Myelin plasticity during early literacy training in at-risk pre-readers.

A growing body of neuroimaging evidence shows that white matter can change as a result of experience and structured learning. Although the majority of previous work has used diffusion MRI to characterize such changes in white matter, diffusion metrics offer limited biological specificity about which microstructural features may be driving white matter plasticity. Recent advances in myelin-specific MRI techniques offer a promising opportunity to assess the specific contribution of myelin in learning-related plasticity. Here we describe the application of such an approach to examine structural plasticity during an early intervention in preliterate children at risk for dyslexia. To this end, myelin water imaging data were collected before and after a 12-week period in (1) at-risk children following early literacy training (n = 13-24), (2) at-risk children engaging with other non-literacy games (n = 10-17) and (3) children without a risk receiving no training (n = 11-22). Before the training, regional risk-related differences were identified, showing higher myelin water fraction (MWF) in right dorsal white matter in at-risk children compared to the typical control group. Concerning intervention-specific effects, our results revealed an increase across left-hemispheric and right ventral MWF over the course of training in the at-risk children receiving early literacy training, but not in the at-risk active control group or the no-risk typical control group. Overall, our results provide support for the use of myelin water imaging as a sensitive tool to investigate white matter and offer a first indication of myelin plasticity in young children at the onset of literacy acquisition.

Neurobiological predispositions for musicality: White matter in infancy predicts school-age music aptitude.

Musical training has long been viewed as a model for experience-dependent brain plasticity. Reports of musical training-induced brain plasticity are largely based on cross-sectional studies comparing musicians to non-musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre-existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school-age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract in infancy is associated with school-age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter-hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build. RESEARCH HIGHLIGHTS: Structural organization of the right corticospinal tract in infancy is associated with school-age musical aptitude skills. Longitudinal associations between the right corticospinal tract in infancy and school-age rhythmic music aptitude skills remain significant even when controlling for language ability. Findings support the notion of predispositions for success in music, and suggest that musical predispositions likely build upon a neural structural scaffold established in infancy. Findings support the working hypothesis that a dynamic interaction between predisposition and experience established in infancy shape the trajectory of long-term musical development.

Speech perception deficits and the effect of envelope-enhanced story listening combined with phonics intervention in pre-readers at risk for dyslexia.

Developmental dyslexia is considered to be most effectively addressed with preventive phonics-based interventions, including grapheme-phoneme coupling and blending exercises. These intervention types require intact speech perception abilities, given their large focus on exercises with auditorily presented phonemes. Yet some children with (a risk for) dyslexia experience problems in this domain due to a poorer sensitivity to rise times, i.e., rhythmic acoustic cues present in the speech envelope. As a result, the often subtle speech perception problems could potentially constrain an optimal response to phonics-based interventions in at-risk children. The current study therefore aimed (1) to extend existing research by examining the presence of potential speech perception deficits in pre-readers at cognitive risk for dyslexia when compared to typically developing peers and (2) to explore the added value of a preventive auditory intervention for at-risk pre-readers, targeting rise time sensitivity, on speech perception and other reading-related skills. To obtain the first research objective, we longitudinally compared speech-in-noise perception between 28 5-year-old pre-readers with and 30 peers without a cognitive risk for dyslexia during the second half of the third year of kindergarten. The second research objective was addressed by exploring growth in speech perception and other reading-related skills in an independent sample of 62 at-risk 5-year-old pre-readers who all combined a 12-week preventive phonics-based intervention (GraphoGame-Flemish) with an auditory story listening intervention. In half of the sample, story recordings contained artificially enhanced rise times (GG-FL_EE group, n = 31), while in the other half, stories remained unprocessed (GG-FL_NE group, n = 31; Clinical Trial Number S60962-https://www.uzleuven.be/nl/clinical-trial-center). Results revealed a slower speech-in-noise perception growth in the at-risk compared to the non-at-risk group, due to an emerged deficit at the end of kindergarten. Concerning the auditory intervention effects, both intervention groups showed equal growth in speech-in-noise perception and other reading-related skills, suggesting no boost of envelope-enhanced story listening on top of the effect of combining GraphoGame-Flemish with listening to unprocessed stories. These findings thus provide evidence for a link between speech perception problems and dyslexia, yet do not support the potential of the auditory intervention in its current form.

