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This study utilized a neuroimaging task to assess working memory (WM) network recruitment during single word reading. Associations between WM and reading comprehension skills are well documented. Several converging models suggest WM may also contribute to foundational reading skills, but few studies have assessed this contribution directly. Two groups of children (77 developmental dyslexia (DD), 22 controls) completed a functional magnetic resonance imaging (fMRI) task to identify activation of a priori defined regions of the WM network. fMRI trials consisted of familiar word, pseudoword, and false font stimuli within a 1-back oddball task to assess how activation in the WM network differs in response to stimuli that can respectively be processed using word recognition, phonological decoding, or non-word strategies. Results showed children with DD recruited WM regions bilaterally in response to all stimulus types, whereas control children recruited left-lateralized WM regions during the pseudoword condition only. Group-level comparisons revealed activation differences in the defined WM network regions for false font and familiar word, but not pseudoword conditions. This effect was driven by increased activity in participants with DD in right hemisphere frontal, parietal, and motor regions despite poorer task performance. Findings suggest the WM network may contribute to inefficient decoding and word recognition strategies in children with DD., Competing Interests: Declaration of competing interest none., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite reading being an essential and almost universal skill in the developed world, reading proficiency varies substantially from person to person. To study why, the fMRI field is beginning to turn from single-word or nonword reading tasks to naturalistic stimuli like connected text and listening to stories. To study reading development in children just beginning to read, listening to stories is an appropriate paradigm because speech perception and phonological processing are important for, and are predictors of, reading proficiency. Our study examined the relationship between behavioral reading-related skills and the neural response to listening to stories in the fMRI environment. Functional MRI were gathered in a 3T TIM-Trio scanner. During the fMRI scan, children aged approximately 7 years listened to professionally narrated common short stories and answered comprehension questions following the narration. Analyses of the data used inter-subject correlation (ISC), and representational similarity analysis (RSA). Our primary finding is that ISC reveals areas of increased synchrony in both high- and low-performing emergent readers previously implicated in reading ability/disability. Of particular interest are that several previously identified brain regions (medial temporal gyrus (MTG), inferior frontal gyrus (IFG), inferior temporal gyrus (ITG)) were found to "synchronize" across higher reading ability participants, while lower reading ability participants had idiosyncratic activation patterns in these regions. Additionally, two regions (superior frontal gyrus (SFG) and another portion of ITG) were recruited by all participants, but their specific timecourse of activation depended on reading performance. These analyses support the idea that different brain regions involved in reading follow different developmental trajectories that correlate with reading proficiency on a spectrum rather than the usual dichotomy of poor readers versus strong readers., (Published by Elsevier Ltd.)

Recent work using fMRI inter-subject correlation analysis has provided new information about the brain's response to video and audio narratives, particularly in frontal regions not typically activated by single words. This approach is very well suited to the study of reading, where narrative is central to natural experience. But since past reading paradigms have primarily presented single words or phrases, the influence of narrative on semantic processing in the brain - and how that influence might change with reading ability - remains largely unexplored. In this study, we presented coherent stories to adolescents and young adults with a wide range of reading abilities. The stories were presented in alternating visual and auditory blocks. We used a dimensional inter-subject correlation analysis to identify regions in which better and worse readers had varying levels of consistency with other readers. This analysis identified a widespread set of brain regions in which activity timecourses were more similar among better readers than among worse readers. These differences were not detected with standard block activation analyses. Worse readers had higher correlation with better readers than with other worse readers, suggesting that the worse readers had "idiosyncratic" responses rather than using a single compensatory mechanism. Close inspection confirmed that these differences were not explained by differences in IQ or motion. These results suggest an expansion of the current view of where and how reading ability is reflected in the brain, and in doing so, they establish inter-subject correlation as a sensitive tool for future studies of reading disorders., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored., Methods: Participants were 3 rd and 4 th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants., Results: DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found., Conclusions: Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Educational neuroscience approaches have helped to elucidate the brain basis of Reading Disability (RD) and of reading intervention response; however, there is often limited translation of this knowledge to the broader scientific and educational communities. Moreover, this work is traditionally lab-based, and thus the underlying theories and research questions are siloed from classroom practices. With growing awareness of the neurobiological origins of RD and increasing popularity of putative "brain-based" approaches in clinics and classrooms, it is imperative that we create more direct and bidirectional communication between scientists and practitioners. Such direct collaborations can help dispel neuromyths, and lead to increased understanding of the promises and pitfalls of neuroscience approaches. Moreover, direct partnerships between researchers and practitioners can lead to greater ecological validity in study designs to improve upon the translational potential of findings. To this end, we have forged collaborative partnerships, and built cognitive neuroscience laboratories within independent reading disabilities schools. This approach affords frequent and ecologically valid neurobiological assessment as children's reading improves in response to intervention. It also permits the creation of dynamic models of leading and lagging relationships of students' learning, and identification of individual-level predictors of intervention response. The partnerships also provide in-depth knowledge of student characteristics and classroom practices, which, when combined with the data we acquire, may facilitate optimization of instructional approaches. In this commentary, we discuss the creation of our partnerships, the scientific problem we are addressing (variable response to reading intervention), and the epistemological significance of researcher-practitioner bi-directional learning., Competing Interests: We have no conflicts of interest to disclose.

