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Development of human brain connectivity in health and disease


White matter development in the human brain undergoes a uniquely extended developmental trajectory, and the maturation of this complex network of connections is broadly relatable to real-world measures of cognitive ability. We begin this dissertation with a review of the literature on structural brain development, in order to provide a useful background layer for our discussion (Chapter 1). Next, we report a case study investigating white matter abnormalities in the context of prenatal methamphetamine exposure, and their cognitive correlates (Chapter 2). Then we describe our successfully-funded NIH grant proposal to 1) develop novel image analysis techniques for investigating white matter connectivity, and 2) apply them to the study of a) typical frontal lobe white matter maturation, b) its relation to executive functioning, and c) how these processes are affected by prenatal alcohol exposure (Chapter 3). The results of this effort are described in Chapter 4, Chapter 5, and Chapter 6. Finally, we supplement the work on our UCLA cohort with exciting results from two large, multi-site, collaborative efforts: 1) ADHD-200, an initiative to employ brain mapping findings in a machine learning environment for the diagnostic classification of individual subjects with attention deficit hyperactivity disorder (ADHD) (Chapter 7), and 2) PING (the Pediatric Imaging, Neurocognition, and Genetics study), where we are leading an effort to provide the most comprehensive mapping to-date of typical white matter development (Chapter 8).

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