Continuity and discontinuity in human cortical development and change from embryonic stages to old age

The human cerebral cortex is highly regionalized. We aimed to test whether principles of regionalization could be traced from embryonic development throughout the human lifespan. A data-driven fuzzy-clustering approach was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) over 1.5 years (n = 301, 4-12 years). First, the SA clusters were compared to patterns from embryonic cortical development. The earliest sign of cortical regionalization is the emergence of morphometric gradients in the cerebral vesicles, with a major gradient running along the anterior-posterior (AP) axis. We found that the principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the embryonic morphometric AP gradient. Second, embryonic factors showing a clear AP gradient were identified, and tests revealed significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT cluster showed distinguishable lifespan trajectories in a larger longitudinal dataset (4-88 years, 1633 observations). This means that regions that developed together also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample, but otherwise regionalized CT development adhered more to the genetic boundaries. Finally, SA and CT clusters showed differential relationships to cognitive functions. In sum, the results suggest that development of cortical regionalization is a continuous process from the embryonic stage throughout human life.\n\nSignificance statement (120 words)The protomap and the radial unit theories of brain development have shown that graded expression patterns of several factors are responsible for shaping the ultimately highly partitioned and specialized neocortical landscape. The present study shows that the major anterior-posterior gradient of embryonic development can be detected in the regional cortical expansion profiles of children. The study further demonstrates that brain regions that develop together during childhood also tend to change together throughout the lifespan. This suggests that regional cortical development is a continuous process through the entire life, and that early-life factors have life-long impacts on this process.