Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes

Benjamín Garzón,Jan Axelsson,Katrine Riklund,Martin Lövdén,Marc Guitart-Masip,Lars Bäckman,Lieke De Boer,Lars Nyberg

doi:10.1007/s00429-020-02205-4

Abstract

With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.

Highlights

Aging produces changes in the coupling between spontaneous oscillations of the blood oxygen level-dependent (BOLD) signal (Andrews-Hanna et al 2007; Damoiseaux et al 2008; Ferreira et al 2016), which is commonly termed functional connectivity (FC)
We investigated whether the aging effects in FC were related to those in Binding potential (BP) and gray matter density (GMD) across regions of interest (ROIs)
Using global signal regression (GSR) had an impact on the estimates of aging effects and weakened but did not eliminate the relationships we report with BP

Summary

Introduction

Aging produces changes in the coupling between spontaneous oscillations of the blood oxygen level-dependent (BOLD) signal (Andrews-Hanna et al 2007; Damoiseaux et al 2008; Ferreira et al 2016), which is commonly termed functional connectivity (FC). FC increases have been reported between left and right hippocampus (Salami et al 2014, 2016) These results indicate that the effects of aging are heterogeneous across connections, and suggest the existence of a shift in the pattern of functional connections with increasing age, rather than a global, homogeneous change. The set of functional connections for all possible pairs of regions from a parcellation covering the brain comprehensively constitutes a functional connectome. This can be represented as a graph consisting of a set of nodes (regions) linked by edges (functional connections), and its FC values

Methods

Results

Discussion

Conclusion