Short superficial white matter and aging: a longitudinal multi-site study of 1,293 subjects and 2,711 sessions

Abstract

It is estimated that short association fibers, or 'U-shaped' fibers running immediately beneath the cortex, may make up as much as 60% of the total white matter volume. However, these have been understudied relative to the long-range association, projection, and commissural fibers of the brain. This is largely because of limitations of diffusion MRI fiber tractography, which is the primary methodology used to non-invasively study the white matter connections. Inspired by recent anatomical considerations and methodological improvements in U-fiber tractography, we aim to characterize changes in these fiber systems in cognitively normal aging, which provide insight into the biological foundation of age-related cognitive changes, and a better understanding of how age-related pathology differs from healthy aging. To do this, we used three large, longitudinal and cross-sectional datasets (N = 1293 subjects, 2711 sessions) to quantify microstructural features and length/volume features of several U-fiber systems. We find that axial, radial, and mean diffusivities show positive associations with age, while fractional anisotropy has negative associations with age in superficial white matter throughout the entire brain. These associations were most pronounced in the frontal, temporal, and temporoparietal regions. Moreover, measures of U-fiber volume and length decrease with age in a heterogenous manner across the brain, with prominent effects observed for pre- and post-central gyri. These features, and their variations with age, provide the background for characterizing normal aging, and, in combination with larger association pathways and gray matter microstructural features, may provide insight into fundamental mechanisms associated with aging and cognition.

Superficial white matter across the lifespan: volume, thickness, change, and relationship with cortical features

“…Finally, the rates decline in late aging, although at a much smaller magnitude. However, it is these declines that should be studied, both in terms of volumetric and microstructure-based features (Phillips et al, 2013; Phillips et al, 2016; Schilling et al, 2022b)), as they relate to normal and abnormal aging.…”

Imaging the structural connectome with hybrid diffusion MRI-microscopy tractography

“…For example, future work could use the hybrid method to study the superficial white matter short association fibres that connect neighbouring cortical regions with a U-shaped trajectory ("U-fibres") 66 . These fibres can be challenging to reconstruct using dMRI-data alone due to their highly curved appearance and close proximity to the grey matter 67,68 . However, superficial fibres are often clearly visible within myelin-sensitive microscopy data 69 .…”