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

BACKGROUND: Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation ("activate") and induce inhibitory effects via cTBS ("fire"). METHODS: Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. RESULTS: The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. CONCLUSION: The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.

Prolonged tinnitus suppression after short-term acoustic stimulation.

BACKGROUND: Tinnitus suppression following acoustic stimulation is a well-known phenomenon also termed residual inhibition (RI). Some individuals may experience prolonged RI (PRI), which can last for several hours or even days, after a single short-term acoustic stimulation. Exact mechanisms of this phenomenon are unknown and current evidence anecdotal. OBJECTIVES: The aim of our report is to collect, present, and discuss cases of PRI from our studies on acoustic stimulation in tinnitus with the aim to better understand this phenomenon as well as its implications for individualized treatments. METHODS: We pooled cases of PRI from four of our studies with a total sample size of n = 130. The criterion was set on a PRI duration which is at least sustained twice as long as the acoustic stimulation duration. RESULTS: We report a total number of about 5% of all participants experiencing some form of PRI, with rates of 3%-7% across the individual studies. PRI lasted from 20 min up to several days and was induced by the first stimulus in four out of six cases. Four out of six individuals experiencing PRI were female and PRI mostly occurred when acoustic stimuli were matched to the frequency or type of the tinnitus. CONCLUSION: PTS seems to be elicitable in a small subset of tinnitus patients which could inform future individualized treatment options. Future studies should investigate if and how identified factors like stimulus type, position, sex, and chronification grade uphold experimental scrutiny. We propose that the set of methods is furthermore extended with neurophysiology in particular.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

Amplitude Modulated Noise for Tinnitus Suppression in Tonal and Noise-Like Tinnitus.

BACKGROUND: The phenomenon of short-term tinnitus suppression by different forms of acoustic stimulation is referred to as residual inhibition (RI). RI can be triggered in the majority of tinnitus cases and was found to be depending on the used intensity, length or types of sounds. Past research already stressed the impact of noise stimulation as well as the superiority of amplitude modulated (AM) pure tones at the individual tinnitus frequency for RI in tonal tinnitus. Recently a novel approach for the determination of noise-like tinnitus characteristics was proposed. OBJECTIVES: The aim of the present study was to investigate whether in participants with noise-like tinnitus RI can be increased by AM noise stimuli according to the individual tinnitus frequency range. METHODS: For this purpose the individual tinnitus characteristics (noise-like and tonal tinnitus) of 29 people affected by tinnitus (mean age = 55.59, 7 females, mean tinnitus duration = 159.97 months) were assessed via customizable noise-band matching. The objective was to generate bandpass filtered stimuli according to the individual tinnitus sound (individualized bandpass filtered [IBP] sounds). Subsequently, various stimuli differing in bandpass filtering and AM were tested with respect to their potential to induce RI. Participants were acoustically stimulated with 7 different types of stimuli for 3 min each and had to rate the loudness of their tinnitus after each stimuli. RESULTS: Results indicate a general efficacy of noise stimuli for the temporary suppression of tinnitus, but no significant differences between AM and unmodulated IBP. Significantly better effects were observed for the subgroup with noise-like tinnitus (n = 14), especially directly after stimulation offset. CONCLUSIONS: The study at hand provides further insights in potential mechanisms behind RI for different types of tinnitus. Beyond that, derived principles may qualify for new or extend current tinnitus sound therapies.