Effect of Simultaneous Use of Neuromodulation and Acoustic Stimulation in the Management of Tinnitus

Abstract

Tinnitus is a relatively common disorder with a heterogeneous nature. Combining methods in its treatment may offergreater effectiveness. We aim to explore the impact of concurrently applying tRNS neuromodulation and acousticstimulation for tinnitus control. Thirty-two tinnitus patients participated in this study, divided into two groups. Thefirst group underwent 8 sessions of electrical stimulation (tRNS) and acoustic stimulation simultaneously, while thesecond group received only tRNS. The outcomes were assessed using psychoacoustic evaluation and tinnitushandicap inventory (THI) and visual analog scale (VAS) for loudness and annoyance of tinnitus. The SF-36questionnaire was utilized to evaluate the quality of life before, and immediately after intervention and at one monthfollow-up. A notable reduction in tinnitus loudness was observed in both groups. There were significant differences inTHI scores before and after the intervention for both groups. However, the first group exhibited larger effect sizes forchanges in loudness and THI scores. The scores of the SF-36 questionnaire improved in both groups, the increase ingeneral health and emotional scores was particularly significant in the first group. According to the results of thisstudy, using electrical and acoustic stimulation simultaneously with dual-modality stimulation is more effective inreducing the loudness and annoyance of tinnitus, compared to the use of electrical stimulation alone.

Introduction

Tinnitus is characterized by a persistent perception of sound without an external source. Statistical studies indicate that approximately 10 to 20% of adults experience tinnitus, with 2 to 3% experiencing severe impacts on their quality of life. (1–2). Chronic tinnitus typically involves persistent sound perception, resistance to treatment, and accompanying distress. Furthermore, tinnitus may coincide with sleep disturbances, cognitive issues, anxiety, and emotional challenges. These characteristics may stem from an individual’s difficulty in habituating to the sound [1–3].

Despite the relatively high prevalence of tinnitus, no definite and selective treatment has yet been identified for it [4]. Various methods such as sound therapy, TRT, cognitive behavioral therapy, magnetic stimulation, electrical stimulation, and music therapy have been used to control tinnitus. The absence of a definitive treatment for tinnitus is partly attributed to its heterogeneous nature and the incomplete understanding of its pathophysiology. Neuroimaging studies have identified various brain regions implicated in tinnitus, including the prefrontal cortex, cingulate cortex, amygdala, hippocampus, and parahippocampus. These regions exhibit functional connections with the auditory cortex, collectively forming what is known as the “tinnitus network“ [5–7].

Within each brain network, multiple nodes possess diverse structural and functional connectivity. Rich hubs refer to nodes exhibiting the highest functional connectivity, capable of modulating the function of other nodes within the same or different networks. For instance, the dorsolateral prefrontal cortex (DLPFC) serves as a rich hub, influencing the function of other areas such as the auditory cortex and the anterior cingulate cortex (ACC). Leveraging the network model can offer valuable insights into developing tinnitus treatment strategies involving neuromodulation [7–10].

Neuromodulation is a technique that directly addresses nerve activity by employing methods such as electrical or magnetic stimulation, or the introduction of chemicals to specific parts of the body. This approach induces changes or regulation of nerve activity, offering potential therapeutic benefits for various conditions [11]. After neuromodulation, alterations in neuron function occur through changes in the active or passive function of ion channels, adjustments in presynaptic release, or modifications in postsynaptic responsiveness. In the context of tinnitus treatment, neuromodulation techniques primarily involve non-invasive approaches such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS). tDCS utilizes low-intensity direct current, while tACS employs alternating current [12, 13]. tRNS is a form of electrical stimulation utilized in tinnitus relief. It involves a modified version of white noise spanning the frequency range of 0.1 to 640 Hz. Several electrophysiological studies have highlighted fewer side effects, such as itching and burning sensations, associated with the application of tRNS compared to other forms of electrical stimulation [14–18]. The findings of some studies have also shown more effectiveness in the use of tRNS than tDCS and tACS in tinnitus control [1, 19–22].

Sound therapy has been formally recognized and employed as a therapeutic approach for managing tinnitus. This method involves augmenting external sounds within the auditory system, which in turn diminishes the perception of tinnitus [23–26]. fMRI studies have revealed alterations in various nerve centers after the implementation of sound therapy. These changes include heightened activity in regions such as the posterior cingulate cortex, anterior cingulate cortex, angular gyrus, and inferior frontal gyrus [27, 28]. Indeed, the brain centers highlighted are associated with functions pertinent to both the generation and alleviation of tinnitus, implicated in emotion regulation and self-awareness processes [23].

Given the noteworthy impact of tRNS compared to other forms of electrical stimulation in ameliorating tinnitus, alongside the established efficacy of sound therapy in tinnitus management, this study aims to explore the combined effect of these two methods on tinnitus. To the best of our knowledge, the simultaneous application of sound therapy and repeated sessions of tRNS for tinnitus control has not been investigated in prior studies. Therefore, this research seeks to fill this gap in the literature and elucidate the potential synergistic effects of combining these interventions.

