Developmental Dyslexia (DD) is a strongly heritable specific learning disability of neurobiological origin, but the underlying neural mechanisms are largely unknown. Although DD is not diagnosed until a child has failed to learn to read, usually in late elementary school, after reading impairments and associated psychological burdens manifest, interventions are most effective in younger children. Thus, to date, DD is generally diagnosed after the most effective time for intervention has passed. A tentative pathway between genetic effects, early brain development, and behavior in DD has been proposed but only a few studies have examined longitudinal brain development in infants at risk for DD and none have investigated the development of brain structure or metabolic function. Furthermore, although behavioral research has demonstrated a strong relationship between reading skills in parents and their children, the intergenerational transmission of structural and functional brain alterations in DD is unknown. Building on our previous work, which showed atypical functional and structural brain development in infants, preschoolers, and kindergarteners at-risk for dyslexia, the goal of this proposed project is to characterize trajectories of early brain development in infants with (FHD+) and without (FHD-) a familial risk for DD from early infancy through elementary school and to further examine intergenerational transmission of brain alterations associated with DD in child-parent dyads. We will utilize a longitudinal approach and MR measures will be obtained in a new infant cohort, and an existing child cohort for which infant data have already been collected. Furthermore, the parents of all children will be examined. Using functional and structural magnetic resonance imaging as well as magnetic resonance spectroscopy and behavioral measures, Aim 1 (cross-sectional) will characterize atypical structural, functional and metabolic brain development in FHD+ compared to FHD- infants and children at 5 time points.
Aim 2 (longitudinal) utilizes growth curve and trajectory analyses to characterize and compare developmental trajectories of FHD+ and FHD- infants from infancy through elementary school.
Aim 3 will examine the intergenerational transmission of brain structure/function critical for reading as well as behavioral reading skills in children-parent dyads. The current practice of DD diagnosis only after years of reading failure is detrimental to the well-being of children and their families who experience the psychosocial implications of DD for years prior to diagnosis. Identifying the underlying neural mechanisms of DD in infancy is highly innovative and has the potential to inform early identification of children at risk and the development of early preventive and intervention strategies during a period of heightened brain plasticity. It may also draw increased research attention to this age group (infancy) in DD and has the potential to provide a model for longitudinal studies of other developmental disabilities. It can further highlight the importance of examining brain development trajectories starting in infancy to illuminate emerging brain-behavior associations across the developmental timeline.

Public Health Relevance

Developmental Dyslexia (DD) is a strongly heritable specific learning disability of neurobiological origin that occurs in up to 50% of children with an affected first-degree relative, but the underlying neural mechanisms are largely unknown. Previous evidence from research in humans and animals has suggested that brain alterations in DD are likely to exist from birth, but the developmental trajectories of these brain alterations from infancy to adulthood as well as their heritability patterns are largely unknown. The proposed study aims to characterize trajectories of early structural, functional, and metabolic brain development in infants with and without a familial risk of DD and further aims to examine intergenerational transmission of brain alterations associated with DD. Identifying the underlying neural mechanisms of DD in infancy has the potential to inform early identification of children at risk for DD and promote the development of early preventive strategies during a period of heightened brain plasticity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD065762-09
Application #
9762148
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Miller, Brett
Project Start
2011-03-15
Project End
2021-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
9
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Boston Children's Hospital
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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

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