Vagus nerve stimulation for tinnitus: A review and perspective.

Vagus nerve stimulation is a promising new tool in the treatment of chronic tinnitus. Current protocols involve pairing sounds, which exclude the tinnitus frequency, with simultaneous vagus nerve stimulation (VNS). This is based on extensive preclinical animal studies that demonstrate that pairing non-tinnitus sounds with VNS results in a tonotopic map plasticity. It is thought that by expanding the non-tinnitus sound representation, it is possible to overturn the expanded tonotopic map associated with the tinnitus frequency in these animal models. These findings have been translated into a clinical approach, where a clinically significant, but moderate improvement, in tinnitus distress and a modest benefit in tinnitus loudness perception has been shown. Yet, 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. In conclusion, although the potential to use VNS to drive neural plasticity to reduce or eliminate the neural drivers of ongoing tinnitus is exciting, much work is needed to more completely understand the neural basis of tinnitus and to develop tailored therapies to address the suffering caused by this heterogeneous condition. Whether pairing of the vagus stimulation with non-tinnitus or tinnitus-matched sounds is essential is still to be determined.