Search

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.)

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.

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.

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.

An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft-antenna). The graft-antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft-antenna and stimulated by the TMS for 1 h per week. The graft-antenna is an innovative and minimally-invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair., Competing Interests: The authors declare no conflict of interest.

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.

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.)

Background: Extracellular matrices (ECMs) are often used in reconstructive surgery to enhance tissue regeneration and remodeling. Sutures and staples are currently used to fix ECMs to tissue although they can be invasive devices. Other sutureless and less invasive techniques, such as photochemical tissue bonding, cannot be coupled to ECMs because of their intrinsic opacity to light., Results: We succeeded in fabricating a biocompatible and adhesive device that is based on ovine forestomach matrix (OFM) and a chitosan adhesive. The natural opacity of the OFM has been overcome by adding the adhesive into the matrix that allows for the light to effectively penetrate through it. The OFM-chitosan device is semitransparent (attenuation length ~ 106 µm) and can be photoactivated by green light to bond to tissue. This device does not require sutures or staples and guarantees a bonding strength of ~ 23 kPa., Conclusions: A new semitransparent and biocompatible bandage has been successfully fabricated and characterized for sutureless tissue bonding.

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.)

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.)

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.

Sutureless procedures for wound repair and closure have recently integrated nanostructured devices to improve their effectiveness and clinical outcome. This review highlights the major advances in gecko-inspired bioadhesives that relies mostly on van der Waals bonding forces. These are challenged by the moist environment of surgical settings that weaken adherence to tissue. The incorporation of nanoparticles in biomatrices and their role in tissue repair and drug delivery is also reviewed with an emphasis on procedures involving adhesives that are laser-activated. Nanostructured adhesive devices have the advantage of being minimally invasive to tissue, can seal wounds, and deliver drugs in situ. All these tasks are very difficult to accomplish by sutures or staples that are invasive to host organs and often cause scarring., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

A range of chitosan-based biomaterials have recently been used to perform sutureless, laser-activated tissue repair. Laser-activation has the advantage of bonding to tissue through a non-contact, aseptic mechanism. Chitosan adhesive films have also been shown to adhere to sheep intestine strongly without any chemical modification to chitosan. In this study, we continue to investigate chitosan adhesive films and explore the impact on the tissue repair strength and tensile strength characteristics of four types of adhesive film based on chitosan with different molecular weight and degree of deacetylation. Results showed that adhesives based on chitosan with medium molecular weight achieved the highest bonding strength, tensile strength and E-modulus when compared to the other adhesives., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

The purpose of the study was to identify structural brain differences in school-age children with residual speech sound errors. Voxel based morphometry was used to compare gray and white matter volumes for 23 children with speech sound errors, ages 8;6-11;11, and 54 typically speaking children matched on age, oral language, and IQ. We hypothesized that regions associated with production and perception of speech sounds would differ between groups. Results indicated greater gray matter volumes for the speech sound error group relative to typically speaking controls in bilateral superior temporal gyrus. There was greater white matter volume in the corpus callosum for the speech sound error group, but less white matter volume in right lateral occipital gyrus. Results may indicate delays in neuronal pruning in critical speech regions or differences in the development of networks for speech perception and production., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We employed brain-behavior analyses to explore the relationship between performance on tasks measuring phonological awareness, pseudoword decoding, and rapid auditory processing (all predictors of reading (dis)ability) and brain organization for print and speech in beginning readers. For print-related activation, we observed a shared set of skill-correlated regions, including left hemisphere temporoparietal and occipitotemporal sites, as well as inferior frontal, visual, visual attention, and subcortical components. For speech-related activation, shared variance among reading skill measures was most prominently correlated with activation in left hemisphere inferior frontal gyrus and precuneus. Implications for brain-based models of literacy acquisition are discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

For accurate reading comprehension, readers must first learn to map letters to their corresponding speech sounds and meaning and then they must string the meanings of many words together to form a representation of the text. Furthermore, readers must master the complexities involved in parsing the relevant syntactic and pragmatic information necessary for accurate interpretation. Failure in this process can occur at multiple levels and cognitive neuroscience has been helpful in identifying the underlying causes of success and failure in reading single words and in reading comprehension. In general, neurobiological studies of skilled reading comprehension indicate a highly overlapping language circuit for single word reading, reading comprehension and listening comprehension with largely quantitative differences in a number of reading and language related areas. This paper reviews relevant research from studies employing neuroimaging techniques to study reading with a focus on the relationship between reading skill, single word reading, and text comprehension.