There is now considerable evidence regarding the types of interventions that are effective at remediating reading disabilities on average. It is generally unclear, however, what predicts the magnitude of individual-level change following a given intervention. We examine new predictors of intervention gains that are theoretically grounded in computational models of reading and focus on individual differences in the functional organization of the reading system. Specifically, we estimate the extent to which children with reading disabilities (n=118 3 rd -4 th graders) rely on two sources of information during an oral word reading task - print-speech correspondences and semantic imageability - before and after a phonologically-weighted intervention. We show that children who relied more on print-speech regularities and less on imageability pre-intervention had better intervention gains. In parallel, children who over the course of the intervention exhibited greater increases in their reliance on print-speech correspondences and greater decreases in their reliance on imageability had better intervention outcomes. Importantly, these two factors were differentially related to specific reading task outcomes, with greater reliance on print-speech correspondences associated with pseudoword naming, while (lesser) reliance on imageability related to word reading and comprehension. We discuss the implications of these findings for theoretical models of reading acquisition and educational practice.

Decades of research have led to several competing theories regarding the neural contributors to impaired reading. But how can we know which theory (or theories) identifies the types of markers that indeed differentiate between individuals with reading disabilities (RD) and their typically developing (TD) peers? To answer this question, we propose a new analytical tool for theory evaluation and comparison, grounded in the Bayesian latent-mixture modeling framework. We start by constructing a series of latent-mixture classification models, each reflecting one existing theoretical claim regarding the neurofunctional markers of RD (highlighting network-level differences in either mean activation, inter-subject heterogeneity, inter-region variability, or connectivity). Then, we run each model on fMRI data alone (i.e., while models are blind to participants' behavioral status), which enables us to interpret the fit between a model's classification of participants and their behavioral (known) RD/TD status as an estimate of its explanatory power. Results from n=127 adolescents and young adults (RD: n=59; TD: n=68) show that models based on network-level differences in mean activation and heterogeneity failed to differentiate between TD and RD individuals. In contrast, classifications based on variability and connectivity were significantly associated with participants' behavioral status. These findings suggest that differences in inter-region variability and connectivity may be better network-level markers of RD than mean activation or heterogeneity (at least in some populations and tasks). More broadly, the results demonstrate the promise of latent-mixture modeling as a theory-driven tool for evaluating different theoretical claims regarding neural contributors to language disorders and other cognitive traits., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Parallel cohorts of Hebrew speakers learning English in the U.S., and American-English speakers learning Hebrew in Israel were tracked over the course of two years of immersion in their L2. We utilised a functional MRI semantic judgement task with print and speech tokens, as well as a battery of linguistic and cognitive behavioural measures prior to and after immersion, to track changes in both L1 and L2 processing. fMRI activation for print tokens produced a similar network of activation in both English and Hebrew, irrespective of L1 or L2 status. Significant convergence of print and speech processing was also observed in both languages across a network of left-hemisphere regions joint for both L1 and L2. Despite significant increases in behavioural measures of L2 proficiency, only a few signs of longitudinal change in L2 brain activation were found. In contrast, L1 showed widespread differences in processing across time, suggesting that the neurobiological footprint of reading is dynamic and plastic even in adults, with L2 immersion impacting L1 processing. Print/speech convergence showed little longitudinal change, suggesting that it is a stable marker of the differences in L1 and L2 processing across L2 proficiency., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Spatial normalization plays an essential role in multi-subject MRI and functional MRI (fMRI) experiments by facilitating a common space in which group analyses are performed. Although many prominent adult templates are available, their use for pediatric data is problematic. Generalized templates for pediatric populations are limited or constructed using older methods that result in less ideal normalization., Objective: The Haskins pediatric templates and atlases aim to provide superior registration and more precise accuracy in labeling of anatomical and functional regions essential for all fMRI studies involving pediatric populations., Materials and Methods: The Haskins pediatric templates and atlases were generated with nonlinear methods using structural MRI from 72 children (age range 7-14 years, median 10 years), allowing for a detailed template with corresponding parcellations of labeled atlas regions. The accuracy of these templates and atlases was assessed using multiple metrics of deformation distance and overlap., Results: When comparing the deformation distances from normalizing pediatric data between this template and both the adult templates and other pediatric templates, we found significantly less deformation distance for the Haskins pediatric template (P<0.0001). Further, the correct atlas classification was higher using the Haskins pediatric template in 74% of regions (P<0.0001)., Conclusion: The Haskins pediatric template results in more accurate correspondence across subjects because of lower deformation distances. This correspondence also provides better accuracy in atlas locations to benefit structural and functional imaging analyses of pediatric populations.

Understanding how pre-literate children's language abilities and neural function relate to future reading ability is important for identifying children who may be at-risk for reading problems. Pre-literate children are already proficient users of spoken language and their developing brain networks for language become highly overlapping with brain networks that emerge during literacy acquisition. In the present longitudinal study, we examined language abilities, and neural activation and connectivity within the language network in pre-literate children (mean age = 4.2 years). We tested how language abilities, brain activation, and connectivity predict children's reading abilities 1 year later (mean age = 5.2 years). At Time 1, children (n = 37) participated in a functional near infrared spectroscopy (fNIRS) experiment of speech processing (listening to words and pseudowords) and completed a standardized battery of language and cognitive assessments. At Time 2, children (n = 28) completed standardized reading assessments. Using psychophysiological interaction (PPI) analyses, we observed significant connectivity between the left IFG and right STG in pre-literate children, which was modulated by task (i.e., listening to words). Neural activation in left IFG and STG and increased task-modulated connectivity between the left IFG and right STG was predictive of multiple reading outcomes. Increased connectivity was associated later with increased reading ability., (© 2020 John Wiley & Sons Ltd.)

