Atypical White Matter Connectivity in Dyslexic Readers of a Fairly Transparent Orthography

Atypical structural properties of the brain’s white matter bundles have been associated with failing reading acquisition in developmental dyslexia. Because these white matter properties may show dynamic changes with age and orthographic depth, we examined fractional anisotropy (FA) along 16 white matter tracts in 8- to 11-year-old dyslexic (DR) and typically reading (TR) children learning to read in a fairly transparent orthography (Dutch). Our results showed higher FA values in the bilateral anterior thalamic radiations of DRs and FA values of the left thalamic radiation scaled with behavioral reading-related scores. Furthermore, DRs tended to have atypical FA values in the bilateral arcuate fasciculi. Children’s age additionally predicted FA values along the tracts. Together, our findings suggest differential contributions of cortical and thalamo-cortical pathways to the developing reading network in dyslexic and typical readers, possibly indicating prolonged letter-by-letter reading or increased attentional and/or working memory demands in dyslexic children during reading

Longitudinal Task-Related Functional Connectivity Changes Predict Reading Development

Longitudinal studies suggest developmentally dependent changes in lexical processing during reading development, implying a change in inter-regional functional connectivity over this period. The current study used functional magnetic resonance imaging (fMRI) to explore developmental changes in functional connectivity across multiple runs of a rhyming judgment task in young readers (8–14 years) over an average 2.5-year span. Changes in functional segregation are correlated with and predict changes in the skill with which typically developing children learn to apply the alphabetic principle, as measured by pseudoword decoding. This indicates a developmental shift in the proportion of specialized functional clusters is associated with changes in reading skill and suggests a dependency of reading development on changes of particular neural pathways, specifically decreases in transitivity is indicative of greater network integration. This work provides evidence that characteristics of these pathways, quantified using graph-theoretic metrics, can be used to predict individual differences in reading development

Brain Networks Supporting Literacy Development

The development of fluent reading requires coordinated development of key fiber pathways. While several fiber pathways have been implicated in reading, including the recently re-identified vertical occipital fasciculus (VOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus and its 3 components, and inferior fronto-occipital fasciculus (IFOF), whether these fiber pathways support reading in young children with little to no exposure to print remains poorly understood. Consequently, over the course of three studies, the current dissertation aimed to narrow this research gap by addressing the following research questions: 1) Which fiber pathways support early literacy skill in young children 5-10 years old? 2) Are microstructural properties of these tracts predictive of age-related changes in reading across an interval of two years? 3) Do different components of the recently identified VOF differentially support reading? To answer these questions, we used diffusion-weighted imaging to measure white-matter development and to relate the microstructural properties of each fiber pathway to early literacy and literacy development. We report several novel findings that contribute to our growing understanding of the white matter connections supporting early literacy and literacy. For the first time, these studies revealed that the re-identified VOF can be reliably tracked in young children, bilaterally and is composed of three main components, which project from occipital temporal sulcus to angular, and middle and superior occipital gyri. We also found that the left AF, bilateral ILF, and particular components of the VOF play a role in early literacy and literacy development. Implications for contemporary models of reading development are discussed

Structure-function relationships in human brain development

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis. Page 125 blank.Includes bibliographical references.The integration of anatomical, functional, and developmental approaches in cognitive neuroscience is essential for generating mechanistic explanations of brain function. In this thesis, I first establish a proof-of-principle that neuroanatomical connectivity, as measured with diffusion weighted imaging (DWI), can be used to calculate connectional fingerprints that are sufficient to delineate fine anatomical distinctions in the human brain (Chapter 2). Next, I describe the maturation of structural connectivity patterns by applying these connectional fingerprints to over a hundred participants ranging from five to thirty years of age, and show that these connectional patterns have different developmental trajectories (Chapter 3). I then illustrate how anatomical connections may shape (or in turn be shaped by) function and behavior, within the framework of reading ability and describe how white matter tract integrity may predict future acquisition of reading ability in children (Chapter 4). I conclude by summarizing how these experiments offer testable hypotheses of the maturation of structure and function. Studying the complex interplay between structure, function, and development will get us closer to understanding both the constraints present at birth, and the effect of experience, on the biological mechanisms underlying brain function.by Zeynep Mevhibe Saygin.Ph.D

