An examination of the reliability of seed-to-seed resting state functional connectivity in tinnitus patients

Resting state functional connectivity (RS-FC) studies of tinnitus over the years have produced inconsistent results. While findings can be organized into broad categories, such as increased correlations between auditory and limbic areas in tinnitus patients and a disrupted default mode network, there has been little one-to-one correspondence of results across RS-FC studies of tinnitus. While some of this variation can be explained by the heterogeneity of the tinnitus population, including tinnitus severity, the sources of variability in RS-FC of tinnitus patients are unclear. To directly assess the reliability of RS-FC measures in tinnitus, both tinnitus and control participants from two different sites (University of Illinois at Urbana-Champaign, or UIUC, and the Wilford Hall Ambulatory Surgical Center, or WHASC, at the Lackland Airforce Base in San Antonio, Texas) participated in two resting state MRI scans separated by exactly one week. Seed-to-seed analysis assessing correlations between the fMRI activity of 27 regions in the default mode, dorsal attention, auditory, visual, salience, and emotional processing networks were examined in control and tinnitus participants separately for each site. Additionally, heart rate and respiration measures were collected at UIUC, and the effect of extra physiological corrections using these measures on reliability was examined within the UIUC participants. Intra-class correlation coefficients (ICCs) were used as the measure of reliability. Overall, RS-FC in a seed-to-seed analysis was as reliable in tinnitus participants as it was in control participants in the seed regions examined. As previously shown in studies of participants with normal hearing sensitivity, intra-network reliability was higher than inter-network reliability. Related to this, stronger correlations between two seed regions were predictive of stronger reliability of the connectivity between those regions. These effects were seen in both control and tinnitus populations. Additional physiological corrections did not have a significant impact on the ICC values. The current study demonstrates that, on a whole-brain level, RS-FC assessed via seed-to-seed analysis is reliable in tinnitus participants. We therefore must look to other sources as potential causes of discrepancies across studies, such as variability within analysis techniques or within the behavioral characteristics of tinnitus participants.