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bioRxiv · 10.64898/2026.10.15.759438

Distinct spatial organization of human hippocampal perfusion and microvascular pulsatility across age

Guo, F.·Kim, A. J.·Zhao, C.·Dong, T.·Liu, Z.·Yang, Z.·Jann, K.·Shao, X.·Jahanshad, N.·Mather, M.·Wang, D. J.
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Abstract

Arterial pulsation can modulate neuronal activity through mechanosensitive pathways in mice, but whether vascular pulsatility is similarly related to neural organization in humans remains unclear. Here, using 7T MRI in 35 young and older adults, we mapped cerebral perfusion and microvascular volumetric pulsatility index (mvPI) across the unfolded hippocampus and integrated these measures with histological, electrophysiological, and transcriptomic reference maps. Perfusion and mvPI exhibited distinct spatial organization and age-related differences. In young adults, perfusion preferentially corresponded to parvalbumin-interneuron density and beta/gamma distribution, whereas mvPI was associated with theta-band distribution. A number of associations detected in young adults were not detected in the older adults maps. Spectral simulations showed qualitative similarity to heartbeat-related phase resetting as one possible explanation for the mvPI-theta relationship, while spatial transcriptomics revealed perivascular enrichment of PIEZO2, a candidate mediator of vascular mechanotransduction. Together, these findings establish perfusion and tissue-level pulsatility as distinct dimensions of human hippocampal vascular organization and provide a framework for investigating their relationships with neural dynamics across aging.

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Guo, F., Kim, A. J., Zhao, C., Dong, T., Liu, Z., Yang, Z., Jann, K., Shao, X., Jahanshad, N., Mather, M., Wang, D. J.. 2026-10-21. Distinct spatial organization of human hippocampal perfusion and microvascular pulsatility across age. https://doi.org/10.64898/2026.10.15.759438

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