Invariant structural and functional brain regions associated with tinnitus: A meta-analysis

by John C. Moring, Fatima T. Husain, Jodie Gray, Crystal Franklin, Alan L. Peterson, Patricia A. Resick, Amy Garrett, Carlos Esquivel, Peter T. Fox

Tinnitus is a common, functionally disabling condition of often unknown etiology. Neuroimaging research to better understand tinnitus is emerging but remains limited in scope. Voxel-based physiology (VBP) studies detect tinnitus-associated pathophysiology by group-wise contrast (tinnitus vs controls) of resting-state indices of hemodynamics, metabolism, and neurovascular coupling. Voxel-based morphometry (VBM) detects tinnitus-associated neurodegeneration by group-wise contrast of structural MRI. Both VBP and VBM studies routinely report results as atlas-referenced coordinates, suitable for coordinate-based meta-analysis (CBMA). Here, 17 resting-state VBP and 8 VBM reports of tinnitus-associated regional alterations were meta-analyzed using activation likelihood estimation (ALE). Acknowledging the need for data-driven insights, ALEs were performed at two levels of statistical rigor: corrected for multiple comparisons and uncorrected. The corrected ALE applied cluster-level inference thresholding by intensity (z-score > 1.96; p < 0.05) followed by family-wise error correction for multiple comparisons (p < .05, 1000 permutations) and fail-safe correction for missing data. The corrected analysis identified one significant cluster comprising five foci in the posterior cingulate gyrus and precuneus, that is, not within the primary or secondary auditory cortices. The uncorrected ALE identified additional regions within auditory and cognitive processing networks. Taken together, tinnitus is likely a dysfunction of regions spanning multiple canonical networks that may serve to increase individuals’ interoceptive awareness of the tinnitus sound, decrease capacity to switch cognitive sets, and prevent behavioral and cognitive attention to other stimuli. It is noteworthy that the most robust tinnitus-related abnormalities are not in the auditory system, contradicting collective findings of task-activation literature in tinnitus.