Effectiveness of bimodal auditory and electrical stimulation in patients with tinnitus: A feasibility study

Spencer, Shikha; Mielczarek, Marzena; Olszewski, Jurek; Sereda, Magdalena; Joossen, Iris; Vermeersch, Hanne; Gilles, Annick; Michiels, Sarah

doi:10.3389/fnins.2022.971633

Cited by 7 publications

(9 citation statements)

References 72 publications

(105 reference statements)

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“…In a study by Hall et al, acoustic coordinated reset neuromodulation, a unimodal auditory stimulation paradigm that was hypothesized to desynchronize pathological brain activity, led to no significant improvement for participants who used it, which was consistent with animal-model studies that have reported auditory-only treatment to be ineffective in reducing tinnitus . Transcutaneous electrical stimulation of the tongue combined with auditory stimuli resulted in statistically but not clinically significant reduction in the TFI scores 9 to 12 weeks after receiving treatment . Changing the stimuli halfway through the treatment resulted in an additional mean reduction to reach a clinically significant decrease at the 12-week point .…”

Section: Discussionmentioning

confidence: 61%

“…The treatment led to a statistically but not clinically significant reduction in TFI score of 6.9 points 9 to 12 weeks after treatment. Of 29 participants, only 6 could modulate their tinnitus (eg, somatic tinnitus), and the study was insufficiently powered to compare the effect of bisensory stimulation on patients with vs without somatic tinnitus …”

Section: Discussionmentioning

confidence: 99%

“…Of 29 participants, only 6 could modulate their tinnitus (eg, somatic tinnitus), and the study was insufficiently powered to compare the effect of bisensory stimulation on patients with vs without somatic tinnitus. 29 None of these studies used a control or sham group or nontreatment group; thus, all participants were aware that they were receiving an active treatment, increasing the risk for placebo effects. 30 In contrast, the current trial had a control or sham group that received auditory-only stimulation.…”

Section: Comparisons To Other Treatmentsmentioning

confidence: 99%

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Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

et al. 2023

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ImportanceAnimal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; however, precise treatment using bisensory (auditory and somatosensory) stimuli can reverse altered neural patterns and lessen tinnitus.ObjectiveTo confirm and extend the findings of a pilot study, which suggested an increased efficacy of bisensory stimulation, to a clinical trial with a greater duration and greater number of participants.Design, Setting, and ParticipantsThis double-blind, crossover, single-center randomized clinical trial was conducted from March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System in Ann Arbor, Michigan. Eligibility criteria included bothersome tinnitus (Tinnitus Functional Index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatments in the 6 months prior to the trial. Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment. Results were analyzed using intent-to-treat (ITT) and per protocol (PP) populations.InterventionPrecisely timed bisensory (combined auditory and somatosensory) treatment was delivered through a portable, custom, take-home device that was provided to each participant for daily, at-home treatments. Group 1 participants received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Group 2 participants received the auditory-only treatment first, followed by a washout phase, and then the bisensory treatment followed by a second washout phase.Main Outcomes and MeasuresPrimary end points were changes in TFI score and tinnitus loudness level from baseline through week 6 and week 12.ResultsOf 337 screened individuals, 99 (mean [SD] age, 47 [12.7] years; 59 males [60%]; 85 with non-Hispanic White [86%] race and ethnicity) were enrolled into the study and randomized to treatment group 1 (n = 49) or group 2 (n = 50). The active but not the control treatment resulted in clinically significant decreases in TFI scores at week 6 of phase 1 (ITT population: –12.0 [95% CI, –16.9 to –7.9] points; P &lt; .001; PP population: –13.2 [95% CI, –16.0 to –10.5] points; P &lt; .001). Decreases in tinnitus loudness level were greater than 6 dB sensation level (SL; &gt;half as loud) at week 6 for the bisensory treatment group, with little effect for the auditory-only treatment control group at week 6 of phase 1 (ITT population: –5.8 [95% CI, –9.5 to –2.2] dB; P = .08; PP population: –7.2 [95% CI, –11.4 to –3.1] dB; P = .03), and up to 11 dB SL at week 12 of phase 2 (ITT population: –10.9 [95% CI, –15.2 to –6.5] dB; P = .001; PP population: –14.1 [95% CI, –18.4 to –9.8] dB; P &lt; .001). Decreased tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect.Conclusions and RelevanceThis trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms can result from using an extended treatment duration.Trial RegistrationClinicalTrials.gov Identifier: NCT03621735

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Comparisons To Other Treatmentsmentioning

confidence: 99%

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Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

et al. 2023

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“…People with severe tinnitus are often afflicted with depression, anxiety, and sleep disturbance, which adversely affect their life quality. 24 Despite numerous studies on tinnitus, the mechanism underlying tinnitus is still not fully understood, highlighting the need of further exploration. Salicylate, an ototoxic drug, has been widely adopted to induce tinnitus.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus

Zhu

Chen

et al. 2023

J Neurol Surg B Skull Base

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Purpose Tinnitus is a phantom perception of sound in the absence of acoustic source. Previous evidence has indicated that miR-375-3p is downregulated in rats with tinnitus in comparison to the controls. Nevertheless, its molecular mechanism underlying tinnitus pathogenesis is unclarified. Methods SH-SY5Y cells were differentiated into neuronlike cells and stimulated with salicylate to mimic tinnitus in vitro. Immunofluorescence staining was utilized for measuring expression of NR2B (glutamate ionotropic receptor NMDA type subunit 2B). Intracellular reactive oxygen species (ROS) level was determined using DCFH-DA assay kit. Real-time quantitative polymerase chain reaction as well as western blotting was utilized for examining RNA and protein levels. Luciferase reporter assay was implemented for verifying the interaction between miR-375-3p and ELAVL4 (ELAV-like RNA-binding protein 4). Results Salicylate treatment enhanced levels of NR2B and the early immediate gene ARC as well as ROS production. miR-375-3p was downregulated in salicylate-treated group. Overexpressing miR-375-3p attenuated the effects induced by salicylate in SH-SY5Y cells. miR-375-3p targeted ELAVL4 and upregulating ELAVL4 reversed miR-375-3p upregulation–triggered effects on SH-SY5Y cells under salicylate treatment. Conclusion miR-375-3p mitigates salicylate-triggered neuronal injury in SH-SY5Y cells by regulating ELAVL4 expression.

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“…HNS offers a novel approach grounded in the intricate neural circuitry associated with auditory processing. Recent studies have investigated the modulatory effects of HNS on the central auditory system, suggesting its potential to influence the aberrant neural activity implicated in tinnitus generation 49,50 . The hypoglossal nerve, traditionally recognized for its role in tongue motor control, now presents an intriguing target for neuromodulation-based interventions for tinnitus.…”

Section: Progressive Tinnitus Management (Ptm)mentioning

confidence: 99%

Tinnitus News, Review, and Update: 2024

Beck,

Darrow

2024

The Hearing Journal

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Effectiveness of bimodal auditory and electrical stimulation in patients with tinnitus: A feasibility study

Cited by 7 publications

References 72 publications

Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus

Tinnitus News, Review, and Update: 2024

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