Word learning is critical for the development of reading and language comprehension skills. Although previous studies have indicated that word learning is compromised in children with reading disability (RD) or developmental language disorder (DLD), it is less clear how word learning difficulties manifest in children with comorbid RD and DLD. Furthermore, it is unclear whether word learning deficits in RD or DLD include difficulties with offline consolidation of newly learned words. In the current study, we employed an artificial lexicon learning paradigm with an overnight design to investigate how typically developing (TD) children (N = 25), children with only RD (N = 93), and children with both RD and DLD (N = 34) learned and remembered a set of phonologically similar pseudowords. Results showed that compared to TD children, children with RD exhibited: (i) slower growth in discrimination accuracy for cohort item pairs sharing an onset (e.g. pibu-pibo), but not for rhyming item pairs (e.g. pibu-dibu); and (ii) lower discrimination accuracy for both cohort and rhyme item pairs on Day 2, even when accounting for differences in Day 1 learning. Moreover, children with comorbid RD and DLD showed learning and retention deficits that extended to unrelated item pairs that were phonologically dissimilar (e.g. pibu-tupa), suggestive of broader impairments compared to children with only RD. These findings provide insights into the specific learning deficits underlying RD and DLD and motivate future research concerning how children use phonological similarity to guide the organization of new word knowledge., (© 2020 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

The BDNF gene is a prominent promoter of neuronal development, maturation and plasticity. Its Val 66 Met polymorphism affects brain morphology and function within several areas and is associated with several cognitive functions and neurodevelopmental disorder susceptibility. Recently, it has been associated with reading, reading-related traits and altered neural activation in reading-related brain regions. However, it remains unknown if the intermediate phenotypes (IPs, such as brain activation and phonological skills) mediate the pathway from gene to reading or reading disability. By conducting a serial multiple mediation model in a sample of 94 children (age 5-13), our findings revealed no direct effects of genotype on reading. Instead, we found that genotype is associated with brain activation in reading-related and more domain general regions which in turn is associated with phonological processing which is associated with reading. These findings suggest that the BDNF-Val 66 Met polymorphism is related to reading via phonological processing and functional activation. These results support brain imaging data and neurocognitive traits as viable IPs for complex behaviors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neuroimaging studies of basic achievement skills - reading and arithmetic - often control for the effect of IQ to identify unique neural correlates of each skill. This may underestimate possible effects of common factors between achievement and IQ measures on neuroimaging results. Here, we simultaneously examined achievement (reading and arithmetic) and IQ measures in young adults, aiming to identify MRI correlates of their common factors. Resting-state fMRI (rs-fMRI) data were analyzed using two metrics assessing local intrinsic functional properties; regional homogeneity (ReHo) and fractional amplitude low frequency fluctuation (fALFF), measuring local intrinsic functional connectivity and intrinsic functional activity, respectively. ReHo highlighted the thalamus/pulvinar (a subcortical region implied for selective attention) as a common locus for both achievement skills and IQ. More specifically, the higher the ReHo values, the lower the achievement and IQ scores. For fALFF, the left superior parietal lobule, part of the dorsal attention network, was positively associated with reading and IQ. Collectively, our results highlight attention-related regions, particularly the thalamus/pulvinar as a key region related to individual differences in performance on all the three measures. ReHo in the thalamus/pulvinar may serve as a tool to examine brain mechanisms underlying a comorbidity of reading and arithmetic difficulties, which could co-occur with weakness in general intellectual abilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Statistical views of literacy development maintain that proficient reading requires the assimilation of myriad statistical regularities present in the writing system. Indeed, previous studies have tied statistical learning (SL) abilities to reading skills, establishing the existence of a link between the two. However, some issues are currently left unanswered, including questions regarding the underlying bases for these associations as well as the types of statistical regularities actually assimilated by developing readers. Here we present an alternative approach to study the role of SL in literacy development, focusing on individual differences among beginning readers. Instead of using an artificial task to estimate SL abilities, our approach identifies individual differences in children's reliance on statistical regularities as reflected by actual reading behavior. We specifically focus on individuals' reliance on regularities in the mapping between print and speech versus associations between print and meaning in a word naming task. We present data from 399 children, showing that those whose oral naming performance is impacted more by print-speech regularities and less by associations between print and meaning have better reading skills. These findings suggest that a key route by which SL mechanisms impact developing reading abilities is via their role in the assimilation of sub-lexical regularities between printed and spoken language -and more generally, in detecting regularities that are more reliable than others. We discuss the implications of our findings to both SL and reading theories.

