HUMAN CORTEX DEVELOPMENT - ESTIMATES OF NEURONAL NUMBERS INDICATE MAJOR LOSS LATE DURING GESTATION

This morphometric study explores temporal and topographic changes in t he estimated neuronal number in human neocortex during the latter half of gestation and early infancy. Neuronal estimates estimates are calc ulated from standardized measurements of cortical layer thickness and neuronal density in 6 neocortical regions in 9 human brains ranging fr om 17 weeks of. gestation to 13 weeks postnatally. Layer thickness inc reases linearly with age while the average neuronal density first incr eases, then reaches a maximum at 20 weeks of gestation, and progressiv ely declines. The sum of layer thickness times layer density estimates the number of neurons in a cortical column with a fixed surface area and a length that is equal to the cortical thickness. To derive an est imate of potentially overproduced neurons, the number of neurons in ea ch cortical column was corrected for surface growth and for cortex gyr ation. These data show that a large percent of cortical neurons presen t at 20 weeks of gestation are used to populate the expanding cortex. Nevertheless, the growth-corrected data suggest that a substantial ove rproduction and secondary reduction of cortical neurons takes place ma inly during the last quarter of gestation. The corrected mean number o f neurons reaches a maximum at 28 weeks of gestation and then declines by similar to 70% to achieve a stable number of neurons around birth. This estimated number of neurons is significantly higher at 28 to 32 weeks of gestation than at 17 to 20 gestational weeks and at 0 to 13 p ostnatal weeks. These data imply that physiologic neuronal death (apop tosis) may play a major role in early human cortex development.