Background: Tinnitus-the perception of sound in the absence of an external source is a common condition, highly impactful condition for which treatment options are limited. Based on the limited available evidence, transcranial direct current stimulation (tDCS) has shown promise for suppressing, or reducing, tinnitus salience. Unlike existing tinnitus interventions, which aim to help patients to better cope with tinnitus, tDCS has the potential to address the tinnitus percept itself. Methods: Protocol for a triple-blinded randomised sham-controlled pilot trial, aimed at informing a future clinical trial for tDCS-based tinnitus treatment. 40 participants, will be randomised to receive ten sessions of either active or sham tDCS over a 2-week period. Proof of concept will be measured by protocol compliance, attrition, and tolerance. Tinnitus loudness, symptom severity, and other relevant outcomes will be measured using self-report measures and electroencephalography. Conclusions: The study’s primary aims are to assess the tolerability of multiple tDCS treatments in tinnitus patients by way of treatment adherence and satisfaction, devise an evidence-based protocol and derive a minimum sample size for a future controlled efficacy trial. Secondary aims are to compare different subjective measures of tinnitus, as well as electrophysiological measures of underlying brain activity and to explore the feasibility of individualised head and current flow modelling for the development of future individualised treatment regimens using structural magnetic resonance imaging data acquired in a subset of our patients. The results will yield new insights into tinnitus mechanism and treatment-related changes. Trial Registration: This study is registered at ClinicalTrials.gov (NCTNCT06628414).

Background/Objectives: Vagus Nerve Stimulation (VNS) has been suggested as a treatment for tinnitus, but its effect on the condition remains unclear. Ultrasonic Vagus Nerve Stimulation (U-VNS) involves non-invasive stimulation of the auricular branch of the vagus nerve, potentially providing an alternative to traditional VNS. To pre-emptively address some of the methodological challenges of future trials investigating U-VNS, a highly blindable sham device is needed. This study aimed to (1) investigate the effectiveness of blinding of a U-VNS device and (2) record any adverse effects, including any negative effects on tinnitus loudness, alongside their onset and duration. Methods: In this single-blind randomized controlled study, 20 volunteers with chronic tinnitus received two 29 min sessions of true U-VNS followed by sham U-VNS, or vice versa. Sessions were a week apart, and in a randomized order. The effectiveness of blinding and adverse effects, including changes in tinnitus loudness, were measured using self-report questionnaires. Results: James' Blinding Index revealed that blinding was highly effective in both the real U-VNS condition, BI = 0.79, 95% CI (0.61-0.92), and the sham condition, BI = 0.76, 95% CI (0.60-0.89). Adverse effects were uncommon and mild, primarily consisting of sensations on the skin beneath the transducer. For most participants, tinnitus loudness either decreased or stayed the same in both conditions. Conclusions: A high level of blinding was achieved, suggesting that the ZenBud sham device may be suitable as an effective placebo control in future trials. Adverse effects were uncommon and mild. These findings will help inform the design of future clinical trials to evaluate the safety and efficacy of U-VNS.

Background: Transcranial direct current stimulation (tDCS) involves the application of weak electric currents (typically 0.5–2 mA) via scalp electrodes to promote neuroplastic changes that modulate behaviour or cortical activity. Although there have been promising results in eliminating tinnitus or reducing its loudness or severity, there is also a high degree of inter-individual variability. This may be due to anatomical differences and their influence on the resulting electric field. To optimise and personalise tDCS protocols, computational electric field models based on individual clinical imaging may be utilised to give insight into the induced electric field during tDCS and inform more effective protocols for targeted stimulation. To our knowledge, there are currently no standards for current modelling or reviews which detail the optimal parameters for conducting current modelling studies for tDCS. Objectives: The aim of this review is to investigate the methodology of current modelling studies for tDCS so that informed, personalised protocols can be designed by modelling the electric field of the brain during tDCS for tinnitus. By considering the impact of individual anatomical differences on the electric field induced by tDCS, targeted protocols could be developed to reduce tinnitus loudness and severity in a systematic and predictable way. Design: The protocol for this review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) Checklist. Using online databases, records were identified based on a keyword search for records relevant to current modelling for tDCS, including peer-reviewed papers, clinical trials, the grey literature, theses, dissertations, and conference abstracts. Four thousand two hundred and fifty-three records were retrieved from thirteen online databases and include 4186 records from the initial search completed between May and July 2024, and 67 records from an updated search completed in August 2025. A further 596 records were retrieved from Google Scholar (501 from the initial search and 95 from the updated search). One hundred and fourteen records met our criteria for inclusion. Each record was charted by two separate reviewers, with attention to the modelling pipeline and predicted values in peak and range of electric field magnitude. Results: There was a consensus that, despite model parameters and pipelines, there was inter-individual variability in the predicted electric fields. The reviewed records highlighted the impact of individual differences, including age, sex, and anatomical variation, on the predicted electric field during tDCS. Increased age was often associated with age-related brain atrophy and high relative cerebrospinal fluid volume, which was a significant influence on the resulting E-field intensity and distribution. Conclusions: When creating personalised tDCS protocols for tinnitus, the model parameters and sources of variability (i.e., morphology, age, and sex) should be carefully considered to achieve the desired stimulation outcomes, particularly in regard to applied current intensity.

