James R. Booth, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): We have formulated a developmental neuro-cognitive model of lexical processing in normal readers based on cross-sectional functional magnetic resonance imaging (fMRI) data and we have collected our first longitudinal data on these children 2 years after their initial assessment. The proposed grant will longitudinally follow normal children (7- to 17- year-olds) and children with reading disorders (11- to 15-year-olds) when they perform a variety of tasks. These tasks include orthographic (spelling), phonological (rhyming) and semantic (meaning) judgments in the visual and auditory modalities. Not only is this proposal innovative because we use a variety of tasks, but we also have multiple perceptual controls and multiple parametric manipulations of difficulty, so we can more effectively examine developmental and group effects specific to aspects of lexical processing. Furthermore, our paradigms allow an examination of priming and lexical effects (e.g. word frequency, phonological consistency and orthographic consistency) so observed developmental and group differences are not likely to be due to specific characteristics of the tasks. The overall aim of this study is to determine whether different groups have different developmental trajectories. A longitudinal design is crucial to rule out cohort effects and to examine the predictability of the individual's subsequent brain development from their earlier reading skill and brain activation patterns. In addition to examining whether higher and lower skill normal readers have different developmental trajectories, we will examine whether dyslexic readers with specific deficits in decoding orthographic stimuli have different developmental trajectories from language-impaired readers with deficits in decoding orthographic stimuli in addition to general language processing deficits. We will also compare children with disorders to age-match versus reading-match normal readers to address the question of developmental delay versus deviance. Our general hypothesis is that individual differences in brain activation between readers will increase with age. This will be tested using hierarchical linear modeling to examine growth curves in the rate of change (e.g. slope) and in the shape of change (e.g. acceleration). We will use this technique to look at developmental changes in signal intensity in our critical regions of interest, but also for changes in effective connectivity using Dynamic Causal Modeling (DCM). PUBLIC HEALTH RELEVANCE This proposal will give us basic information about how the brains of typical children change throughout childhood and adolescence during reading and language processing, but also how the brains of children with reading and language disorders differ in their development. The relevance of this grant to biomedical issues is that it has implications for diagnosis and intervention in children with reading and language disorders. [unreadable] [unreadable] [unreadable]

1: Summary Math disability affects about 6% of the childhood population and continues into adolescence, and therefore, represents a major biomedical issue. Neuropsychological and neuroimaging studies in adults have implicated the intra-parietal sulcus and middle frontal gyrus in quantity comparison (e.g. subtraction), but have implicated temporo- parietal cortex and inferior frontal gyrus in verbal retrieval of math facts (e.g. multiplication). Neuroimaging research in adults has also suggested that reliance on the verbal retrieval system increases with practice and it is utilized more for easier problems. Behavioral research suggests there are developmental increases in the reliance on the verbal retrieval system and that some children with math disability show pronounced deficits in this system. Behavioral research has also shown that some children with math disability have a reading disability, and some have suggested that children with a math and reading disability (MD+RD) should have a deficit in the verbal retrieval system, whereas children with a math disability only (MD) should have a deficit in the quantity comparison system. Although there has been a substantial amount of neuroimaging research in adults and behavioral research in children, very little is known about the neural basis of math development or of math disability in children. This project will use functional magnetic resonance imaging (fMRI) to examine the neural development of quantity comparison (i.e. subtraction) and verbal retrieval (i.e. multiplication) in typically developing children (10- to 14-year-olds) and to examine the neural bases of math disability in children with and without co-morbid reading disability. We will examine differences in signal intensity using conventional fMRI analyses, but we will also examine differences in effective connectivity using dynamic causal modeling (DCM). This project will employ easier versus harder tasks to more effectively delineate brain regions involved in different forms of math processing, a longitudinal design to examine whether early functioning predicts later development, and reading tasks to determine their inter-relations with math processing. Relevance. This project proposes to examine the neural basis of mathematical development in typically developing children and in children math disability with and without co-morbid reading disability. The results of this project will have implications for the diagnosis and remediation of math disability.

