Cortico-limbic morphology separates tinnitus from tinnitus distress

Abstract

Tinnitus is a common auditory disorder characterized by a chronic ringing or buzzing “in the ear.”Despite the auditory-perceptual nature of this disorder, a growing number of studies have reported neuroanatomical differences in tinnitus patients outside the auditory-perceptual system. Some have used this evidence to characterize chronic tinnitus as dysregulation of the auditory system, either resulting from inefficient inhibitory control or through the formation of aversive associations with tinnitus. It remains unclear, however, whether these “non-auditory” anatomical markers of tinnitus are related to the tinnitus signal itself, or merely to negative emotional reactions to tinnitus (i.e., tinnitus distress). In the current study, we used anatomical MRI to identify neural markers of tinnitus, and measured their relationship to a variety of tinnitus characteristics and other factors often linked to tinnitus, such as hearing loss, depression, anxiety, and noise sensitivity. In a new cohort of participants, we confirmed that people with chronic tinnitus exhibit reduced gray matter in ventromedial prefrontal cortex (vmPFC) compared to controls matched for age and hearing loss. This effect was driven by reduced cortical surface area, and was not related to tinnitus distress, symptoms of depression or anxiety, noise sensitivity, or other factors. Instead, tinnitus distress was positively correlated with cortical thickness in the anterior insula in tinnitus patients, while symptoms of anxiety and depression were negatively correlated with cortical thickness in subcallosal anterior cingulate cortex (scACC) across all groups. Tinnitus patients also exhibited increased gyrification of dorsomedial prefrontal cortex (dmPFC), which was more severe in those patients with constant (vs. intermittent) tinnitus awareness. Our data suggest that the neural systems associated with chronic tinnitus are different from those involved in aversive or distressed reactions to tinnitus.

Differential tinnitus-related neuroplastic alterations of cortical thickness and surface area

“…We were not surprised to notice a relationship between distress and insular morphology as this sub-sylvian area can be conceived as an interface between the auditory system [70,71] and the emotional brain circuitry [72] in the human brain. Along the same lines, Leaver and coworkers [34] observed a positive relationship between tinnitus distress and CT in the left anterior insula. Despite the fact that we report uncorrected results, we think it is appropriate to discuss our findings in light of present knowledge, as other scholars have also established a tight link between tinnitus and the insular region [34,73,74].…”

“…In particular, bilateral 55 peri-auditory regions in the superior temporal lobe [26,27,28] and subcortical areas that are considered as part of the (anatomically ill-defined) limbic system [29,34] often show anatomical changes. However, to date, neither the direction of tinnitus-related changes (increase or decrease of neuroanatomical gray matter (GM)) is clear, nor is it clarified whether the changes in the neural architecture 60 of distinct regions occur independently or are related.…”

“…Thus the question arises whether the inconsistency of available results may be related to methodological limitations of VBM measurements [33]. Certainly, VBM results are not straightforwardly comparable to the results of studies that applied a more innovative approach, namely 'surface-based morphometry' (SBM) in their investigations 75 into the structural signature of tinnitus [34]. As Panizzon and colleagues [36] argued, cortical volume (CV) as measured by the VBM approach is approximately the product of cortical surface area (CSA) and cortical thickness (CT).…”

“…With respect to all this heterogeneity in both the applied measurement techniques and the experimental operationalizations, it is advisable to proceed in small steps. Following suggestions by other scholars [33,48], our approach favors the replication of findings across independent research groups, as well as structural imaging methods (i.e., VBM and SBM) to increase both confidence and credibility of results [34]. Hence, we decided to replicate a large sample of recently published data that was intended to measure tinnitus-related structural changes of the human cortex [1].…”

“…Notably, the procedures for measuring CT have been validated against both histological analysis [56] and manual measurements [57,58,59], and have been shown to be reliable [60]. For the statistical analysis, each participant's reconstructed brain was morphed to an average spherical surface and smoothed using a FWHM kernel of 10 mm as applied in previous work [34]. CT is defined by the shortest distance between the gray/white matter border and pial surfaces, while CSA is the mean area of the triangular region at the respective surface data point (vertex).…”