Age-Related Intrinsic Functional Connectivity Changes of Locus Coeruleus from Childhood to Older Adults

Abstract

The locus coeruleus is critical for selective information processing by modulating the brain’s connectivity configuration. Increasingly, studies have suggested that LC controls sensory inputs at the sensory gating stage. Furthermore, accumulating evidence has shown that young children and older adults are more prone to distraction and filter out irrelevant information less efficiently, possibly due to the unoptimized LC connectivity. However, the LC connectivity pattern across the life span is not fully examined yet, hampering our ability to understand the relationship between LC development and the distractibility. In this study, we examined the intrinsic network connectivity of the LC using a public fMRI dataset with wide-range age samples. Based on LC-seed functional connectivity maps, we examined the age-related variation in the LC connectivity with a quadratic model. The analyses revealed two connectivity patterns explicitly. The sensory-related brain regions showed a positive quadratic age effect (u-shape), and the frontal regions for the cognitive control showed a negative quadratic age effect (inverted u-shape). Our results imply that such age-related distractibility is possibly due to the impaired sensory gating by the LC and the insufficient top-down controls by the frontal regions. We discuss the underlying neural mechanisms and limitations of our study.

The increased functional connectivity between the locus coeruleus and supramarginal gyrus in insomnia disorder with acupuncture modulation

“…Therefore, it is difficult to determine whether insomnia or anxiety and depression had a greater impact on the FC of LC-IFG and LC-SMG in that study. The FC of LC is also influenced by age, differences in demographic characteristics can also contribute to inconsistent results ( Zhang et al, 2016 ; Song et al, 2021 ). In addition, the difference in the method of LC localization may also play roles.…”

Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions

“…Electrophysiological studies report non-overlapping spontaneous activation dynamics from different sites in the LC that associate with and drive different cortical states, suggesting the presence of distinct neural ensembles in the LC that regulate multiple cortical states, instead of a homogeneous arousal-related release of noradrenaline across the cortex (41). Although fMRI provides a comprehensive view of LC function due to this nucleus’ extensive and diffuse cortical projections, this technique is limited by low spatial resolution, which could explain why previous resting-state fMRI studies focused on the LC obtained inconsistent results (16,17). The high connectivity heterogeneity of the LC shown in our study indicates that using the LC as a single, homogeneous ROI might not be the best approach to assess connectivity in this region.…”

“…This is important because this region modulates various behavioral functions and widespread brain regions in a very precise manner (15). Furthermore, studies using fMRI to describe connectivity in the LC report heterogeneous results -possibly because the localization methods, the studied populations and preprocessing pipelines often differ (16)(17)(18)(19) -and a similarity gradient-based approach might be better suited to characterize its functional organization by mitigating the effect of heterogeneous individual differences in connectivity and imaging acquisition-related noise, since it is less affected by e.g. ROI inaccuracies (20).…”

Influence of age and cognitive performance on resting-state functional connectivity of dopaminergic and noradrenergic centres

“…It was shown that the relationship between age and LC connectivity may be more complex than just linear decrease (Jacobs et al, 2018; I. Song et al, 2021). Different results might have been obtained if the older group was divided into middle-aged adults (55-65) and older (65-80) adults.…”

“…A curvilinear association between the age and functional connectivity of the left LC to the bilateral cortical areas such as temporal pole, posterior middle temporal gyrus angular gyrus, and inferior frontal gyrus, as well as right posterior cingulate cortex was observed by Jacobs and colleagues (Jacobs et al, 2018). Recently, Song, Neal and Lee found a positive quadratic relationship between the age and LC connectivity with sensory regions and a negative quadratic association between the age and LC connectivity with frontal regions (Song et al, 2021).…”