Aberrant allometric scaling of cortical folding in preterm-born adults

A universal allometric scaling law has been proposed to describe cortical folding of the mammalian brain as a function of the product of cortical surface area and the square root of cortical thickness across different mammalian species including humans. Since these cortical properties are vulnerable to developmental disturbances caused by preterm birth in humans, and since these alterations are related to cognitive impairments, we tested (i) whether cortical folding in preterm-born adults follows this cortical scaling law, and (ii) the functional relevance of potential scaling aberrances. We analyzed the cortical scaling relationship in a large and prospectively collected cohort of 91 very premature-born (<32 weeks of gestation and/or birthweight <1500 g, VP/VLBW) adults and 105 full-term (FT) controls at 26 years of age based on total surface area, exposed surface area, and average cortical thickness measured with structural magnetic resonance imaging and surface-based morphometry. We found that the slope of the log-transformed cortical scaling relationship was significantly altered in VP/VLBW adults (VP/VLBW: 1.24, FT: 1.14, p = 0.018). More specifically, the slope was significantly altered in male VP/VLBW adults (VP/VLBW: 1.24, FT: 1.00, p = 0.031), while there was no significant difference in the slope of female VP/VLBW adults (VP/VLBW: 1.27, FT: 1.12, p = 0.225). Furthermore, offset was significantly lower compared to FT controls in both male (VP/VLBW: -0.546, FT: -0.538, p = 0.001) and female VP/VLBW adults (VP/VLBW: -0.545, FT: -0.538, p = 0.023), indicating a systematic shift of the regression line after preterm birth. Gestational age had a significant effect on the slope in VP/VLBW adults, and more specifically in male VP/VLBW adults, indicating that the difference in slope is specifically related to preterm birth. The shape or tension term of the scaling law had no significant effect on cognitive performance while the size of the cortex did. Results demonstrate altered scaling of cortical surface and cortical thickness in very premature-born adults. Data suggest altered mechanical forces acting on the cortex after preterm birth