In both children and adults there is large variability in reading skill, with approximately 5-10% of individuals characterized as having reading disability; these individuals struggle to learn to read despite adequate intelligence and opportunity. Although it is well established that a substantial portion of this variability is attributed to the genetic differences between individuals, specifics of the connections between reading and the genome are not understood. This article presents data that suggest that variation in the COMT gene, which has previously been associated with variation in higher-order cognition, is associated with reading and reading-related skills, at the level of both brain and behavior. In particular, we found that the COMT Val/Met polymorphism at rs4680, which results in the substitution of the ancestral Valine (Val) by Methionine (Met), was associated with better performance on a number of critical reading measures and with patterns of functional neural activation that have been linked to better readers. We argue that this polymorphism, known for its broad effects on cognition, may modulate (likely through frontal lobe function) reading skill., (© 2012 Blackwell Publishing Ltd.)

Potocki-Lupski syndrome (PTLS; OMIM 610883) is a genomic syndrome that arises as a result of a duplication of 17p11.2. Although numerous cases of individuals with PTLS have been presented in the literature, its behavioral characterization is still ambiguous. We present a male child with a de novo dup(17)(p11.2p11.2) and he does not possess any autistic features, but is characterized by severe speech and language impairment. In the context of the analyses of this patient and other cases of PTLS, we argue that the central feature of the syndrome appears to be related to diminished speech and language capacity, rather than the specific social deficits central to autism., (Published by Elsevier B.V.)

Purpose: To examine neural response to spoken and printed language in children with speech sound errors (SSE)., Method: Functional magnetic resonance imaging was used to compare processing of auditorily and visually presented words and pseudowords in 17 children with SSE, ages 8;6[years;months] through 10;10, with 17 matched controls., Results: When processing spoken words and pseudowords, the SSE group showed less activation than typically speaking controls in left middle temporal gyrus. They also showed greater activation than controls in several cortical and subcortical regions (e.g., left superior temporal gyrus, globus pallidus, insula, fusiform, and bilateral parietal regions). In response to printed words and pseudowords, children with SSE had greater activation than controls in regions including bilateral fusiform and anterior cingulate. Some differences were found in both speech and print processing that that may be associated with children with SSE failing to show common patterns of task-induced deactivation and/or attentional resource allocation., Conclusion: Compared with controls, children with SSE appear to rely more on several dorsal speech perception regions and less on ventral speech perception regions. When processing print, numerous regions were observed to be activated more for the SSE group than for controls.

This study examined fMRI activation when perceivers either passively observed or observed and imitated matched or mismatched audiovisual ("McGurk") speech stimuli. Greater activation was observed in the inferior frontal gyrus (IFG) overall for imitation than for perception of audiovisual speech and for imitation of the McGurk-type mismatched stimuli than matched audiovisual stimuli. This unique activation in the IFG during imitation of incongruent audiovisual speech may reflect activation associated with direct matching of incongruent auditory and visual stimuli or conflict between category responses. This study provides novel data about the underlying neurobiology of imitation and integration of AV speech.

We provide an illustration of an application of the elastic net to a large number of common genetic variants in the context of the search for the genetic bases of an endophenotype conceivably related to individual differences in learning. GABA concentration in the occipital cortex, a critical area for reading, was obtained in a group (n = 76) of children aged 6-10 years. Two extreme groups, high and low, were selected for genotyping with the 650Y Illumina array chip (Ilmn650Y). An elastic net approach was applied to the resulting SNP dataset; 100 SNPs were identified for each chromosome as "interesting" based on having the highest absolute value coefficients. The analyses highlighted chromosomes 15 and 20, which contained 55 candidate genes. The STRING partner analyses of the associated proteins pointed to a number of related genes, most notably, GABA and NTRK receptors.

Early language development sets the stage for a lifetime of competence in language and literacy. However, the neural mechanisms associated with the relative advantages of early communication success, or the disadvantages of having delayed language development, are not well explored. In this study, 174 elementary school-age children whose parents reported that they started forming sentences 'early', 'on-time' or 'late' were evaluated with standardized measures of language, reading and spelling. All oral and written language measures revealed consistent patterns for 'early' talkers to have the highest level of performance and 'late' talkers to have the lowest level of performance. We report functional magnetic resonance imaging data from a subset of early, on-time and late talkers matched for age, gender and performance intelligence quotient that allows evaluation of neural activation patterns produced while listening to and reading real words and pronounceable non-words. Activation in bilateral thalamus and putamen, and left insula and superior temporal gyrus during these tasks was significantly lower in late talkers, demonstrating that residual effects of being a late talker are found not only in behavioural tests of oral and written language, but also in distributed cortical-subcortical neural circuits underlying speech and print processing. Moreover, these findings suggest that the age of functional language acquisition can have long-reaching effects on reading and language behaviour, and on the corresponding neurocircuitry that supports linguistic function into the school-age years.

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 2010 Elsevier Inc. All rights reserved.)

