Synchronous Changes of Cortical Thickness and Corresponding White Matter Microstructure During Brain Development...

Cortical thickness (CT) changes during normal brain development is associated with complicated cellular and molecular processes including synaptic pruning and apoptosis. In parallel, the microstructural enhancement of developmental white matter (WM) axons with their neuronal bodies in the cerebral cortex has been widely reported with measurements of metrics derived from diffusion tensor imaging (DTI), especially fractional anisotropy (FA). We hypothesized that the changes of CT and microstructural enhancement of corresponding axons are highly interacted during development. DTI and T1-weighted images of 50 healthy children and adolescents between the ages of 7 and 25 years were acquired. With the parcellated cortical gyri transformed from T1-weighted images to DTI space as the tractography seeds, probabilistic tracking was performed to delineate the WM fibers traced from specific parcellated cortical regions. CT was measured at certain cortical regions and FA was measured from the WM fibers traced from same cortical regions. The CT of all frontal cortical gyri, including Brodmann areas 4, 6, 8, 9, 10, 11, 44, 45, 46, and 47, decreased significantly and heterogeneously; concurrently, significant, and heterogeneous increases of FA of WM traced from corresponding regions were found. We further revealed significant correlation between the slopes of the CT decrease and the slopes of corresponding WM FA increase in all frontal cortical gyri, suggesting coherent cortical pruning and corresponding WM microstructural enhancement. Such correlation was not found in cortical regions other than frontal cortex. The molecular and cellular mechanisms of these synchronous changes may be associated with overlapping signaling pathways of axonal guidance, synaptic pruning, neuronal apoptosis, and more prevalent interstitial neurons in the prefrontal cortex. Revealing the coherence of cortical and WM structural changes during development may open a new window for understanding the underlying mechanisms of developing brain circuits and structural abnormality associated with mental disorders.