Abstract
A common finding in the aging literature is that of the brain's decreased within‐ and increased between‐network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS functioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam‐CAN) population‐based cohort. Our results show that ARAS‐cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age‐related differences in connectivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connectivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS–cortical connectivity relates to cognitive performance with age.
Highlights
As people age from young to older adulthood, several changes are commonly observed in the brain's functional network organization, including reduced suppression of the default mode network during task performance, differences in network interactivity, and decreased network segregation (Bethlehem et al, 2020; Chan, Park, Savalia, Petersen, & Wig, 2014; Damoiseaux, 2017; Ferreira et al, 2016; Grady, 2012; Spreng, Wojtowicz, & Grady, 2010; Turner & Spreng, 2015)
We examined functional connectivity within/between four cortical association networks previously shown to become less segregated with age (i.e., default mode network (DMN), salience network (SN), dorsal attention network (DAN), frontoparietal control network (FPCN)—see Section 2)
Differences therein, (b) test whether age differences in connectivity within and between association networks relate to age differences in ascending reticular activating system (ARAS)-association network connectivity, and (c) evaluate the relationship between ARAS–cortical connectivity and cognitive performance
Summary
As people age from young to older adulthood, several changes are commonly observed in the brain's functional network organization, including reduced suppression of the default mode network during task performance, differences in network interactivity, and decreased network segregation (Bethlehem et al, 2020; Chan, Park, Savalia, Petersen, & Wig, 2014; Damoiseaux, 2017; Ferreira et al, 2016; Grady, 2012; Spreng, Wojtowicz, & Grady, 2010; Turner & Spreng, 2015). A diffuse set of neuronal projections from multiple brainstem nuclei stimulate the cerebral cortex via ascending pathways that project to the thalamus, posterior hypothalamus, basal forebrain, and directly to the cortex itself (Jones, 2003) These thalamic and extrathalamic ascending pathways include, but are not limited to, glutamatergic fibers from the parabrachial complex, cholinergic fibers from the pedunculopontine nucleus, noradrenergic fibers from the locus coeruleus, dopaminergic fibers from the ventral tegmental area, and serotonergic fibers from the raphe nuclei (Edlow et al, 2012). This complex set of neurotransmitter pathways that compose the ARAS continuously interact with and modulate one another on route to the cortex, affecting brain functioning and influencing many aspects of cognition (Briand, Gritton, Howe, Young, & Sarter, 2007; Handra et al, 2019; Lobo & Summavielle, 2016)
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