White Matter Structural Connectivity Is Not Correlated to Cortical Resting-State Functional Connectivity over the Healthy Adult Lifespan.

Adrian Tsang,Signe L Bray,Roberto C Sotero,Richard Frayne,Cheryl R Mccreary,Moiz Hafeez,Bradley G Goodyear,Catherine A Lebel

doi:10.3389/fnagi.2017.00144

Abstract

Structural connectivity (SC) of white matter (WM) and functional connectivity (FC) of cortical regions undergo changes in normal aging. As WM tracts form the underlying anatomical architecture that connects regions within resting state networks (RSNs), it is intuitive to expect that SC and FC changes with age are correlated. Studies that investigated the relationship between SC and FC in normal aging are rare, and have mainly compared between groups of elderly and younger subjects. The objectives of this work were to investigate linear SC and FC changes across the healthy adult lifespan, and to define relationships between SC and FC measures within seven whole-brain large scale RSNs. Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data were acquired from 177 healthy participants (male/female = 69/108; aged 18–87 years). Forty cortical regions across both hemispheres belonging to seven template-defined RSNs were considered. Mean diffusivity (MD), fractional anisotropy (FA), mean tract length, and number of streamlines derived from DTI data were used as SC measures, delineated using deterministic tractography, within each RSN. Pearson correlation coefficients of rs-fMRI-obtained BOLD signal time courses between cortical regions were used as FC measure. SC demonstrated significant age-related changes in all RSNs (decreased FA, mean tract length, number of streamlines; and increased MD), and significant FC decrease was observed in five out of seven networks. Among the networks that showed both significant age related changes in SC and FC, however, SC was not in general significantly correlated with FC, whether controlling for age or not. The lack of observed relationship between SC and FC suggests that measures derived from DTI data that are commonly used to infer the integrity of WM microstructure are not related to the corresponding changes in FC within RSNs. The possible temporal lag between SC and FC will need to be addressed in future longitudinal studies to better elucidate the links between SC and FC changes in normal aging.

Highlights

It is widely accepted that the normal human aging process involves changes in the brain’s structural and functional connections
Metrics derived from diffusion tensor imaging (DTI) are used to quantify the white matter (WM) microstructure [termed structural connectivity (SC)], and correlations of the blood oxygen level dependent (BOLD) time signals computed from resting-state functional MRI (rs-fMRI) are used to quantify the strength of resting state functional connections between distinct gray matter (GM) regions [termed functional connectivity (FC)]
As there are only few studies in literature that investigated the relationship between SC and FC over the adult lifespan, and the results reported are related to certain specific GM regions and WM tracts, a study that investigates more broadly across multiple commonly described resting state networks (RSNs) and the associated WM tracts is warranted in normal subjects over a wide age span

Summary

Introduction

It is widely accepted that the normal human aging process involves changes in the brain’s structural and functional connections. Understanding these changes will greatly improve our ability to diagnose and treat age-related neurodegenerative diseases, such as Alzheimer’s Disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s Disease (PD) (Pievani et al, 2014; Iturria-Medina and Evans, 2015; Gao and Wu, 2016). Noninvasive neuroimaging techniques including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) permit the investigation of white and gray matter connectivity in the brain. As functionally linked cortical regions are connected anatomically via the underlying WM architecture (van den Heuvel et al, 2009), investigating SC and FC simultaneously to determine their interrelationship has the potential to provide a better, more comprehensive, understanding of the brain changes associated with aging

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