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

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

Fiber Pathways for Language in the Developing Brain: A Diffusion Tensor Imaging (DTI) Study

The present study characterized two fiber pathways important for language, the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF) and the frontal aslant tract (FAT), and related these tracts to speech, language, and literacy skill in children five to eight years old. We used Diffusion Tensor Imaging (DTI) to characterize the fiber pathways and administered several language assessments. The FAT was identified for the first time in children. Results showed no age-related change in integrity of the FAT, but did show age-related change in the left (but not right) SLF/AF. Moreover, only the integrity of the right FAT was related to phonology but not audiovisual speech perception, articulation, language, or literacy. Both the left and right SLF/AF related to language measures, specifically receptive and expressive language, and language content. These findings are important for understanding the neurobiology of language in the developing brain, and can be incorporated within contemporary dorsal-ventral-motor models for language

Visual word recognition insights from MEG and implications for developmental dyslexia

The ability to fluently and, seemingly effortlessly, read words is one of few uniquely special human attributes, but one which has assumed inordinate significance because of the role that this activity has come to have in modern society. A disadvantage in reading ability not only has profound personal impact for the individuals concerned, but in terms of economic and social problems also has a wider negative influence on society at large. According to current government figures in the UK, some 22% of 11 year olds do not reach the minimum standard required in English national curriculum tests. Despite its importance, however, the scientific understanding of the neural basis of reading, and more particularly the visual aspect of visual word recognition, is relatively poorly understood. Thus far, a coherent overarching model, that spans the various conceptual levels, from behaviour through functional description to neuroanatomy, has proven extraordinarily challenging to elucidate. A fuller understanding of the computational processing and neurophysiological basis of how the reading system functions would therefore represent significant progress. As with most complex behaviours, visual word recognition is thought to result from the dynamic interplay between the elements of a distributed cortical and sub-cortical network. To fully understand how visual word recognition is achieved therefore, and how it may fail in developmental dyslexia, we need to identify not only the necessary and sufficient complement of nodes that comprise this network – its functional anatomy - but we also need to understand how information flows through this network with time and indeed how the structure of the network itself may adapt in both the short and long term. In this chapter we take a historical approach to reviewing recent MEG (magnetoencephalography) research which elucidates these temporal dynamics, focusing particularly on events with the first 300ms of a visually presented word, and which we believe should set crucial constraints on models of visual word recognition and reading

A narrative review of the anatomy and function of the white matter tracts in language production and comprehension

Much is known about the role of cortical areas in language processing. The shift towards network approaches in recent years has highlighted the importance of uncovering the role of white matter in connecting these areas. However, despite a large body of research, many of these tracts’ functions are not well-understood. We present a comprehensive review of the empirical evidence on the role of eight major tracts that are hypothesized to be involved in language processing (inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, and frontal aslant tract). For each tract, we hypothesize its role based on the function of the cortical regions it connects. We then evaluate these hypotheses with data from three sources: studies in neurotypical individuals, neuropsychological data, and intraoperative stimulation studies. Finally, we summarize the conclusions supported by the data and highlight the areas needing further investigation

