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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 500–800 ms 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • Working memory contributes differently to early reading in children with dyslexia. • FMRI protocol localised working memory network during decoding and word recognition. • In strong readers, network activity increased during phonetic decoding trials only. • In poor readers, activity increased for all trial types despite lower task accuracy. • Working memory may act as compensatory system for early reading skills in dyslexia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• 75 adolescents read and heard time-locked narratives during an fMRI scan. • Inter-subject correlation (ISC) was used to analyze reading ability's impact. • ISC was more sensitive to individual differences in reading ability than GLMs. • Reading ability affects brain activity in more regions than previously thought. • Worse readers had more idiosyncratic responses than better readers across the brain. 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. [ABSTRACT FROM AUTHOR]

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. • rs7230525-T allele is associated with lower scores on phonological working memory. • rs7230525-T allele is associated with functional neural activation in the right IPL. • Common SETBP1 variants affect multiple components of reading. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Prematurely born children are at increased risk for language deficits at school age and beyond, but the neurobiological basis of these findings remains poorly understood. Thirty-one PT adolescents (600–1250g birth weight) and 36 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children-III (WISC-III), the Peabody Picture Vocabulary Test-Revised (PPVT-R), the Comprehensive Test of Phonological Processing (CTOPP) and the Test of Word Reading Efficiency (TOWRE) at 16years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. PT subjects scored significantly lower on all components of the WISC-III (p <0.05) compared to term subjects, but there was no significant difference in PPVT-R scores between the groups. Functional connectivity (fcMRI) between Wernicke''s area (left BA 22) and the right supramarginal gyrus (BA 40) was increased in preterm subjects relative to term controls (p =0.03), and the strength of this connection was inversely related to performance on both the PPVT-R (R 2 =0.553, p =0.002), and the verbal comprehension index (R 2 =0.439, p =0.019). Preterm adolescents engage a dorsal right hemisphere region for language at age 16years. Those with the greatest cognitive deficits demonstrate increasing reliance on this alternate pathway. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

: BackgroundA range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading.: MethodsFunctional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1–9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28).: ResultsImmediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions.: ConclusionsThese data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading. [Copyright &y& Elsevier]

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. • Cohorts of L2 (Hebrew/English) learners were tracked over two years of immersion. • fMRI scans probed neurological changes in L1 and L2 print and speech processing. • Greater proficiency in L2 led to few longitudinal changes in L2 brain activation. • L1 processing remains plastic in adults and is impacted by L2 immersion. • Print/speech conversion is a longitudinally stable marker of both L1 and L2 reading. [ABSTRACT FROM AUTHOR]