White matter development and neurodevelopmental abnormalities
Date
2020-04-23
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Abstract
White matter undergoes profound growth over the course of neurodevelopment, with maturational changes in properties such as axon orientation dispersion, axon/neurite density, and the cross-sectional diameter of axon fiber bundles. These changes are believed to be important for cognitive-behavioral maturation. Such maturation is particularly rapid during early childhood, though how specific white matter properties develop during this period is unclear. Early childhood is also a period wherein symptoms of neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), become more prominent. Atypical white matter maturation is theorized to contribute to cognitive-behavioral deficits in ASD at later stages of development, though determining the specific structural properties and anatomical location of abnormalities has been challenging. The overall goal of this thesis was to characterize developmental trajectories of specific white matter properties during early childhood and determine if these properties are abnormal in ASD and underlie core behavioral deficits. To achieve this goal, I conducted two studies in children ages 4-8 years investigating developmental changes in 1) axonal orientation dispersion and neurite density, and 2) axon density and fiber bundle cross-sectional size. Building off these studies, I then investigated abnormalities in axon density and fiber cross-section in adolescents-adults with ASD and explored their relation to social difficulties. I found that metrics sensitive to neurite/axon density and fiber cross-section, but not axon orientation dispersion increased profoundly in most fiber bundles during early childhood. Some overlapping temporospatial maturation trends were observed across metrics, though each followed relatively unique trajectories. A metric sensitive to axon density was reduced globally and in specific fiber bundles in ASD; more severe reductions in the major interhemispheric tract of the brain predicted greater social difficulties. Findings from this thesis suggest that early childhood is an important period for axon/neurite density and tract macrostructural growth, with heterochronous change in these properties. Findings in ASD suggest maturation of axon density may go astray prior to adolescence – potentially in early childhood, infancy or fetal development – and contribute to behavioral deficits. This evidence has broad implications to understanding typical and atypical white matter development and how changes in specific structural features contribute to cognitive-behavioral maturation.
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Keywords
Magnetic resonance imaging, White matter, Autism Spectrum Disorder, Early childhood
Citation
Dimond, D. L. (2020). White matter development and neurodevelopmental abnormalities (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.