Abstract
Extensive preclinical animal studies show that that pairing nontinnitus sounds with vagus nerve stimulation (VNS) results in tonotopic map plasticity, normalizing the abnormal tonotopic map that has been linked to hearing loss and consequently potentially, albeit indirectly, to tinnitus.
Based on this preclinical work, VNS has been proposed as a novel treatment for chronic tinnitus. Current protocols involve pairing sounds, which exclude the tinnitus frequency, with concurrent VNS.
These findings have been translated into a clinically applicable approach in human studies, demonstrating a statistically significant, clinically small, but inconsistent improvement in tinnitus distress (17.7 points on THI but no significant improvement on other tinnitus distress measures) and a very modest benefit in tinnitus loudness (±1.2–1.8/10). This marginally reaches the minimal clinically important difference of 1.5. Yet, these outcomes are not better than VNS without sound presentation, as shown by a retrospective study in epilepsy patients, in which tinnitus loudness improved by 2/10 points on a VAS after VNS without sound presentation.
From a theoretical perspective, pairing tinnitus-matched sound to VNS may produce tinnitus improvement by Pavlovian conditioning, in which the distressful tinnitus sound becomes associated with a relaxing “rest and digest” response from activation of the vagus nerve. If this hypothesis is correct, beneficial effects should be achieved with paired sounds that resemble the tinnitus sounds as much as possible, i.e., the opposite of what is currently proposed.
In conclusion, although the potential to use VNS to drive neural plasticity to reduce or eliminate tinnitus is exciting, much research is needed to better understand the neural basis of tinnitus and to develop tailored therapies for this heterogeneous condition. Whether pairing of the vagus stimulation with nontinnitus or tinnitus-matched sounds is essential is still to be determined.