Healthy aging is accompanied by disruptions in the functional modular organization of the human brain. Cross-sectional studies have shown age-related reductions in the functional segregation and distinctiveness of brain networks. However, less is known about the longitudinal changes in brain functional modular organization and their associations with aging-related cognitive decline. We examined age-and aging-related changes in functional architecture of the cerebral cortex using a dataset comprising a cross-sectional healthy young cohort of 57 individuals (mean Ϯ SD age, 23.71 Ϯ 3.61 years, 22 males) and a longitudinal healthy elderly cohort of 72 individuals (mean Ϯ baseline age, 68.22 Ϯ 5.80 years, 39 males) with 2-3 time points (18-24 months apart) of task-free fMRI data. We found both cross-sectional (elderly vs young) and longitudinal (in elderly) global decreases in network segregation (decreased local efficiency), integration (decreased global efficiency), and module distinctiveness (increased participation coefficient and decreased system segregation). At the modular level, whereas cross-sectional analyses revealed higher participation coefficient across all modules in the elderly compared with young participants, longitudinal analyses revealed focal longitudinal participation coefficient increases in three higherorder cognitive modules: control network, default mode network, and salience/ventral attention network. Cross-sectionally, elderly participants also showed worse attention performance with lower local efficiency and higher mean participation coefficient, and worse global cognitive performance with higher participation coefficient in the dorsal attention/control network. These findings suggest that healthy aging is associated with whole-brain connectome-wide changes in the functional modular organization of the brain, accompanied by loss of functional segregation, particularly in higher-order cognitive networks.

The insula and the anterior cingulate cortex are core brain regions that anchor the salience network, one of several large-scale intrinsic functional connectivity networks that have been derived consistently using resting-state functional magnetic resonance imaging (fMRI). While several studies have shown that the insula and anterior cingulate cortex play important roles in interoceptive awareness, no study to date has examined the association between intrinsic salience network connectivity and interoceptive awareness. In this study, we sought to test this idea in 26 healthy young participants who underwent a resting-state fMRI scan and a heartbeat counting task outside the scanner in the same session. Greater salience network connectivity in the posterior insula (but not the anterior cingulate cortex) using independent component analysis correlated with higher accuracy in the heartbeat counting task. Furthermore, using seed-based approach, greater interoceptive accuracy was associated with greater intrinsic connectivity of all insular functional subdivisions to salience network regions, including the anterior insula, orbitofrontal cortex, ventral striatum and midbrain. These associations remained after correcting for voxel-wise grey matter volumes. The findings underscore the critical role of insular salience network intrinsic connectivity in interoceptive awareness and pave the way for future investigations into how salience network dysconnectivity affects interoceptive awareness in brain disorders.

Little is known about the interaction between Alzheimer’s disease and cerebrovascular disease with respect to network degeneration. Chong et al. demonstrate differential functional and structural network changes in patients with Alzheimer’s disease with and without cerebrovascular disease, suggesting that the two groups may have different underlying pathologies.