Lifespan trajectory of claustrum volume in humans – effect of age, hemisphere, and sex, and association with cognitive performance

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 Alzheimer's disease, on claustrum function and structure, it is poorly understood how non-pathologic biological conditions effect the claustrum. This study aimed to investigate the lifespan trajectory of claustrum volumes including the effect of age, hemisphere, and sex and the association with cognitive performance. We used T1-weighted 3 Tesla MRI scans of 3474 healthy participants aged 1 to 80 years, using deep learning-based automated claustrum segmentation, and normative modeling to delineate lifespan trajectories of claustrum volumes for both hemispheres and sexes. Ordinary least squares regression analyses were applied to further characterize age, hemisphere, and sex effects. Cognitive performance scores were linked to claustrum volume using multiple linear regression analyses. Lifespan analysis revealed a trajectory of rapid claustrum volume increase from infancy to adolescence (∼1-15 years), a plateau phase from early to middle adulthood (∼15-40 years), and a subsequent decline from middle adulthood to old age (∼40-80 years). The right claustrum was on average larger than the left one across all ages. Overall, females had larger total intracranial volume-adjusted claustrum volumes than males across the lifespan. Claustrum volumes were associated with total cognition and attention scores in individuals from 8 to 65 years. Results demonstrate a distinct effect of age, hemisphere, and sex on claustrum volume as well as its association with general cognitive performance and attention. Data provide a comprehensive framework for claustrum lifespan trajectories relevant for studying claustrum alterations in neurodevelopmental and neurodegenerative disorders.