Scatterplot of ICC for connections with vs. without GSR.

<p>GSR tends to reduce the reliability of connections (i.e., regression lines are under y = x when ICC >0.3 for the young group and ICC >0.15 for the old group). Each data point indicates a significant connection from each group. Black lines represent linear regression fits of the data and red lines represent y = x.</p

Scan 1 <i>vs.</i> scan 2 <i>vs.</i> scan 3.

<p>Group-averaged correlations from each scan session are plotted against each other. High consistency of RSFC from scan to scan is observed independent of aging and GSR factor. Overlaid blue lines represent linear regression fits of the data points and the <i>r</i>-values of the fit represent Pearson correlations of the data points.</p

Kendall’s <i>W</i> between-subject within scan.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049847#pone-0049847-t008" target="_blank"><b>Table 8</b></a> Listed are the mean and standard deviation of Kendall’s <i>W</i> between subjects within scan for all, significant, non-significant, positive significant and negative significant correlations.</p

Age-Related Differences in Test-Retest Reliability in Resting-State Brain Functional Connectivity

<div><p>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 <a href="http://www.nitrc.org/projects/fcon_1000">www.nitrc.org/projects/fcon_1000</a>. 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 <em>z</em>-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 (<em>p</em>-value = 0.028) and without GSR (<em>p</em>-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.</p> </div

Effects of aging and GSR on brain functional networks.

<p>Pie chart illustrates the proportion of significant and reliable functional connections within each network. Binomial proportion tests showed aging was associated with significant decreases in reliable connections between-network but increases within sensorimotor and fronto-parietal networks. Each percentage number indicates the proportion of functional connections within corresponding networks.</p

Reliability of RSFC <i>vs.</i> magnitude of functional connections in the young group.

<p>A left shift of data points indicates a reduction in the magnitude of functional connections when GSR is applied. The Wilcoxon signed-rank test shows reduced ICC values when GSR is applied (<i>p</i>-value <0.0001). Each data point represents a correlation that is significant both with and without GSR. Linear regression fits were overlaid on the data.</p

Effects of aging and GSR on reliability of RSFC.

<p>Frequency plots of multi-scan ICCs for significant and reliable correlations (i.e., <i>p</i>-value <0.05 adjusted by FDR correction, ICC >0.5) showed pronounced decreases in significant and reliable (SigRe) correlations with aging and GSR. (Y–Young, O–Old, wGSR–with GSR, woGSR–without GSR).</p

Effects of aging and GSR on stability of RSFC within-subject across scans.

<p>Frequency plots of Kendall’s <i>W</i> across scan sessions for significant correlations showed pronounced decreases in Sig. correlations with GSR. High stability of RSFC from scan to scan remains independent of aging effects.</p

Effects of GSR on brain functional networks.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049847#pone-0049847-t004" target="_blank"><b>Table 4</b></a> Binomial proportion test showed the proportion of reliable functional connections was significantly affected by GSR both within- and between-network.</p

Multi-scan ICC measures.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049847#pone-0049847-t001" target="_blank"><b>Table 1</b></a> Listed are the mean and standard deviation of multi-scan ICCs given for all, significant, non-significant, positive significant or negative significant correlations for each group with and without GSR.</p