Unraveling individual differences in learning potential: A dynamic framework for the case of reading development.

Children show an enormous capacity to learn during development, but with large individual differences in the time course and trajectory of learning and the achieved skill level. Recent progress in developmental sciences has shown the contribution of a multitude of factors including genetic variation, brain plasticity, socio-cultural context and learning experiences to individual development. These factors interact in a complex manner, producing children's idiosyncratic and heterogeneous learning paths. Despite an increasing recognition of these intricate dynamics, current research on the development of culturally acquired skills such as reading still has a typical focus on snapshots of children's performance at discrete points in time. Here we argue that this 'static' approach is often insufficient and limits advancements in the prediction and mechanistic understanding of individual differences in learning capacity. We present a dynamic framework which highlights the importance of capturing short-term trajectories during learning across multiple stages and processes as a proxy for long-term development on the example of reading. This framework will help explain relevant variability in children's learning paths and outcomes and fosters new perspectives and approaches to study how children develop and learn.

Attentional modulation of neural sound tracking in children with and without dyslexia.

Auditory selective attention forms an important foundation of children's learning by enabling the prioritisation and encoding of relevant stimuli. It may also influence reading development, which relies on metalinguistic skills including the awareness of the sound structure of spoken language. Reports of attentional impairments and speech perception difficulties in noisy environments in dyslexic readers are also suggestive of the putative contribution of auditory attention to reading development. To date, it is unclear whether non-speech selective attention and its underlying neural mechanisms are impaired in children with dyslexia and to which extent these deficits relate to individual reading and speech perception abilities in suboptimal listening conditions. In this EEG study, we assessed non-speech sustained auditory selective attention in 106 7-to-12-year-old children with and without dyslexia. Children attended to one of two tone streams, detecting occasional sequence repeats in the attended stream, and performed a speech-in-speech perception task. Results show that when children directed their attention to one stream, inter-trial-phase-coherence at the attended rate increased in fronto-central sites; this, in turn, was associated with better target detection. Behavioural and neural indices of attention did not systematically differ as a function of dyslexia diagnosis. However, behavioural indices of attention did explain individual differences in reading fluency and speech-in-speech perception abilities: both these skills were impaired in dyslexic readers. Taken together, our results show that children with dyslexia do not show group-level auditory attention deficits but these deficits may represent a risk for developing reading impairments and problems with speech perception in complex acoustic environments. RESEARCH HIGHLIGHTS: Non-speech sustained auditory selective attention modulates EEG phase coherence in children with/without dyslexia Children with dyslexia show difficulties in speech-in-speech perception Attention relates to dyslexic readers' speech-in-speech perception and reading skills Dyslexia diagnosis is not linked to behavioural/EEG indices of auditory attention.

Sensitivity to syllable stress regularities in externally but not self-triggered speech in Dutch.

Several theories of predictive processing propose reduced sensory and neural responses to anticipated events. Support comes from magnetoencephalography/electroencephalography (M/EEG) studies, showing reduced auditory N1 and P2 responses to self-generated compared to externally generated events, or when the timing and form of stimuli are more predictable. The current study examined the sensitivity of N1 and P2 responses to statistical speech regularities. We employed a motor-to-auditory paradigm comparing event-related potential (ERP) responses to externally and self-triggered pseudowords. Participants were presented with a cue indicating which button to press (motor-auditory condition) or which pseudoword would be presented (auditory-only condition). Stimuli consisted of the participant's own voice uttering pseudowords that varied in phonotactic probability and syllable stress. We expected to see N1 and P2 suppression for self-triggered stimuli, with greater suppression effects for more predictable features such as high phonotactic probability and first-syllable stress in pseudowords. In a temporal principal component analysis (PCA), we observed an interaction between syllable stress and condition for the N1, where second-syllable stress items elicited a larger N1 than first-syllable stress items, but only for externally generated stimuli. We further observed an effect of syllable stress on the P2, where first-syllable stress items elicited a larger P2. Strikingly, we did not observe motor-induced suppression for self-triggered stimuli for either the N1 or P2 component, likely due to the temporal predictability of the stimulus onset in both conditions. Taking into account previous findings, the current results suggest that sensitivity to syllable stress regularities depends on task demands.

Early reading skills and the ventral occipito-temporal cortex organization.

Learning to read impacts the way the ventral occipitotemporal cortex (VOT) reorganizes. The postulated underlying mechanism of neuronal recycling was recently revisited. Neuroimaging data showed that voxels weakly specialized for visual processing keep their initial category selectivity (i.e., object or face processing) while acquiring an additional and stronger responsivity to written words. Here, we examined a large and diverse group of six-year-olds prior to formal literacy training (N = 72) using various data analysis techniques (univariate, multivariate, rapid adaptation) and types of stimuli (print, false fonts, houses, faces) to further explore how VOT changes and adapts to the novel skill of reading. We found that among several visual stimuli categories only print activated a wide network of language related areas outside of the bilateral visual cortex, and the level of reading skill was related to the strength of this activation, showing the development of the reading circuit. Rapid adaptation was not directly related to the level of reading skill in the young children studied here, but it clearly revealed the emergence of the reading network in readers. Most importantly, we found that the reorganization of the VOT is not in fact an "invasion" by reading acquisition-voxels previously activated for faces started to respond more for print, while at the same time keeping their previous function. We can thus conclude that the revised hypothesis of neuronal recycling is supported by our data.

