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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Miller, Brett
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Yu, Xi; Zuk, Jennifer; Gaab, Nadine (2018) What Factors Facilitate Resilience in Developmental Dyslexia? Examining Protective and Compensatory Mechanisms Across the Neurodevelopmental Trajectory. Child Dev Perspect 12:240-246
Yu, Xi; Raney, Talia; Perdue, Meaghan V et al. (2018) Emergence of the neural network underlying phonological processing from the prereading to the emergent reading stage: A longitudinal study. Hum Brain Mapp 39:2047-2063
Zuk, Jennifer; Perdue, Meaghan V; Becker, Bryce et al. (2018) Neural correlates of phonological processing: Disrupted in children with dyslexia and enhanced in musically trained children. Dev Cogn Neurosci 34:82-91
Zuk, Jennifer; Gaab, Nadine (2018) Evaluating predisposition and training in shaping the musician's brain: the need for a developmental perspective. Ann N Y Acad Sci :
Ozernov-Palchik, Ola; Norton, Elizabeth S; Wang, Yingying et al. (2018) The relationship between socioeconomic status and white matter microstructure in pre-reading children: A longitudinal investigation. Hum Brain Mapp :
Raschle, Nora Maria; Becker, Bryce Larkin Chessell; Smith, Sara et al. (2017) Investigating the Influences of Language Delay and/or Familial Risk for Dyslexia on Brain Structure in 5-Year-Olds. Cereb Cortex 27:764-776
Ozernov-Palchik, Ola; Norton, Elizabeth S; Sideridis, Georgios et al. (2017) Longitudinal stability of pre-reading skill profiles of kindergarten children: implications for early screening and theories of reading. Dev Sci 20:
Wang, Yingying; Mauer, Meaghan V; Raney, Talia et al. (2017) Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls. Cereb Cortex 27:2469-2485
Langer, Nicolas; Peysakhovich, Barbara; Zuk, Jennifer et al. (2017) White Matter Alterations in Infants at Risk for Developmental Dyslexia. Cereb Cortex 27:1027-1036
Powers, Sara J; Wang, Yingying; Beach, Sara D et al. (2016) Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study. Ann Dyslexia 66:337-360

Showing the most recent 10 out of 25 publications