Quantifying the Timing of Gyral and Sulcal Formation Relative to Growth in the Ferret Cerebral Cortex

Mounting evidence indicates that the cerebral cortical folding pattern conveys information relevant to brain function, as well as the developmental trajectory, leading to the observed pattern at maturity. However, relatively little is known about the biomechanics of gyral and sulcal formation. Ferrets are a tractable animal model for studying folding, in which this process occurs over the first 40 days of postnatal life. Recently, high-resolution magnetic resonance brain imaging data have been made available for a template representing 10 ferrets (5 male, 5 female) at 6 equally spaced time points ranging from postnatal days (P)8 to P38.

For each hemisphere, cerebral cortex surface models representing the template brain at each of the six ages were registered to one another using the anatomical multimodal surface matching (aMSM) algorithm. Local cerebral cortical curvature was determined at each surface vertex at each developmental age, and the T2-weighted images were used to determine cortical thickness at each surface vertex. Relative surface area expansion between pairs of time points was also mapped onto each surface vertex. Systematic comparisons were performed between cortical growth and changes in curvature that accompany gyral and sulcal formation. The sequence of changes of these anatomical characteristics was delineated during folding.

The cerebral cortex transitions between two patterns of regionally varying cortical thickness. In early stages of gyral and sulcal formation, the cortex is relatively thick in regions destined to exhibit high magnitudes of surface curvature (folding), regardless of whether the region will become part of a gyrus or a sulcus. In the mature brain, a different regional pattern of thickness is achieved in which gyral cortex is thicker than sulcal cortex. Surface area expansion is also observed to relate to folding, as reflected in the regional pattern of surface curvature changes. Over a given developmental interval, changes in surface curvature are positively correlated with subsequent surface area expansion but negatively correlated with previous surface area expansion.

These comparisons lay out a sequence of growth and folding events. First, relative thickening of the cortex occurs in regions that will be gyral and sulcal at maturity. These regions undergo increases in curvature, facilitating surface area increases in the folded cortex. During the final phases of fold formation, the rate of thickness increase in gyri outpaces that in sulci.