DESCRIPTION (provided by applicant): This project will examine the neural basis of language development using functional magnetic resonance imaging (fMRI). In a longitudinal design, young children will be given word level and sentence level tasks that tap into phonological, semantic and morpho-syntactic processing. We hypothesize that temporo-parietal cortex becomes more specialized over development for distinct linguistic representations through increasing interaction (i.e. connectivity) with frontal cortex. Specialization should be characterized by increases in differential responses in temporo-parietal cortex to tasks tapping into distinct aspects of linguistic function. This project will test the interactive-specialization model that makes clear predictions of developmental brain differences [1, 2], but has little direct neuroimaging evidence to support it [19]. The central tenet of this model is that interaction between brain regions drives the specialization of brain regions for making certain computations. An extension of the interactive-specialization model predicts that children with LI should have lack of specialization in temporo-parietal cortex perhaps due to altered interaction between temporo-parietal and frontal regions. Functional connectivity between brain regions will be measured with Psychophysiological Interaction (PPI) and specialization will be measured with activation differences, but also with Representational Similarity Analysis (RSA). Examination of language development in the transition from preschool to elementary school is important because this transition is marked by mastery of complex morpho-syntactic principles, elaboration and refinement of semantic representations, and by increases in children's ability to process phonemic information. Central to testing our overarching hypothesis is quantifying brain changes in young children, and differences that emerge in language impairment (LI). Previous fMRI studies have generally used cross-sectional designs and have only examined one age group, have examined a wide age range (i.e. from kindergarten through adolescence) and/or have not examined multiple linguistic processes. Moreover, only a handful of neuroimaging studies have examined the brain basis of LI in children. Our project will overcome these shortcomings by using a longitudinal approach to examine the development of multiple linguistic processes in young children. Longitudinal approaches are rarely used in the developmental neuroimaging literature, but are crucial for gaining insights into what mechanisms drive language development. A significant strength of our project is the use of theoretically motivated experimental tasks based on extensive behavioral literature to investigate innovative ideas regarding brain development in young children. The use of sophisticated change models will also allow us to determine whether the longitudinal growth in language impairment represents a quantitative versus qualitative difference and whether neuroimaging measures can be used to uniquely predict those children who are likely to fall further behind in language processing.

PROJECT SUMMARY Many deaf and hard-of-hearing (DHH) children struggle with reading and the severity of the impairment for some children increases with age. Despite this, we know very little about the brain mechanisms for successful reading in DHH children, or whether reliance on certain mechanisms differs with communication mode. We do not know why some DHH children are good readers and other are not. We take advantage of the large individual differences in reading skill to determine how better reading relies on different mechanisms and whether this varies with communication modes. This project uses functional magnetic resonance imaging (fMRI) in 10- to 15-year-old hearing children as well as in DHH children with predominant signed language, predominant oral language, or bimodal language. The innovative longitudinal approach follows children two years later and allows an investigation of how reading gains are related to brain changes over time and whether this varies with age. The overarching theory of reading acquisition is the Triangle Model which has three representational systems, including orthography (spelling), phonology (sound) and semantics (meaning), as well as pathways for mapping between these systems. A fundamental strength of this project is extending the well-developed Triangle Model to formulate the first neurocognitive model of reading in DHH children. Our project tests critical assumptions of the Triangle Model including the nature of orthographic representations, of orthographic to phonological mapping and of orthographic to semantic mapping. We test how these components are related to skill and developmental change over time in DHH children with different communication modes. Another innovative aspect of the project is the use of `localizer' fMRI tasks to independently identify regions associated with phonological mechanisms in temporo-parietal cortex during speech reading, signed language and spoken phonology, as well as regions associated with semantic mechanisms in middle temporal gyrus. The use of independent localizer tasks provides fundamental advances in our understanding of the underlying neural mechanisms involved in skilled reading in DHH children. Children also complete two reading fMRI tasks, one involving rhyming judgments and the other involving meaning judgments to words presented visually. Not only do we examine how phonological and semantic mechanisms are related to reading, but our novel approach also examines connectivity of these regions with fusiform cortex involved in orthographic processing. In addition to the fMRI measures, all children complete an extensive battery of state-of-the-art behavioral tests measuring signed language, oral language and reading. The focus of the project is on individual differences on word decoding as this is a critical building block to reading, but we also examine behavioral differences in reading comprehension.