Contributions of short- and long-range white matter tracts in dynamic compensation with aging.

Optimal brain function is shaped by a combination of global information integration, facilitated by long-range connections, and local processing, which relies on short-range connections and underlying biological factors. With aging, anatomical connectivity undergoes significant deterioration, which affects the brain's overall function. Despite the structural loss, previous research has shown that normative patterns of functions remain intact across the lifespan, defined as the compensatory mechanism of the aging brain. However, the crucial components in guiding the compensatory preservation of the dynamical complexity and the underlying mechanisms remain uncovered. Moreover, it remains largely unknown how the brain readjusts its biological parameters to maintain optimal brain dynamics with age; in this work, we provide a parsimonious mechanism using a whole-brain generative model to uncover the role of sub-communities comprised of short-range and long-range connectivity in driving the dynamic compensation process in the aging brain. We utilize two neuroimaging datasets to demonstrate how short- and long-range white matter tracts affect compensatory mechanisms. We unveil their modulation of intrinsic global scaling parameters, such as global coupling strength and conduction delay, via a personalized large-scale brain model. Our key finding suggests that short-range tracts predominantly amplify global coupling strength with age, potentially representing an epiphenomenon of the compensatory mechanism. This mechanistically explains the significance of short-range connections in compensating for the major loss of long-range connections during aging. This insight could help identify alternative avenues to address aging-related diseases where long-range connections are significantly deteriorated.