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

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

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

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

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

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

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

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.)

Developmental dyslexia (decoding-based reading disorder; RD) is a complex trait with multifactorial origins at the genetic, neural, and cognitive levels. There is evidence that low-level sensory-processing deficits precede and underlie phonological problems, which are one of the best-documented aspects of RD. RD is also associated with impairments in integrating visual symbols with their corresponding speech sounds. Although causal relationships between sensory processing, print-speech integration, and fluent reading, and their neural bases are debated, these processes all require precise timing mechanisms across distributed brain networks. Neural excitability and neural noise are fundamental to these timing mechanisms. Here, we propose that neural noise stemming from increased neural excitability in cortical networks implicated in reading is one key distal contributor to RD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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

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.)

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.

Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder.

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.

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.

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.

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

Background: This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes., Methods: Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27)., Results: Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies., Conclusions: These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Background: Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words)., Methods: We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words., Results: Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children., Conclusions: These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults.

Advances in neurobiological research have created new opportunities for understanding and exploring dyslexia. The purpose of this article is to (a) provide a straightforward, although not overly simplified, overview of neurological research on dyslexia and (b) make connections between neurological research and classroom interventions for students with dyslexia. Key ideas are that neuroscience confirms the importance of systematic phonics instruction, neuroimaging has led to new ideas about how dyslexia might be treated, and specific brain regions and pathways are involved in reading. Educational neuroscience remains in early stages, but the immediate relevance for the classroom is emerging.

This article proposes a neurobiological account of reading and reading disability suggesting that for normally developing readers, the dorsal (tempo-parietal) circuit predominates at first, and in conjunction with premotor systems, is associated with analytic processing necessary for learning to integrate orthographic with phonological and lexical-semantic features of printed words. The ventral (occipito-temporal) circuit underlies fluency in word recognition. (Contains references.) (Author/DB)

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.

Converging evidence from a number of neuroimaging studies, including our own, suggest that fluent word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system is functionally disrupted in developmental dyslexia. Reading disabled readers, relative to nonimpaired readers, demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers the dorsal circuit predominates at first, and is associated with analytic processing necessary for learning to integrate orthographic features with phonological and lexical-semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word identification system which underlies fluent word recognition in skilled readers. MRDD Research Reviews 6:207–213, 2000. © 2000 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]