Nadine Gaab - US grants

DESCRIPTION (provided by applicant): Developmental dyslexia (DD) is one of the most prominent specific learning disabilities, affecting 5-17% of children. Heritability of DD has been supported by strong evidence from molecular-genetic studies and from studies of twins and families with DD. Substantial evidence suggests that neurological abnormalities underlie DD in children and adults. Multiple functional neuroimaging studies comparing adults and children with DD to typical controls have observed dysfunctions within various brain regions. Differences in the neural correlates of language and auditory processing have also been observed in infants with a family history of reading or language impairments compared to those without. Additionally, it has been suggested that the functional differences observed in children with DD may be related to morphological brain differences. Measures of brain volume have revealed structural abnormalities in children and adults with a diagnosis of DD in regions that broadly overlap with observed functional differences. A number of key questions remain unanswered. We do not know whether observed functional and structural brain differences associated with DD are present prior to reading onset in those who will later receive a diagnosis. We do not know whether these functional and structural differences could be exploited to predict later reading outcome. It also remains unclear how key skills that are impaired in those with DD (e.g., phonological processing and rapid auditory processing) develop in children as they move from the pre-reading to the skilled reading stage. Additionally, we do not know how these impaired skills affect the later developmental trajectory of reading fluency. These open questions make it apparent that while we know much about the brain of individuals with DD, this knowledge has not yet led to a comprehensive examination of the pre-reading brain to investigate the predictive value of neural pre-markers for DD and to characterize the developmental trajectories of functional and structural brain measures in children with and without a family history of DD. We will make these missing connections by examining 60 pre-readers with and 60 pre-readers without a family history of DD by following their reading development longitudinally from the pre-reading stage until third grade. Specifically, we will determine: 1. If the functional brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 1);2. If the structural brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 2);3. How key reading skills (phonological processing, rapid auditory processing and reading fluency) develop as children move from being pre-readers to skilled readers (Specific Aim 3);and 4. Which single predictor, or set of predictors, obtained from pre-readers and/or beginning readers will best predict reading outcome in children after three years of reading instruction.(Specific Aim 4) Overall, the aim of the proposed study is to comprehensively characterize brain function and morphology in children with and without a family history of DD prior to the onset of reading and longitudinally follow these children's brain development. Achieving this aim using functional and structural brain indices, as well as psychometric and psychophysical measures, will allow us to identify which marker or markers can be used to best predict later reading outcome. The proposed research has crucial clinical, psychological and social implications. Studies show that children with learning disabilities are less likely than their peers to receive a high school diploma [8] or to enroll in programs of higher education. Children who struggle in school are also more apt to enter the juvenile justice system. The early identification of predictors for reading disability is essential for the development and improvement of early intervention programs. More importantly, identifying these early predictors may prevent the clinical, psychological and social impact of DD.

