Population-level age effects on the white matter structure subserving cognitive flexibility in the human brain

Abstract

AbstractCognitive flexibility, a cognition crucial for adaptive behavior, involves multi-scale functioning across several neuronal organization levels. While the neural underpinnings of flexibility have been studied for decades, limited knowledge exist about the structure and differentiation of the white matter subserving brain regions implicated in cognitive flexibility. Neural changes that occur over the lifespan have an impact in the brain’s white matter organization and, thereby, may alter cognitive flexibility abilities. This study investigates the population-level relationship between cognitive flexibility and macromolecular properties of white matter across two periods of adulthood, aiming to discern how these associations vary over different life stages and brain tracts. A novel method to study age-effects in the brain’s structure-function associations is proposed. First, the white matter structure implicated in cognitive flexibility was delineated by tracing in the Human Connectome Project tractography template the pathways subserving neural regions derived via meta-analysis of set-shifting. Then, a cohort analysis was performed to characterize related brain features using a subset of the UKBiobank MRI data which has a companion functional/behavioral dataset.1We found that (1)the wiring of cognitive flexibility is defined by specialized tracts, which present undifferentiated features early in adulthood, and significantly differentiated types in later life. (2)These MRI-derived properties are correlated with individual subprocesses of cognition which intimately relate to the latent construct of cognitive flexibility function (switch, inhibition, and updating).2(3)In late life, myelin-related homogeneity of specific white matter tracts implicated in cognitive flexibility declines as a function of chronological age—a phenomenon not observed in early life. Our findings support the age-related differentiation of white matter tracts implicated in cognitive flexibility as a natural substrate of brain adaptive function.Significance StatementCognitive flexibility, a cognition that facilitates adaptation to environmental demands, involves complex brain processes. During the lifespan, brain changes affecting the brain’s structural organization are theorized to impact cognitive flexibility. This study characterizes how the brain’s connectivity is correlated with cognitive flexibility throughout adulthood. By analyzing macromolecular properties of white matter, this study found that certain parts of the brain’s wiring related to cognitive flexibility become more distinct with advanced age. This age-related distinction of the wiring implicated in cognitive flexibility appears as a natural, underlying characteristic of the human brain which may impact specific aspects of thinking, like shifting between tasks or updating information.