Home language and literacy environment and its relationship to socioeconomic status and white matter structure in infancy.

The home language and literacy environment (HLLE) in infancy has been associated with subsequent pre-literacy skill development and HLLE at preschool-age has been shown to correlate with white matter organization in tracts that subserve pre-reading and reading skills. Furthermore, childhood socioeconomic status (SES) has been linked with both HLLE and white matter organization. It is important to understand whether the relationships between environmental factors such as HLLE and SES and white matter organization can be detected as early as infancy, as this period is characterized by rapid brain development that may make white matter pathways particularly susceptible to these early experiences. Here, we hypothesized that HLLE (1) relates to white matter organization in pre-reading and reading-related tracts in infants, and (2) mediates a link between SES and white matter organization. To test these hypotheses, infants (mean age: 8.6 ± 2.3 months, N = 38) underwent diffusion-weighted imaging MRI during natural sleep. Image processing was performed with an infant-specific pipeline and fractional anisotropy (FA) was estimated from the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF) bilaterally using the baby automated fiber quantification method. HLLE was measured with the Reading subscale of the StimQ (StimQ-Reading) and SES was measured with years of maternal education. Self-reported maternal reading ability was also quantified and applied to our statistical models as a proxy for confounding genetic effects. StimQ-Reading positively correlated with FA in left AF and to maternal education, but did not mediate the relationship between them. Taken together, these findings underscore the importance of considering HLLE from the start of life and may inform novel prevention and intervention strategies to support developing infants during a period of heightened brain plasticity.

Myelin water fraction in relation to fractional anisotropy and reading in 10-year-old children.

Diffusion-weighted imaging studies have repeatedly shown that white matter correlates with reading throughout development. However, the neurobiological interpretation of this relationship is constrained by the limited microstructural specificity of diffusion imaging. A critical component of white matter microstructure is myelin, which can be investigated noninvasively using MRI. Here, we examined the link between myelin water fraction (MWF) and reading ability in 10-year-old children (n = 69). To better understand this relationship, we additionally investigated how these two variables relate to fractional anisotropy (FA; a common index of diffusion-weighted imaging). Our analysis revealed that lower MWF coheres with better reading scores in left-hemispheric tracts relevant for reading. While we replicated previous reports on a positive relationship between FA and MWF, we did not find any evidence for an association between reading and FA. Together, these findings contrast previous research suggesting that poor reading abilities might be rooted in lower myelination and emphasize the need for further longitudinal research to understand how this relationship evolves throughout reading development. Altogether, this study contributes important insights into the role of myelin-related processes in the relationship between reading and white matter structure.

Feasibility, Enjoyment, and Language Comprehension Impact of a Tablet- and GameFlow-Based Story-Listening Game for Kindergarteners: Methodological and Mixed Methods Study.

BACKGROUND: Enjoyment plays a key role in the success and feasibility of serious gaming interventions. Unenjoyable games will not be played, and in the case of serious gaming, learning will not occur. Therefore, a so-called GameFlow model has been developed, which intends to guide (serious) game developers in the process of creating and evaluating enjoyment in digital (serious) games. Regarding language learning, a variety of serious games targeting specific language components exist in the market, albeit often without available assessments of enjoyment or feasibility. OBJECTIVE: This study evaluates the enjoyment and feasibility of a tablet-based, serious story-listening game for kindergarteners, developed based on the principles of the GameFlow model. This study also preliminarily explores the possibility of using the game to foster language comprehension. METHODS: Within the framework of a broader preventive reading intervention, 91 kindergarteners aged 5 years with a cognitive risk for dyslexia were asked to play the story game for 12 weeks, 6 days per week, either combined with a tablet-based phonics intervention or control games. The story game involved listening to and rating stories and responding to content-related questions. Game enjoyment was assessed through postintervention questionnaires, a GameFlow-based evaluation, and in-game story rating data. Feasibility was determined based on in-game general question response accuracy (QRA), reflecting the difficulty level, attrition rate, and final game exposure and training duration. Moreover, to investigate whether game enjoyment and difficulty influenced feasibility, final game exposure and training duration were predicted based on the in-game initial story ratings and initial QRA. Possible growth in language comprehension was explored by analyzing in-game QRA as a function of the game phase and baseline language skills. RESULTS: Eventually, data from 82 participants were analyzed. The questionnaire and in-game data suggested an overall enjoyable game experience. However, the GameFlow-based evaluation implied room for game design improvement. The general QRA confirmed a well-adapted level of difficulty for the target sample. Moreover, despite the overall attrition rate of 39% (32/82), 90% (74/82) of the participants still completed 80% of the game, albeit with a large variation in training days. Higher initial QRA significantly increased game exposure (ß=.35; P<.001), and lower initial story ratings significantly slackened the training duration (ß=-0.16; P=.003). In-game QRA was positively predicted by game phase (ß=1.44; P=.004), baseline listening comprehension (ß=1.56; P=.002), and vocabulary (ß=.16; P=.01), with larger QRA growth over game phases in children with lower baseline listening comprehension skills (ß=-0.08; P=.04). CONCLUSIONS: Generally, the story game seemed enjoyable and feasible. However, the GameFlow model evaluation and predictive relationships imply room for further game design improvements. Furthermore, our results cautiously suggest the potential of the game to foster language comprehension; however, future randomized controlled trials should further elucidate the impact on language comprehension.

