Atypical White Matter Connectivity in Dyslexic Readers of a Fairly Transparent Orthography.

Atypical structural properties of the brain's white matter bundles have been associated with failing reading acquisition in developmental dyslexia. Because these white matter properties may show dynamic changes with age and orthographic depth, we examined fractional anisotropy (FA) along 16 white matter tracts in 8- to 11-year-old dyslexic (DR) and typically reading (TR) children learning to read in a fairly transparent orthography (Dutch). Our results showed higher FA values in the bilateral anterior thalamic radiations of DRs and FA values of the left thalamic radiation scaled with behavioral reading-related scores. Furthermore, DRs tended to have atypical FA values in the bilateral arcuate fasciculi. Children's age additionally predicted FA values along the tracts. Together, our findings suggest differential contributions of cortical and thalamo-cortical pathways to the developing reading network in dyslexic and typical readers, possibly indicating prolonged letter-by-letter reading or increased attentional and/or working memory demands in dyslexic children during reading.

Altered patterns of directed connectivity within the reading network of dyslexic children and their relation to reading dysfluency.

Reading is a complex cognitive skill subserved by a distributed network of visual and language-related regions. Disruptions of connectivity within this network have been associated with developmental dyslexia but their relation to individual differences in the severity of reading problems remains unclear. Here we investigate whether dysfunctional connectivity scales with the level of reading dysfluency by examining EEG recordings during visual word and false font processing in 9-year-old typically reading children (TR) and two groups of dyslexic children: severely dysfluent (SDD) and moderately dysfluent (MDD) dyslexics. Results indicated weaker occipital to inferior-temporal connectivity for words in both dyslexic groups relative to TRs. Furthermore, SDDs exhibited stronger connectivity from left central to right inferior-temporal and occipital sites for words relative to TRs, and for false fonts relative to both MDDs and TRs. Importantly, reading fluency was positively related with forward and negatively with backward connectivity. Our results suggest disrupted visual processing of words in both dyslexic groups, together with a compensatory recruitment of right posterior brain regions especially in the SDDs during word and false font processing. Functional connectivity in the brain's reading network may thus depend on the level of reading dysfluency beyond group differences between dyslexic and typical readers.

Cognitive and familial risk evidence converged: A data-driven identification of distinct and homogeneous subtypes within the heterogeneous sample of reading disabled children.

The evident degree of heterogeneity observed in reading disabled children has puzzled reading researchers for decades. Recent advances in the genetic underpinnings of reading disability have indicated that the heritable, familial risk for dyslexia is a major risk factor. The present data-driven, classification attempt aims to revisit the possibility of identifying distinct cognitive deficit profiles in a large sample of second to fourth grade reading disabled children. In this sample, we investigated whether genetic and environmental risk factors are able to distinguish between poor reader subtypes. In this profile, we included reading-related measures of phonemic awareness, letter-speech sound processing and rapid naming, known as candidate vulnerability markers associated with dyslexia and familial risk for dyslexia, as well as general cognitive abilities (non-verbal IQ and vocabulary). Clustering was based on a 200 multi-start K-means approach. Results revealed four emerging subtypes of which the first subtype showed no cognitive deficits underlying their poor reading skills (Reading-only impaired poor readers). The other three subtypes shared a core phonological deficit (PA) with a variable and discriminative expression across the other underlying vulnerability markers. More specific, type 2 showed low to poor performance across all reading-related and general cognitive abilities (general poor readers), type 3 showed a specific letter-speech sound mapping deficit next to a PA deficit (PA-LS specific poor readers) and type 4 showed a specific rapid naming deficit complementing their phonological weakness (PA-RAN specific poor readers). The first three poor reader profiles were more characterized by variable environmental risk factor, while the fourth, PA-RAN poor reader subtype showed a significantly strong familial risk for dyslexia. Overall, when we zoom in on the heterogeneous phenomenon of reading disability, unique and distinct cognitive subtypes can be identified, distinguishing between those poor readers more influences by the role of genes and those more influenced by environmental risk factors. Taking into account this diversity of distinct cognitive subtypes, instead of looking at the reading disabled sample as a whole, will help tailor future diagnostic and intervention efforts more specifically to the needs of children with such a specific deficit and risk pattern, as well as providing a more promising way forward for genetic studies of dyslexia.

A Randomized Controlled Trial on The Beneficial Effects of Training Letter-Speech Sound Integration on Reading Fluency in Children with Dyslexia.

