Disruption of Large-Scale Brain Systems in Advanced Aging

Abstract

Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition.

Development of large-scale functional networks over the lifespan

“…For the lower frequencies below 4 Hz we found evidence for a reduction of functional network size across the lifespan. This result fits well into the "disconnection hypothesis" (Geschwind, 1965) and is consistent with other results demonstrating a disruption of large-scale brain systems as measured by low-frequency fMRI correlations (Andrews-Hanna et al, 2007;Bai et al, 2008;Greicius et al, 2004;Rombouts et al, 2005;Sorg et al, 2007). For the 2-4 Hz frequency range, our results suggest a continuous change of functional connectivity across adulthood between 18 and 89 years rather than a rapid drop in older age.…”

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

“…As for the cluster in the left anterior intraparietal sulcus and its seed-related network, they best fitted one bilateral component comprising the intraparietal sulcus extending to the precuneus (goodness of fit: cluster = 1.60; network = 1.44, Figure 3 A). The intraparietal sulcus is a crucial part of the dorsal attention network, which supports goal-directed attention (Corbetta & Shulman, 2002;Fox, Corbetta, Snyder, Vincent, & Raichle, 2006) and is affected by aging (Andrews-Hanna et al, 2007). The templatematching provided two best-fits for this component: the limbic template, which includes the precuneus as the independent component, and the dorsal attention network (Figure 3 B), confirming that the latter is a good candidate (Supplemental Figure S2)" (p. 20).…”

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

“…The direct assessment of electrical brain activity and the adaptability of this experimental paradigm of neuroimaging of infraslow resting-state activity may provide a critical platform to probe mechanistic questions regarding the nature and function of infraslow activity in a manner that may synergistically complement concurrent ongoing fc-fMRI studies. Evidence suggesting that alterations in infraslow resting-state networks are associated with neurodegenerative disease processes has raised the potential of novel therapeutic biomarker identification 19,[64][65][66] . Our data and approach in combination with the availability of animal models of neurodegenerative and psychiatric disease and the use of novel optogenetic tools from which to probe circuit and brain function may effectively compliment human clinical setting investigations and aid in increasing our understanding of the underlying basis of these networks and their pathological regional network dysfunction.…”