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people.

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Altered brain network topology during speech tracking in developmental dyslexia.

Developmental dyslexia is often accompanied by altered phonological processing of speech. Underlying neural changes have typically been characterized in terms of stimulus- and/or task-related responses within individual brain regions or their functional connectivity. Less is known about potential changes in the more global functional organization of brain networks. Here we recorded electroencephalography (EEG) in typical and dyslexic readers while they listened to (a) a random sequence of syllables and (b) a series of tri-syllabic real words. The network topology of the phase synchronization of evoked cortical oscillations was investigated in four frequency bands (delta, theta, alpha and beta) using minimum spanning tree graphs. We found that, compared to syllable tracking, word tracking triggered a shift toward a more integrated network topology in the theta band in both groups. Importantly, this change was significantly stronger in the dyslexic readers, who also showed increased reliance on a right frontal cluster of electrodes for word tracking. The current findings point towards an altered effect of word-level processing on the functional brain network organization that may be associated with less efficient phonological and reading skills in dyslexia.

Longitudinal changes in cortical responses to letter-speech sound stimuli in 8-11 year-old children.

While children are able to name letters fairly quickly, the automatisation of letter-speech sound mappings continues over the first years of reading development. In the current longitudinal fMRI study, we explored developmental changes in cortical responses to letters and speech sounds across 3 yearly measurements in a sample of 18 8-11 year old children. We employed a text-based recalibration paradigm in which combined exposure to text and ambiguous speech sounds shifts participants' later perception of the ambiguous sounds towards the text. Our results showed that activity of the left superior temporal and lateral inferior precentral gyri followed a non-linear developmental pattern across the measurement sessions. This pattern is reminiscent of previously reported inverted-u-shape developmental trajectories in children's visual cortical responses to text. Our findings suggest that the processing of letters and speech sounds involves non-linear changes in the brain's spoken language network possibly related to progressive automatisation of reading skills.

Neural correlates of error-monitoring and mindset: Back to the drawing board?

The different ways students deal with mistakes is an integral part of mindset theory. While previous error-monitoring studies found supporting neural evidence for mindset-related differences, they may have been confounded by overlapping stimulus processing. We therefore investigated the relationship between mindset and event-related potentials (ERPs) of error-monitoring (response-locked Ne, Pe), with and without overlap correction. In addition, besides behavioral measures of remedial action after errors (post-error slowing and accuracy), we investigated their neural correlates (stimulus-locked N2). Results indicated comparable Ne, but larger Pe amplitudes in fixed-minded students; however, after overlap correction, the Pe results were rendered non-significant. A likely explanation for this overlap was a near-significant effect of mindset on the preceding stimulus P3. Finally, although N2 was larger for trials following errors, mindset was unrelated. The current study shows that the relationship between error-monitoring and mindset is more complex and should be reconsidered. Future studies are advised to explore stimulus processing as well, and if needed, to correct for stimulus overlap. In addition, contextual influences on and individual variation in error-monitoring need more scrutiny, which may contribute to refining mindset theory.

Neurophysiological tracking of speech-structure learning in typical and dyslexic readers.

Statistical learning, or the ability to extract statistical regularities from the sensory environment, plays a critical role in language acquisition and reading development. Here we employed electroencephalography (EEG) with frequency-tagging measures to track the temporal evolution of speech-structure learning in individuals with reading difficulties due to developmental dyslexia and in typical readers. We measured EEG while participants listened to (a) a structured stream of repeated tri-syllabic pseudowords, (b) a random stream of the same isochronous syllables, and (c) a series of tri-syllabic real Dutch words. Participants' behavioral learning outcome (pseudoword recognition) was measured after training. We found that syllable-rate tracking was comparable between the two groups and stable across both the random and structured streams of syllables. More importantly, we observed a gradual emergence of the tracking of tri-syllabic pseudoword structures in both groups. Compared to the typical readers, however, in the dyslexic readers this implicit speech structure learning seemed to build up at a slower pace. A brain-behavioral correlation analysis showed that slower learners (i.e., participants who were slower in establishing the neural tracking of pseudowords) were less skilled in phonological awareness. Moreover, those who showed stronger neural tracking of real words tended to be less fluent in the visual-verbal conversion of linguistic symbols. Taken together, our study provides an online neurophysiological approach to track the progression of implicit learning processes and gives insights into the learning difficulties associated with dyslexia from a dynamic perspective.

Cortical responses to letters and ambiguous speech vary with reading skills in dyslexic and typically reading children.