UNLABELLED: A recent account of dyslexia assumes that a failure to develop automated letter-speech sound integration might be responsible for the observed lack of reading fluency. This study uses a pre-test-training-post-test design to evaluate the effects of a training program based on letter-speech sound associations with a special focus on gains in reading fluency. A sample of 44 children with dyslexia and 23 typical readers, aged 8 to 9, was recruited. Children with dyslexia were randomly allocated to either the training program group (n = 23) or a waiting-list control group (n = 21). The training intensively focused on letter-speech sound mapping and consisted of 34 individual sessions of 45 minutes over a five month period. The children with dyslexia showed substantial reading gains for the main word reading and spelling measures after training, improving at a faster rate than typical readers and waiting-list controls. The results are interpreted within the conceptual framework assuming a multisensory integration deficit as the most proximal cause of dysfluent reading in dyslexia. TRIAL REGISTRATION: ISRCTN register ISRCTN12783279.

Crossmodal deficit in dyslexic children: practice affects the neural timing of letter-speech sound integration.

A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills remains unknown. In this research, we examined changes in event-related potential (ERP) measures of letter-speech sound integration over a 6-month period during which 9-year-old dyslexic readers (n = 17) followed a training in letter-speech sound coupling next to their regular reading curriculum. We presented the Dutch spoken vowels /a/ and /o/ as standard and deviant stimuli in one auditory and two audiovisual oddball conditions. In one audiovisual condition (AV0), the letter "a" was presented simultaneously with the vowels, while in the other (AV200) it was preceding vowel onset for 200 ms. Prior to the training (T1), dyslexic readers showed the expected pattern of typical auditory mismatch responses, together with the absence of letter-speech sound effects in a late negativity (LN) window. After the training (T2), our results showed earlier (and enhanced) crossmodal effects in the LN window. Most interestingly, earlier LN latency at T2 was significantly related to higher behavioral accuracy in letter-speech sound coupling. On a more general level, the timing of the earlier mismatch negativity (MMN) in the simultaneous condition (AV0) measured at T1, significantly related to reading fluency at both T1 and T2 as well as with reading gains. Our findings suggest that the reduced neural integration of letters and speech sounds in dyslexic children may show moderate improvement with reading instruction and training and that behavioral improvements relate especially to individual differences in the timing of this neural integration.

Orthographic dependency in the neural correlates of reading: evidence from audiovisual integration in English readers.

Reading skills are indispensible in modern technological societies. In transparent alphabetic orthographies, such as Dutch, reading skills build on associations between letters and speech sounds (LS pairs). Previously, we showed that the superior temporal cortex (STC) of Dutch readers is sensitive to the congruency of LS pairs. Here, we used functional magnetic resonance imaging to investigate whether a similar congruency sensitivity exists in STC of readers of the more opaque English orthography, where the relation among LS pairs is less reliable. Eighteen subjects passively perceived congruent and incongruent audiovisual pairs of different levels of transparency in English: letters and speech sounds (LS; irregular), letters and letter names (LN; fairly transparent), and numerals and number names (NN; transparent). In STC, we found congruency effects for NN and LN, but no effects in the predicted direction (congruent > incongruent) for LS pairs. These findings contrast with previous results obtained from Dutch readers. These data indicate that, through education, the STC becomes tuned to the congruency of transparent audiovisual pairs, but suggests a different neural processing of irregular mappings. The orthographic dependency of LS integration underscores cross-linguistic differences in the neural basis of reading and potentially has important implications for dyslexia interventions across languages.

Reduced neural integration of letters and speech sounds in dyslexic children scales with individual differences in reading fluency.

The acquisition of letter-speech sound associations is one of the basic requirements for fluent reading acquisition and its failure may contribute to reading difficulties in developmental dyslexia. Here we investigated event-related potential (ERP) measures of letter-speech sound integration in 9-year-old typical and dyslexic readers and specifically test their relation to individual differences in reading fluency. We employed an audiovisual oddball paradigm in typical readers (n = 20), dysfluent (n = 18) and severely dysfluent (n = 18) dyslexic children. In one auditory and two audiovisual conditions the Dutch spoken vowels/a/and/o/were presented as standard and deviant stimuli. In audiovisual blocks, the letter 'a' was presented either simultaneously (AV0), or 200 ms before (AV200) vowel sound onset. Across the three children groups, vowel deviancy in auditory blocks elicited comparable mismatch negativity (MMN) and late negativity (LN) responses. In typical readers, both audiovisual conditions (AV0 and AV200) led to enhanced MMN and LN amplitudes. In both dyslexic groups, the audiovisual LN effects were mildly reduced. Most interestingly, individual differences in reading fluency were correlated with MMN latency in the AV0 condition. A further analysis revealed that this effect was driven by a short-lived MMN effect encompassing only the N1 window in severely dysfluent dyslexics versus a longer MMN effect encompassing both the N1 and P2 windows in the other two groups. Our results confirm and extend previous findings in dyslexic children by demonstrating a deficient pattern of letter-speech sound integration depending on the level of reading dysfluency. These findings underscore the importance of considering individual differences across the entire spectrum of reading skills in addition to group differences between typical and dyslexic readers.