BACKGROUND/OBJECTIVES:Both invasive and non-invasive electrical stimulation of the vagus nerve have been studied as potential treatments for neurological conditions, with mixed results. Ultrasonic Vagus Nerve Stimulation (U-VNS), which non-invasively stimulates the auricular branch of the vagus nerve using ultrasound, may offer a more targeted and effective approach than electric currents. To facilitate future clinical trials of U-VNS, this study aimed to (1) investigate the effectiveness of blinding of a U-VNS device versus a sham device and (2) record the type, onset, and duration of any adverse effects resulting from U-VNS. METHODS:In this single-blind randomised controlled study, twenty healthy volunteers were randomly assigned to receive either a 30 min session of true U-VNS and a 30 min session of sham stimulation 1 week later, or vice versa. The effectiveness of blinding and the occurrence of adverse effects were measured using self-report questionnaires. RESULTS:James' Blinding Index showed that blinding using the sham device was highly effective in both the real U-VNS condition, BI = 0.9 (95% CI: 0.7-1.0), and the sham condition, BI = 1.0 (95% CI: 1.0-1.0). The adverse effects reported were mild, transient, and mostly related to sensations on the skin immediately under the transducer of the device. CONCLUSIONS:A high level of blinding effectiveness can be achieved for U-VNS by using a sham device. Adverse effects are generally mild and transient. These findings will inform the design of future clinical trials of U-VNS.

Cochlear implantation is an effective intervention to restore useful aspects of hearing function in adults with severe-to-profound hearing loss. Tinnitus, the perception of sound in the absence of an external source, is common in people with severe-to-profound hearing loss. Existing evidence suggests cochlear implantation may be effective in reducing the negative impact of tinnitus in this population. However, this is contradicted by data suggesting that up to half of cochlear implant recipients experience tinnitus, and that some of these patients who did not have tinnitus before cochlear implantation experience it after surgery or cochlear implant activation. Most evidence on the effects of cochlear implantation on tinnitus comes from secondary data in cochlear implant studies primarily concerned with hearing-related outcomes. Hence, the quality of the evidence for effects on tinnitus is low and not suitable to inform clinical recommendations or decision-making. This study will systematically collect data on tinnitus and tinnitus-related outcomes from patients at multiple points during the cochlear implant pathway to characterise changes in tinnitus. This will improve our understanding of the effects of cochlear implantation for tinnitus in adults with severe to profound hearing loss and inform the design of clinical trials of cochlear implantation for tinnitus.

(1) Background: Tinnitus involves the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source. For many people, tinnitus is a disorder associated with symptoms of emotional distress, cognitive dysfunction, autonomic arousal, behavioural changes, and functional disability. Many symptoms can be addressed effectively using education or cognitive behavioural therapy. However, there is no treatment that effectively reduces or alters tinnitus-related neurophysiological activity and thus the tinnitus percept. In this systematic review, we evaluated the effectiveness of neuromodulation therapies for tinnitus that explicitly target pathological synchronous neural activity. (2) Methods: Multiple databases were searched for randomised controlled trials of neuromodulation interventions for tinnitus in adults, with 24 trials included. The risk of bias was assessed, and where appropriate, meta-analyses were performed. (3) Results: Few trials used acoustic, vagal nerve, or transcranial alternating current stimulation, or bimodal stimulation techniques, with limited evidence of neuromodulation or clinical effectiveness. Multiple trials of transcranial direct current stimulation (tDCS) were identified, and a synthesis demonstrated a significant improvement in tinnitus symptom severity in favour of tDCS versus control, although heterogeneity was high. (4) Discussion: Neuromodulation for tinnitus is an emerging but promising field. Electrical stimulation techniques are particularly interesting, given recent advances in current flow modelling that can be applied to future studies.

(1) Background: Tinnitus is the awareness of a sound in the absence of an external source. It affects around 10–15% of people, a significant proportion of whom also experience symptoms such as depression or anxiety that negatively affect their quality of life. Transcranial direct current stimulation (tDCS) is a technique involving constant low-intensity direct current delivered via scalp electrodes. It is a potential treatment option for tinnitus, as well as tinnitus-related conditions such as depression and anxiety. This systematic review estimates the effects of tDCS on outcomes relevant to tinnitus. In addition, it sheds light on the relationship between stimulation parameters and the effect of tDCS on these outcomes; (2) Methods: Exhaustive searches of electronic databases were conducted. Randomised controlled trials were included if they reported at least one of the following outcomes: tinnitus symptom severity, anxiety, or depression. Where available, data on quality of life, adverse effects, and neurophysiological changes were also reviewed. GRADE was used to assess the certainty in the estimate; (3) Results: Meta-analyses revealed a statistically significant reduction in tinnitus (moderate certainty) and depression (low certainty)-but not anxiety-following active tDCS compared to sham control. Network meta-analyses revealed potential optimal stimulation parameters; (4) Conclusions: The evidence synthesised in this review suggests tDCS has the potential to reduce symptom severity in tinnitus and depression. It further narrows down the number of potentially optimal stimulation parameters.

