Resting-state functional connectivity and local activity differences across bothersome and non-bothersome tinnitus...

This study aimed to characterize resting-state functional differences across clinically defined bothersome tinnitus, non-bothersome tinnitus, and hospital-based non-tinnitus control groups, focusing on imaging differences related to tinnitus phenotype.

This case-control study included 61 patients with bothersome tinnitus (BT), 52 with non-bothersome tinnitus (NBT), and 50 hospital-based non-tinnitus controls. Resting-state fMRI scans were acquired, and the data were analyzed using fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and seed-based functional connectivity (FC) using broad bilateral temporal lobe regions of interest to assess temporal-related network connectivity, including temporal-limbic interactions. Group comparisons were performed using ANCOVA controlling for demographic, audiological, physiological, sleep-related, and emotional covariates, cluster-level FDR-corrected p < 0.05. Exploratory correlation analyses were further conducted to examine associations between extracted imaging indices and clinical measures, as well as potential relationships among significant imaging findings.

Resting-state fMRI revealed significant group differences in functional connectivity between the bilateral temporal lobe seed and the left ACC/mOFC cluster. Post hoc analyses showed stronger connectivity in BT than in NBT, whereas BT did not differ significantly from hospital-based non-tinnitus controls. A similar pattern was observed for ReHo in the medial superior frontal gyrus, with lower values in NBT than in both BT and controls. fALFF analyses showed region-specific differences across temporal, frontal, insular, occipital, supramarginal, and postcentral regions, with the most consistent differences observed between BT and NBT. Exploratory analyses showed no significant FC-ReHo correlation within the BT group, and no associations between imaging indices and clinical or audiological measures survived FDR correction. In sensitivity analyses retaining the original covariate structure and additionally adjusting for tinnitus loudness VAS, most BT-NBT differences were attenuated, suggesting that these imaging differences may partly reflect tinnitus loudness or related clinical burden.

Resting-state FC, fALFF, and ReHo measures revealed phenotype-related functional differences between BT and NBT. Because several key measures did not differ between BT and hospital-based non-tinnitus controls, these findings should be interpreted as group-level imaging features across tinnitus phenotypes, not as BT-specific abnormalities.