Claustrum volume in human lifespan trajectory and effect of age, hemisphere, and sex

Ayyildiz, S.; Neubauer, A.; Thalhammer, M.; Li, H. B.; Wendt, J.; Menegaux, A.; Hippen, R.; Schmitz-Koep, B.; Schinz, D.; Zimmer, C.; Ayyildiz, B.; Ors, A.; Bamac, B.; Hedderich, D.; Sorg, C.

doi:10.1101/2025.09.09.675215

bioRxiv · 10.1101/2025.09.09.675215

Claustrum volume in human lifespan trajectory and effect of age, hemisphere, and sex

Ayyildiz, S.·Neubauer, A.·Thalhammer, M.·Li, H. B.·Wendt, J.·Menegaux, A.·Hippen, R.·Schmitz-Koep, B.·Schinz, D.·Zimmer, C.·Ayyildiz, B.·Ors, A.·Bamac, B.·Hedderich, D.·Sorg, C.

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Abstract

The human claustrum is a bilateral, thin, irregularly shaped gray matter structure located between the striatum and insula. While previous research demonstrated the effect of distinct medical conditions, such as prematurity, schizophrenia, and Alzheimers disease, on claustrum function and structure, it is poorly understood how non-pathologic biological conditions effect the claustrum. This study aimed to investigate the effect of age, hemisphere, and sex on claustrum volume. We used T1-weighted 3 Tesla MRI scans of 3,474 healthy participants ranging from 1 to 80 years of age, deep learning-based automated claustrum segmentation, and a normative modeling approach to delineate lifespan trajectories of claustrum volumes for both hemispheres and sexes. Additionally, ordinary least squares regression analyses were applied to further characterize age, hemisphere, and sex effect. Lifespan analysis revealed a trajectory of rapid claustrum volume increase from infancy to adolescence ([~] 1-15 years, annual growth 39.300 mm3/year), a plateau phase from early to middle adulthood ([~] 15-40 years, annual change 0.153 mm3/year), and a subsequent decline from middle adulthood to old age ([~] 40-80 years, annual decrease 10.325 mm3/year). The right claustrum was on average larger than the left one across all ages. Finally, overall, females had larger total intracranial volume-adjusted claustrum volumes than males across the lifespan. Results demonstrate a distinct effect of age, hemisphere, and sex on claustrum volume. Data provide a comprehensive framework for sex- and hemisphere-sensitive claustrum structure lifespan trajectories relevant for studying neurodevelopmental and neurodegenerative effects on the claustrum.

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Ayyildiz, S., Neubauer, A., Thalhammer, M., Li, H. B., Wendt, J., Menegaux, A., Hippen, R., Schmitz-Koep, B., Schinz, D., Zimmer, C., Ayyildiz, B., Ors, A., Bamac, B., Hedderich, D., Sorg, C.. 2025-09-15. Claustrum volume in human lifespan trajectory and effect of age, hemisphere, and sex. https://doi.org/10.1101/2025.09.09.675215

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