From histology to macroscale function in the human amygdala

Auer, Hans; Benkarim, Oualid; Royer, Jessica; Valk, Sofie; Bernhardt, Boris C.; Wang, Yezhou; Paquola, Casey; Cabalo, Donna Gift; DeKraker, Jordan; Rodriguez-Cruces, Raul

doi:10.1101/2024.07.09.602743

Preprint

FZJ-2025-01524

From histology to macroscale function in the human amygdala

Auer, H. ; Cabalo, D. G. ; Rodriguez-Cruces, R. ; Benkarim, O. ; Paquola, C.FZJ* ; DeKraker, J. ; Wang, Y. ; Valk, S.FZJ* ; Bernhardt, B. C. ; Royer, J. (Corresponding author)

2024

[10.1101/2024.07.09.602743]

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Please use a persistent id in citations: doi:10.1101/2024.07.09.602743 doi:10.34734/FZJ-2025-01524

Abstract: The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post mortem histology and in vivo MRI at ultrahigh fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as medio-lateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.

Note: H.A. acknowledges funding from the Fonds de la Recherche du Québec – Nature et Technologie (FRQNT) Master’s Training Scholarship. D.G.C. acknowledges support from FRQ-Sante and Savoy Foundation. J.R. acknowledges support from CIHR. B.C.B. acknowledges support from NSERC, CIHR, SickKids Foundation, BrainCanada, Future Leaders Research Grant, Helmholtz International BigBrain Analytics and Learning Laboratory (HIBALL), Healthy Brains and Healthy Lives, FRQS, and the Canada Research Chairs program.

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