Investigating the impact of early literacy training on white matter structure in prereaders at risk for dyslexia.

Recent prereading evidence demonstrates that white matter alterations are associated with dyslexia even before the onset of reading instruction. At the same time, remediation of reading difficulties is suggested to be most effective when provided as early as kindergarten, yet evidence is currently lacking on the early neuroanatomical changes associated with such preventive interventions. To address this open question, we investigated white matter changes following early literacy intervention in Dutch-speaking prereaders (aged 5-6 years) with an increased cognitive risk for developing dyslexia. Diffusion-weighted images were acquired before and after a 12-week digital intervention in three groups: (i) at-risk children receiving phonics-based training (n = 31); (ii) at-risk children engaging with active control training (n = 25); and (iii) typically developing children (n = 27) receiving no intervention. Following automated quantification of white matter tracts relevant for reading, we first examined baseline differences between at-risk and typically developing children, revealing bilateral dorsal and ventral differences. Longitudinal analyses showed that white matter properties changed within the course of the training; however, the absence of intervention-specific results suggests that these changes rather reflect developmental effects. This study contributes important first insights on the neurocognitive mechanisms of intervention that precedes formal reading onset.

Ahead of maturation: Enhanced speech envelope training boosts rise time discrimination in pre-readers at cognitive risk for dyslexia.

Dyslexia has frequently been related to atypical auditory temporal processing and speech perception. Results of studies emphasizing speech onset cues and reinforcing the temporal structure of the speech envelope, that is, envelope enhancement (EE), demonstrated reduced speech perception deficits in individuals with dyslexia. The use of this strategy as auditory intervention might thus reduce some of the deficits related to dyslexia. Importantly, reading-skill interventions are most effective when they are provided during kindergarten and first grade. Hence, we provided a tablet-based 12-week auditory and phonics-based intervention to pre-readers at cognitive risk for dyslexia and investigated the effect on auditory temporal processing with a rise time discrimination (RTD) task. Ninety-one pre-readers at cognitive risk for dyslexia (aged 5-6) were assigned to two groups receiving a phonics-based intervention and playing a story listening game either with (n = 31) or without (n = 31) EE or a third group playing control games and listening to non-enhanced stories (n = 29). RTD was measured directly before, directly after and 1 year after the intervention. While the groups listening to non-enhanced stories mainly improved after the intervention during first grade, the group listening to enhanced stories improved during the intervention in kindergarten and subsequently remained stable during first grade. Hence, an EE intervention improves auditory processing skills important for the development of phonological skills. This occurred before the onset of reading instruction, preceding the maturational improvement of these skills, hence potentially giving at risk children a head start when learning to read. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=e0BfT4dGXNA.

Digital Game-Based Phonics Instruction Promotes Print Knowledge in Pre-Readers at Cognitive Risk for Dyslexia.

