Structural Heterogeneity in Neuronal Aging: Insights From Micro and Macro Structural Neuroimaging

Neuroimaging research is making unprecedented gains towards a better understanding of what constitutes healthy brain structure and function in aging. Decades, if not centuries, of ex vivo histological work have demonstrated the complexity of cytoarchitectural and myeloarchitectural underpinnings of neuronal organization that we are only beginning to investigate in the living brain. With advancing techniques, we can now investigate in vivo estimates quantifying biological proxies of structural brain health. The current studies aimed to capitalize on both our histological understanding of the architectural features defining brain structure, and modern neuroimaging estimates of structural health, to expand upon our understanding of the processes involved in nominal brain aging. In a healthy lifespan sample of adults, we acquired multiple neuroimaging sequences designed to characterize the health of gray and white matter tissue compartments. By mapping these estimates to a cytoarchitecturally defined brain atlas we were able to 1) examine the regional differentiation of the coupling of gray matter morphometry and health proxies from the neighboring white matter most likely to innervate these regions and 2) investigate the age-related associations between estimates of neurite health and organization within the gray matter of specific cortical types. We found that there were regionally distinct patterns of association that generally pointed to an age-related vulnerability of structure in higher-order cognitive centers. These regions demonstrated greater coupling in morphometry with neighboring white matter health proxies, as well as elevated organizational heterogeneity within these cortical types. Our results demonstrate that aging trajectories in brain structure follow specific patterns that map on to several key theories posited in prior research such as retrogenesis, phylogenetic, or ontogenetic precedence. However, these findings provide novel evidence emphasizing the importance of myelin content and plasticity as well as the role of glia, specifically oligodendrocyte function, and the high cost of brain maintenance, prompting further investigation of additional conceptualizations of structural brain aging.