Brain-potential analysis of visual word recognition in dyslexics and typically reading children.

The specialization of visual brain areas for fast processing of printed words plays an important role in the acquisition of reading skills. Dysregulation of these areas may be among the deficits underlying developmental dyslexia. The present study examines the specificity of word activation in dyslexic children in 3rd grade by comparing early components of brain potentials elicited by visually presented words vs. strings of meaningless letter-like symbols. Results showed a more pronounced N1 component for words compared to symbols for both groups. The dyslexic group revealed larger left-lateralized, word-specific N1 responses than the typically reading group. Furthermore, positive correlations between N1 amplitudes and reading fluency were found in the dyslexic group. Our results support the notion of N1 as a sensitive index of visual word processing involved in reading fluency.

Numerical predictors of arithmetic success in grades 1-6.

Math relies on mastery and integration of a wide range of simpler numerical processes and concepts. Recent work has identified several numerical competencies that predict variation in math ability. We examined the unique relations between eight basic numerical skills and early arithmetic ability in a large sample (N = 1391) of children across grades 1-6. In grades 1-2, children's ability to judge the relative magnitude of numerical symbols was most predictive of early arithmetic skills. The unique contribution of children's ability to assess ordinality in numerical symbols steadily increased across grades, overtaking all other predictors by grade 6. We found no evidence that children's ability to judge the relative magnitude of approximate, nonsymbolic numbers was uniquely predictive of arithmetic ability at any grade. Overall, symbolic number processing was more predictive of arithmetic ability than nonsymbolic number processing, though the relative importance of symbolic number ability appears to shift from cardinal to ordinal processing.

Cognitive subtypes of mathematics learning difficulties in primary education.

It has been asserted that children with mathematics learning difficulties (MLD) constitute a heterogeneous group. To date, most researchers have investigated differences between predefined MLD subtypes. Specifically MLD children are frequently categorized a priori into groups based on the presence or absence of an additional disorder, such as a reading disorder, to examine cognitive differences between MLD subtypes. In the current study 226 third to six grade children (M age=131 months) with MLD completed a selection of number specific and general cognitive measures. The data driven approach was used to identify the extent to which performance of the MLD children on these measures could be clustered into distinct groups. In particular, after conducting a factor analysis, a 200 times repeated K-means clustering approach was used to classify the children's performance. Results revealed six distinguishable clusters of MLD children, specifically (a) a weak mental number line group, (b) weak ANS group, (c) spatial difficulties group, (d) access deficit group, (e) no numerical cognitive deficit group and (f) a garden-variety group. These findings imply that different cognitive subtypes of MLD exist and that these can be derived from data-driven approaches to classification. These findings strengthen the notion that MLD is a heterogeneous disorder, which has implications for the way in which intervention may be tailored for individuals within the different subtypes.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

What basic number processing measures in kindergarten explain unique variability in first-grade arithmetic proficiency?

Relations between children's mathematics achievement and their basic number processing skills have been reported in both cross-sectional and longitudinal studies. Yet, some key questions are currently unresolved, including which kindergarten skills uniquely predict children's arithmetic fluency during the first year of formal schooling and the degree to which predictors are contingent on children's level of arithmetic proficiency. The current study assessed kindergarteners' non-symbolic and symbolic number processing efficiency. In addition, the contribution of children's underlying magnitude representations to differences in arithmetic achievement was assessed. Subsequently, in January of Grade 1, their arithmetic proficiency was assessed. Hierarchical regression analysis revealed that children's efficiency to compare digits, count, and estimate numerosities uniquely predicted arithmetic differences above and beyond the non-numerical factors included. Moreover, quantile regression analysis indicated that symbolic number processing efficiency was consistently a significant predictor of arithmetic achievement scores regardless of children's level of arithmetic proficiency, whereas their non-symbolic number processing efficiency was not. Finally, none of the task-specific effects indexing children's representational precision was significantly associated with arithmetic fluency. The implications of the results are 2-fold. First, the findings indicate that children's efficiency to process symbols is important for the development of their arithmetic fluency in Grade 1 above and beyond the influence of non-numerical factors. Second, the impact of children's non-symbolic number processing skills does not depend on their arithmetic achievement level given that they are selected from a nonclinical population.