Dyslexia is targeted most effectively when (1) interventions are provided preventively, before the onset of reading instruction, and (2) remediation programs combine letter-sound training with phoneme blending. Given the growing potential of technology in educational contexts, there has been a considerable increase of letter-sound trainings embedded in digital serious games. One such intervention is GraphoGame. Yet, current evidence on the preventive impact of GraphoGame is limited by the lack of adaptation of the original learning content to the skills of pre-readers, short training duration, and a restricted focus on explicitly trained skills. Therefore, the current study aims at investigating the impact of a preventive, and pre-reading adapted GraphoGame training (i.e., GraphoGame-Flemish, GG-FL) on explicitly trained skills and non-specifically trained phonological and language abilities. Following a large-scale screening (N = 1225), the current study included 88 pre-reading kindergarteners at cognitive risk for dyslexia who were assigned to three groups training either with GG-FL (n = 31), an active control game (n = 29), or no game (n = 28). Before and after the 12-week intervention, a variety of reading-related skills were assessed. Moreover, receptive letter knowledge and phonological awareness were measured every three weeks during the intervention period. Results revealed significantly larger improvements in the GG-FL group on explicitly trained skills, i.e., letter knowledge and word decoding, without finding transfer-effects to untrained phonological and language abilities. Our findings imply a GG-FL-driven head start on early literacy skills in at-risk children. A follow-up study should uncover the long-term impact and the ability of GG-FL to prevent actual reading failure.

A three-time point longitudinal investigation of the arcuate fasciculus throughout reading acquisition in children developing dyslexia.

Although the neural basis of dyslexia has intensively been investigated, results are still unclear about the existence of a white matter deficit in the arcuate fasciculus (AF) throughout development. To unravel this ambiguity, we examined the difference in fractional anisotropy (FA) of the AF between children developing dyslexia and children developing typical reading skills in a longitudinal sample with three MRI time points throughout reading development: the pre-reading stage (5-6 years old), the early reading stage (7-8 years old) and the advanced reading stage (9-10 years old). Applying along-the-tract analyses of white matter organization, our results confirmed that a white matter deficit existed in the left AF prior to the onset of formal reading instruction in children who developed dyslexia later on. This deficit was consistently present throughout the course of reading development. Additionally, we evaluated the use of applying a continuous approach on the participants' reading skills rather than the arbitrary categorization in individuals with or without dyslexia. Our results confirmed the predictive relation between FA and word reading measurements later in development. This study supports the use of longitudinal approaches to investigate the neural basis of the developmental process of learning to read and the application of triangulation, i.e. using multiple research approaches to help gain more insight and aiding the interpretation of obtained results.

Imaging the rapidly developing brain: Current challenges for MRI studies in the first five years of life.

Rapid and widespread changes in brain anatomy and physiology in the first five years of life present substantial challenges for developmental structural, functional, and diffusion MRI studies. One persistent challenge is that methods best suited to earlier developmental stages are suboptimal for later stages, which engenders a trade-off between using different, but age-appropriate, methods for different developmental stages or identical methods across stages. Both options have potential benefits, but also biases, as pipelines for each developmental stage can be matched on methods or the age-appropriateness of methods, but not both. This review describes the data acquisition, processing, and analysis challenges that introduce these potential biases and attempts to elucidate decisions and make recommendations that would optimize developmental comparisons.

The relation between neurofunctional and neurostructural determinants of phonological processing in pre-readers.

Phonological processing skills are known as the most robust cognitive predictor of reading ability. Therefore, the neural determinants of phonological processing have been extensively investigated by means of either neurofunctional or neurostructural techniques. However, to fully understand how the brain represents and processes phonological information, there is need for studies that combine both methods. The present study applies such a multimodal approach with the aim of investigating the pre-reading relation between neural measures of auditory temporal processing, white matter properties of the reading network and phonological processing skills. We administered auditory steady-state responses, diffusion-weighted MRI scans and phonological awareness tasks in 59 pre-readers. Our results demonstrate that a stronger rightward lateralization of syllable-rate (4 Hz) processing coheres with higher fractional anisotropy in the left fronto-temporoparietal arcuate fasciculus. Both neural features each in turn relate to better phonological processing skills. As such, the current study provides novel evidence for the existence of a pre-reading relation between functional measures of syllable-rate processing, structural organization of the arcuate fasciculus and cognitive precursors of reading development. Moreover, our findings demonstrate the value of combining different neural techniques to gain insight in the underlying neural systems for reading (dis)ability.

