Chronic tinnitus and the limbic system: Reappraising brain structural effects of distress and affective symptoms

Abstract

Chronic tinnitus has been associated with brain structural changes in both the auditory system as well as limbic system. While there is considerable inconsistency across brain structural findings, growing evidence suggests that distress and other non-auditory symptoms modulate effects. In this study we addressed this issue, testing the hypothesis that limbic changes in tinnitus relate to both disease-related distress as well as co-morbid psychopathology. We obtained high-resolution structural magnetic resonance imaging (MRI) scans from a total of 125 subjects: 59 patients with bilateral chronic tinnitus (29 with a co-morbid psychiatric condition, 30 without), 40 healthy controls and 26 psychiatric controls with depression/anxiety disorders (without tinnitus). Voxel-based morphometry with the CAT12 software package was used to analyse data. First, we analysed data based on a 2 × 2 factorial design (tinnitus; psychiatric co-morbidity), showing trend-level effects for tinnitus in ROI analyses of the anterior cingulate cortex and superior/transverse temporal gyri, and for voxel-based analysis in the left parahippocampal cortex. Multiple regression analyses showed that the parahippocampal finding was mostly predicted by tinnitus rather than (dimensional) psychopathology ratings. Comparing only low-distress tinnitus patients (independent of co-morbid conditions) with healthy controls also showed reduced left parahippocampal grey matter. Our findings demonstrate that depression and anxiety (not only subjective distress) are major modulators of brain structural effects in tinnitus, calling for a stronger consideration of psychopathology in future neurobiological and clinical studies of tinnitus.

Keywords: Anxiety; Co-morbidity; Depression; Distress; Limbic system; Tinnitus; Voxel-based morphometry (VBM).

Fig. 1

Results of two-sample t-test between low-distress tinnitus patients and healthy controls presented as maximum intensity projections and overlays on an average image of all participants, (A) significant clusters of decreased GMV in patients, (B) significant clusters of increased GMV in patients.

Fig. 2

Main effect of tinnitus diagnosis in the 2 × 2 factorial ANOVA presented as maximum intensity projections and section overlays on an average image of all participants.

Fig. 3

Bar graphs illustrating predictive values of the four to five main factors contributing to GMV decrease in low-distress tinnitus patients compared to healthy controls in (A) left parahippocampal gyrus (accuracy 53.7%), (B) and (C) left middle cingulate gyrus (accuracy 57.1% resp. 29.9%) and (D) left ACC (accuracy 55.5%). TIV – total intracranial volume, HAM-D – Hamilton depression inventory, EHI – Edinburgh handedness inventory, Tin_dg – tinnitus diagnosis, SCL – symptom checklist 90 revised (SOM – subscale for somatoform symptoms, INT – subscale for symptoms of social insecurity, PHO – phobic symptoms), HAM-A – Hamilton anxiety inventory, 4-PTA_r – right-sided 4- pure tone audiogram.

Fig. 4

Bar graphs illustrating predictive values of the four to eight main factors contributing to GMV decrease as the main effect of tinnitus (with and without psychiatric comorbidity) compared to controls with and without psychiatric illness in (A) left parahippocampal gyrus (accuracy 44.3%), (B) right inferior parietal gyrus (accuracy 43.9%) and (C) right precuneus (accuracy 33.4%). TIV – total intracranial volume, Tin_dg – tinnitus diagnosis, SCL – symptom checklist 90 revised (PSY – subscale for psychotic symptoms, PAR – subscale for paranoid symptoms, OBS – subscale for obsessive-compulsive symptoms, Z – subscale for sleep disturbances), BDI-2 – Beck's depression inventory, HAM-A – Hamilton anxiety inventory, HADS-A – anxiety subscale of hospital anxiety and depression scale.