Tinnitus Rehabilitation Through Electrical Stimulation as a Neuromodulation Method: A Scoping Review

Abstract

Background

Tinnitus is the perception of sound without any external sound source, affecting about 10–15% of the world’s population. Electrical stimulation, especially transcranial direct current stimulation (tDCS), has shown promising and also heterogeneous results in improving tinnitus symptoms. The present study is a review of the clinical effectiveness and ideal stimulation parameters of the tDCS in tinnitus rehabilitation studies.

Methods

The study was conducted based on PRISMA guidelines and through PubMed and Scopus databases and Google Scholar search engines from 1990 to 2024. Only controlled and randomized trials that used tDCS for tinnitus rehabilitation were considered.

Results

Based on the entry criteria, 14 articles were selected. 12 studies reported some degrees of improvement in symptoms following tDCS sessions, while two did not report any improvement. The maximum number of sessions was 10, and the duration of sessions was 10 to 20 min. The usual current intensities were 1–2 mA. The auditory cortex and dorsolateral prefrontal cortex (DLPFC) were the selected sites for electrical stimulation.

Conclusion

The tDCS can be considered an effective technique for tinnitus management in some patients with tinnitus. One of the main challenges in using tDCS for such patients is its standard stimulus parameters. Randomized, double-blind, placebo-controlled trials with a large homogenous sample size are recommended to reach a definitive conclusion about the standard stimulus parameters of tDCS for tinnitus management.

Introduction

Tinnitus is the perception of sound in the absence of any external sound source, which is related to plastic changes in the auditory cortex caused by the replacement mechanism associated with auditory deafferentation [1]. Studies show that increased neural spontaneous activity in different levels of the auditory system and changes in the cortical tonotopic organization are associated with the tinnitus compliant as a different cause from presbycusis or noise exposure to Covid 19 [2]. These data are consistent with the thalamocortical dysrhythmia (TCD) model. TCD is explained by the changes in brain oscillations: delta (0.5–3 Hz) theta (4–7 Hz), alpha (8–12 Hz), beta (12.5–30 Hz), and gamma (30–60 Hz). TCD suggests that tinnitus is caused by spontaneous, continuous theta/gamma band activity, which results from hyperpolarization of the medial geniculate body as specific nuclei in the thalamus. Under normal conditions, auditory stimuli increase thalamocortical rhythms to gamma band activity. However, in the deafferentation model, the oscillatory activity decreases from alpha to theta band instead of increasing to gamma activity, and increased gamma band activity in lateral zones was observed, resulting in reduced lateral inhibition known as the “edge effect” [1].

Tinnitus can be considered an emergent network property of multiple, dynamically adaptive, partially overlapping auditory and non-auditory brain networks. These networks are composed of different brain areas In particular, the dorsolateral prefrontal cortex (DLPFC) seems to play a special role in auditory processing, auditory memory storage, exerting primary inhibitory modulation of input to the primary auditory cortex, auditory attention, and modulating top-down auditory processing [3]. DLPFC activity is also associated with the emotional signs that usually reported in tinnitus patients with high levels of anxiety and distress. The DLPFC regulates the involved emotional centers in tinnitus sufferers such as anterior cingulate cortex, which is the origin of top-down inhibitory signals, insula, and amygdala. In this regard, it seems that stimulation of DLPFC and other involved cortical centers may effectively control tinnitus perception in sufferers [4]. Another important cortical region in tinnitus networks is the Left Temporal Area (LTA). Shekhawat and colleagues believed that the lower part of the LTA contains an important neural network that affects the primary auditory cortex in 41 and 42 Brodman areas, the associative auditory cortex in 21 and 22 Bradman areas, and the limbic system, including the hippocampus and amygdala. It is logical that the direct stimulation of LTA affects the perception of tinnitus, induces inhibitory activities, and suppresses tinnitus. However, this effect is not sustained based on the research findings [5, 6].