Material and Method

In this study, 32 participants (14 female) with chronic tinnitus (lasting more than 6 months) were recruited. Individuals with a history of neurological disorders, epilepsy, pacemaker usage, pregnant women, and those exhibiting hearing thresholds exceeding 25 dB in the frequency range of 250 to 8000 Hz were excluded from the study. Statistical analyses were performed using spss software(V26).

The participants were randomly allocated into two groups. The first group underwent 8 sessions of simultaneous electrical and acoustic stimulation, while the second group received only electrical stimulation.

Prior to any intervention, the participants underwent hearing assessments conducted by an experienced audiologist. Psychoacoustic evaluations of tinnitus, encompassing pitch and loudness matching of tinnitus, minimum masking level, and residual inhibition (RI), were performed. Psychometric evaluations utilized the Persian version of the Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) to assess loudness and annoyance. Additionally, participants completed a quality of life questionnaire (SF-36).

THI is one of the most reliable tinnitus self-assessment questionnaires, which includes 25 questions and examines various functional and emotional aspects of tinnitus. The loudness and annoyance of tinnitus were evaluated with the VAS scale, during which the individual gives a score from 0 to 10 depending on the severity of the tinnitus problem. To determine the effectiveness of the intervention, psychoacoustic and psychometric evaluations are repeated after the intervention and so 1 month later.

tRNS was performed using a Segalsteam device (Farmed Iran). A current of 2 milliamps at the high-frequency range (100–640 Hz) was provided using a pair of electrodes with a surface area of ​​35 cm2 and covered with a sponge soaked in normal saline. The electrodes were placed at the prefrontal cortex (positive at the f3 and the negative electrode at the f4 according to the 10–20 international electroencephalography system). Presentation sessions of tRNS were performed during three weeks with a minimum interval of two days between each session. The duration of stimulation in each session was 20 min.

The acoustic stimulus was wideband noise that was produced using the Adobe Audition program in the frequency range of 100 to 20,000 Hz with an amplitude difference of less than 1 dB in this frequency range. Broadband noise was presented to the ears of the first group for 20 min through headphones simultaneously with the presentation bifrontal electrical stimulation (tRNS).

All the methods of this study have been approved by the ethics committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1401.982) and registered under the number IRCT20120215009014N462.

Results

The participants of this study were 32 patients with chronic tinnitus (14 women and 18 men). The mean age was 46.54 ± 8.67 years (range 23–61 years). These patients were divided into two groups. The first group included 8 women and 9 men and the second group included 6 women and 9 men. 14 patients had tinnitus in the left ear, 11 patients had tinnitus in the right ear, and 7 patients had tinnitus in both ears. The average duration of tinnitus onset was 18 ± 21 months. The mean VAS score of loudness and annoyance before the intervention was 6.43 ± 1.9 and 5.98 ± 1.4, respectively.

The average loudness of tinnitus based on psychoacoustic evaluation after 8 sessions of electric and acoustic stimulation simultaneously in the first group and 8 sessions of tRNS in the second group showed a significant reduction compared to before the intervention, and this reduction was greater in the first group (Table 1).

Table 1.

Comparison of the loudness of tinnitus, before and after intervention and 1month follow-up between two groups

	before	after	1month follow	p value	effect size
group1	5.86	4.75	4.49	0.001	0.672
group2	5.73	5.31	5.36	0.031	0.576

Table 2 illustrates the effect of combined electrical and acoustic stimulation on tinnitus, as quantified by the THI scores. For the first group, which received both electrical and acoustic stimulation, there was a notable reduction in average THI scores, indicating a significant improvement in the perceived handicap from tinnitus. This improvement was statistically significant immediately following the intervention and persisted at the 1-month follow-up, underscoring the lasting impact of the treatment. The effect size of THI reduction in the first group surpassed that in the second group, highlighting the enhanced efficacy of combining treatments.

Table 2.

Comparison of THI scores, before and after intervention and 1month follow-up between two groups

	before	after	1month follow	p value	effect size
group1	49.85	43.09	42.68	0.001	0.949
group2	50.06	46.17	49.45	0.001	0.989

Regarding VAS assessments, both groups exhibited a decrease in scores for loudness and annoyance post-intervention, indicating an overall reduction in the perceived severity and disturbance of tinnitus. However, this decrease was only statistically significant in the first group, suggesting that the simultaneous application of electrical and acoustic stimulation was more effective in reducing the subjective loudness and annoyance of tinnitus than electrical stimulation alone (Table 3). This differential outcome emphasizes the potential benefit of a multimodal treatment approach in managing tinnitus symptoms.

Table 3.