Research using functional and structural magnetic resonance imaging has identified areas of reduced brain activation and gray matter volume in children and adults with reading disability, but associations between cortical structure and individual differences in reading in typically developing children remain underexplored. Furthermore, the majority of research linking gray matter structure to reading ability quantifies gray matter in terms of volume, and cannot specify unique contributions of cortical surface area and thickness to these relationships. Here, we applied a continuous analytic approach to investigate associations between distinct surface-based properties of cortical structure and individual differences in reading-related skills in a sample of typically developing young children. Correlations between cortical structure and reading-related skills were conducted using a surface-based vertex-wise approach. Cortical thickness in the left superior temporal cortex was positively correlated with word and pseudoword reading performance. The observed positive correlation between cortical thickness in the left superior temporal cortex and reading may have implications for the patterns of brain activation that support reading., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Decreased activation to print in the left ventral, dorsal, and anterior pathways has been implicated in readers with dyslexia (DRs) but also is characteristic for typical beginning readers. Because most studies have compared DRs with their age-matched peers, the observed results could represent a dyslexia phenotype or a developmental delay. This study aimed to disentangle reading and dyslexia effects using 2 control groups matched for age and skill and a longitudinal design., Method: Brain response for print was compared in DRs and typical readers (TRs) who, at the beginning of schooling (time point 1 [TP]; 6-7 years old), read on average 3 words per minute, as did DRs at TP1, but improved their reading to an average level, and advanced readers (ARs) who at TP1 read as well as DRs 2 years later (TP3; 8-9 years old). The TR and DR groups were tracked longitudinally to observe neurodevelopmental changes., Results: At TP1, DRs did not differ from TRs. Over time, only TRs developed a neural circuit for reading in the left inferior frontal and fusiform gyri. At TP3, DRs exhibited hypo-activation in these areas compared with age-matched (TRs at TP3) and reading-matched (ARs at TP1) controls. At TP3, TRs showed hypo-activation in the left frontal and bilateral ventral occipital regions compared with ARs, but these effects were nonoverlapping with DR hypo-activations and are partly explained by IQ., Conclusion: Decreased activation of the left fusiform and inferior frontal gyri to print in DRs results from an atypical developmental trajectory of reading and cannot be explained solely by lower reading skills., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Reading is a learned activity that engages multiple cognitive systems. In a cohort of typical and struggling adult readers we show evidence that successful oral reading of real words is related to gamma-amino-butyric acid (GABA) concentration in the higher-order language system, whereas reading of unfamiliar pseudo-words is not related to GABA in this system. We also demonstrate the capability of resting state functional connectivity (rsFC) combined with GABA measures to predict single real word compared to pseudo-word reading performance. Results show that the strength of rsFC between left fusiform gyrus (L-FG) and higher-order language systems predicts oral reading behavior of real words, irrespective of the local concentration of GABA. On the other hand, pseudo-words, which require grapheme-to-phoneme conversion, are not predicted by the connection between L-FG and higher-order language system. This suggests that L-FG may have a multi-functional role: lexical processing of real words and grapheme-to-phoneme processing of pseudo-words. Additionally, rsFC between L-FG, pre-motor, and putamen areas are positively related to the oral reading of both real and pseudo-words, suggesting that text may be converted into a phoneme sequence for speech initiation and production regardless of whether the stimulus is a real word or pseudo-word. In summary, from a systems neuroscience perspective, we show that: (i) strong rsFC between higher order visual, language, and pre-motor areas can predict and differentiate efficient oral reading of real and pseudo-words. (ii) GABA measures, along with rsFC, help to further differentiate the neural pathways for previously learned real words versus unfamiliar pseudo-words.

Many studies have established a link between phonological abilities (indexed by phonological awareness and phonological memory tasks) and typical and atypical reading development. Individuals who perform poorly on phonological assessments have been mostly assumed to have underspecified (or "fuzzy") phonological representations, with typical phonemic categories, but with greater category overlap due to imprecise encoding. An alternative posits that poor readers have overspecified phonological representations, with speech sounds perceived allophonically (phonetically distinct variants of a single phonemic category). On both accounts, mismatch between phonological categories and orthography leads to reading difficulty. Here, we consider the implications of these accounts for online speech processing. We used eye tracking and an individual differences approach to assess sensitivity to subphonemic detail in a community sample of young adults with a wide range of reading-related skills. Subphonemic sensitivity inversely correlated with meta-phonological task performance, consistent with overspecification.

The aim of the current study was to develop an fMRI task capable of characterizing individual differences in reading and attentional domains. Forty-nine students with a range of reading and attentional control abilities completed an event-related fMRI oddball task consisting of printed word and false font stimuli. Reading network activation was assessed by contrasting printed words with false font stimuli. Left inferior frontal gyrus and superior/middle temporal gyrus showed a main effect of stimulus type. The magnitude of the difference in activation between words and false font was correlated with word reading for both regions and reading fluency for superior/middle temporal gyrus. Regions including bilateral middle cingulate, insula and right inferior frontal gyrus showed a main effect of trial type. The difference in activation between oddball and standard trials in the right superior/middle temporal gyrus and left cerebellum was correlated with attentional control measures. Results indicate the task tapped both reading and attentional control resources. Understanding the contribution of the neural networks supporting each of these domains may provide insight into the shared neural deficits underlying the co-morbidity between developmental dyslexia and attention deficit hyperactivity disorder., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epidemiological population studies highlight the presence of substantial individual variability in reading skill, with approximately 5-10% of individuals characterized as having specific reading disability (SRD). Despite reported substantial heritability, typical for a complex trait, the specifics of the connections between reading and the genome are not understood. Recently, the SETBP1 gene has been implicated in several complex neurodevelopmental syndromes and disorders that impact language. Here, we examined the relationship between common polymorphisms in this gene, reading, and reading associated behaviors using data from an ongoing project on the genetic basis of SRD (n = 135). In addition, an exploratory analysis was conducted to examine the relationship between SETBP1 and brain activation using functional magnetic resonance imaging (fMRI; n = 73). Gene-based analyses revealed a significant association between SETBP1 and phonological working memory, with rs7230525 as the strongest associated single nucleotide polymorphism (SNP). fMRI analysis revealed that the rs7230525-T allele is associated with functional neural activation during reading and listening to words and pseudowords in the right inferior parietal lobule (IPL). These findings suggest that common genetic variation within SETBP1 is associated with reading behavior and reading-related brain activation patterns in the general population., (Copyright © 2018. Published by Elsevier Ltd.)