In recent years, the use of neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS), neurofeedback, transcutaneous electrical nerve stimulation (TENS), and transcranial direct current stimulation (tDCS) has become common and has been successful to some extent. The most conventional type of electrical stimulation for tinnitus inhibition is tDCS. tDCS is a safe, cost-effective, and less invasive method compared with other neuromodulation techniques such as rTMS [7]. Various hypotheses have been proposed to explain the therapeutic results of tDCS in tinnitus symptoms. The first hypothesis is focused on the theory of disturbing neural network activity associated with tinnitus. The second hypothesis is that repeated tDCS sessions can decrease or increase the neural excitability of the affected areas depending on the electrode’s polarity. These excitability changes can lead to neuroplasticity with tinnitus therapeutic effects on involved neural networks. Clinical trials have shown that tDCS over the DLPFC or Auditory Cortex in the LTA region may produce transient or short-lasting effects in decrease tinnitus awareness and annoyance in patients [8]. tDCS can alter gamma-aminobutyric acid (GABA), glutamate, acetylcholine, serotonin, and dopamine systems. These modifications are likely to affect the plasticity process [9]. tDCS also decreases GABA in resting-state networks by decreasing GABA concentrations as an inhibitory neurotransmitter and increasing glutamate and glutamine concentrations as an excitatory neurotransmitter. tDCS also increases the brain-derived neurotrophic factors, N-Methyl-D-aspartate (NMDA), as the short-term and long-term effects of tDCS are not observed after blocking Na + channels or after administration of NMDA receptor antagonists [10].

Through the explained mechanisms, tDCS seems to have promising results in improving tinnitus symptoms. However, recent studies reported considerable heterogeneity in tDCS effectiveness for tinnitus improvement. One of the important factors for this heterogeneity is related to the stimulation parameters. The present study aimed not only to explain the clinical effectiveness of tDCS in tinnitus rehabilitation but also to investigate the ideal stimulation parameters.

Materials and Methods

Source of Information

The study was conducted based on PRISMA guidelines and through the PubMed (1990–2024) and Scopus (1990–2024) databases, as well as Google Scholar (1989–2024) search engine findings. Only controlled and randomized trials that used tDCS for tinnitus rehabilitation were considered in the current study. The initial search, based on the following keywords, yielded 56 articles. The keywords used were neural modulation, tinnitus, electrical stimulation, and transcranial direct current stimulation.

Study Selection Criteria

The inclusion criteria were as follows:

• Clinical trials that only used tDCS for tinnitus rehabilitation with sham or control groups.

• Having quantitative or qualitative scales before and after treatment.

• Including patients over 18 years.

• English studies having available full-text.

We excluded abstracts without full-text, case reports or series, and non-English published articles. Based on these criteria, 56 articles, including 46 research articles and 10 review articles, were selected. After the first review of these articles by two members of the research team, 10 articles were selected that explained the details of the tDCS parameters (including electrode array, electrode area, number of sessions, intensity and duration of stimulation, and measurement tools) in their methods. Based on the references in these selected articles, four more articles were found, and finally, 14 articles were considered for the current review study. The PRISMA flow chart of the current study is shown in Fig. 1.

Fig. 1.

The PRISMA flow chart of the study

Results

In the 14 reviewed articles, 557 patients with an average of 47 years old and an average of tinnitus period of about 5 years were studied. 2–10 (mean = 6 sessions) tDCS sessions we held. Most of these studies used 2 mA for current intensity and 20 min of tDCS stimulation as the selected duration. The main results of the 14 reviewed articles are summarized in Table 1.

Table 1.

Stimulation parameters, measurement tools, and main results in the 14 selected studies

