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.

Public Health Relevance

Developmental dyslexia (DD) is one of the most prominent specific learning disabilities in school-age children and familial occurrences and twin studies strongly support a genetic basis for DD. Neuroimaging studies have revealed functional and structural differences within various brain regions in school-age children and adults with a diagnosis of DD compared to controls. The proposed study will investigate whether these observed differences in functional and structural neuroanatomy can already be observed in 4-6 year old children prior to reading onset and how structural and functional brain networks develop longitudinally in these children from the pre-reading stage until third grade. The proposed study further aims to determine which single predictor or set of predictors best predicts reading outcome in children and whether neuroimaging measures have any predictive value. Early identification of predictors for reading ability and disability will not only help to prevent the social and psychological implications of DD but will also be essential for the development and implementation of new remediation programs.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD065762-02
Application #
8240401
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Miller, Brett
Project Start
2011-03-15
Project End
2016-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
2
Fiscal Year
2012
Total Cost
$642,133
Indirect Cost
$273,090
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Raschle, Nora M; Stering, Patrice L; Meissner, Sarah N et al. (2014) Altered neuronal response during rapid auditory processing and its relation to phonological processing in prereading children at familial risk for dyslexia. Cereb Cortex 24:2489-501
Raschle, Nora Maria; Zuk, Jennifer; Gaab, Nadine (2012) Functional characteristics of developmental dyslexia in left-hemispheric posterior brain regions predate reading onset. Proc Natl Acad Sci U S A 109:2156-61
Raschle, Nora; Zuk, Jennifer; Ortiz-Mantilla, Silvia et al. (2012) Pediatric neuroimaging in early childhood and infancy: challenges and practical guidelines. Ann N Y Acad Sci 1252:43-50