Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial

Abstract

More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen’s d effect size for full treatment period per arm and outcome measure ranged from − 0.7 to − 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.

Bimodal stimulation for the reduction of tinnitus using vibration on the skin

“…The experimental group showed improvements in their TFI score that match or exceed previous research employing electric shocks on the tongue instead of vibrations on the wrist. Conlon et al (2020Conlon et al ( , 2022 found TFI improvements at week 12 between -10 and -15 points for three experimental groups, while Marks et al (2018) found an average TFI improvement of -8 points over 4 weeks. In comparison, our experimental group showed improvement of -14.3 for all participants, and -21.8 for those with moderate to severe tinnitus (baseline TFI score 50+).…”

“…The results of this study lay the framework for future research to investigate how different patterns and frequency ranges of tones affect the efficacy of treatment. Conlon et al (2022) showed that changing the parameter settings after 6 weeks of treatment allowed study participants to continue to make progress for an additional 6 weeks. This was an improvement on the findings of their prior study in which study participants experienced the greatest amount of progress in the first 6 weeks, but then plateaued for the final 6 weeks.…”

“…Shocks on the tongue were used based on the hypothesis that the key to bimodal stimulation was activity in the dorsal cochlear nucleus, where information from the ears first converges with haptic stimulation from the head and neck; therefore, tactile stimulation of the tongue seemed to be the appropriate haptic input. Next, other researchers demonstrated that bimodal stimulation works with a variety of timing characteristics between shock and tone and that the treatment had high compliance and satisfaction rates (Conlon et al 2020, 2022), although it should be noted that this paper did not present a control group.…”

“…Bimodal stimulation is a relatively new treatment used to alleviate the symptoms of tinnitus. Researchers demonstrated that pairing auditory tones with small shocks on the tongue reduced the symptoms of tinnitus (Conlon et al, 2020(Conlon et al, , 2022Marks et al, 2018;Riffle et al, 2021). In those studies, the tongue was chosen based on the hypothesis that bimodal stimulation requires synchronous activity in the dorsal cochlear nucleus, where information from the ears first converges with haptic stimulation from the head and neck (Kaltenbach et al, 2005); therefore, tactile stimulation of the tongue seemed to be the appropriate haptic input.…”

Activate & fire: a feasibility study in combining acoustic stimulation and continuous theta burst stimulation in chronic tinnitus

“…The concept of bimodal auditory and central stimulation has already been investigated by combinations of acoustic stimulation/ sound therapies with transcranial direct current stimulation, likewise demonstrating inconclusive findings so far [53][54][55]. However, acoustic stimulation combined with stimulation of cranial nerves such as the vagus or the trigeminal nerve shows promising findings [56][57][58][59].…”