Recent evidence has shown that convergence of print and speech processing across a network of primarily left-hemisphere regions of the brain is a predictor of future reading skills in children, and a marker of fluent reading ability in adults. The present study extends these findings into the domain of second-language (L2) literacy, through brain imaging data of English and Hebrew L2 learners. Participants received an fMRI brain scan, while performing a semantic judgement task on spoken and written words and pseudowords in both their L1 and L2, alongside a battery of L1 and L2 behavioural measures. Imaging results show, overall, show a similar network of activation for reading across the two languages, alongside significant convergence of print and speech processing across a network of left-hemisphere regions in both L1 and L2 and in both cohorts. Importantly, convergence is greater for L1 in occipito-temporal regions tied to automatic skilled reading processes including the visual word-form area, but greater for L2 in frontal regions of the reading network, tied to more effortful, active processing. The main groupwise brain effects tell a similar story, with greater L2 than L1 activation across frontal, temporal and parietal regions, but greater L1 than L2 activation in parieto-occipital regions tied to automatic mapping processes in skilled reading. These results provide evidence for the shifting of the reading networks towards more automatic processing as reading proficiency rises and the mappings and statistics of the new orthography are learned and incorporated into the reading system.

The overarching goal of the new Florida State University/Haskins Laboratory/University of Connecticut Learning Disability (LD) Hub project is to align computational and behavioral theories of individual word reading development more closely with the challenges of learning to read a quasi-regular orthography (i.e., English) for both typically developing (TD) children and, more specifically, children with dyslexia. Our LD Hub adopts an integrated approach to better understand the neurocognitive bases of individual differences in word reading development by specifically examining the experiential (exogenous) and child-specific (endogenous) factors that determine acquisition of orthographic-phonological knowledge at different subword granularities using behavioral and computational modeling. Findings are intended to enrich understanding of the processes that influence individual differences in word reading development in TD and dyslexic children and significantly inform issues of practice (e.g., curriculum, instruction, diagnosis, and intervention). Here, we briefly provide the rationale for the Hub and present findings from the initial behavioral and computational modeling studies., (© 2019 Wiley Periodicals, Inc.)

To investigate the neural basis of a common statistical learning mechanism involved in motor sequence learning and decoding, we recorded same participants' brain activation in a serial reaction time (SRT) and word reading task using functional magnetic resonance imaging. In the SRT, a manual response was made depending on the location of a visual cue, and the order of the locations was either fixed or random. In the word reading task, visual words were passively presented. Compared to less skilled readers, more skilled readers showed greater differences in activation in the inferior frontal gyrus pars triangularis (IFGpTr) and the insula between the ordered and random condition in the SRT task and greater activation in those regions in the word reading task. It suggests that extraction of statistically predictable patterns in the IFGpTr and insula contributes to both motor sequence learning and orthographic learning, and therefore predicts individual differences in decoding skill.

As children learn to read they become sensitive to context-dependent vowel pronunciations in words, considered a form of statistical learning. The work of Treiman and colleagues demonstrated that readers' vowel pronunciations depend on the consonantal context in which the vowel occurs and reading experience. We examined child- and nonword-factors associated with children's assignment of more vs. less frequent grapheme-phoneme correspondences (GPC) to vowel pronunciations as a function of rime coda in monosyllabic nonwords. Students ( N =96) in grades 2-5 read nonwords in which more vs. less frequent vowel GPCs were wholly supported or partially favored by the rime unit. Two explanatory item-response models were developed using alternative nonword scoring procedures. Use of less frequent vowel GPCs was predicted by set for variability, word reading, and rime support for the context-dependent vowel pronunciation. We interpret the results within a developmental word reading model in which initially incomplete and oversimplified GPC representations become more context-dependent with reading experience.

This study presents the implementation of a within-subject neural decoder, based on Support Vector Machines, and its application for the classification of distributed patterns of hemodynamic activation, measured with Functional Near Infrared Spectroscopy (fNIRS) on children, in response to meaningful and meaningless auditory stimuli. Classification accuracy nominally exceeds chance level for the majority of the participants, but fails to reach statistical significance. Future work should investigate whether individual differences in classification accuracy may relate to other characteristics of the children, such as their cognitive, speech or reading abilities.