Authors and year	Electrode array	Intensity, duration	Area of electrodes	Measurement tools	Main results
Garin et al. [11]	Anode on left LTA/cathode between T and F8	1 mA, 20 min	35 cm2 50 cm2	Loudness VAS* Distress VAS* TQ* BDI	Anodal and cathodal tDCS over LTA made change of loudness perceived by patient Rate of improvement was better in Anodal tDCS
Frank et al. [12]	Anode on right DLPFC/cathode on left DLPFC	1.5 mA, 30 min	NR NR	Loudness VAS* Distress VAS* TQ BDI THI	Bifrontal stimulation by tDCS has Little effect on loudness and distress The impact of tDCS is gender-specific, so that women improvement more than men
Faber et al. [13]	In six cases anode on right DLPFC/in nine cases anode on left DLPFC	1.5 mA, 20 min	35 cm2 35 cm2	Loudness VAS Distress VAS* HADS	Bifrontal stimulation by tDCS was effective on distress, but ineffective on loudness Anodal tDCS over right DLPFC changes the anxiety of the patients and anodal tDCS over left DLPFC changes the depression
Cavalcanti et al. [14]	Anode on right DLPFC/cathode on left DLPFC	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS THI	Multi-session stimulation with tDCS has no statistically significant effect on VAS and THI
Pal et al. [15]	One anode on prefrontal (Fz, F3, F4)/two cathodes on T3 and T4	2 mA, 20 min	75 cm2 35 cm2 35 cm2	Loudness VAS Distress VAS HADS CGI STSS	Provide a five-session anodal tDCS to the DLPFC and cathode to the AC, does not improve the tinnitus
Forogh et al. [16]	Anode on left LTA/cathode on right supra orbital	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS Distress VAS THI CGI	Multi-session tDCS over LTA has relatively improvement on loudness and distress VAS, although the improvement was not statistically significant
Rabau et al. [17]	Anode on right DLPFC/cathode on left DLPFC	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS* THI* HQ	No difference for tinnitus loudness and the distress experienced between the placement of the cathode on the left DLPFC or on the shoulder
Abtahi, et al. [18]	Anode and cathode positioned on T3 or T4	2 mA, 20 min	35 cm2	Loudness VAS*	Anodal tDCS was more effective in tinnitus patient (than cathodal or sham tDCS)
Shekhwat et al. [19]	Anode on right DLPFC/cathode on left DLPFC	1.5 or 2 mA, 20 or 30 min	35 cm2 35 cm2	Loudness VAS*	There was no significant difference between the intensity and duration of stimulation The effect of tDCS plateaued after 6 session
Souza et al. [20]	Anode on left LTA/cathode on right DLPFC	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS* Distress VAS* THI* EEG	Improvement in tinnitus symptoms as well as a modulation of cortical electrical activity
Mares et al. [21]	Anode on right DLPFC/cathode on left DLPFC	1.5 mA, 20 min	25 cm2 25 cm2	TFI ITHQ* BDI BREF*	Long term effect of tDCS on tinnitus in 6 months
Rashidi et al. [22]	Anode on left AC/cathode on right AC	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS* Distress VAS* THI*	Repeated sessions of bilateral auditory cortex stimulation improve chronic tinnitus symptoms until 1 month follow up
Han et al. [23]	Anode on right DLPFC/cathode on left DLPFC (F3,F4)	2 mA, 20 min	35 cm2 35 cm2	Loudness VAS* Distress VAS* BDI* THI*	Dual session tDCS in the week demonstrated more sustain suppression effect than single session a week
Mahmoodi et al. [24]	Anode on left DLPFC/cathode on right DLPFC	2 mA, 20 min	35 cm2 35 cm2	THI* ANT EEG	Bifrontal tDCS potentially improved attentional network in tinnitus sufferers

*Questionnaires with significant differences between before and after tDCS.intervention

Loudness and distress caused by tinnitus were evaluated by the visual analog scales (VAS) in 12 articles. In eight studies, the VAS results of loudness before and after tDCS were significantly different, and the average reported improvement was one score. In other studies, no significant differences were reported. In eight studies, researchers assessed tinnitus distress with a VAS in addition to tinnitus loudness. The results of distress VAS improved only in six studies [11–13, 20, 22, 23]. However, no significant difference was reported in two studies [15, 16]. In addition to the VAS tool, the Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ) were used. Three of eight studies did not show a significant difference in THI scores before and after tDCS [12, 14, 16]. THI scores before and after tDCS differed significantly in five of the eight studies [17, 20, 22–24]. The average improvement score was 17. A statistically significant decrease in TQ scores was observed in one study [11], inconsistent with Frank and co-workers’ study [12]. Another study showed a statistically significant decrease in the Tinnitus Functional Index (TFI) and in the subdomains of the Iowa Tinnitus Handicap Questionnaire (ITHQ) [21]. In some studies, the Beck Depression Inventory (BDI) and Clinical Global Impression Scale (CGI) were also used. In one study, the difference between BDI scores before and after the intervention was significant [23]. However, in the other study, no significant difference was observed. Mares and colleagues evaluated the WHO-Quality of Life BREF and reported the short-term negative effects in the psychological domain [21].

Discussion

In the 14 selected articles of this study, no association between a specific cause and improvement from tDCS was reported. 12 studies showed some beneficial effects of tDCS on tinnitus management, confirming that tDCS can improve tinnitus to some extent just in some clients, at least based on the questionnaire output. Two other studies reported no improvement [14, 15]. Because of the heterogeneity of the study populations and the differences in tDCS protocols, the improvement rates varied. In the following, we discuss tDCS stimulation parameters that used in different studies and the results of their applications.