Using functional magnetic resonance imaging, we investigated multimodal (visual and auditory) semantic and unimodal (visual only) phonological processing in reading disabled (RD) adolescents and non-impaired (NI) control participants. We found reduced activation for RD relative to NI in a number of left-hemisphere reading-related areas across all processing tasks regardless of task type (semantic vs. phonological) or modality (auditory vs. visual modality). Moreover, activation differences in these regions, which included the inferior frontal gyrus, the superior temporal gyrus, and the occipitotemporal region, were largely independent of in-scanner performance in our auditory semantic task. That is, although RD participants and NI participants differed in performance in visually presented conditions, they did not differ significantly in the auditory condition, yet similar patterns of reduced activation were observed in these regions across conditions. These findings indicate a neurobiological marker in RD that is independent of task, modality, or performance. These findings are discussed in the context of current neurobiological models of RD.

Debate surrounds the precise cortical location and timing of access to phonological information during visual word recognition. Therefore, using whole-head magnetoencephalography (MEG), we investigated the spatiotemporal pattern of brain responses induced by a masked pseudohomophone priming task. Twenty healthy adults read target words that were preceded by one of three kinds of nonword prime: pseudohomophones (e.g., brein-BRAIN), where four of five letters are shared between prime and target, and the pronunciation is the same; matched orthographic controls (e.g., broin-BRAIN), where the same four of five letters are shared between prime and target but pronunciation differs; and unrelated controls (e.g., lopus-BRAIN), where neither letters nor pronunciation are shared between prime and target. All three priming conditions induced activation in the pars opercularis of the left inferior frontal gyrus (IFGpo) and the left precentral gyrus (PCG) within 100 ms of target word onset. However, for the critical comparison that reveals a processing difference specific to phonology, we found that the induced pseudohomophone priming response was significantly stronger than the orthographic priming response in left IFG/PCG at approximately 100 ms. This spatiotemporal concurrence demonstrates early phonological influences during visual word recognition and is consistent with phonological access being mediated by a speech production code.

Using fMRI, we explored the relationship between phonological awareness (PA), a measure of metaphonological knowledge of the segmental structure of speech, and brain activation patterns during processing of print and speech in young readers from 6 to 10 years of age. Behavioral measures of PA were positively correlated with activation levels for print relative to speech tokens in superior temporal and occipito-temporal regions. Differences between print-elicited activation levels in superior temporal and inferior frontal sites were also correlated with PA measures with the direction of the correlation depending on stimulus type: positive for pronounceable pseudowords and negative for consonant strings. These results support and extend the many indications in the behavioral and neurocognitive literature that PA is a major component of skill in beginning readers and point to a developmental trajectory by which written language engages areas originally shaped by speech for learners on the path toward successful literacy acquisition.

Mixed sex bays are a reality on most Emergency Assessment Units (EAU). However, they are controversial having recently been the focus of political and media attention. We adapted a validated patient satisfaction questionnaire to seek the views of 1000 emergency admissions regarding mixed sex accommodation. Of 1000 respondents, 925 (92%) had been in bays and 665 (66%) shared with the opposite sex. Most 579/665 (87%) were comfortable with this, 97% (966/1000) feeling there was sufficient level of privacy, all (1000/1000) felt they were given privacy when needed. When asked "given the nature and function of EAU would you be willing to share with the opposite sex if it meant a shorter stay?", 857 (86%) said yes. Our study demonstrates that whilst single sex accommodation is ideal it is not the most important factor to most patients admitted to EAU.

Functional neuroimaging studies indicate that a primary marker of specific reading disability (RD) is reduced activation of left hemisphere (LH) posterior regions during performance of reading tasks. However, the severity of this disruption, and the extent to which these LH systems might be available for reading under any circumstances, is unclear at present. Experiment 1 examined the cortical effects of stimulus manipulations (frequency, imageability, consistency) that have known facilitative effects on reading performance for both nonimpaired (NI) and RD readers. Experiment 2 examined stimulus repetition, another facilitative variable, in an additional sample of adolescent NI and RD readers. For NI readers, factors that made words easier to process were associated with relatively reduced activation. For RD readers, facilitative factors resulted in increased activation in these same reading-related sites, suggesting that the LH reading circuitry in adolescent RD is poorly trained but not wholly disrupted.

