Sound-Paired Vagus Nerve Stimulation for Tinnitus: A Safety and Feasibility Trial

Objectives Tinnitus is the perception of sound in the absence of an external source, which is associated with unpleasantness and suffering in tinnitus disorder. Vagus nerve stimulation (VNS), paired with nontinnitus sounds, has shown promise in reversing tonotopic map changes seen in tinnitus. Alternatively, pairing a replica of the tinnitus sound with parasympathetic VNS could reduce tinnitus salience through Pavlovian reconditioning. We evaluated the safety and feasibility of paired and unpaired noninvasive VNS and tinnitus-matched auditory stimulation (AS) and assessed the effects on clinical outcomes, as well as activity and functional connectivity within tinnitus-related networks. Materials and Methods Participants ( N = 30, n = 10 in each group) with chronic, pure-tone tinnitus were randomized to receive simultaneous VNS and AS (sympathetic), AS delayed by five seconds after VNS onset (parasympathetic), or randomly placed VNS and AS (placebo). Participants received nine sessions of treatment over three weeks. We assessed safety and feasibility measures and tinnitus loudness ratings, as well as measures of psychologic distress, sleep, and electroencephalographic changes. Outcomes were collected at baseline, immediately post treatment, and at one-month follow-up. Results No serious adverse events were reported, and the paired stimulation treatment was feasible. No significant differences were found between groups for changes in tinnitus loudness or tinnitus functional index. The delayed AS group showed significantly reduced tinnitus unpleasantness, anxiety, and Pittsburgh Sleep Quality Index scores. Electroencephalographic changes were identified in regions involved in tinnitus and unpleasant sound processing. Conclusions VNS paired with tinnitus-matched sound was safe and feasible. Exploratory analyses suggested possible reductions in tinnitus sound unpleasantness, sleep dysfunction, and anxiety in the delayed AS group. A fully powered trial with predefined efficacy outcomes and appropriate correction for multiple comparisons is warranted to confirm these findings, verify parasympathetic activation from noninvasive VNS, and investigate the longer-term effects of this intervention.