In Vivo Quantification of White Matter Pathways in the Human Hippocampus

The hippocampus is a key structure in cognition. Although much research has focused on defining the functions of its anatomically distinct subfields, the communication among these subfields within the hippocampal circuit, supported by white matter pathways, is theoretically key to emergent cognitive function. Yet, hippocampal white matter connections in humans have not been fully explored in vivo. By leveraging diffusion-weighted imaging and a large healthy sample (N = 653), we developed a processing pipeline for in vivo quantification of human hippocampal pathways. We provided evidence for monosynaptic and trisynaptic pathway-related connections in humans, supporting the described hippocampal circuit in ex vivo and animal studies. In addition to hemispheric and sex differences, the individual variability in hippocampal pathways was linked to cognitive abilities. Thus, in vivo characterization of human hippocampal pathways highlights the individual differences within these structures and paves the way for their implications in cognition, aging, and diseases.