Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction

Abstract

Introduction: Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy.

Methods: Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data.

Results: The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires.

Conclusion: TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS.

Keywords: neuromodulation; parasympathetic; patients; stress; tinnitus; vagus.

FIGURE 1

(A) The most common cause of tinnitus was acoustic overstimulation (noise-induced tinnitus, NIT; 47%), followed by self-reported stress (6%), otitis media (4%) and other causes (2%). The cause was unknown in 40%. (B) The most common tinnitus frequency was between 7 and 9 kHz (27%), (marked as 8), followed by 11–14 kHz (19%), (marked as 12), 9–11 kHz (14%), (marked as 10), 5–7 kHz (13%), (marked as 6). In 9 patients (5%) tinnitus frequency was >14.0 kHz, in 17 patients (10 %) between 3 and 5 kHz (marked as 4), in 11 patients (7 %) between 1 and 3 kHz (marked as 2) and in seven patients (4%) < 1.0 kHz.

FIGURE 2

THI was between 34 and 100 in 81% of patients. The mean THI value was 55 and the mean VAS-scaled (0–100) values of both loudness and annoyance were 55. Tinnitus was associated with sleep disturbances in 92% and with anxiety in 96%, both being severe or very severe (>50/100 in VAS scale) in 57% and 54% of patients, respectively.

FIGURE 3

Correlations between HRV parameters between Group A (below 41 years) and Group B (above 63 years) shown in Table 2. The taVNS-induced numerical increases of these three HRV parameters were greater in the older group. However, only the RMSSD changes reached statistical significance.

FIGURE 4

Comparison between taVNS responses and questionnaire-based clinical data and tinnitus frequency in groups A (super-responders) and B (non-responders), shown in Table 3. The mean values of THI, sleep disturbance, anxiety and tinnitus frequency were all greater in group A, but the differences were not statistically significant. Error bars represent standard deviations. THI = tinnitus handicap inventory.

FIGURE 5

(A) Results of 1-year-follow-up outcome of 113 patients of which 78 (69%) data was received. Tinnitus annoyance had decreased in 72% and tinnitus-triggered stress in 82%. Symptoms had increased in 2%. (B) 76% of patients reported that they had benefited from TCPT treatment, including taVNS; 41% would recommend and 52% possibly recommend TCPT plus taVNS t for a friend or relative if suffering from similar health problems. (C) Of the components of treatment, counseling was reported most helpful (score 3.4 from the range 1–5), followed by taVNS (3.1) and sound therapy (2.8).

FIGURE 6

(A) Summary of the hypothesis. Noise exposure (most commonly music) causes dysfunction/damage in the high-frequency (>6.0 kHz) region of the cochlea) in >85% of patients. This leads to high-pitched tinnitus, most commonly at about 8.0 kHz. Bioelectrical impulse flow from the damaged cochlear region toward auditory cortex diminishes or ceases (”dead” region). This leads to reduced (inhibitory) regulation with subsequent neuronal hyperactivity in the central auditory pathway, first in the auditory nuclei of brainstem, later in the auditory cortex. The normal (spontaneous) alpha activity (in EEG) changes to gamma activity. The central auditory pathway is intimately connected to the limbic system (that controls emotions). Tinnitus is experienced as an emotionally negative sensation including uncertainties and fears (”what is this all about?”; “does it ever go away?”). Thereby, the perceptive (hearing) network is connected to the distress network (stress). The stressor leads to imbalance of the central autonomous network (CAN) with hyperactivity of the sympathetic nervous system (flight or fight or freeze response) and, correspondingly reduced activity of the parasympathetic nervous system (PNS) (relax, calm down). (B) Vagus nerve is the main player of the PNS. Therefore, activation of the vagal system increases PNS activity. For taVNS we have used a specially designed Salustim device that uses an ear-clip electrode inserted to the tragus and electrically stimulates ABVN. The taVNS reverses sympathetic hyperactivity in the limbic system and the CAN imbalance toward parasympathetic direction. Reduction of distress also facilitates the reversal of gamma-hyperactivity back to normal alpha-activity in the auditory central pathway.