THE DEVELOPMENT OF BRAIN STRUCTURE AND CONNECTIVITY

The human brain undergoes profound structural changes with development. It does not mature by simply growing, rather the transition to adulthood is a dynamic process with regionally specific patterns. However, there is no consensus on the timing and shape of growth trajectories of brain structures. In this thesis we capitalize on advances in multimodal MRI and use longitudinal study designs to map structural brain maturation and connectivity in typical and atypical children and adolescents. Our results showed that the cortex is thinning starting in early childhood. Cortical surface area on the other hand is expanding till mid-adolescence. The timing of these patterns differ per cortical region, thus each region has a unique developmental pattern that may provide important information on the timing of sensitive periods. The white matter wiring pattern shows a heterogeneous developmental pattern that mimics developmental changes observed for grey matter. These results indicate that the brain is structured and wired differently in childhood adolescence and again in adulthood. Studying the developmental pattern of different cortical dimensions may also help us better understand underlying mechanisms involved in developmental disorders. We showed that children with ADHD have smaller cortical surface area but relatively preserved cortical thickness. Another clinical group, adolescents at Ultra high risk for psychosis (UHR), showed developmental differences in surface area in addition to stable differences. This indicates that in children with ADHD early (perhaps even prenatally) mechanisms, important for cortical development, are affected as reflected in the stable reductions. In UHR individuals, on the other hand, mechanisms that affect developmental trajectories might be disturbed. The observed rapid changes in grey matter areas and white matter connections during childhood and adolescence and smaller changes in adulthood, suggest that over the course of development the brain shifts from a relatively malleable state into a more stable and efficient one. This thesis is a small step in unraveling the brain behavior relationship and may help us understand when the brain is most malleable and adaptive.