Abstract
As the COMT polymorphism is especially prominent in the prefrontal cortex and has been associated with auditory gating, we hypothesize that tinnitus patients with this polymorphism have altered activity in the ventromedial prefrontal/anterior cingulate areas that modulates the tinnitus percept. To test this, we recruited a total of 40 tinnitus subjects and 20 healthy controls for an EEG study. A comparison between tinnitus subjects and healthy controls and their frequency of being Val/Val genotype or Met carriers (including Val/Met and Met/Met genotype) shows no significant effect, suggesting that the distributions for the tinnitus and healthy groups are similar. Our results show that an interaction between the amount of hearing loss and the COMT Val158Met polymorphism can increase susceptibility to the clinical manifestation of tinnitus. We further demonstrate that the parahippocampus becomes involved in tinnitus in patients with hearing loss that are Met carriers. In these patients, the parahippocampus sends more tinnitus information to the pregenual anterior cingulate cortex and auditory cortex that is specifically related with increased loudness. At the same time, the pregenual anterior cingulate cortex, which normally functions as a gatekeeper, is not cancelling this auditory information, ultimately leading to increased tinnitus loudness.
•Hearing loss and the COMT Val158Met polymorphism interaction increases the clinical manifestation of tinnitus.•Parahippocampus becomes involved in tinnitus in patients with hearing loss that are Met carriers.•Parahippocampus sends tinnitus related information to the pregenual anterior cingulate cortex.•Pregenual anterior cingulate cortex, which normally functions as a gatekeeper, is not cancelling this auditory information, leading to increased tinnitus loudness.