Increased fiber density of the fornix in patients with chronic tinnitus revealed by diffusion-weighted MRI

Abstract

Up to 45% of the elderly population suffer from chronic tinnitus - the phantom perception of sound that is often perceived as ringing, whistling or hissing “in the ear” without external stimulation. Previous research investigated white-matter changes in tinnitus patients using diffusion-weighted magnetic resonance imaging (DWI) to assess measures such as fractional anisotropy (a measure of microstructural integrity of fiber tracts) or mean diffusivity (a measure for general water diffusion). However, findings overlap only minimally and are sometimes even contradictory. We here present the first study encompassing higher diffusion data that allow to focus on changes in tissue microstructure, such as number of axons (fiber density) and macroscopic alterations, including axon diameter (fiber bundle cross section), as well as a combination of both measures. In order to deal with the crossing-fibers-problem, we applied a fixel-based analysis using a constrained spherical deconvolution signal modeling approach. We investigated differences between tinnitus patients and control participants as well as how cognitive abilities and tinnitus distress are related to changes in white matter morphology in chronic tinnitus. For that aim, 20 tinnitus patients and 20 control participants, matched in age, sex and hearing loss, underwent DWI, audiometric and cognitive assessments, and filled in questionnaires targeting anxiety and depression. Our results showed increased fiber density in the fornix in tinnitus patients compared to control participants. The fornix, as a major output pathway of the hippocampus, constitutes an important part of the limbic system. The observed changes might, therefore, reflect compensatory structural alterations related to the processing of negative emotions accompanying chronic tinnitus.

What is the role of the hippocampus and parahippocampal gyrus in the persistence of tinnitus?

“…Additionally, here we have intentionally focused particularly on the hippocampal system, to consider the nature of tinnitus as a persistent memory, a cognitive process in which the hippocampus/PHG are most‐commonly implicated, rather than discussing in detail other mechanisms behind tinnitus that are undoubtedly relevant. These mechanisms have implicated several other brain regions beyond the hippocampus and auditory system, including nucleus accumbens, ventromedial prefrontal cortex, thalamic reticular nucleus, middle frontal gyrus, fornix, and precuneus (Leaver et al, 2011 ; Rauschecker et al, 2010 ; Rauschecker et al, 2015 ; Rosemann & Rauschecker, 2022 ; Rosemann & Rauschecker, 2023a ; Rosemann & Rauschecker, 2023b ), cerebellum (Bauer et al, 2013 ; Mennink et al, 2022 ), insula (Chen et al, 2023 ; Lenhardt et al, 2008 ), and cingulate cortex (Chen, Liu, et al, 2018 ; Golm et al, 2013 ). These structures likely play roles in tinnitus that are not necessarily mutually exclusive, including—but not limited to—those involved in persistence of a memory trace, gating of pathological auditory activity and emotional responses to a chronic phantom percept.…”