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

Abstract

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.

Do “Ten simple rules for neuroimaging meta-analysis” receive equal attention and accurate quotation? An examination on the quotations to an influential neuroimaging meta-analysis guideline

“… Error class Quotation example Rationale 1 “ The dual threshold CBMA ALE was conducted with cluster-level threshold and family-wise error rate of p < 0.05, 1000 thresholding permutations, and intensity threshold of p < 0.05. The intensity threshold was chosen based on the recommendations for conducting neuroimaging meta -analyses [26].” From ( Moring et al, 2022 ). ( Müller et al, 2018 ) mentioned that voxel-level cluster forming threshold should be p < 0.001, not < 0.05.…”

The Impact of Sleep Quality on Cognitive Function in Patients with Chronic Subjective Tinnitus

“…In recent years, more and more studies have shown that subjective tinnitus is a central nervous system symptom that involves global neural function remodeling, 14 , 15 and the impact of tinnitus on patient cognitive function has also received increasing attention from researchers. 1 However, as a common accompanying symptom of tinnitus, sleep disorders are also an important risk factor for individual cognitive impairment.…”

Endocannabinoid system components as potential neuroimmune therapeutic targets in tinnitus

“…Tinnitus has been well known for millennia, yet pathophysiology is poorly understood, despite progress in technological advances, neuroimaging studies, and various models that have not yielded effective treatment for the subjective type of tinnitus. As suggested by others a paradigm shift may be necessary for tinnitus including neuroimaging approaches to recognizing the effects from specific regions across canonical networks beyond the auditory resting state network ( 51 ), and the quantum tunneling ion model. Many facets of tinnitus including the pathophysiology, and objective detection are poorly defined, and currently, there is no sufficient high-level evidence to support effective therapeutic approaches in tinnitus.…”