Age-related differences in test-retest reliability in resting-state brain functional connectivity.

Jie Song,Bharat B Biswal,Veena A Nair,Alok S Desphande,Svyatoslav Vergun,Timothy B Meier,Dana L Tudorascu,Mary E Meyerand,Rasmus M Birn,Vivek Prabhakaran,Pierre Bellec

doi:10.1371/journal.pone.0049847

Abstract

Resting-state functional MRI (rs-fMRI) has emerged as a powerful tool for investigating brain functional connectivity (FC). Research in recent years has focused on assessing the reliability of FC across younger subjects within and between scan-sessions. Test-retest reliability in resting-state functional connectivity (RSFC) has not yet been examined in older adults. In this study, we investigated age-related differences in reliability and stability of RSFC across scans. In addition, we examined how global signal regression (GSR) affects RSFC reliability and stability. Three separate resting-state scans from 29 younger adults (18–35 yrs) and 26 older adults (55–85 yrs) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available as part of the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 92 regions of interest (ROIs) with 5 cubic mm radius, derived from the default, cingulo-opercular, fronto-parietal and sensorimotor networks, were previously defined based on a recent study. Mean time series were extracted from each of the 92 ROIs from each scan and three matrices of z-transformed correlation coefficients were created for each subject, which were then used for evaluation of multi-scan reliability and stability. The young group showed higher reliability of RSFC than the old group with GSR (p-value = 0.028) and without GSR (p-value <0.001). Both groups showed a high degree of multi-scan stability of RSFC and no significant differences were found between groups. By comparing the test-retest reliability of RSFC with and without GSR across scans, we found significantly higher proportion of reliable connections in both groups without GSR, but decreased stability. Our results suggest that aging is associated with reduced reliability of RSFC which itself is highly stable within-subject across scans for both groups, and that GSR reduces the overall reliability but increases the stability in both age groups and could potentially alter group differences of RSFC.

Highlights

Since the discovery that the human brain at rest consists of spatially distributed but functionally connected regions in which coherent patterns of low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal are temporally correlated [1], resting-state functional MRI has been used extensively for investigating brain functional connectivity (FC)
We found that Resting-state functional connectivity (RSFC) is more reliable for the young group and highly consistent for both groups, and that, consistent with previous studies [12,24,27,28], regressing the global signal altered group differences of between-region functional connections
Multi-scan Intraclass Correlation coefficients (ICC) for statistically significant and positive significant correlations with global signal regression (GSR) across subjects in each group exhibited higher degree of test-retest reliability compared with non-significant, and/or negative significant correlations

Summary

Introduction

Since the discovery that the human brain at rest consists of spatially distributed but functionally connected regions in which coherent patterns of low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal are temporally correlated [1], resting-state functional MRI (rs-fMRI) has been used extensively for investigating brain functional connectivity (FC). Resting-state functional connectivity (RSFC) provides insight into the large scale structure of interactions between brain regions that support the integrated deviations of disease states from normally observed human health. These deviations may be a fundamental causative factor in both neuropathologic and neurodevelopmental conditions such as dementia [2,3], autism [4,5,6], schizophrenia [7,8,9], depression [10,11] and other conditions. The modular organization of structural brain networks was similar between the young and middle age groups, but quite different from the old group based on an analysis of topological organization of structural brain networks in healthy individuals [19]. The main purpose of this study is to investigate test-retest reliability and stability of the RSFC parameters in both young and old groups

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Conclusion