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Prenatal exposure to active maternal tobacco smoking elevates risk of cognitive and auditory processing deficits, and of smoking in offspring. Recent preclinical work has demonstrated a sex-specific pattern of reduction in cortical cholinergic markers following prenatal, adolescent, or combined prenatal and adolescent exposure to nicotine, the primary psychoactive component of tobacco smoke. Given the importance of cortical cholinergic neurotransmission to attentional function, we examined auditory and visual selective and divided attention in 181 male and female adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Groups did not differ in age, educational attainment, symptoms of inattention, or years of parent education. A subset of 63 subjects also underwent functional magnetic resonance imaging while performing an auditory and visual selective and divided attention task. Among females, exposure to tobacco smoke during prenatal or adolescent development was associated with reductions in auditory and visual attention performance accuracy that were greatest in female smokers with prenatal exposure (combined exposure). Among males, combined exposure was associated with marked deficits in auditory attention, suggesting greater vulnerability of neurocircuitry supporting auditory attention to insult stemming from developmental exposure to tobacco smoke in males. Activation of brain regions that support auditory attention was greater in adolescents with prenatal or adolescent exposure to tobacco smoke relative to adolescents with neither prenatal nor adolescent exposure to tobacco smoke. These findings extend earlier preclinical work and suggest that, in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention, with concomitant alterations in the efficiency of neurocircuitry supporting auditory attention.

Using functional magnetic resonance imaging, we explored the role of semantics in mediating orthographic-to-phonological processing in reading aloud, focusing on the interaction of imageability with spelling-to-sound consistency for low-frequency words. Behaviorally, high-imageable words attenuate the standard latency and accuracy disadvantage for low-frequency inconsistent words relative to their consistent counterparts. Neurobiologically, high-imageable words reduced consistency-related activation in the inferior frontal gyrus but increased posterior activation in the angular and middle temporal gyri, representing a possible neural signature of the tradeoff between semantics and phonology in reading aloud. We discuss implications for neurobiological models of reading in terms of understanding the interplay among areas associated with component processes and suggest that the results constitute an important step toward integrating neurobiological and computational models of reading.

Background: In adult animals and humans, nicotine can produce short-term cognitive enhancement and, in some cases, neuroprotection. Recent work in animals, however, suggests that exposure to nicotine during adolescence might be neurotoxic. We tested for evidence of acute and chronic effects of tobacco smoking on cognition in adolescents who smoked tobacco daily and were compared with adolescent nonsmokers., Methods: Verbal working memory, verbal learning and memory, selective, divided, sustained attention, mood, symptoms of nicotine withdrawal, and tobacco craving were examined in 41 adolescent daily smokers and 32 nonsmokers who were similar in age, gender, and education. Analyses were controlled for general intelligence, reading achievement, parental educational attainment, baseline affective symptoms, and lifetime exposure to alcohol and cannabis., Results: In adolescent smokers, cessation of tobacco use increased tobacco craving, symptoms of nicotine withdrawal, and depressed mood. Adolescent smokers were found to have impairments in accuracy of working memory performance irrespective of recency of smoking. Performance decrements were more severe with earlier age of onset of smoking. Adolescent smokers experienced further disruption of working memory and verbal memory during smoking cessation. As a group, male smokers initiated smoking at an earlier age than female smokers and were significantly more impaired during tests of selective and divided attention than female smokers and nonsmokers., Conclusions: Adolescent daily tobacco smokers experience acute impairments of verbal memory and working memory after smoking cessation, along with chronic decrements in cognitive performance that are consistent with preclinical evidence that neurotoxic effects of nicotine are more severe when exposure to nicotine occurs at earlier periods in development.

A series of experiments studied the effects of repetition of printed words on (1) lexical decision (LD) and naming (NAM) behavior and (2) concomitant brain activation. It was hypothesized that subword phonological analysis (assembly) would decrease with increasing word familiarity and the greater decrease would occur in LD, a task that is believed to be less dependent on assembly than naming. As a behavioral marker of assembly, we utilized the regularity effect (the difference in response latency between words with regular versus irregular spelling-sound correspondences). In addition to repetition, stimulus familiarity was manipulated by word frequency and case alternation. Both experiments revealed an initial latency disadvantage for low frequency irregular words suggesting that assembly is the dominant process in both tasks when items are unfamiliar. As items become more familiar with repetition, the regularity effect disappeared in LD but persisted in NAM. Brain activation patterns for repeated words that were observed in fMRI paralleled the behavioral studies in showing greater reductions in activity under lexical decision than naming for regions previously identified as involved in assembly.

fMRI was used to investigate the separate influences of orthographic, phonological, and semantic processing on the ability to learn new words and the cortical circuitry recruited to subsequently read those words. In a behavioral session, subjects acquired familiarity for three sets of pseudowords, attending to orthographic, phonological, or (learned) semantic features. Transfer effects were measured in an event-related fMRI session as the subjects named trained pseudowords, untrained pseudowords, and real words. Behaviorally, phonological and semantic training resulted in better learning than did orthographic training. Neurobiologically, orthographic training did not modulate activation in the main reading regions. Phonological and semantic training yielded equivalent behavioral facilitation but distinct functional activation patterns, suggesting that the learning resulting from these two training conditions was driven by different underlying processes. The findings indicate that the putative ventral visual word form area is sensitive to the phonological structure of words, with phonologically analytic processing contributing to the specialization of this region.