Decreased segregation of brain systems across the healthy adult lifespan

Abstract

Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age.

Keywords: aging; brain networks; connectome; memory; resting-state correlations.

Fig. 1.

Network nodes are defined using putative area centers from RSFC-boundary mapping and labeled by RSFC systems. (A) RSFC-boundary mapping (37) parcellation map depicts the probability of RSFC pattern transitions across the cortical surface. (B) The local minima of the parcellation map were identified, and 3-mm–radius disks were created around these positions to represent the locations of putative area centers along the cortical surface. Disks served as network nodes (n = 441). (C) RSFC systems defined by Power et al. (19). (D) Surface disks labeled by RSFC system membership.

Fig. 2.

Increasing adult age is associated with decreasing segregation of brain systems. (A) Mean within-system RSFC decreases with age, and mean between-system RSFC increases with age. (B) Mean node-to-node correlation matrix (10 systems) of each age cohort. Nodes are grouped according to system labeling (Fig. 1D); color bars along axes represent system labels (see legend to the right). Within-system RSFC (on matrix-diagonal) exhibits decreasing strength across cohorts, whereas between-system RSFC (off matrix-diagonal) exhibits increasing strength across cohorts. The latter pattern is apparent particularly for a subset of between-system relationships. For example, RSFCs of the frontal–parietal control or the ventral attention system (highlighted with a white box) with other brain systems (e.g., default system; white arrows) are increasingly greater (yellow/orange colors) from younger to older adult cohorts. (C) Mean system segregation decreases with age, reflecting proportionally greater between-system correlations relative to within-system correlations. (D) Mean network participation coefficient exhibits an age-associated increase, supporting observations related to system segregation. For each scatterplot, a line reflecting the linear regression between age and the dependent variable is depicted.

Fig. 3.

Sensory-motor and association systems exhibit distinct patterns of age-associated differences in segregation. Locally weighted scatterplot smoothing (LOESS) graphs depict (A) the linear association between decreasing sensory-motor system segregation and increasing age and (B) the quadratic association between decreasing association system segregation and increasing age. Decreases in association system segregation exhibit an inflection point reflecting accelerated reductions starting at an approximate age of 50 y (red dotted line). (C) Spring-embedded layouts of the 10 systems (4% edge density) of the four cohorts’ mean correlation matrices (Fig. 2B). Sensory-motor systems exhibit progressive age-accompanied reductions in both within-system correlations and segregation with other systems (e.g., the visual system, highlighted by the arrows). Association systems exhibit prominent and sudden decreases in segregation with other systems starting in middle-late adulthood [e.g., the frontal–parietal control (in yellow) and cingulo-opercular control systems (in purple) exhibit less within-system connectivity and greater between-system connectivity in middle late and older adult cohorts, highlighted by the circle].

Fig. 4.

Greater association system segregation is associated with superior long-term episodic memory, independent of age. (A) Episodic memory scores are predicted by participants’ association system segregation. Data points are color coded by participants’ age cohort to demonstrate that the relationship between memory and association system segregation is independent of age. (B) Relationship between episodic memory and segregation of association systems from other association systems and (C) segregation of association systems from sensory-motor systems. For each scatterplot, a line reflecting the linear regression between episodic memory scores and system segregation is depicted.