DESCRIPTION (provided by applicant): Developmental dyslexia (DD) is one of the most prominent specific learning disabilities, affecting 5-17% of children. Heritability of DD has been supported by strong evidence from molecular-genetic studies and from studies of twins and families with DD. Substantial evidence suggests that neurological abnormalities underlie DD in children and adults. Multiple functional neuroimaging studies comparing adults and children with DD to typical controls have observed dysfunctions within various brain regions. Differences in the neural correlates of language and auditory processing have also been observed in infants with a family history of reading or language impairments compared to those without. Additionally, it has been suggested that the functional differences observed in children with DD may be related to morphological brain differences. Measures of brain volume have revealed structural abnormalities in children and adults with a diagnosis of DD in regions that broadly overlap with observed functional differences. A number of key questions remain unanswered. We do not know whether observed functional and structural brain differences associated with DD are present prior to reading onset in those who will later receive a diagnosis. We do not know whether these functional and structural differences could be exploited to predict later reading outcome. It also remains unclear how key skills that are impaired in those with DD (e.g., phonological processing and rapid auditory processing) develop in children as they move from the pre-reading to the skilled reading stage. Additionally, we do not know how these impaired skills affect the later developmental trajectory of reading fluency. These open questions make it apparent that while we know much about the brain of individuals with DD, this knowledge has not yet led to a comprehensive examination of the pre-reading brain to investigate the predictive value of neural pre-markers for DD and to characterize the developmental trajectories of functional and structural brain measures in children with and without a family history of DD. We will make these missing connections by examining 60 pre-readers with and 60 pre-readers without a family history of DD by following their reading development longitudinally from the pre-reading stage until third grade. Specifically, we will determine: 1. If the functional brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 1); 2. If the structural brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 2); 3. How key reading skills (phonological processing, rapid auditory processing and reading fluency) develop as children move from being pre-readers to skilled readers (Specific Aim 3); and 4. Which single predictor, or set of predictors, obtained from pre-readers and/or beginning readers will best predict reading outcome in children after three years of reading instruction.(Specific Aim 4) Overall, the aim of the proposed study is to comprehensively characterize brain function and morphology in children with and without a family history of DD prior to the onset of reading and longitudinally follow these children's brain development. Achieving this aim using functional and structural brain indices, as well as psychometric and psychophysical measures, will allow us to identify which marker or markers can be used to best predict later reading outcome. The proposed research has crucial clinical, psychological and social implications. Studies show that children with learning disabilities are less likely than their peers to receive a high school diploma [8] or to enroll in programs of higher education. Children who struggle in school are also more apt to enter the juvenile justice system. The early identification of predictors for reading disability is essential for the development and improvement of early intervention programs. More importantly, identifying these early predictors may prevent the clinical, psychological and social impact of DD.

SUMMARY Arithmetic and reading are the most fundamental skills acquired during elementary school and are crucial for successful academic achievement, employment prospects, and mental health. Despite the significance of arithmetical and reading skills, many children and adults in developed societies exhibit deficient reading and arithmetical abilities. Accumulating evidence suggests a strong neurocognitive and genetic link between reading and arithmetic, with high co-occurrence rates of both reading and arithmetical learning difficulties. However, the developmental trajectories of typical and atypical arithmetical and reading skills have been predominantly studied apart and potential shared mechanisms of typical and atypical reading and arithmetic development are unknown. This application proposes a longitudinal investigation that aims to (a) compare typical and atypical developmental trajectories of reading and arithmetic from kindergarten to third grade, (b) characterize similarities, differences, and classification power of neural and cognitive measures to profile the shared mechanisms underlying arithmetic and reading, and (c) determine a set of predictors in kindergarten predicting arithmetic and reading outcome after four years of formal instruction. Employing a longitudinal study design, the proposed project aims to investigate the developmental relationships of reading and arithmetic in the typical and atypical development of arithmetical skills from the beginning of kindergarten to third grade, in 180 children with either a familial risk for arithmetic difficulties (AD), a familial risk for reading difficulties (RD), or without any familial risk for reading or arithmetical difficulties, using functional and structural brain measures and behavioral correlates. Neural correlates of arithmetic, reading, and related sub- skills, together with a comprehensive psychometric battery measuring reading and arithmetical development and domain-general and domain-specific skills, will be examined four times over four years during critical stages of acquiring literacy and numerical concepts. By targeting children with a family history of AD and RD, and due to the genetic profile overlap of these two conditions, the probability of children exhibiting atypical reading and arithmetic development is increased, which will allow us to study and compare the developmental trajectories of both typical and atypical reading and arithmetical skills. This study has the potential to provide a model for understanding developmental learning disabilities, their underlying mechanisms, and their co-occurrence. The current focus on a reactive, deficit-driven instead of a preventive model in the field of learning disabilities is detrimental for students, as interventions have been proven to be most effective at an earlier age of heightened brain plasticity and because of the implications for mental health in struggling students as a result of a ?wait-to-fail? approach. Understanding the shared and distinct underlying cognitive and neural mechanisms between typical and atypical arithmetic and reading skills and their precursors are of great significance for the development of early screening, diagnostic, and intervention tools.