Charting the functional relevance of Broca's area for visual word recognition and picture naming in Dutch using fMRI-guided TMS.

Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Broca's area (specifically pars opercularis of left inferior frontal gyrus and precentral gyrus; LIFGpo/PCG) within ∼100ms of viewing a word. This is consistent with Broca's area involvement in fast phonological access during visual word recognition. Here we used online transcranial magnetic stimulation (TMS) to investigate whether LIFGpo/PCG is necessary for (not just correlated with) visual word recognition by ∼100ms. Pulses were delivered to individually fMRI-defined LIFGpo/PCG in Dutch speakers 75-500ms after stimulus onset during reading and picture naming. Reading and picture naming reactions times were significantly slower following pulses at 225-300ms. Contrary to predictions, there was no disruption to reading for pulses before 225ms. This does not provide evidence in favour of a functional role for LIFGpo/PCG in reading before 225ms in this case, but does extend previous findings in picture stimuli to written Dutch words.

Predictors of developmental dyslexia in European orthographies with varying complexity.

BACKGROUND: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. METHODS: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). RESULTS: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. CONCLUSIONS: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

Evidence for a specific cross-modal association deficit in dyslexia: an electrophysiological study of letter-speech sound processing.

The phonological deficit theory of dyslexia assumes that degraded speech sound representations might hamper the acquisition of stable letter-speech sound associations necessary for learning to read. However, there is only scarce and mainly indirect evidence for this assumed letter-speech sound association problem. The present study aimed at clarifying the nature and the role of letter-speech sound association problems in dyslexia by analysing event-related potentials (ERP) of 11-year-old dyslexic children to speech sounds in isolation or combined with letters, which were presented either simultaneously with or 200 ms before the speech sounds. Recent studies with normal readers revealed that letters systematically modulated speech sound processing in an early (mismatch negativity or MMN) and late (Late Discriminatory Negativity or LDN) time-window. The amplitude of the MMN and LDN to speech sounds was enhanced when speech sounds were presented with letters. The dyslexic readers in the present study, however, did not exhibit any early influences of letters on speech sounds even after 4 years of reading instruction, indicating no automatic integration of letters and speech sounds. Interestingly, they revealed a systematic late effect of letters on speech sound processing, probably reflecting the mere association of letters and speech sounds. This pattern is strongly divergent from that observed in age-matched normal readers, who showed both early and late effects, but reminiscent of that observed in beginner normal readers in a previous study (Froyen, Bonte, van Atteveldt & Blomert, 2009). The finding that the quality of letter-speech sound processing is directly related to reading fluency urges further research into the role of audiovisual integration in the development of reading failure in dyslexia.

The neural signature of orthographic-phonological binding in successful and failing reading development.

Learning to read in alphabetic orthographies starts with learning a script code consisting of letter-speech sound pairs. Although children know which letters belong to which speech sounds within months, it takes much longer to automatically integrate them into newly constructed audiovisual objects. This extended learning process corresponds with observations that reliable letter and word specific activations in the fusiform cortex also occur relatively late in reading development. The present review discusses electrophysiological and neuroimaging studies of the nature and mechanisms involved in letter-speech sound integration in normal and dyslexic readers. It is demonstrated that letter-speech sound associations do not develop in parallel with visual letter recognition but immediately work in concert to form orthographic-phonological bonds which remain active even in experienced reading. Effective letter-speech sound integration may be necessary for reliable letter recognition to develop. In contrast, it is this basic integration of letters and speech sounds which poses an immediate problem for beginning dyslexic readers, and remains problematic in adult dyslexic readers. It is hypothesized that a specific orthographic-phonological binding deficit may not only act as a proximal cause for reading deficits in dyslexia, but may also explain the notorious lack of reading fluency. Finally, it is suggested that similar integrated audiovisual representations may also exist for larger grain-sizes in the same posterior occipitotemporal/inferoparietal network as identified for orthographic-phonological integration of letters and speech sounds.

Support systems for poor readers: empirical data from six EU member states.

