Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI

Abstract

The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI.

Bayesian exponential random graph modeling of whole-brain structural networks across lifespan

“…local clustering and global efficiency) over all age categories, in contrast with previous literature showing alterations in both structural (Dennis et al, 2013;Gong et al, 2009;Hagmann et al, 2010;Montembeault et al, 2012;Otte et al, 2015;Wu et al, 2012;Zhu et al, 2012) and functional brain networks across life-span (Achard and Bullmore, 2007;Betzel et al, 2014;Meier et al, 2012;Meunier et al, 2009;Nathan Spreng and Schacter, 2012;Simpson and Laurienti, 2015;Smit et al, 2016;Wang et al, 2012). Furthermore, our findings are also in contrast with significant differences found in a previous exponential random graph modeling study in functional networks , and a recently developed similar approach (also discussed below) which revealed differences in functional networks across the lifespan, such as older adults having stronger connections between highly clustered nodes, or less assortativity in visual and multisensory regions (Simpson and Laurienti, 2015).…”

“…the average shortest path length, maximum betweenness centrality or overall clustering coefficient) (Bullmore and Sporns, 2009) and/or network properties such as small-worldness, rich club connectedness (Bullmore and Sporns, 2012;Cao et al, 2014) and modularity (Rubinov and Sporns, 2010). In the past decade, multiple studies have shown that normal aging is associated with substantial alterations in NeuroImage 135 (2016) [79][80][81][82][83][84][85][86][87][88][89][90][91] structural Dennis et al, 2013;Gong et al, 2009;Hagmann et al, 2010;Lim et al, 2015;Montembeault et al, 2012;Otte et al, 2015;Wu et al, 2012;Zhu et al, 2012) and functional (Achard and Bullmore, 2007;Andrews-Hanna et al, 2007;Betzel et al, 2014;Meier et al, 2012;Meunier et al, 2009;Nathan Spreng and Schacter, 2012;Wang et al, 2012) brain networks. Some of these studies focused on specific age categories: childhood to adulthood (Dennis et al, 2013;Hagmann et al, 2010) or young and older adults (e.g.…”

Brain functional connectivity in regions that exhibit age-related cortical thinning

“…These findings strengthen the notion that the brain becomes less functionally segregated with aging, as different areas interactions become stronger to the detriment of intraregional interactions (FERREIRA et al, 2016). Studies show interhemispheric connections tend to show higher proportions of linearly decreasing connectivities (WANG et al, 2012).…”

“…Results in this same vein have been previously reported (FERREIRA et al, 2016;GEERLIGS et al, 2015;SONG et al, 2014), though contrasting our specific results, such as proportions of increased or decreased correlations, with the literature is made difficult due to the different ROI definitions, e.g. studies using random parcellations tend to have uniformly sized Contrary to the morphometric analyses, here the linear hypothesis is much more reasonable and parsimonious due to the sheer number of hypotheses being tested, which is equal to 10878, even though evidences of nonlinear functional connectivity trajectories exist (WANG et al, 2012).…”

Changes in the Network Eigen Entropy of resting-state functional brains across the lifespan

“…Meanwhile, resting-state functional magnetic resonance imaging (rs-fMRI) studies have researched age-related changes in functional connectivity patterns in the whole-brain network across the lifespan [2,3]. However these studies have focused mainly on partial brain attributes rather than integrated communication across brain regions and the organization or order of the brain across the lifespan.…”