Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation

Abstract

The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors.SIGNIFICANCE STATEMENT Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18–88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability.

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

“…Most prominent alterations were increased correlations (e.g., DAN-MN) and decreased anticorrelations (e.g., DMN-SN) between networks in the transition from young to middle adulthood. Our observations strongly support accumulating evidence for enhanced communication between functional networks with aging (Chan et al, 2014; Geerligs et al, 2015; Turner and Spreng, 2015; Gallen et al, 2016; Spreng et al, 2016; Tsvetanov et al, 2016). Increased correlations and decreased anticorrelations between networks both reflect reduced selectivity and specificity in the brain’s intrinsic functional architecture.…”

Thalamic functional connectivity and its association with behavioral performance in older age

“…However, for this data set, resting‐state fluctuation amplitude (an index of vascular reactivity) did not show any regional age differences (data not presented here). Nonetheless, novel modeling methods such as generative modeling, which allows for the effects of neural connectivity to be separated from the hemodynamic component, have previously been demonstrated to be useful in studies of older adults (Tsvetanov et al., 2016) and should be considered as an alternative to the global removal method we utilized in this study. These factors remain complex methodological issues for the field of brain aging research that require further investigation.…”

Impact of early life adversity and tryptophan depletion on functional connectivity in menopausal women: A double-blind, placebo-controlled crossover study

“…High ACE participants displayed lower within-network connectivity in both the discovery and replication datasets. Connectivity within functional networks has been shown to underlie multiple cognitive domains including working memory (Dosenbach et al, 2007; Fair et al, 2007a; Power et al, 2010; Tsvetanov et al, 2016). Decrements in working memory are associated with lower connectivity within default and cingulo-opercular networks (Vaidya and Gordon, 2013).…”

“…There is growing evidence that the functional connectivity between brain regions as part of larger cognitive systems is critical to maintaining intact executive function (reviewed by Vaidya and Gordon, 2013). A recent large neuroimaging study in healthy adults ages 18–88 demonstrated that the degree of connectivity between and within large-scale brain networks becomes increasingly important to maintaining cognitive performance as we age (Tsvetanov et al, 2016). Additionally, altered neural connectivity has been suggested as a potential marker of menopausal women who may be at risk of late-life cognitive dysfunction (Vega et al, 2016).…”

“…In healthy adults, early life trauma is associated with decreased connectivity between regions within the same network as well as increased connectivity between regions in different networks (Philip et al, 2013). Such patterns of dysconnectivity are associated with poorer working memory across the lifespan (Tsvetanov et al, 2016). …”