Structure–function multi‐scale connectomics reveals a major role of the fronto‐striato‐thalamic circuit in brain aging

Abstract

Physiological aging affects brain structure and function impacting morphology, connectivity, and performance. However, whether some brain connectivity metrics might reflect the age of an individual is still unclear. Here, we collected brain images from healthy participants (N = 155) ranging from 10 to 80 years to build functional (resting state) and structural (tractography) connectivity matrices, both data sets combined to obtain different connectivity features. We then calculated the brain connectome age—an age estimator resulting from a multi‐scale methodology applied to the structure–function connectome, and compared it to the chronological age (ChA). Our results were twofold. First, we found that aging widely affects the connectivity of multiple structures, such as anterior cingulate and medial prefrontal cortices, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus, and temporal pole. Second, we found that the connectivity between basal ganglia and thalamus to frontal areas, also known as the fronto‐striato‐thalamic (FST) circuit, makes the major contribution to age estimation. In conclusion, our results highlight the key role played by the FST circuit in the process of healthy aging. Notably, the same methodology can be generally applied to identify the structural–functional connectivity patterns correlating to other biomarkers than ChA.

A longitudinal characterization of perfusion in the aging brain and associations with cognition and neural structure

“…A growing body of volumetric (Hughes et al, 2012;Van Der Werf et al, 2001), task-based fMRI (Fan, McCandliss, Fossella, Flombaum, & Posner, 2005;Minzenberg, Laird, Thelen, Carter, & Glahn, 2009), and lesion studies (Carrera & Bogousslavsky, 2006) have together suggested that the thalamus is a critical structure for executive functions and processing speed. Recent work leveraging functional and structural imaging to investigate the brain's connectome suggested that disruption of the fronto-striatal-thalamic circuit may indeed play a key role in human brain aging (Bonifazi et al, 2018). Evidence is accumulating, particularly in animal models, that suggests this thalamo-prefrontal circuit is integral for executive functions (Ouhaz, Fleming, & Mitchell, 2018;Parnaudeau, Bolkan, & Kellendonk, 2018).…”

“…Evidence is accumulating, particularly in animal models, that suggests this thalamo-prefrontal circuit is integral for executive functions (Ouhaz, Fleming, & Mitchell, 2018;Parnaudeau, Bolkan, & Kellendonk, 2018). Recent work leveraging functional and structural imaging to investigate the brain's connectome suggested that disruption of the fronto-striatal-thalamic circuit may indeed play a key role in human brain aging (Bonifazi et al, 2018).…”

Interaction information along lifespan of the resting brain dynamics reveals a major redundant role of the default mode network

“…The functional connectivity (FC) patterns at rest have been shown to be altered in different pathological conditions such as deficit of consciousness [10,11,12,13], schizophrenia [14,15], epilepsy [16] and Alzheimer's Disease [17,18,19,20,21]. Here, following a recent study [22] combining functional and structural multi-scale connectivity along lifespan, we address how redundancy and synergy varies from young to old people, within an age interval of 10 to 80 years old, that as far as we know, has not been addressed before.…”

“…The brain was divided in 2,514 brain regions that we grouped into modules using the brain hierarchical atlas (BHA), developed in [31] and applied by the authors in a traumatic injury study [32] and in a lifespan study [22]. The BHA is available to download at http://www.nitrc.org/projects/biocr_hcatlas/.…”

Hyperconnectivity of the default mode network in multiorgan dysfunction syndrome

“…Of special interest for clinical studies, it has been widely shown that different RSNs become altered in different pathological conditions such as deficit of consciousness [26,27,28,29,30], schizophrenia [31,32], epilepsy [33], Alzheimer's Disease [34,35,36,37,38,39] and healthy aging [40]. As far as we know, what RSN is altered after MODS has not been yet addressed.…”