One of the most important parameters in tDCS protocol is the site of stimulation. Four studies selected the LTA as an anode electrode zone, but eight placed an anode electrode on the DLPFC. In only one study, the anode was placed on the prefrontal cortex, and two cathodes were placed on T3 and T4 [15]. In one study, anode and cathode were placed on the left and right auditory cortex [21]. Each study reports the researcher’s logic for choosing the stimulation positions based on the known tinnitus networks. However, most selected DLPFC and LTA with no significant difference in tinnitus improvement. The reasons for these researchers to stimulate the DLPFC and LTA go back to the findings of two previous studies [4, 25]. Shekhawat and his colleagues also believed that the lower part of the LTA contains an important neural network that affects Brodmann’s areas 41 and 42 and Brodmann’s areas 21 and 22 and the limbic system, and its stimulation has a direct effect on tinnitus perception [5]. In only one study with a 6-month follow-up, the stability of the long-term effect of this electrode arrangement was reported [21]. Bifrontal tDCS for tinnitus patients was first introduced by Vanneste and co-workers based on previous studies reporting the clinical benefits of bifrontal tDCS in the treatment of major depression, impulsivity, and chronic pain. Bifrontal tDCS has been proposed to enhance deficient top-down inhibitory mechanisms in tinnitus and induce auditory sensory gating in the anterior cingulate cortex [4]. Vannest and colleagues have also suggested that bifrontal tDCS may interfere with the emotional processing of tinnitus through modulating cortico-subcortical and cortico-cortical pathways. One of the fundamental steps towards a better understanding of the underlying mechanisms of tDCS is a better understanding of which brain regions are affected by tDCS and how. The data obtained in Parazini’s study showed that LTA tDCS leads to a wide asymmetric distribution and amplitude not only in the cortex area larger than the target brain area but also in other subcortical and deeper structures. In contrast, DLPFC tDCS resulted in symmetric stimulation predominantly focused on DLPFC structures themselves. It seems that the main reason for this is the relative locations of the electrodes on the brain. For LTA tDCS, the anode and cathode are located on opposite sides of the brain, resulting in a more widespread current/electric field distribution [26]. Miranda and colleagues modeled the current distribution during tDCS. They found that based on the location, size, and number of electrodes used, the percentage of current reaching the brain varied from 39 to 59 percent of the used current [27]. To improve the tDCS protocol in terms of placing the optimal stimulation site for tinnitus treatment, Ridder De and Vanneste (n = 675) compared the efficacy of the electroencephalography (EEG)-based tDCS method with the standard bifrontal tDCS method. They reported no significant difference in improving the symptoms [28]. Despite all this evidence, there is still no consensus on the proper location of the electrode as an optimal parameter for transcranial direct current stimulation in patients with tinnitus.

Another challenging issue in tDCS protocols is the polarity of the electrodes. The 14 studies reviewed in this article used anodal tDCS. Anodal tDCS causes depolarization of resting membrane potentials, while cathodal tDCS reduces cortical excitability by inducing hyperpolarization of resting membrane potentials [8]. Most studies have shown that the use of anodal tDCS leads to a better improvement of tinnitus compared with cathodal tDCS. The increased excitability of the cerebral cortex caused by anodal tDCS may contradict the claim that tinnitus results from increased excitability in some parts of the cortex [12, 14, 15]. However, Fregni and his colleagues proposed a solution to this ambiguity. Accordingly, the size of the electrodes should be 35 cm² or more. Joss and colleagues recommended using higher current intensity for cathodal tDCS to have the same effect as anodal tDCS [29]. Studies show that single-session cathodal tDCS is ineffective in treating tinnitus because cathodal tDCS is not strong enough to disrupt or modulate the abnormal cortical activity associated with tinnitus. In this regard, repeated sessions of cathodal tDCS may have therapeutic effects on tinnitus based on theoretical and experimental results. Therefore, it is better to design more frequent tDCS sessions, longer session durations, and higher intensities to investigate the effects of cathodal tDCS on tinnitus [28].

