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

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.