White matter development and neurodevelopmental abnormalities

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dc.contributor.advisorBray, Signe L.
dc.contributor.authorDimond, Dennis Louis
dc.contributor.committeememberLebel, Catherine A.
dc.contributor.committeememberSears, Christopher R.
dc.contributor.committeememberSilk, Timothy J.
dc.contributor.committeememberDunn, Jeff F.
dc.date2020-11
dc.date.accessioned2020-04-24T18:24:47Z
dc.date.available2020-04-24T18:24:47Z
dc.date.issued2020-04-23
dc.description.abstractWhite 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.en_US
dc.identifier.citationDimond, D. L. (2020). White matter development and neurodevelopmental abnormalities (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37718
dc.identifier.urihttp://hdl.handle.net/1880/111880
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectMagnetic resonance imagingen_US
dc.subjectWhite matteren_US
dc.subjectAutism Spectrum Disorderen_US
dc.subjectEarly childhooden_US
dc.subject.classificationNeuroscienceen_US
dc.subject.classificationHuman Developmenten_US
dc.subject.classificationPsychology--Behavioralen_US
dc.titleWhite matter development and neurodevelopmental abnormalitiesen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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