Brain structural predispositions for music and language processing

[eng] It has been shown that music and language training can elicit plastic changes on brain structure and function bringing along behavioural benefits. For instance, musicians have been reported to have better auditory discrimination including pitch and speech-in-noise perception, motor-synchronization, verbal memory and general IQ than individuals without formal musical background. Also, bilinguals have shown higher executive function and attention-related abilities than monolinguals. Furthermore, altered functional and structural connectivity can be tracked to brain areas related to the activities most frequently performed by both musicians (instrumentalists and singers) and linguistic experts (such as bilinguals or professional phoneticians). While research in the last decade has devoted important effort to the study of brain plasticity, only a few investigations have addressed the connection between the initial functional or structural properties of brain networks related to auditory-motor function and subsequent language or musical training. Indeed, brain structural markers such as grey matter volume/density or white-matter diffusivity measurements from diffusion tensor imaging (DTI) data, as well as functional measurements from task- related activity or resting-state data from magnetic resonance imaging (MRI) or electroenceplhalography (EEG) have been demonstrated to correlate with consecutive performance and learning in the auditory-motor domain. The main goal of the present dissertation was twofold: we aimed to further the existing knowledge regarding brain plasticity elicited during putative sensitive periods and after long-term music practice, and to explore the white-matter pathways that predict linguistic or musical skills at baseline . Our secondary goals were to confirm previous findings regarding the brain structures involved in music and language processing, as well as to provide evidence of the benefits of usingstructural measurements and correlational analyses between imaging and behavioural data to study inter-individual differences. Study I focused on the comparison between professional pianists and non- musicians observing a complex pattern of increases and decreases in grey matter volume. In comparison to non-musician individuals, pianists showed greater grey matter volume in areas related to motor skill and the automatization of learned movements, as well as reinforcement learning and emotional processing. On the other hand, regions associated to sensorimotor control, score reading and auditory and musical perception presented a reduction in grey matter volume. Study II explored the relationship between white-matter structural properties of the arcuate fasciculus (AF) and the performance of native German speakers in a foreign- language (Hindi) sentence and word imitation task. We found that a greater left lateralization of the AF volume predicted performance on the imitation task. This result was confirmed by using not only a manual deterministic approach but also an automatic atlas-based fibre-reconstruction method, which in addition pointed out to a specific region in the anterior half of the left AF as the most related to imitation ability. Study III aimed to investigate whether the white-matter structural connectivity of the pathways previously described as targets for plasticity mechanisms in professional musicians predicted musical abilities in non-musicians. We observed that the white- matter microstructural organization of the right hemisphere pathways involved in motor-control (corticospinal tract) and auditory-motor transformations (AF) correlated with the performance of non-musician individuals during the initial stages of rhythmic and melodic learning. The present work confirmed the involvement of several brain structures previously described to display plastic effects associated to music and language training in the first stages of audio-motor learning. Furthermore, they challenge previous views regarding music-induced plasticity by showing that expertise is not always or uniquely correlated with increases in brain tissue. This raises the question of the role of efficiency mechanisms derived from professional-like practice. Most importantly, the results from these three studies converge in showing that a prediction-feedback-feedforward loop for auditory-motor processing may be crucially involved in both musical and language learning and skills. We thus suggest that brain auditory-motor systems previously described as participating in native language processing (cortical areas of the dorsal route for language processing and the AF that connects them) may also be recruited during exposure to new linguistic or musical material, being refined after sustained music practice.[spa] Estudios previos muestran que la formación musical y lingüística provoca cambios plásticos en las estructuras y funciones cerebrales, acompañándose también de beneficios conductuales. Por ejemplo, se ha descrito que los músicos poseen mejores habilidades de discriminación auditiva (incluyendo la percepción tonal y la discriminación del habla en un ambiente ruidoso), una mayor capacidad de sincronización motora, así como mejor memoria verbal y coeficiente intelectual general en comparación con personas sin formación musical. Paralelamente, los bilingües muestran mejores funciones ejecutivas y habilidades relacionadas con la atención en comparación con individuos monolingües. Además, las alteraciones en la conectividad cerebral funcional y estructural pueden ser rastreadas estudiando las áreas cerebrales relacionadas con las actividades más utilizadas por músicos (instrumentistas y cantantes) y expertos lingüísticos (como bilingües o fonetistas profesionales). Pese a que en la última década se han dedicado esfuerzos importantes en el campo de la investigación sobre la plasticidad cerebral, sólo unos pocos estudios han