Pre-literacy heterogeneity in Dutch-speaking kindergartners: latent profile analysis.

Research demonstrated that a dyslexia diagnosis is mainly given after the most effective time for intervention has passed, referred to as the dyslexia paradox. Although some pre-reading cognitive measures have been found to be strong predictors of early literacy acquisition, i.e., phonological awareness (PA), letter knowledge (LK), and rapid automatized naming (RAN), more insight in the variability of pre-reading profiles might be of great importance for early identification of children who have an elevated risk for developing dyslexia and to provide tailor-made interventions. To address this issue, this study used a latent profile analysis (LPA) to disentangle different pre-reading profiles in a sample of 1091 Dutch-speaking kindergartners. Four profiles emerged: high performers (16.50%), average performers (40.24%), below-average performers with average IQ (25.57%), and below-average performers with below-average IQ (17.69%). These results suggested two at-risk profiles diverging in IQ, which are presumably more likely to develop dyslexia later on. Although below-average profiles differed significantly in rapid naming and IQ, no clear evidence for the double-deficit theory was found in Dutch-speaking kindergartners. Educational level and reading history of the parents appeared to be predictive for children's classification membership. Our results point towards the heterogeneity that is already present in kindergartners and the possibility to identify at-risk profiles prior to reading instruction, which may be the foundation for earlier targeted interventions. However, more extended research is needed to determine the stability of these profiles across time and across different languages.

Research Insights on Neural Effects of Auditory Deprivation and Restoration in Unilateral Hearing Loss: A Systematic Review.

Neuroplasticity following bilateral deafness and auditory restoration has been repeatedly investigated. In clinical practice, however, a significant number of patients present a severe-to-profound unilateral hearing loss (UHL). To date, less is known about the neuroplasticity following monaural hearing deprivation and auditory input restoration. This article provides an overview of the current research insights on the impact of UHL on the brain and the effect of auditory input restoration with a cochlear implant (CI). An exhaustive systematic review of the literature was performed selecting 38 studies that apply different neural analyses techniques. The main results show that the hearing ear becomes functionally dominant after monaural deprivation, reshaping the lateralization of the neural network for auditory processing, a process that can be considered to influence auditory restoration. Furthermore, animal models predict that the onset time of UHL impacts auditory restoration. Hence, the results seem to advocate for early restoration of UHL, although further research is required to disambiguate the effects of duration and onset of UHL on auditory restoration and on structural neuroplasticity following UHL deprivation and restoration. Ongoing developments on CI devices compatible with Magnetic Resonance Imaging (MRI) examinations will provide a unique opportunity to investigate structural and functional neuroplasticity following CI restoration more directly.

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.

Atypical gray matter in children with dyslexia before the onset of reading instruction.

Many studies have focused on neuroanatomical anomalies in dyslexia, yet primarily in school-aged children and adults. In the present study, we investigated gray matter surface area and cortical thickness at the pre-reading stage in a cohort of 54 children, 31 with a family risk for dyslexia and 23 without a family risk for dyslexia, of whom 16 children developed dyslexia. Surface-based analyses in the core regions of the reading network in the left hemisphere and in the corresponding right hemispheric regions were performed in FreeSurfer. Results revealed that pre-readers who develop dyslexia show reduced surface area in bilateral fusiform gyri. In addition, anomalies related to a family risk for dyslexia, irrespectively of later reading ability, were observed in the area of the bilateral inferior and middle temporal gyri. Differences were apparent in surface area, as opposed to cortical thickness. Results indicate that the neuroanatomical anomalies, since they are observed in the pre-reading phase, are not the consequence of impoverished reading experience.

The interplay of socio-economic status represented by paternal educational level, white matter structure and reading.

