Abstract
Recent studies have demonstrated that connector hubs, regions considered critical for the flow of information across neural systems, are mostly involved in neurodegenerative dementia. Considering that aging can significantly affect the brain’s intrinsic connectivity, identifying aging’s impact on these regions’ overall connection strength is important to differentiate changes associated with healthy aging from neurodegenerative disorders. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of 175 healthy volunteers aging from 21 to 86 years old, we computed an intrinsic connectivity contrast (ICC) metric, which quantifies a region’s overall connectivity strength, for whole brain, short-range, and long-range connections and examined age-related changes of this metric over the adult lifespan. We have identified a limited number of hub regions with ICC values that showed significant negative relationship with age. These include the medial precentral/midcingulate gyri and insula with both their short-range and long-range (and thus whole-brain) ICC values negatively associated with age, and the angular, middle frontal, and posterior cingulate gyri with their long-range ICC values mainly involved. Seed-based connectivity analyses further confirmed that these regions are connector hubs with connectivity profile that strongly overlapped with multiple large-scale brain networks. General cognitive performance was not associated with these hubs’ ICC values. These findings suggest that even healthy aging could negatively impact the efficiency of regions critical for facilitating information transfer among different functional brain networks. The extent of the regions involved, however, was limited.
Highlights
Studies have shown that the human brain is functionally organized into several large-scale networks, which can be identified using the spontaneous low frequency fluctuations of resting state functional magnetic resonance imaging data (Biswal et al, 1995; Greicius et al, 2003; Beckmann et al, 2005; Seeley et al, 2007)
Cortical hubs characterized by significant long-range intrinsic connectivity contrast (ICC) values were observed in regions associated with the core neurocognitive networks such as the bilateral middle frontal gyrus, angular/supramarginal gyrus, inferior/middle temporal gyrus, precuneus/posterior cingulate gyrus, and midcingulate gyrus, among others (Figure 2C)
Healthy aging is associated with whole-brain intrinsic functional connectivity changes even in the absence of neurodegenerative diseases
Summary
Studies have shown that the human brain is functionally organized into several large-scale networks, which can be identified using the spontaneous low frequency fluctuations of resting state functional magnetic resonance imaging (fMRI) data (Biswal et al, 1995; Greicius et al, 2003; Beckmann et al, 2005; Seeley et al, 2007). Some of these so-called resting state networks (RSNs), or their precursors, can already be identified even in the infant brain (Fransson et al, 2007; Smyser et al, 2010). Its dysfunctions are associated with behavioral and cognitive impairments in several neurological and psychiatric disorders (Buckner et al, 2009; van den Heuvel et al, 2013; van den Heuvel and Sporns, 2013; Dai et al, 2015) and could provide novel insight into the pathomechanism of cognitive decline (Ogura et al, 2019)
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