tratado de investigar la conexión entre las propiedades iniciales del cerebro, en cuanto a las funciones y estructuras que se relacionan con las funciones auditivo-motoras, y el posterior aprendizaje musical o del lenguaje. Sin embargo, los marcadores estructurales cerebrales, tales como volumen/densidad de materia gris o medidas de difusividad en la sustancia blanca a partir de datos de imagen del tensor de difusión, así como medidas funcionales de la actividad relacionada con una tarea o datos de resting-state (estado de reposo) obtenidos por resonancia magnética o electroencefalografía, han demostrado que pueden correlacionar con el rendimiento y el aprendizaje en el dominio auditivo- motor. En la presente tesis pretendíamos ampliar nuestro conocimiento en cuanto a la plasticidad cerebral obtenida durante los supuestos “períodos sensibles” y después de la práctica musical mantenida en el tiempo, por un lado, y explorar las vías de sustancia blanca que pueden predecir habilidades lingüísticas o musicales al inicio del aprendizaje, por otro lado. Como objetivos secundarios, queríamos confirmar resultados previos con respecto a las estructuras cerebrales involucradas en el procesamiento de la música y el lenguaje, así como apoyar el uso de mediciones estructurales y enfoques correlacionales (entre datos de neuroimagen y conductuales) para estudiar las diferencias inter- individuales. El Estudio I se centró en la comparación entre pianistas profesionales y no músicos, observando un complejo patrón de aumentos y disminuciones en el volumen de materia gris. En comparación con los individuos no músicos, los pianistas mostraron mayor volumen de sustancia gris en áreas relacionadas con la habilidad motora y la automatización de movimientos aprendidos, así como el aprendizaje a través del refuerzo y el procesamiento emocional, mientras que las regiones asociadas al control sensoriomotor, lectura de partituras y percepción auditiva y musical presentaron una reducción del volumen de materia gris. El Estudio II exploró la relación entre las propiedades estructurales de la materia blanca del fascículo arqueado (AF por sus siglas en inglés) y el rendimiento de hablantes nativos de alemán en una tarea de imitación de frases y palabras en una lengua extranjera (hindi). Encontramos que una mayor lateralización del volumen de AF hacia la izquierda predecía el desempeño en la tarea de imitación. Este resultado se confirmó utilizando no sólo un enfoque determinístico-manual sino también una reconstrucción automática (basada en atlas anatómicos) de las fibras de sustancia blanca que, además, señalaba una región específica en la mitad anterior del AF izquierdo como la más relacionada con las capacidades de imitación. El Estudio III tenía como objetivo investigar si la conectividad estructural de vías de sustancia blanca anteriormente descritas como dianas para los mecanismos de plasticidad en músicos profesionales, podría predecir las habilidades musicales en los no músicos. Se observó que la organización micro-estructural de la materia blanca en el hemisferio derecho en vías involucradas en el control motor (tracto corticoespinal) y en transformaciones auditivo-motoras (AF) correlacionaba con el desempeño de individuos no músicos en las etapas iniciales del aprendizaje rítmico y melódico. El presente trabajo ha confirmado la implicación en las primeras etapas del aprendizaje audio-motor de varias estructuras cerebrales que previamente habían mostrado efectos plásticos asociados al aprendizaje musical y del lenguaje. Además, estos resultados desafían las opiniones anteriores sobre la plasticidad inducida por la experiencia musical al demostrar que la experiencia no se correlaciona siempre ni únicamente con un aumento del tejido cerebral, y planteando así preguntas sobre los mecanismos de eficiencia derivados de la práctica musical a nivel profesional. Más importante aún es que los resultados de estos tres estudios convergen mostrando que un bucle de predicción–retroalimentación (feedback)–alimentación directa (feedforward) para el procesamiento auditivo-motor puede estar implicado de manera crucial tanto en el aprendizaje musical como en el aprendizaje de idiomas. Por tanto, sugerimos que los sistemas auditivo-motrices del cerebro, que previamente se habían descrito como participantes en el procesamiento del lenguaje nativo (áreas corticales involucradas en la vía dorsal para el procesamiento del lenguaje, y el AF, que las conecta) también pueden ser reclutados durante la exposición a material lingüístico o musical nuevo, siendo refinado tras años de práctica musical activ

Fixing fluency: Neurocognitive assessment of a dysfluent reading intervention

The ability to read is essential to attain society’s literacy demands. Unfortunately, a significant percentage of the population experiences major difficulties in mastering reading and spelling skills. Individuals diagnosed with developmental dyslexia are at severe risk for adverse academic, economic, and psychosocial consequences, thus requiring clinical intervention. To date, there is no effective remediation for the lack of reading fluency, which remains as the most persistent symptom in dyslexia. This thesis aims at identifying factors involved in the failure to develop a functional reading network as well as factors of treatment success in addressing the notorious ‘fluency barrier’ in dyslexia. The present work combines a theoretical framework of dyslexia based on the multisensory integration deficit with recent advances in our knowledge of the brain networks specialized for reading. This thesis uses a longitudinal design including both behavioral and neurophysiological measures in dyslexics at 3rd grade of school. Between measurements, we provide an intervention aimed at improving reading fluency by training automation of letter-speech sound mappings. The studies presented in this thesis contribute to our understanding of dyslexics’ deficits and their remediation