A child's school achievement is influenced by environmental factors. The environmental factors, when represented by socio-economic status (SES) of the family, have been demonstrated to be related to the reading skills of a child. The neural correlates of the relation between SES and reading have been less thoroughly investigated. The present study expands current research by exploring the relation between SES, quantified by paternal educational level, reading of the offspring and the structure of white matter pathways in the left hemisphere as derived from DTI-based tractography analyses. Therefore, three dorsal white matter pathways, i.e. the long, anterior and posterior segments of the arcuate fasciculus (AF), and three ventral white matter pathways, i.e. the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the uncinate fasciculus (UF), were manually dissected in the left hemisphere of 34 adolescents with a wide range of reading skills. The results demonstrated a relation between word reading, SES quantified by paternal educational level, and fractional anisotropy (FA) within the left dorsal AF segment and the left ventral UF. Thus, the present study proposes a relationship between paternal educational level and a specific white matter pathway that is important for reading, aiming to guide future research that can determine processes underlying this relationship.

Multi-method brain imaging reveals impaired representations of number as well as altered connectivity in adults with dyscalculia.

Two hypotheses have been proposed about the etiology of neurodevelopmental learning disorders, such as dyslexia and dyscalculia: representation impairments and disrupted access to representations. We implemented a multi-method brain imaging approach to directly investigate these representation and access hypotheses in dyscalculia, a highly prevalent but understudied neurodevelopmental disorder in learning to calculate. We combined several magnetic resonance imaging methods and analyses, including univariate and multivariate analyses, functional and structural connectivity. Our sample comprised 24 adults with dyscalculia and 24 carefully matched controls. Results showed a clear deficit in the non-symbolic magnitude representations in parietal, temporal and frontal regions, as well as hyper-connectivity in visual brain regions in adults with dyscalculia. Dyscalculia in adults was thereby related to both impaired number representations and altered connectivity in the brain. We conclude that dyscalculia is related to impaired number representations as well as altered access to these representations.

Grapheme-Phoneme Learning in an Unknown Orthography: A Study in Typical Reading and Dyslexic Children.

In this study, we examined the learning of new grapheme-phoneme correspondences in individuals with and without dyslexia. Additionally, we investigated the relation between grapheme-phoneme learning and measures of phonological awareness, orthographic knowledge and rapid automatized naming, with a focus on the unique joint variance of grapheme-phoneme learning to word and non-word reading achievement. Training of grapheme-phoneme associations consisted of a 20-min training program in which eight novel letters (Hebrew) needed to be paired with speech sounds taken from the participant's native language (Dutch). Eighty-four third grade students, of whom 20 were diagnosed with dyslexia, participated in the training and testing. Our results indicate a reduced ability of dyslexic readers in applying newly learned grapheme-phoneme correspondences while reading words which consist of these novel letters. However, we did not observe a significant independent contribution of grapheme-phoneme learning to reading outcomes. Alternatively, results from the regression analysis indicate that failure to read may be due to differences in phonological and/or orthographic knowledge but not to differences in the grapheme-phoneme-conversion process itself.

Evaluation of methods for volumetric analysis of pediatric brain data: The childmetrix pipeline versus adult-based approaches.

Pediatric brain volumetric analysis based on Magnetic Resonance Imaging (MRI) is of particular interest in order to understand the typical brain development and to characterize neurodevelopmental disorders at an early age. However, it has been shown that the results can be biased due to head motion, inherent to pediatric data, and due to the use of methods based on adult brain data that are not able to accurately model the anatomical disparity of pediatric brains. To overcome these issues, we proposed childmetrix, a tool developed for the analysis of pediatric neuroimaging data that uses an age-specific atlas and a probabilistic model-based approach in order to segment the gray matter (GM) and white matter (WM). The tool was extensively validated on 55 scans of children between 5 and 6 years old (including 13 children with developmental dyslexia) and 10 pairs of test-retest scans of children between 6 and 8 years old and compared with two state-of-the-art methods using an adult atlas, namely icobrain (applying a probabilistic model-based segmentation) and Freesurfer (applying a surface model-based segmentation). The results obtained with childmetrix showed a better reproducibility of GM and WM segmentations and a better robustness to head motion in the estimation of GM volume compared to Freesurfer. Evaluated on two subjects, childmetrix showed good accuracy with 82-84% overlap with manual segmentation for both GM and WM, thereby outperforming the adult-based methods (icobrain and Freesurfer), especially for the subject with poor quality data. We also demonstrated that the adult-based methods needed double the number of subjects to detect significant morphological differences between dyslexics and typical readers. Once further developed and validated, we believe that childmetrix would provide appropriate and reliable measures for the examination of children's brain.