Abstract
The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.
Highlights
The default mode network (DMN) is a widely studied, readily replicated neural network that has been implicated in a wide range of disorders affecting cognition, including neurological disorders, psychiatric disorders, and developmental disorders
The Laird meta-analytic connectivity model (MACM) model did not fit any of the individual age groups with acceptable levels of fit based on RMSEA, though it provided a reasonable fit of the entire subject pool as a whole (Tables 4, 5)
This study demonstrates progressive, bidirectional functional connectivity changes within the DMN in healthy aging, using Structural equation modeling (SEM) to quantify per-decade path coefficients
Summary
MotivationThe default mode network (DMN) is a widely studied, readily replicated neural network that has been implicated in a wide range of disorders affecting cognition, including neurological disorders (temporal lobe epilepsy, Ji et al, 2013; Parkinson’s disease, Liu et al, 2013), psychiatric disorders (schizophrenia, Garrity et al, 2007; depression, Sheline et al, 2009), and developmental disorders (autism, Kennedy et al, 2006). The precuneus (Volkow et al, 2002) and posterior cingulate cortex (Minoshima et al, 1997; Johnson et al, 1998), two key hubs in the DMN, show significantly decreased cerebral glucose metabolism and blood flow and significantly increased variability in metabolic activity in patients with Alzheimer’s disease. The DMN has been demonstrated to have unique metabolic characteristics, with a much higher rate of non-oxidative glucose consumption than other brain regions and networks (Vlassenko et al, 2010) This metabolic profile likely is due to the high tonic neural activity levels in the DMN and likely underlies its susceptibility to pathology (Sperling et al, 2009; Villain et al, 2010). Core areas of the DMN, including the posterior cingulate cortex, inferior parietal lobules, and medial temporal lobes, have been shown to be involved in scene construction of past and fictitious events (Hassabis et al, 2007; Kim, 2012; Andrews-Hanna et al, 2014)
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