Abnormal brain maturation is believed to contribute to the path physiology and etiology of a number of mental health and psychiatric disorders, amongst them autism, schizophrenia, attention deficit and obsessive-compulsive disorder. A critical component of brain maturation is the process of myelination, the development of the fatty myelin layer surrounding white matter axons, which speeds information transfer between discrete brain regions. Despite the crucial role myelination plays in normal brain function, though the establishment and maintenance of these efficient communication pathways;to date little is known quantitatively about the spatial and temporal evolution of myelination. Moreover, the relationships between myelin maturation and cognitive and behavioral development, for example the evolution of motor coordination, language or visual reception, remain poorly understood. This proposal aims to address both of these deficiencies in knowledge, performing the first quantitative and longitudinal study of myelination during healthy neurodevelopment. Paired with synchronized cognitive and behavioral assessments, this data will provide a new vista of normal brain development. This normative dataset will be uniquely positioned to facilitate specific quantitative comparisons between healthy and suspected abnormal development, allowing researchers to identify and establish the spatial and temporal patterns of relevant deficits. The ultimate goals of this research are to quantitatively map the myelination trajectory over the first 5 years of life in a healthy population, and to examine relationships between myelin maturation and cognitive and behavioral development. To achieve this aim, a new method for quantitative myelin imaging, termed mcDESPOT, will first be further develop and optimized for use in pediatric participants. Using this optimized technique, myelin maturation trajectories throughout the brain will be reconstructed by acquiring high-spatial resolution, whole-brain myelin maps at incremented time points throughout development. Following 128 infants (3-24 months of age) and 128 toddlers (2-5 years), scanning and age-appropriate psychometric testing will be performed at effective 3 and 6- month intervals, respectively. Appropriately aligned, this data will result in the creation of 14 age-specific averaged myelin maps, providing the first quantitative description of myelin maturation in vivo. Relationships between these myelin measures and cognition will be investigated through comparison with the cognitive assessments of motor coordination, language and visual reception, providing new insight into how the brain normally develops and which brain regions are involved at each stage.

Public Health Relevance

Relevance: Elucidation of healthy brain and cognitive development is crucial not only for identifying and improving our understanding of relevant deficits associated with psychiatric and mental health disorders, but also as guidance in ongoing social and educational policies. Without robust and detailed knowledge of how the brain typically develops, it is impossible to determine when and where abnormalities associated with psychiatric illness present, and how these abnormalities evolve over time to become frank disorder. Within the healthy population, converging evidence suggests there are limited developmental windows over which new skills, such as a second language, may be optimally learned. With improved knowledge of how and when these systems develop, more fine-tuned and effective educational policies may be put into place.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1-ERB-L (06))
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Rossi, Andrew
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Brown University
Schools of Engineering
United States
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Remer, Justin; Croteau-Chonka, Elise; Dean 3rd, Douglas C et al. (2017) Quantifying cortical development in typically developing toddlers and young children, 1-6 years of age. Neuroimage 153:246-261
Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T et al. (2016) White matter maturation profiles through early childhood predict general cognitive ability. Brain Struct Funct 221:1189-203
Dean 3rd, Douglas C; O'Muircheartaigh, Jonathan; Dirks, Holly et al. (2016) Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging. Neuroimage 132:225-237
Croteau-Chonka, Elise C; Dean 3rd, Douglas C; Remer, Justin et al. (2016) Examining the relationships between cortical maturation and white matter myelination throughout early childhood. Neuroimage 125:413-421
Dean 3rd, Douglas C; O'Muircheartaigh, Jonathan; Dirks, Holly et al. (2015) Characterizing longitudinal white matter development during early childhood. Brain Struct Funct 220:1921-33
Deoni, Sean C L; Dean 3rd, Douglas C; Remer, Justin et al. (2015) Cortical maturation and myelination in healthy toddlers and young children. Neuroimage 115:147-61
Dean 3rd, Douglas C; O'Muircheartaigh, Jonathan; Dirks, Holly et al. (2015) Estimating the age of healthy infants from quantitative myelin water fraction maps. Hum Brain Mapp 36:1233-44
Deoni, Sean C L; Kolind, Shannon H (2015) Investigating the stability of mcDESPOT myelin water fraction values derived using a stochastic region contraction approach. Magn Reson Med 73:161-9
Dean 3rd, Douglas C; Dirks, Holly; O'Muircheartaigh, Jonathan et al. (2014) Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep. Pediatr Radiol 44:64-72
Dean 3rd, Douglas C; Jerskey, Beth A; Chen, Kewei et al. (2014) Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA Neurol 71:11-22

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