Early functional organization of the anterior and posterior hippocampus in the fetal brain

The hippocampus, in both children and adults, has shown functional specialization along its long axis, with the anterior region associated with emotional processing and the posterior region with spatial memory and navigation. This specialization is also reflected in separate patterns of functional connectivity, but it is unclear whether it is present before birth. Here, we collected resting-state fMRI data in 51 healthy third-trimester fetuses to examine long-axis functional specialization in utero. Using structural regions of interest in the anterior and posterior hippocampus, a seed-based connectivity analysis was performed. We identified distinct networks of functional organization for the anterior and posterior hippocampus. These patterns showed spatial organization and anticorrelation consistent with long-axis specialization. While less mature than those observed in postnatal human and preclinical models, the fetal patterns suggest that the foundation for hippocampal functional differentiation supporting early affective and cognitive processing is already present before birth. Key points We used resting-state fMRI in the third trimester fetal brain to examine the functional projections of the anterior and posterior hippocampus. We identified distinct networks of functional organization that were independently related to the anterior and posterior hippocampus. The groundwork for the specificity of the hippocampus is being laid in utero, with functional anticorrelation contributing to the separation between long-axis segments.