GYRIFICATION DURING EARLY HUMAN FETAL BRAIN DEVELOPMENT

Our study provides the first detailed analysis of the initial morphogenetic events leading to the formation of permanent neocortical sulci during early human brain development. We analyzed 56 fetal brain autopsies from 9 to 28 gestational weeks (GW). Seventeen specimens were processed for serial coronal sectioning (10 µm thickness), while thirty-nine underwent macroscopic anatomical examination. We characterized the emerging gyrification patterns and identified two distinct types of primary neocortical folds: whole-wall hemispheric folds and cortical plate folds. Before 11GW, neocortical folding appeared irregular. By 11GW, the Sylvian fissure and the olfactory sulcus were consistently identifiable; the lunate sulcus was present in one-third of the cases. Folds were observed in both the anterior and posterior regions of the medial hemispheric surface, with up to three transient folds identifiable in the anterior part of the medial wall. From 12GW onward, the calcarine and parieto-occipital sulci became regularly apparent on the posteromedial surface. These folds exhibited a characteristic, statistically significant thinning at their fundi. A significant finding was the transient smoothing of specific sulci by 18–20GW. After 20GW, a consistent sequence of sulcal emergence was observed, including the parieto-occipital, cingulate, central, superior frontal, superior temporal, precentral, and postcentral sulci, among others. Notably, the calcarine sulcus displayed smoothing later than other sulci, at 23–24GW, and was consistently present thereafter. Our findings demonstrate that neocortical folding commences earlier than traditionally accepted and follows predictable, organized patterns with distinct histological signatures. The discovery of transient smoothing reveals a dynamic, non-linear process of gyrification.