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.

Thalamus is a common locus of reading, arithmetic, and IQ: Analysis of local intrinsic functional properties.

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.

Individual differences in subphonemic sensitivity and phonological skills.

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.

Examining individual differences in reading and attentional control networks utilizing an oddball fMRI task.

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.

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.

Individual differences in decoding skill, print exposure, and cortical structure in young adults.

This exploratory study investigated relations between individual differences in cortical grey matter structure and young adult readers' cognitive profiles. Whole-brain analyses revealed neuroanatomical correlations with word and nonword reading ability (decoding), and experience with printed matter. Decoding was positively correlated with grey matter volume (GMV) in left superior temporal sulcus, and thickness (GMT) in right superior temporal gyrus. Print exposure was negatively correlated with GMT in left inferior frontal gyrus (pars opercularis) and left fusiform gyrus (including the visual word form area). Both measures also correlated with supramarginal gyrus (SMG), but in spatially distinct subregions: decoding was positively associated with GMV in left anterior SMG, and print exposure was negatively associated with GMT in left posterior SMG. Our comprehensive approach to assessment both confirms and refines our understanding of the novel relation between the structure of pSMG and proficient reading, and unifies previous research relating cortical structure and reading skill.

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.

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.

The real-time prediction and inhibition of linguistic outcomes: Effects of language and literacy skill.

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.

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.

Relationships Between Impulsivity, Anxiety, and Risk-Taking and the Neural Correlates of Attention in Adolescents.

Although impulsivity, anxiety, and risk-taking may relate to attentional processes, little research has directly investigated how each may be associated with specific facets of attentional processes and their underlying neural correlates. Nineteen adolescents performed a functional magnetic resonance imaging task involving simple, selective, and divided attention. Out-of-scanner-assessed impulsivity, anxiety, and risk-taking scores were not correlated with each other and showed task-phase-specific patterns of association. Results are discussed in light of research and theory suggesting a relationship between these domains and attention and may serve to focus future research aiming to understand these relationships.

Vocabulary does not complicate the simple view of reading.

Gough and Tunmer's (1986) simple view of reading (SVR) proposed that reading comprehension (RC) is a function of language comprehension (LC) and word recognition/decoding. Braze et al. (2007) presented data suggesting an extension of the SVR in which knowledge of vocabulary (V) affected RC over and above the effects of LC. Tunmer and Chapman (2012) found a similar independent contribution of V to RC when the data were analyzed by hierarchical regression. However, additional analysis by factor analysis and structural equation modeling indicated that the effect of V on RC was, in fact, completely captured by LC itself and there was no need to posit a separate direct effect of V on RC. In the present study, we present new data from young adults with sub-optimal reading skill (N = 286). Latent variable and regression analyses support Gough and Tunmer's original proposal and the conclusions of Tunmer and Chapman that V can be considered a component of LC and not an independent contributor to RC.

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.

Language differences in the brain network for reading in naturalistic story reading and lexical decision.

Differences in how writing systems represent language raise important questions about whether there could be a universal functional architecture for reading across languages. In order to study potential language differences in the neural networks that support reading skill, we collected fMRI data from readers of alphabetic (English) and morpho-syllabic (Chinese) writing systems during two reading tasks. In one, participants read short stories under conditions that approximate natural reading, and in the other, participants decided whether individual stimuli were real words or not. Prior work comparing these two writing systems has overwhelmingly used meta-linguistic tasks, generally supporting the conclusion that the reading system is organized differently for skilled readers of Chinese and English. We observed that language differences in the reading network were greatly dependent on task. In lexical decision, a pattern consistent with prior research was observed in which the Middle Frontal Gyrus (MFG) and right Fusiform Gyrus (rFFG) were more active for Chinese than for English, whereas the posterior temporal sulcus was more active for English than for Chinese. We found a very different pattern of language effects in a naturalistic reading paradigm, during which significant differences were only observed in visual regions not typically considered specific to the reading network, and the middle temporal gyrus, which is thought to be important for direct mapping of orthography to semantics. Indeed, in areas that are often discussed as supporting distinct cognitive or linguistic functions between the two languages, we observed interaction. Specifically, language differences were most pronounced in MFG and rFFG during the lexical decision task, whereas no language differences were observed in these areas during silent reading of text for comprehension.

Neural correlates of language and non-language visuospatial processing in adolescents with reading disability.

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.

Neural division of labor in reading is constrained by culture: a training study of reading Chinese characters.

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.

Glutamate and choline levels predict individual differences in reading ability in emergent readers.

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.