hemispheric asymmetry in cortical thickness was functionally related to a stronger left hemispheric lateralization of neural synchronization to stimuli presented at the phonemic rate in skilled readers, the same anatomical index in dyslexics was related to a stronger right hemispheric dominance for neural synchronization to syllabic-rate auditory stimuli. These data suggest that the acoustic sampling deficit in development dyslexia might be linked to an atypical specialization of the auditory cortex to both low and high frequency amplitude modulations.

TMS on right frontal eye fields induces an inflexible focus of attention.

The focus of spatial attention can be not only oriented to a particular location, but also adjusted in its size to select visual information from a narrow (zoom-in) or broad (zoom-out) region of the visual field. Attentional orienting, saccades programming, and visual search have been linked to the frontal eye fields (FEF) activity. However, the FEF causal role in the frontoparietal network for the attentional focus size modulation remains unclear. Here, we delivered single-pulse transcranial magnetic stimulation (TMS) on FEF while participants performed an attentional zooming task. They were asked to detect a visual target appearing at 3 eccentricities from the fixation. Two cue types modulated the size of the attended region: a small cue was employed to narrow the attentional focus, whereas a large cue induced participants to broaden the attended region. Results showed that TMS delivered on the right FEF, but not on the left FEF, was able to interfere with both zoom-in and zoom-out attentional mechanisms. Our results provide the first evidence of the right FEF casual role in the attentional zooming control and give new insights into the neural mechanisms of dysfunctional spatial attention deployment shown in neurodevelopmental disorders, such as autism and dyslexia.

How the visual aspects can be crucial in reading acquisition? The intriguing case of crowding and developmental dyslexia.

Developmental dyslexia (DD) is the most common neurodevelopmental disorder (about 10% of children across cultures) characterized by severe difficulties in learning to read. According to the dominant view, DD is considered a phonological processing impairment that might be linked to a cross-modal, letter-to-speech sound integration deficit. However, new theories-supported by consistent data-suggest that mild deficits in low-level visual and auditory processing can lead to DD. This evidence supports the probabilistic and multifactorial approach for DD. Among others, an interesting visual deficit that is often associated with DD is excessive visual crowding. Crowding is defined as difficulty in the ability to recognize objects when surrounded by similar items. Crowding, typically observed in peripheral vision, could be modulated by attentional processes. The direct consequence of stronger crowding on reading is the inability to recognize letters when they are surrounded by other letters. This problem directly translates to reading at a slower speed and being more prone to making errors while reading. Our aim is to review the literature supporting the important role of crowding in DD. Moreover, we are interested in proposing new possible studies in order to clarify whether the observed excessive crowding could be a cause rather than an effect of DD. Finally, we also suggest possible remediation and even prevention programs that could be based on reducing the crowding in children with or at risk for DD without involving any phonological or orthographic training.

[Visual perception abilities in children with reading disabilities]. / Visuelle Wahrnehmungsleistungen bei Kindern mit Lese- Rechtschreibstörung.

OBJECTIVE: Visual perceptual abilities are increasingly being neglected in research concerning reading disabilities. This study measures the visual perceptual abilities of children with disabilities in reading. METHOD: The visual perceptual abilities of 35 children with specific reading disorder and 30 controls were compared using the German version of the Developmental Test of Visual Perception ­ Adolescent and Adult (DTVP-A). RESULTS: 11 % of the children with specific reading disorder show clinically relevant performance on the DTVP-A. The perceptual abilities of both groups differ significantly. No significant group differences exist after controlling for general IQ or Perceptional Reasoning Index, but they do remain after controlling for Verbal Comprehension, Working Memory, and Processing Speed Index. CONCLUSIONS: The number of children with reading difficulties suffering from visual perceptual disorders has been underestimated. For this reason, visual perceptual abilities should always be tested when making a reading disorder diagnosis. Profiles of IQ-test results of children suffering from reading and visual perceptual disorders should be interpreted carefully.

Reading difficulty is associated with failure to lateralize temporooccipital function.

OBJECTIVE: Studies of focal epilepsy have revealed abnormalities of language organization; however, little attention has been paid to disorders of reading in this group. We hypothesized that language functional magnetic resonance imaging (fMRI) would reveal differences in language organization between focal epilepsy patients with and without reading difficulties. METHODS: We conducted language fMRI studies of 10 focal epilepsy patients with reading difficulties, 34 focal epilepsy patients without reading difficulties, and 42 healthy controls. RESULTS: We defined regions of interests on the basis of activation patterns on an orthographic lexical retrieval task. Comparison of activations within these ROIs on a second Noun-Verb task revealed epilepsy-related effects (relative to healthy controls: reduced activation in left inferior frontal cortex), as well as greater activation in the right temporooccipital cortex specific to the reading difficulty group. SIGNIFICANCE: These findings identify a focal epilepsy effect in the left frontal region (present in patients with and without reading difficulties), and a functional abnormality specific to the reading difficulty group localized to right temporooccipital cortex-a region implicated in lexicosemantic processing. Our observations suggest a failure of left hemisphere specialization among focal epilepsy patients with reading difficulties.

[Tourette syndrome and reading disorder in a boy with left parietofrontal tract disruption]. / Trastorno de Tourette y de la lectura en un niño con disrupción del tracto parietofrontal izquierdo.

We present the case of a nine-year-old boy with Tourette syndrome and reading disorder with a history of a severe infectious process in the late neonatal period. Brain MRI showed a left parietal malacotic cavity and diffusion tensor imaging and tractography showed a striking disruption of the white matter bundle that joins the left parietal region with the ipsilateral frontal region with involvement of the left superior longitudinal fasciculus and of the left arcuate fasciculus. Although Tourette syndrome and reading disorder are fundamentally hereditary neuropsychiatric disorders, they can also occur secondary to cerebral alterations like those existing in this boy. The introduction of modern neuroimaging techniques in patients with neuropsychiatric disorders (or the risk of developing them) can be very useful in the diagnosis and prognosis in the future.