Tinnitus is the awareness of sound in the ear or head in the absence of an external source. It affects around 10%-15% of people, and current treatment options are limited. Experimental treatments include various forms of electrical stimulation of the brain. Currently, there is no consensus on the outcomes that should be measured when investigating the efficacy of this type of intervention for tinnitus. OBJECTIVE:This study sought to address this issue by establishing a core domain set: a common standard of what specific tinnitus-related complaints are critically important to assess in all clinical trials of electrical stimulation-based interventions for tinnitus. DESIGN:A two-round Delphi survey was conducted, followed by a stakeholder consensus meeting to identify a core domain set. Setting All data collection took place online PARTICIPANTS: Participants represented one of two stakeholder groups: patients with lived experience of tinnitus and professionals with relevant clinical, commercial or research experience. RESULTS:Stakeholders achieved consensus on the inclusion of ability to ignore, concentration, treatment satisfaction, helplessness (lack of control) and tinnitus intrusiveness in the core domain set, in addition to adverse effects. CONCLUSION:This study established a core domain set for the evaluation of electrical stimulation-based interventions for tinnitus via an e-Delphi study. This core domain set will act as a minimum standard for reporting in future clinical trials of electrical stimulation interventions for tinnitus. Standardisation will facilitate comparability of research findings.

Introduction Tinnitus is the awareness of a sound in the ear or head in the absence of an external source. It affects around 10%–15% of people. About 20% of people with tinnitus also experience symptoms such as depression or anxiety that negatively affect their life. Transcranial direct current stimulation (tDCS) is a technique involving constant low-intensity direct current delivered via electrodes on the head. It is postulated to modulate (suppress or enhance) neural activity in the region between electrodes. As such, it represents a potential treatment option for tinnitus, as well as comorbid depression or anxiety. This systematic review will estimate the effects of tDCS on outcomes relevant to tinnitus. In addition, it will determine whether there is any relationship between stimulation parameters (electrode montage, current intensity, and length and frequency of stimulation sessions) and the effect of tDCS on these outcomes. Methods and analysis Electronic searches for peer-reviewed journal articles will be performed in the Cochrane Register of Studies online (the Cochrane Ear, Nose and Throat Disorders Group Register and CENTRAL, current issue), PubMed, EMBASE, CINAHL, LILACS, KoreaMed, IndMed, PakMediNet, CNKI, AMED, PsycINFO, Web of Science, ClinicalTrials.gov, ICTRP and Google Scholar using the following search terms: transcranial Direct Current Stimulation OR tDCS AND tinnitus OR depression OR anxiety OR quality of life OR adverse effects OR neurophys*. Searches were not limited by date. Methods are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Randomised controlled trials will be included if they report at least one of the following outcomes: tinnitus symptom severity, anxiety or depression as measured by relevant validated instruments. Where available, data on quality of life, adverse effects and neurophysiological changes will also be reviewed. In addition to an analysis of the effect of each parameter, an analysis will be performed to uncover any interactions between parameters. Where appropriate, meta‐analyses will be performed. Ethics and dissemination This systematic review will make use of secondary data only. As no data will be obtained from participants directly, ethical approval has not been sought. No other ethical issues are foreseen. Findings will be submitted for peer-reviewed publication and presented at academic conferences. The results of this review will inform future research. PROSPERO registration number CRD42020185567.

Processing numerosities relies on the innate capacity to understand and manipulate the number of items in a set, and to additional abilities such as inhibitory skills -which are known to be linked to brain oscillations in the alpha range. Whether these inhibitory skills are causally linked to numerosity processing and critical for it is unclear. To address this question, we used alpha-based brain stimulation (transcranial alternate current stimulation, tACS) to target inhibitory abilities in the context of numerosity discrimination. Twenty-nine young adults received bilateral tACS to the parietal lobe, a brain region critical for numerical processes. tACS at target (alpha, 10 Hz), control oscillation frequencies (theta, 4 Hz; beta, 22 Hz; sham, no stimulation), and control areas (bilateral frontal regions) was paired to an established numerosity paradigm that allows distinguishing between congruent and incongruent numerosity trials, the latter requiring to inhibit task-irrelevant information. Performance significantly and specifically worsened in incongruent numerosity trials following bilateral parietal alpha-tACS relative to sham and to the other stimulations used, possibly due to the desynchronization of parietal neuronal oscillations in the alpha range. No significant changes in performance were observed in parietal beta and theta-tACS, relative to sham, nor in frontal alpha-tACS. Likewise, there were no changes in performing congruent numerosity trials. We therefore concluded that parietal alpha oscillations are causally linked to inhibitory abilities, and reinforced the view that these abilities are intrinsic to numerosity discrimination.