The next important issues about this neuromodulator method are the current intensity, duration and number of sessions, and washout periods. In the 14 reviewed studies, the maximum number of sessions was 10, the duration of sessions was 10–20 min, the current intensity was 1–2 mA, and the maximum washout period was 72 h. To optimize the tDCS protocol for tinnitus, Shekhawat and Vanneste designed an experiment to optimize the bifrontal tDCS parameters to the DLPFC for tinnitus suppression with the primary result of tinnitus loudness. They conducted a dose–response trial to optimize current intensity (1.5 and 2 mA), stimulation duration (20 and 30 min), and number of tDCS sessions (2, 4, 6, 8, and 10) with a 3–4 day washout period between each session. Patients received a minimum of two sessions per week and a maximum of 10 sessions during 5 weeks. Their findings showed a significant reduction in the tinnitus loudness after DLPFC-tDCS. In addition, they reported that increasing the number of sessions increased the outcome rate, but after six sessions, no further improvement was observed, and the outcome rate reached a plateau. Shekhawat and others express that six sessions of stimulation of 1.5 mA for 20 min is the optimal protocol in DLPFC-tDCS [19]. They also expressed that six sessions of 2 mA stimulation for 20 min were the optimal protocol for LTA-tDCS [5]. On the other hand, Hyvärinen and co-workers subjected 43 participants with chronic tinnitus to LTA-tDCS and DLPFC-tDCS for 10 sessions on 10 consecutive days. However, tDCS was not effective in suppressing tinnitus. Similar to other trials that did not find a positive effect of tDCS on tinnitus, the washout period in this trial was less than 1 day. This is further evidence that back-to-back sessions on consecutive days are ineffective in suppressing tinnitus and seem to mask the effect of individual sessions. In one study, a washout period of 3–4 days was used between each tDCS session. They recommended a washout period of more than 1 day between tDCS sessions to maintain the effect on tinnitus suppression. Holding sessions on consecutive days does not facilitate the plastic changes that lead to tinnitus suppression [19]. Recent studies recommended 48–72 h washout periods to sustain the improvement effects until 6 months [21, 23].

The next discussion in these studies is the evaluation tools after the intervention. Common tools in studies include questionnaires, event-related potential (ERP), and EEG. In 2012, Adamchic and colleagues showed that changes in loudness and distress are valid and reliable measures of treatment response in patients with chronic tinnitus [30]. Questionnaires such as VAS, THI, and TQ are very helpful in evaluating these two parameters. However, the assessment of tinnitus distress by VAS has conflicting results, possibly because of its subjective nature. This method strongly depends on the mental and psychological condition of the patients. TQ may examine patients’ daily living activities and the psychological aspects of tinnitus. Therefore, it may be a reasonable alternative to VAS [18]. The effectiveness of tDCS was evaluated using questionnaires such as THI and/or TQ, etc., in 14 studies. However, since questionnaires are not objective tools, using ERPs (such as 300p, MMN, and EEG) in combination with conventional questionnaires to evaluate the results of interventions is more favorable.

A study showed significant N1, P2, N2, and P3 latencies shortening after tDCS-HD treatment—moreover, the increase in the amplitude of the P2 and N2 peaks after tDCS-HD was reported. However, ERP changes were not significantly correlated with changes in the total TFI score and patient satisfaction rate [31]. Other studies showed that any part of the inferior parietal prefrontal cortex network can be affected by tDCS, leading to changes in pre-attentive deviance detection assessed through auditory MMN measurements after tDCS intervention [32, 33]. Souza and colleagues and Mahmoodi and co-workers, in a recent randomized clinical trial, combined tDCS and EEG and reported improvement in tinnitus symptoms as well as modulation of cortical electrical activity and attentional network in tinnitus sufferers [20, 24]. It seems that both objective and subjective tools for measuring the consequences of tDCS are important, and conducting correlation between these tools is necessary for future tinnitus studies.

Conclusion

A review of the current clinical trials showed that tDCS has therapeutic results for managing tinnitus to some extent and for some cases. Also, tDCS has beneficial effects on various emotional/cognitive signs associated with tinnitus. However, because of the heterogeneity of the tinnitus population, there is no universal standard tDCS protocol for tinnitus management in clinical applications. It seems that clinical randomized, placebo-controlled, double-blind studies with larger sample sizes are needed to reach a definitive conclusion about the efficacy of tDCS for tinnitus patients.

Declarations

Conflict of interest

No conflict of interest was declared.