This study surveyed and compared support systems for poor readers in six member states of the European Union (EU). The goal was to identify features of effective support systems. A large-scale questionnaire survey was conducted among mainstream teachers (n = 4,210) and remedial teachers (n = 2,395). Results indicate that the six support systems differed substantially, with effective support systems showing high performance on all variables measured. More specifically, effective support systems were characterized by (a) high levels of both teacher and student support and (b) frequent interactions between teachers and remedial teachers as well as between remedial teachers and diagnosticians. The high prevalence of poor reading ability in the current EU member states demonstrates that educational reforms are critically needed. The results of this study provide concrete starting points for improving support systems for poor readers.

Is there a causal link from a phonological awareness deficit to reading failure in children at familial risk for dyslexia?

The knowledge that reading and phonological awareness are mainly reciprocally related has hardly influenced the status of a phonological awareness deficit as the main cause of a reading deficit in dyslexia. Because direct proofs for this theory are still lacking we investigated children at familial risk for dyslexia in kindergarten and first grade. The familial risk was genuine; 40% developed reading deficits in first grade. However, we did not find any relationship between a phonological awareness or other phonological processing deficits in kindergarten and reading deficits in first grade. Finally, we did not find evidence for the claim that a phonological awareness deficit assumedly causes a reading deficit via 'unstable' or otherwise corrupted letter-speech sound associations. Although earlier research indicated letter knowledge as another significant determinant of later reading deficits, we found no support for this claim. Letter knowledge learning and learning to associate and integrate letters and speech sound are different processes and only problems in the latter process seem directly linked to the development of a reading deficit. The nature of this deficit and the impact it might have on multisensory processing in the whole reading network presents a major challenge to future reading and dyslexia research.

Multi-sensory learning and learning to read.

The basis of literacy acquisition in alphabetic orthographies is the learning of the associations between the letters and the corresponding speech sounds. In spite of this primacy in learning to read, there is only scarce knowledge on how this audiovisual integration process works and which mechanisms are involved. Recent electrophysiological studies of letter-speech sound processing have revealed that normally developing readers take years to automate these associations and dyslexic readers hardly exhibit automation of these associations. It is argued that the reason for this effortful learning may reside in the nature of the audiovisual process that is recruited for the integration of in principle arbitrarily linked elements. It is shown that letter-speech sound integration does not resemble the processes involved in the integration of natural audiovisual objects such as audiovisual speech. The automatic symmetrical recruitment of the assumedly uni-sensory visual and auditory cortices in audiovisual speech integration does not occur for letter and speech sound integration. It is also argued that letter-speech sound integration only partly resembles the integration of arbitrarily linked unfamiliar audiovisual objects. Letter-sound integration and artificial audiovisual objects share the necessity of a narrow time window for integration to occur. However, they differ from these artificial objects, because they constitute an integration of partly familiar elements which acquire meaning through the learning of an orthography. Although letter-speech sound pairs share similarities with audiovisual speech processing as well as with unfamiliar, arbitrary objects, it seems that letter-speech sound pairs develop into unique audiovisual objects that furthermore have to be processed in a unique way in order to enable fluent reading and thus very likely recruit other neurobiological learning mechanisms than the ones involved in learning natural or arbitrary unfamiliar audiovisual associations.

Exploring the Role of Low Level Visual Processing in Letter-Speech Sound Integration: A Visual MMN Study.

In contrast with for example audiovisual speech, the relation between visual and auditory properties of letters and speech sounds is artificial and learned only by explicit instruction. The arbitrariness of the audiovisual link together with the widespread usage of letter-speech sound pairs in alphabetic languages makes those audiovisual objects a unique subject for crossmodal research. Brain imaging evidence has indicated that heteromodal areas in superior temporal, as well as modality-specific auditory cortex are involved in letter-speech sound processing. The role of low level visual areas, however, remains unclear. In this study the visual counterpart of the auditory mismatch negativity (MMN) is used to investigate the influences of speech sounds on letter processing. Letter and non-letter deviants were infrequently presented in a train of standard letters, either in isolation or simultaneously with speech sounds. Although previous findings showed that letters systematically modulate speech sound processing (reflected by auditory MMN amplitude modulation), the reverse does not seem to hold: our results did not show evidence for an automatic influence of speech sounds on letter processing (no visual MMN amplitude modulation). This apparent asymmetric recruitment of low level sensory cortices during letter-speech sound processing, contrasts with the symmetric involvement of these cortices in audiovisual speech processing, and is possibly due to the arbitrary nature of the link between letters and speech sounds.