Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

Abstract

As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life.

Structural covariance across the lifespan: Brain development and aging through the lens of inter‐network relationships

“…visual and posterior DMN). These findings are consistent with previous work showing decreased DMN integrity within aging (Andrews-Hanna et al, 2007; Siman-Tov et al, 2016), and increased isolation of frontal from other structures without reduced integrity of homotopic frontal communication (Chen et al, 2011). More generally, these results for middle and older adulthood add to functional evidence that aging is marked by desegregation—i.e.…”

“…More generally, these results for middle and older adulthood add to functional evidence that aging is marked by desegregation—i.e. a decrease in specific network coupling and an increase in inter-network communication (Chan et al, 2014; Chen et al, 2011; Siman-Tov et al, 2016). These findings extend results in functional MRI studies on aging, which suggest that the shift from intra- to inter-network communication reflects de-specialization of function within brain areas and a resulting compensatory inter-network “cross-talk” to support regions with degraded functions (Brier et al, 2014; Chan et al, 2014).…”

Evaluation of the spatial variability in the major resting‐state networks across human brain functional atlases

“…Functionally, RSNs can be divided into those involved in internally guided, higher order mental functions (default‐mode [DMN], central executive [CEN], and salience [SAL] networks) and those supporting externally driven, specialized sensory and motor processing (visual [VIS] and sensorimotor [SMN] networks) (Damoiseaux et al, ; Doucet et al, ; Smith et al, ). Examination of RSNs in healthy populations has been instrumental in identifying processes involved in brain development (Gu et al, ) and aging (Ferreira et al, ; Shaw, Schultz, Sperling, & Hedden, ; Siman‐Tov et al, ) while investigation of RSNs in clinical samples has yielded new insights in disease mechanisms (Dong, Wang, Chang, Luo, & Yao, ; Doucet, Moser, Luber, Leibu, & Frangou, ; Lee, Doucet, Leibu, & Frangou, ; Repovs, Csernansky, & Barch, ).…”

Functional and effective reorganization of the aging brain during unimanual and bimanual hand movements

“…With an ever‐increasing aging society (Krueger et al, ), identifying the neural correlates underpinning the deterioration of motor control has become a primary focus of research (Song et al, ; Tomasi & Volkow, ). Early studies highlighted age‐related structural atrophy and aberrant functional activity in primary and secondary motor areas (Calautti, Serrati, & Baron, ; Mattay et al, ; Sullivan, Rohlfing, & Pfefferbaum, ; Ward, Swayne, & Newton, ), while more recent accounts have selectively focused on altered communication in functional brain networks involved in sensory and cognitive functions (Fujiyama et al, ; King et al, ; Park, Boudrias, Rossiter, & Ward, ; Siman‐Tov et al, ). Despite these quantitative reports, a neurobiological framework consolidating whole‐brain functional connectivity and directionality of information flow within macroscale cortical networks recruited during unimanual and bimanual movements remains to be established in healthy aging.…”

“…, while more recent accounts have selectively focused on altered communication in functional brain networks involved in sensory and cognitive functions (Fujiyama et al, 2016;King et al, 2017;Park, Boudrias, Rossiter, & Ward, 2012;Siman-Tov et al, 2016). Despite these quantitative reports, a neurobiological framework consolidating whole-brain functional connectivity and directionality of information flow within macroscale cortical networks recruited during unimanual and bimanual movements remains to be established in healthy aging.…”