Developmental characteristics of spontaneous activity and functional connectivity in the fetal brain

Abstract Investigating the developmental characteristics of fetal brain functional activity and connectivity is crucial for understanding normal developmental trajectories and enabling early detection and prevention of potential disorders. We comprehensively explored the brain functional developmental characteristics of 82 normal fetuses. We integrated multiple functional magnetic resonance imaging indicators, including amplitude of low-frequency fluctuations, seed-based functional connectivity (FC), and graph theory, and constructed correlation models to examine their relationship with fetal gestational age. As the fetal gestational age increased, spontaneous brain activity decreased in the bilateral thalamus and increased in the bilateral anterior cingulate cortex (ACC). FC between the bilateral thalamus and the left precuneus, superior parietal gyrus, postcentral gyrus, cuneus, superior occipital gyrus, and supplementary motor area also decreased. Furthermore, the degree centrality of the right thalamus increased, and thalamic FC development showed rightward asymmetry. However, ACC-based FC and fetal gestational age were not significantly correlated. This study delineates the developmental characteristics of normal fetal brain functional activity and connectivity from three interrelated and complementary dimensions: local activity intensity, inter-regional coordination, and global network organization. Developmental patterns of spontaneous brain activity and network connectivity in the fetal thalamus and ACC were observed, highlighting thalamic rightward asymmetric development.