Recent work has suggested that variability in levels of neural activation may be related to behavioral and cognitive performance across a number of domains and may offer information that is not captured by more traditional measures that use the average level of brain activation. We examined the relationship between reading skill in school-aged children and neural activation variability during a functional MRI reading task after taking into account average levels of activity. The reading task involved matching printed and spoken words to pictures of items. Single trial activation estimates were used to calculate the mean and standard deviation of children's responses to print and speech stimuli; multiple regression analyses evaluated the relationship between reading skill and trial-by-trial activation variability. The reliability of observed findings from the discovery sample ( n = 44; ages 8-11; 18 female) was then confirmed in an independent sample of children ( n = 32; ages 8-11; 14 female). Across the two samples, reading skill was positively related to trial-by-trial variability in the activation response to print in the left inferior frontal gyrus pars triangularis. This relationship held even when accounting for mean levels of activation. This finding suggests that intrasubject variability in trial-by-trial fMRI activation responses to printed words accounts for individual differences in human reading ability that are not fully captured by traditional mean levels of brain activity. Furthermore, this positive relationship between trial-by-trial activation variability and reading skill may provide evidence that neural variability plays a beneficial role during early reading development. SIGNIFICANCE STATEMENT Recent work has suggested that neural activation variability, or moment-to-moment changes in the engagement of brain regions, is related to individual differences in behavioral and cognitive performance across multiple domains. However, differences in neural activation variability have not yet been evaluated in relation to reading skill. In the current study, we analyzed data from two independent groups of children who performed an fMRI task involving reading and listening to words. Across both samples, reading skill was positively related to trial-by-trial variability in activation to print stimuli in the left inferior frontal gyrus pars triangularis, even when accounting for the more conventional measure of mean levels of brain activity. This finding suggests that neural variability could be beneficial in developing readers., (Copyright © 2018 the authors 0270-6474/18/382982-09$15.00/0.)

Word learning depends not only on efficient online binding of phonological, orthographic and lexical information, but also on consolidation of new word representations into permanent lexical memory. Work on word learning under a variety of contexts indicates that reading and language skill impact facility of word learning in both print and speech. In addition, recent research finds that individuals with language impairments show deficits in both initial word form learning and in maintaining newly learned representations over time, implicating mechanisms associated with maintenance that may be driven by deficits in overnight consolidation. Although several recent studies have explored the neural bases of overnight consolidation of newly learned words, no extant work has examined individual differences in overnight consolidation at the neural level. The current study addresses this gap in the literature by investigating how individual differences in reading and language skills modulate patterns of neural activation associated with newly learned words following a period of overnight consolidation. Specifically, a community sample of adolescents and young adults with significant variability in reading and oral language (vocabulary) ability were trained on two spoken artificial lexicons, one in the evening on the day before fMRI scanning and one in the morning just prior to scanning. Comparisons of activation between words that were trained and consolidated vs. those that were trained but not consolidated revealed increased cortical activation in a number of language associated and memory associated regions. In addition, individual differences in age, reading skill and vocabulary modulated learning rate in our artificial lexicon learning task and the size of the cortical consolidation effect in the precuneus/posterior cingulate, such that older readers and more skilled readers had larger cortical consolidation effects in this learning-critical region. These findings suggest that age (even into late adolescence) and reading and language skills are important individual differences that affect overnight consolidation of newly learned words. These findings have significant implications for understanding reading and language disorders and should inform pedagogical models., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We investigated whether preschoolers with poor phonological awareness (PA) skills had impaired cortical basis for detecting speech feature, and whether speech perception influences future literacy outcomes in preschoolers. We recorded ERP responses to speech in 52 Chinese preschoolers. The results showed that the poor PA group processed speech changes differentially compared to control group in mismatch negativity (MMN) and late discriminative negativity (LDN). Furthermore, speech perception in kindergarten could predict literacy outcomes after literacy acquisition. These suggest that impairment in detecting speech features occurs before formal reading instruction, and that speech perception plays an important role in reading development.

Background: Literacy acquisition is a demanding process that induces significant changes in the brain, especially in the spoken and written language networks. Nevertheless, large-scale paediatric fMRI studies are still limited., Methods: We analyzed fMRI data to show how individual differences in reading performance correlate with brain activation for speech and print in 111 children attending kindergarten or first grade and examined group differences between a matched subset of emergent-readers and prereaders., Results: Across the entire cohort, individual differences analysis revealed that reading skill was positively correlated with the magnitude of activation difference between words and symbol strings in left superior temporal, inferior frontal and fusiform gyri. Group comparisons of the matched subset of pre- and emergent-readers showed higher activity for emergent-readers in left inferior frontal, precentral, and postcentral gyri. Individual differences in activation for natural versus vocoded speech were also positively correlated with reading skill, primarily in the left temporal cortex. However, in contrast to studies on adult illiterates, group comparisons revealed higher activity in prereaders compared to readers in the frontal lobes. Print-speech coactivation was observed only in readers and individual differences analyses revealed a positive correlation between convergence and reading skill in the left superior temporal sulcus., Conclusions: These results emphasise that a child's brain undergoes several modifications to both visual and oral language systems in the process of learning to read. They also suggest that print-speech convergence is a hallmark of acquiring literacy., (© 2017 Association for Child and Adolescent Mental Health.)

Although dyslexia is characterized by a deficit in phonological representations, the nature of this deficit is debated. Previously, it was shown that adults with dyslexia respond differently to online manipulations of auditory feedback. In the present study, we found that individual differences in reading and reading-related skills within a group of 30 children (10-13 years old) with dyslexia were associated with the response to altered feedback. The fractional anisotropy of the arcuate fasciculus/superior longitudinal fasciculus was not directly related to the response to altered feedback. This study corroborates that speech perception-production communication is important for phonological representations and reading.

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).

This chapter introduces the issue, highlighting the importance of early childhood development and learning., (© 2017 Wiley Periodicals, Inc.)

