Will you read how I will read? Naturalistic fMRI predictors of emergent reading.

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.

Tracking second language immersion across time: Evidence from a bi-directional longitudinal cross-linguistic fMRI study.

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.

The Haskins pediatric atlas: a magnetic-resonance-imaging-based pediatric template and atlas.

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.

Individual differences in learning the regularities between orthography, phonology and semantics predict early reading skills.

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.

Common neural basis of motor sequence learning and word recognition and its relation with individual differences in reading skill.

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.

Neurobiological signatures of L2 proficiency: Evidence from a bi-directional cross-linguistic study.

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.

Development and Prediction of Context-Dependent Vowel Pronunciation in Elementary Readers.

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.

Common variation within the SETBP1 gene is associated with reading-related skills and patterns of functional neural activation.

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.

Neurochemistry Predicts Convergence of Written and Spoken Language: A Proton Magnetic Resonance Spectroscopy Study of Cross-Modal Language Integration.

Recent studies have provided evidence of associations between neurochemistry and reading (dis)ability (Pugh et al., 2014). Based on a long history of studies indicating that fluent reading entails the automatic convergence of the written and spoken forms of language and our recently proposed Neural Noise Hypothesis (Hancock et al., 2017), we hypothesized that individual differences in cross-modal integration would mediate, at least partially, the relationship between neurochemical concentrations and reading. Cross-modal integration was measured in 231 children using a two-alternative forced choice cross-modal matching task with three language conditions (letters, words, and pseudowords) and two levels of difficulty within each language condition. Neurometabolite concentrations of Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl-aspartate (NAA) were then measured in a subset of this sample (n = 70) with Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model revealed that the effect of cross-modal word matching mediated the relationship between increased Glu (which has been proposed to be an index of neural noise) and poorer reading ability. In addition, the effect of cross-modal word matching fully mediated a relationship between increased Cho and poorer reading ability. Multilevel mixed effects models confirmed that lower Cho predicted faster cross-modal matching reaction time, specifically in the hard word condition. These Cho findings are consistent with previous work in both adults and children showing a negative association between Cho and reading ability. We also found two novel neurochemical relationships. Specifically, lower GABA and higher NAA predicted faster cross-modal matching reaction times. We interpret these results within a biochemical framework in which the ability of neurochemistry to predict reading ability may at least partially be explained by cross-modal integration.

Cortical Responses to Chinese Phonemes in Preschoolers Predict Their Literacy Skills at School Age.

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.

Individual Differences in Reading Skill Are Related to Trial-by-Trial Neural Activation Variability in the Reading Network.

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.

Neural representations for newly learned words are modulated by overnight consolidation, reading skill, and age.

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.

Prereader to beginning reader: changes induced by reading acquisition in print and speech brain networks.

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.

The BDNF Val66Met polymorphism is associated with structural neuroanatomical differences in young children.

The brain-derived neurotrophic factor (BDNF) Val66Met 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 Val66Met 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 Val66Met 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 Val66Met polymorphism on the structure of the developing brain therefore reflects regionally-specific developmental changes in BDNF expression and cortical maturation trajectories.

Dough, tough, cough, rough: A "fast" fMRI localizer of component processes in reading.

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.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

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.

Print-Speech Convergence Predicts Future Reading Outcomes in Early Readers.

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.

Functionally integrated neural processing of linguistic and talker information: An event-related fMRI and ERP study.

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.

Universal brain signature of proficient reading: Evidence from four contrasting languages.

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.