Fiber-tract development contributes to functional specialization in the human hippocampus

Abstract Fiber-tracts exhibit distinct projection patterns along the anterior–posterior axis of the hippocampus, promoting a specialization in function. This specialization becomes increasingly pronounced throughout child development, with important implications for neurocognitive outcomes. Developmental changes in fiber-tract properties, including intra-axonal cross-sectional area and myelin content, may contribute to this anterior-posterior functional specialization. To test this, we developed a diffusion-MRI tractography pipeline to identify hippocampal fiber-tracts in single subjects, then examined whether age-related differences in total intra-axonal cross-sectional area and myelin content (T1w/T2w) could predict functional specialization in a large cross-sectional sample (N=539, aged 5–21 years). With age, we found that the cross-sectional area of short-range medial-temporal tracts, which primarily target the anterior/body of the hippocampus, exhibited rapid growth. Concomitantly, the cross-sectional area of long-range occipito-parietal tracts, which primarily target the posterior hippocampus, exhibited a modest pruning. Increases in myelin content were relatively homogenous across fiber-tracts. In support of our hypothesis, we found that the cross-sectional area of fiber-tracts significantly predicts the surface-area of an fMRI-defined posterior system; a sensitive marker of functional specialization in the hippocampus. Tracts targeting early visual cortex (V2, V3, V4) showed the strongest association, with statistical modeling indicating a mediating effect of early-visual tract development on the relation between age and functional specialization. These findings provide evidence consistent with a mechanism whereby anatomical neurodevelopment contributes to functional specialization in the human hippocampus. Competing Interest Statement The authors have declared no competing interest. Footnotes Author email addresses: christine.tardif{at}mcgill.ca, sylvain.baillet{at}mcgill.ca, samantha.audrain{at}mcgill.ca, alexander.barnett{at}mcgill.ca, ying.he3{at}mcgill.ca, xiaoqian.chai{at}mcgill.ca Data availability Data necessary to re-create the primary results, including subject-level measures of fiber-tract cross-sectional area, fiber-tract myelin content, and functional-system surface areas, are included in [supplementary_data.csv]. Raw data are openly available, with permissions, from: [https://www.humanconnectome.org/study/hcp-lifespan-development/data-releases]