The brain-derived neurotrophic factor (BDNF) Val 66 Met single nucleotide polymorphism (SNP) has been associated with individual differences in brain structure and function, and cognition. Research on BDNF's influence on brain and cognition has largely been limited to adults, and little is known about the association of this gene, and specifically the Val 66 Met polymorphism, with developing brain structure and emerging cognitive functions in children. We performed a targeted genetic association analysis on cortical thickness, surface area, and subcortical volume in 78 children (ages 6-10) who were Val homozygotes (homozygous Val/Val carriers) or Met carriers (Val/Met, Met/Met) for the Val 66 Met locus using Atlas-based brain segmentation. We observed greater cortical thickness for Val homozygotes in regions supporting declarative memory systems (anterior temporal pole/entorhinal cortex), consistent with adult findings. Met carriers had greater surface area in the prefrontal and parietal cortices and greater cortical thickness in lateral occipital/parietal cortex in contrast to prior adult findings that may relate to performance on cognitive tasks supported by these regions in Met carriers. Finally, we found larger right hippocampal volume in Met carriers, although inconsistent with adult findings (generally reports larger volumes for Val homozygotes), is consistent with a recent finding in children. Gene expression levels vary across different brain regions and across development and our findings highlight the need to consider this developmental change in explorations of BDNF-brain relationships. The impact of the BDNF Val 66 Met polymorphism on the structure of the developing brain therefore reflects regionally-specific developmental changes in BDNF expression and cortical maturation trajectories., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to examine whether developmental dyslexia (DD) is characterized by deficiencies in speech sensory and motor feedforward and feedback mechanisms, which are involved in the modulation of phonological representations., Method: A total of 42 adult native speakers of Dutch (22 adults with DD; 20 participants who were typically reading controls) were asked to produce /bep/ while the first formant (F1) of the /e/ was not altered (baseline), increased (ramp), held at maximal perturbation (hold), and not altered again (after-effect). The F1 of the produced utterance was measured for each trial and used for statistical analyses. The measured F1s produced during each phase were entered in a linear mixed-effects model., Results: Participants with DD adapted more strongly during the ramp phase and returned to baseline to a lesser extent when feedback was back to normal (after-effect phase) when compared with the typically reading group. In this study, a faster deviation from baseline during the ramp phase, a stronger adaptation response during the hold phase, and a slower return to baseline during the after-effect phase were associated with poorer reading and phonological abilities., Conclusion: The data of the current study are consistent with the notion that the phonological deficit in DD is associated with a weaker sensorimotor magnet for phonological representations.

Recent studies have found considerable individual variation in language comprehenders' predictive behaviors, as revealed by their anticipatory eye movements during language comprehension. The current study investigated the relationship between these predictive behaviors and the language and literacy skills of a diverse, community-based sample of young adults. We found that rapid automatized naming (RAN) was a key determinant of comprehenders' prediction ability (e.g., as reflected in predictive eye movements to a white cake on hearing "The boy will eat the white…"). Simultaneously, comprehension-based measures predicted participants' ability to inhibit eye movements to objects that shared features with predictable referents but were implausible completions (e.g., as reflected in eye movements to a white but inedible white car). These findings suggest that the excitatory and inhibitory mechanisms that support prediction during language processing are closely linked with specific cognitive abilities that support literacy. We show that a self-organizing cognitive architecture captures this pattern of results., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the current study, we present a novel fMRI protocol in which words, pseudowords, and other word-like stimuli are passively presented in a rapid, sequential fashion. In this "fast" localizer paradigm, items are presented in groups of four; within sets, words are related in orthographic, phonological, and/or semantic properties. We tested this protocol with a group of skilled adult readers (N=18). Analyses uncovered key regions of the reading network that were sensitive to different component processes at the group level; namely, left fusiform gyrus as well as the pars opercularis subregion of inferior frontal gyrus were sensitive to lexicality; several regions including left precentral gyrus and left supramarginal gyrus were sensitive to spelling-sound consistency; the pars triangularis subregion of inferior frontal gyrus was sensitive to semantic similarity. Additionally, in a number of key brain regions, activation in response to semantically similar words was related to individual differences in reading comprehension outside the scanner. Importantly, these findings are in line with previous investigations of the reading network, yet data were obtained using much less imaging time than comparable paradigms currently available, especially relative to the number of indices of component processes obtained. This feature, combined with the relatively simple nature of the task, renders it appropriate for groups of subjects with a wide range of reading abilities, including children with impairments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes., Competing Interests: The authors have declared that no competing interests exist.

