A Combined Image- and Coordinate-Based Meta-Analysis of Whole-Brain Voxel-Based Morphometry Studies Investigating Subjective Tinnitus

Abstract

Previous voxel-based morphometry (VBM) studies investigating tinnitus have reported structural differences in a variety of spatially distinct gray matter regions. However, the results have been highly inconsistent and sometimes contradictory. In the current study, we conducted a combined image- and coordinate-based meta-analysis of VBM studies investigating tinnitus to identify robust gray matter differences associated with tinnitus, as well as examine the possible effects of hearing loss on the outcome of the meta-analysis. The PubMed and Web of Science databases were searched for studies published up to August 2021. Additional manual searches were conducted for studies published up to December 2021. A whole-brain meta-analysis was performed using Seed-Based d Mapping with Permutation of Subject Images (SDM-PSI). Fifteen studies comprising 423 individuals with tinnitus and either normal hearing or hearing loss (mean age 50.94 years; 173 females) and 508 individuals without tinnitus and either normal hearing or hearing loss (mean age 51.59 years; 234 females) met the inclusion criteria. We found a small but significant reduction in gray matter in the left inferior temporal gyrus for groups of normal hearing individuals with tinnitus compared to groups of hearing-matched individuals without tinnitus. In sharp contrast, in groups with hearing loss, tinnitus was associated with increased gray matter levels in the bilateral lingual gyrus and the bilateral precuneus. Those results were dependent upon matching the hearing levels between the groups with or without tinnitus. The current investigation suggests that hearing loss is the driving force of changes in cortical gray matter across individuals with and without tinnitus. Future studies should carefully account for confounders, including hearing loss, hyperacusis, anxiety, and depression, to identify gray matter changes specifically related to tinnitus. Ultimately, the aggregation of standardized individual datasets with both anatomical and useful phenotypical information will permit a better understanding of tinnitus-related gray matter differences, the effects of potential comorbidities, and their interactions with tinnitus.

Sound-Evoked Neural Activity in Normal Hearing Tinnitus: The Effect of Frequency and Simulation Side

“…Furthermore, both groups (tinnitus and controls) showed a typical pattern of higher cerebral activity contralateral to the stimulated ear [11,25]. These results support the idea that hearing loss, not tinnitus, is the main factor driving functional and neuroanatomical changes in the auditory cortex [3,7,26].…”

Desensitizing nicotinic agents normalize tinnitus-related inhibitory dysfunction in the auditory cortex and ameliorate behavioral evidence of tinnitus

“…For example, Stevens et al (2007) tested the cognitive and attentional abilities of patients with chronic tinnitus and found that patients with chronic tinnitus perform significantly poorer in complex and attention demanding tasks, compared to control groups. These finding suggest complex cell/circuit-specific changes at multiple auditory and non-auditory structures ( Rauschecker et al, 2010 ; Shore et al, 2016 ; Makani et al, 2022 ). Tinnitus-related loss of nAChR-evoked response in the layer 5 PNs observed in this study may contribute to the observed decline in attentional resources seen by Brozoski et al (2019) in this same animal model.…”

Sound-Evoked Neural Activity in Normal-Hearing Tinnitus: Effects of Frequency and Stimulated Ear Side

“…Participants with tinnitus also filled in the Tinnitus Handicap Inventory (THI) [ 16 ] and the Tinnitus Functionality Index (TFI) [ 17 ]. These inventories are consistently used in tinnitus neuroimaging studies [ 7 , 18 ], and their use is recommended in American and European clinical guidelines [ 19 , 20 ]. The tinnitus-related questionnaires serve to assess the severity of tinnitus and its common comorbidities.…”