Comparison of VAS of loudness, before and after intervention and 1month follow-up between two groups

	before	after	1month follow	p value	effect size
group1	6.43	5.15	5.82	0.001	0.780
group2	5.98	5.65	5.68	0.051	0.696

According to the SF-36 questionnaire, the mean scores of physical function were 49.8 ± 7.18 in group 1 and 51.38 ± 12.04 in group 2 before any intervention. After 8 sessions of tRNS and sound therapy in group 1 and 8 sessions of tRNS in group 2, these scores increased to 58.31 and 59.24 in groups 1 and 2 respectively. These increases were statistically significant. The mean scores of general health, social function, and emotional effects were 61.2 ± 6.5 7, 74.8 ± 10.78, and 69.8 ± 8.98, respectively before intervention in group (1) These scores were 59.7 ± 6.97, 70.43 ± 10.03, and 65,9 ± 8.76 for group (2) The scores of the quality of life questionnaire in all four mentioned aspects increased after the intervention in both groups. In the first group, the increase in the general health and emotional score was statistically significant(p < 0.05). In the second group, the increase in the emotional score was significant, and the increase in the general health score and social functions was not significant(p > 0.05).

Discussion

In this research, the impact of dual-modality stimulation, achieved through concurrent application of tRNS and acoustic stimulation, was juxtaposed against the effects of tRNS alone. To this end, 32 individuals experiencing chronic tinnitus were randomly allocated into two grous. The initial group was subjected to 8 sessions of tRNS in conjunction with acoustic stimulation, while the latter group underwent 8 sessions of solely tRNS. To the best of our awareness, this constitutes the inaugural investigation where the amalgamation of tRNS and acoustic stimulation has been employed in the treatment of tinnitus.

The results of this study showed a significant reduction in the loudness and THI scores in both groups, with the reduction being remarkably grater in group 1. There are reports in EEG studies of an increase in alpha waves after using tRNS sessions [29, 30]. Because alpha waves exert an inhibitory influence on other sensory regions, their amplification results in diminished excitability within the auditory cortex, culminating in a reduction of tinnitus loudness. This decrease in both tinnitus loudness and its associated distress following repeated tRNS sessions aligns with the outcomes presented by Mohsen. In his investigation involving 29 tinnitus patients, Mohsen documented a notable decrease in both the loudness and distress of tinnitus after administering 8 sessions of tRNS [31].

Some studies have also used electrical stimulation combined with music for the treatment of tinnitus. The findings of these studies have shown that this combined approach yielded a greater reduction in distress and annoyance of tinnitus [32, 33].

The findings of our study indicate that the additional reduction in tinnitus loudness observed after using simultaneous tRNS and acoustic stimulation is clinically significant and yields a larger effect size compared to using tRNS alone. As illustrated in Table 2, a notable decrease in tinnitus loudness was evident, particularly in the first group, where tRNS was combined with acoustic stimulation to both ears. This reduction in loudness can be attributed to the modulation of the distress network via tRNS stimulation applied to the prefrontal region, as indicated by the VAS results.

Furthermore, as depicted in Table 1, a greater reduction in THI scores was observed in group 1, accompanied by a larger effect size. The improvement in THI scores is likely attributed to the plasticity induced by repeated sessions of tRNS, which modulates abnormal activity in the distress and salience network. The use of acoustic stimulation and sound therapy leads to a person focusing less on tinnitus and reducing sensitivity to tinnitus over time [34].

In the first group, the concurrent application of sound therapy along with electrical stimulation resulted in a decrease in stress and anxiety levels, as well as facilitated habituation to tinnitus. This comprehensive approach contributed to a more significant reduction in THI scores than the second group.

One of the key findings of this study was the observed improvement in sleep quality reported by patients following repeated sessions of tRNS and acoustic stimulation. This improvement is likely attributed to the reduction in anxiety and tinnitus loudness, which typically disrupts sleep. The alleviation of distress and anxiety associated with tinnitus, coupled with the enhancement of sleep quality, ultimately contributed to an improvement in overall quality of life, as indicated by the assessments from the quality of life questionnaires.

Conclusion

The analysis of the study’s findings revealed that employing tRNS in conjunction with acoustic stimulation, which concurrently targets two modalities, resulted in greater improvements in tinnitus compared to using only tRNS. Consequently, given the heterogeneous nature of tinnitus, it is recommended to adopt combined treatments for tinnitus management.

Author Contributions

Maryam Emadi: Corresponding author, Conceptualization, Funding Acquisition, Methodology, Supervision, Writing; Reza Faraji: Conceptualization, Methodology, Review & Editing; Morteza Hamidinahrani: Conceptualization, Funding, Acquisition; Atta Heidari: Conceptualization, Review & Editing.

Funding

This study was financially supported by Hamadan University of Medical Sciences (grant number 14020219905).

Declarations

Ethical Approval

The study protocol was approved by the Medical Ethics Committee of the Hamadan University of Medical Science (as per the Ethics Code IR.UMSHA.REC.1401.982).

Conflict of Interest

The authors declare that they have no conflicting interests.