One of the proposed issues underlying reading difficulties in dyslexia is insufficiently automatized letter-speech sound associations. In the current fMRI experiment, we employ text-based recalibration to investigate letter-speech sound mappings in 8-10 year-old children with and without dyslexia. Here an ambiguous speech sound /a?a/ midway between /aba/ and /ada/ is combined with disambiguating "aba" or "ada" text causing a perceptual shift of the ambiguous /a?a/ sound towards the text (recalibration). This perceptual shift has been found to be reduced in adults but not in children with dyslexia compared to typical readers. Our fMRI results show significantly reduced activation in the left fusiform in dyslexic compared to typical readers, despite comparable behavioural performance. Furthermore, enhanced audio-visual activation within this region was linked to better reading and phonological skills. In contrast, higher activation in bilateral superior temporal cortex was associated with lower letter-speech sound identification fluency. These findings reflect individual differences during the early stages of reading development with reduced recruitment of the left fusiform in dyslexic readers together with an increased involvement of the superior temporal cortex in children with less automatized letter-speech sound associations.

How Learning to Read Changes the Listening Brain.

Reading acquisition reorganizes existing brain networks for speech and visual processing to form novel audio-visual language representations. This requires substantial cortical plasticity that is reflected in changes in brain activation and functional as well as structural connectivity between brain areas. The extent to which a child's brain can accommodate these changes may underlie the high variability in reading outcome in both typical and dyslexic readers. In this review, we focus on reading-induced functional changes of the dorsal speech network in particular and discuss how its reciprocal interactions with the ventral reading network contributes to reading outcome. We discuss how the dynamic and intertwined development of both reading networks may be best captured by approaching reading from a skill learning perspective, using audio-visual learning paradigms and longitudinal designs to follow neuro-behavioral changes while children's reading skills unfold.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

ERP mismatch response to phonological and temporal regularities in speech.

Predictions of our sensory environment facilitate perception across domains. During speech perception, formal and temporal predictions may be made for phonotactic probability and syllable stress patterns, respectively, contributing to the efficient processing of speech input. The current experiment employed a passive EEG oddball paradigm to probe the neurophysiological processes underlying temporal and formal predictions simultaneously. The component of interest, the mismatch negativity (MMN), is considered a marker for experience-dependent change detection, where its timing and amplitude are indicative of the perceptual system's sensitivity to presented stimuli. We hypothesized that more predictable stimuli (i.e. high phonotactic probability and first syllable stress) would facilitate change detection, indexed by shorter peak latencies or greater peak amplitudes of the MMN. This hypothesis was confirmed for phonotactic probability: high phonotactic probability deviants elicited an earlier MMN than low phonotactic probability deviants. We do not observe a significant modulation of the MMN to variations in syllable stress. Our findings confirm that speech perception is shaped by formal and temporal predictability. This paradigm may be useful to investigate the contribution of implicit processing of statistical regularities during (a)typical language development.

Brain activity patterns of phonemic representations are atypical in beginning readers with family risk for dyslexia.

There is an ongoing debate whether phonological deficits in dyslexics should be attributed to (a) less specified representations of speech sounds, like suggested by studies in young children with a familial risk for dyslexia, or (b) to an impaired access to these phonemic representations, as suggested by studies in adults with dyslexia. These conflicting findings are rooted in between study differences in sample characteristics and/or testing techniques. The current study uses the same multivariate functional MRI (fMRI) approach as previously used in adults with dyslexia to investigate phonemic representations in 30 beginning readers with a familial risk and 24 beginning readers without a familial risk of dyslexia, of whom 20 were later retrospectively classified as dyslexic. Based on fMRI response patterns evoked by listening to different utterances of /bA/ and /dA/ sounds, multivoxel analyses indicate that the underlying activation patterns of the two phonemes were distinct in children with a low family risk but not in children with high family risk. However, no group differences were observed between children that were later classified as typical versus dyslexic readers, regardless of their family risk status, indicating that poor phonemic representations constitute a risk for dyslexia but are not sufficient to result in reading problems. We hypothesize that poor phonemic representations are trait (family risk) and not state (dyslexia) dependent, and that representational deficits only lead to reading difficulties when they are present in conjunction with other neuroanatomical or-functional deficits.

Reading-Induced Shifts in Speech Perception in Dyslexic and Typically Reading Children.

One of the proposed mechanisms underlying reading difficulties observed in developmental dyslexia is impaired mapping of visual to auditory speech representations. We investigate these mappings in 20 typically reading and 20 children with dyslexia aged 8-10 years using text-based recalibration. In this paradigm, the pairing of visual text and ambiguous speech sounds shifts (recalibrates) the participant's perception of the ambiguous speech in subsequent auditory-only post-test trials. Recent research in adults demonstrated this text-induced perceptual shift in typical, but not in dyslexic readers. Our current results instead show significant text-induced recalibration in both typically reading children and children with dyslexia. The strength of this effect was significantly linked to the strength of perceptual adaptation effects in children with dyslexia but not typically reading children. Furthermore, additional analyses in a sample of typically reading children of various reading levels revealed a significant link between recalibration and phoneme categorization. Taken together, our study highlights the importance of considering dynamic developmental changes in reading, letter-speech sound coupling and speech perception when investigating group differences between typical and dyslexic readers.

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 × 10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10-8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10-8) and with all the cognitive traits tested (p = 3.07 × 10-8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10-5-10-7]) and negatively associated with ADHD PRS (p ~ [10-8-10-17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.

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.