Phonological processing ability is a key factor in reading acquisition, predicting its later success or causing reading problems when it is weakened. Our aim here was to establish the neural correlates of auditory word rhyming (a standard phonological measure) in 102 young children with (FHD+) and without familial history of dyslexia (FHD-) in a shallow orthography (i.e. Polish). Secondly, in order to gain a deeper understanding on how schooling shapes brain activity to phonological awareness, a comparison was made of children who had had formal literacy instruction for several months (in first grade) and those who had not yet had any formal instruction in literacy (in kindergarten). FHD+ children compared to FHD- children in the first grade scored lower in an early print task and showed longer reaction times in the in-scanner rhyme task. No behavioral differences between FHD+ and FHD- were found in the kindergarten group. On the neuronal level, overall familial risk was associated with reduced activation in the bilateral temporal, tempo-parietal and inferior temporal-occipital regions, as well as the bilateral inferior and middle frontal gyri. Subcortically, hypoactivation was found in the bilateral thalami, caudate, and right putamen in FHD+. A main effect of the children's grade was present only in the left inferior frontal gyrus, where reduced activation for rhyming was shown in first-graders. Several regions in the ventral occipital cortex, including the fusiform gyrus, and in the right middle frontal and postcentral gyri, displayed an interaction between familial risk and grade. The present results show strong influence of familial risk that may actually increase with formal literacy instruction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Speech signals contain information of both linguistic content and a talker's voice. Conventionally, linguistic and talker processing are thought to be mediated by distinct neural systems in the left and right hemispheres respectively, but there is growing evidence that linguistic and talker processing interact in many ways. Previous studies suggest that talker-related vocal tract changes are processed integrally with phonetic changes in the bilateral posterior superior temporal gyrus/superior temporal sulcus (STG/STS), because the vocal tract parameter influences the perception of phonetic information. It is yet unclear whether the bilateral STG is also activated by the integral processing of another parameter - pitch, which influences the perception of lexical tone information and is related to talker differences in tone languages. In this study, we conducted separate functional magnetic resonance imaging (fMRI) and event-related potential (ERP) experiments to examine the spatial and temporal loci of interactions of lexical tone and talker-related pitch processing in Cantonese. We found that the STG was activated bilaterally during the processing of talker changes when listeners attended to lexical tone changes in the stimuli and during the processing of lexical tone changes when listeners attended to talker changes, suggesting that lexical tone and talker processing are functionally integrated in the bilateral STG. It extends the previous study, providing evidence for a general neural mechanism of integral phonetic and talker processing in the bilateral STG. The ERP results show interactions of lexical tone and talker processing 500-800ms after auditory word onset (a simultaneous posterior P3b and a frontal negativity). Moreover, there is some asymmetry in the interaction, such that unattended talker changes affect linguistic processing more than vice versa, which may be related to the ambiguity that talker changes cause in speech perception and/or attention bias to talker changes. Our findings have implications for understanding the neural encoding of linguistic and talker information., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Becoming a skilled reader requires building a functional neurocircuitry for printed-language processing that integrates with spoken-language-processing networks. In this longitudinal study, functional MRI (fMRI) was used to examine convergent activation for printed and spoken language (print-speech coactivation) in selected regions implicated in printed-language processing (the reading network). We found that print-speech coactivation across the left-hemisphere reading network in beginning readers predicted reading achievement 2 years later beyond the effects of brain activity for either modality alone; moreover, coactivation effects accounted for variance in later reading after controlling for initial reading performance. Within the reading network, effects of coactivation were significant in bilateral inferior frontal gyrus (IFG) and left inferior parietal cortex and fusiform gyrus. The contribution of left and right IFG differed, with more coactivation in left IFG predicting better achievement but more coactivation in right IFG predicting poorer achievement. Findings point to the centrality of print-speech convergence in building an efficient reading circuitry in children., (© The Author(s) 2015.)

We propose and test a theoretical perspective in which a universal hallmark of successful literacy acquisition is the convergence of the speech and orthographic processing systems onto a common network of neural structures, regardless of how spoken words are represented orthographically in a writing system. During functional MRI, skilled adult readers of four distinct and highly contrasting languages, Spanish, English, Hebrew, and Chinese, performed an identical semantic categorization task to spoken and written words. Results from three complementary analytic approaches demonstrate limited language variation, with speech-print convergence emerging as a common brain signature of reading proficiency across the wide spectrum of selected languages, whether their writing system is alphabetic or logographic, whether it is opaque or transparent, and regardless of the phonological and morphological structure it represents.

Despite anecdotal evidence of relative visuospatial processing strengths in individuals with reading disability (RD), only a few studies have assessed the presence or the extent of these putative strengths. The current study examined the cognitive and neural bases of visuospatial processing abilities in adolescents with RD relative to typically developing (TD) peers. Using both cognitive tasks and functional magnetic resonance imaging (fMRI) we contrasted printed word recognition with non-language visuospatial processing tasks. Behaviorally, lower reading skill was related to a visuospatial processing advantage (shorter latencies and equivalent accuracy) on a geometric figure processing task, similar to findings shown in two published studies. FMRI analyses revealed key group by task interactions in patterns of cortical and subcortical activation, particularly in frontostriatal networks, and in the distributions of right and left hemisphere activation on the two tasks. The results are discussed in terms of a possible neural tradeoff in visuospatial processing in RD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Word reading in alphabetic language involves a cortical system with multiple components whose division of labor depends on the transparency of the writing system. To gain insight about the neural division of labor between phonology and semantics subserving word reading in Chinese, a deep non-alphabetic writing system, functional magnetic resonance imaging (fMRI) was used to investigate the effects of phonological and semantic training on the cortical circuitry for oral naming of Chinese characters. In a training study, we examined whether a training task that differentially focused readers' attention on the phonological or semantic properties of a Chinese character changes the patterns of cortical activation that was evoked by that character in a subsequent naming task. Our imaging results corroborate that the cortical regions underlying reading in Chinese largely overlap the left-hemisphere reading system responsible for reading in alphabetic languages, with some cortical regions in the left-hemisphere uniquely recruited for reading in Chinese. However, in contrast to findings from studies of English word naming, we observed considerable overlap in the neural activation patterns associated with phonological and semantic training on naming Chinese characters, which we suggest may reflect a balanced neural division of labor between phonology and semantics in Chinese character reading. The equitable division of labor for Chinese reading might be driven by the special statistical structure of the writing system, which includes equally systematic mappings in the correspondences between written forms and their pronunciations and meanings., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.