A multidisciplinary systematic review of the treatment for chronic idiopathic tinnitus.

The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.

Conditions for highly efficient and reproducible round-window stimulation in humans.

Round-window stimulation is a new clinical approach for the application of active middle-ear implants. To investigate factors influencing the efficiency of round-window stimulation, experiments in 6 human temporal bones were performed with different actuator geometries and coupling conditions. The experiments show that the amplitude ratio between stapes and round-window actuator vibration is most efficient when using a 1.0-mm diameter rod with a 30° inclined tip geometry and an attached silicone pad. In this case, the amplitude ratio is 0.34 for frequencies up to 1.5 kHz and 0.27 for frequencies up to 20 kHz, with a standard deviation of only 4-6 dB at most frequencies. The analysis of data presented here and in a companion paper suggests that control of proper round-window membrane pretension as well as the inclined tip geometry are the major requirements for maximal performance.

Accuracy of velocity distortion product otoacoustic emissions for estimating mechanically based hearing loss.

Distortion product otoacoustic emissions (DPOAEs) measured as vibration of the human eardrum have been successfully used to estimate hearing threshold. The estimates have proved more accurate than similar methods using sound-pressure DPOAEs. Nevertheless, the estimation accuracy of the new technique might have been influenced by endogenous noise, such as heart beat, breathing and swallowing. Here, we investigate in an animal model to what extent the accuracy of the threshold estimation technique using velocity-DPOAEs might be improved by reducing noise sources. Velocity-DPOAE I/O functions were measured in normal and hearing-impaired anaesthetized guinea pigs. Hearing loss was either conductive or induced by furosemide injection. The estimated distortion product threshold (EDPT) obtained by extrapolation of the I/O function to the abscissa was found to linearly correlate with the compound action potential threshold at the f(2) frequency, provided that furosemide data were excluded. The standard deviation of the linear regression fit was 6 dB as opposed to 8 dB in humans, suggesting that this accuracy should be achievable in humans with appropriate improvement of signal-to-noise ratio. For the furosemide animals, the CAP threshold relative to the regression line provided an estimate of the functional loss of the inner hair cell system. For mechanical losses in the middle ear and/or cochlear amplifier, DPOAEs measured as velocity of the umbo promise an accuracy of hearing threshold estimation comparable to classical audiometry.

Test-retest repeatability of distortion product otoacoustic emissions.

OBJECTIVES: Distortion product otoacoustic emissions (DPOAE) have become part of routine audiological diagnostics. The large scale of clinical DPOAE applications, such as screening of hearing in infants, objective estimation of hearing status, distinction between cochlear and retrocochlear origin of sensorineural hearing loss, exclusion of psychogenic hearing loss, monitoring of hearing during administration of ototoxic drugs, and others illustrates the significance of this audiological tool. In all diagnostic tests, knowledge about the procedure's test-retest repeatability is of crucial importance, to allow for distinction between measurement deviations and true physiological or pathological changes in monitoring over time. DESIGN: Measurements of DPOAE were performed in triplicate in 80 normally hearing ears of 40 subjects. Both immediate remeasurements with the ear probe left in place [single-fit mode (SF-mode)] and remeasurements after approximately 5 to 10 days [multiple-fit mode (MF-mode)] were included. DPOAE primary tone levels were varied in 5 dB steps from L2 = 60 to 20 dB SPL (L1 = L2 x 0.4 + 39 dB SPL) and within the frequency range f2 = 1 to 6 kHz. Repeatability of DPOAE was evaluated by the standard error of measurement (Sm), reliability (Cronbach alpha), absolute differences between measurements, 95% confidence intervals, and repeatability standard deviations. RESULTS: Sm averaged 0.67 dB over all frequencies and primary tone levels in the SF-mode, and 1.44 dB in the MF-mode, respectively. As expected, test-retest repeatability declined with decreasing primary tone levels; however, repeatability values were still mostly satisfactory with the lower primary tone levels. For the exemplary primary tone level combination of L1/L2 = 63/60 dB SPL, which is close to common clinical paradigms, the difference between two DPOAE measurements under the reported test conditions could be considered statistically significant (p = 0.05) if it exceeded 0.7 to 1.3 dB in the range 1 to 5 kHz and 2.3 dB for 6 kHz in the SF-mode, when compared with 1.8 to 2.7 dB for 1 to 5 kHz and 3.7 dB for 6 kHz in the MF-mode. Signal to noise ratio (SNR) did not seem to have a large influence on repeatability, as long as SNR was within 6 to 35 dB, which covers the range of most clinical DPOAE measurements. CONCLUSIONS: The DPOAE-test-retest study presented here is to our knowledge the first, which combines variation of primary tone levels, assessment of both SF- and MF-modes, and comparison of the two modalities within the same subjects. Although the measurements were conducted under practical conditions resembling the clinical setting, repeatability was generally good. The widely used minimum SNR of 6 dB seems to be a recommendable criterion when considering both practicability and measurement quality under clinical conditions. The current findings underline the suitability of DPOAE as a monitoring tool of cochlear status over time. The data are intended to assist the clinician and the scientist in the correct interpretation of DPOAE level changes in the test-retest situation.

A behavioral paradigm to judge acute sodium salicylate-induced sound experience in rats: a new approach for an animal model on tinnitus.

Behavioral conditioning studies on rats have been proven to be a valid animal model for the evaluation of acute and chronic phantom auditory experience (tinnitus). We developed an animal model for short-term, acute induced phantom auditory sensations in rats. Rats were trained in a conditioning chamber to actively access a liquid feeder whenever a constant white noise sound was present. During silence, no reward was given. Fulfilling the demands of animal protection laws for maximal avoidance of pain and fear, punitive paradigms were maximally reduced. After 15-17 learning sessions, all animals performed more accesses to the reward feeder during periods of sound than during periods of silence. Tinnitus was induced by the administration of sodium salicylate (350 mg/kg body weight) given 3 h before testing. The feeder access activity of a rat treated with salicylate was significantly increased during periods of silence, indicating a phantom auditory experience. The presumptive auditory experience was estimated to be comparable to a white noise sound of about 30 dB SPL rms. The activity increase was less pronounced for lower doses of sodium salicylate (150 mg/kg body weight) and was not found in animals trained on a dark-light paradigm, as expected. As the learning sessions of the operant conditioning were performed without pharmacological treatment, unintentional drug effects, for example, on learning and motivation of a rat were minimized in this behavioral paradigm. Furthermore, the behavioral changes reported here were shown to be a specific drug effect evoking a phantom auditory experience of a rat and cannot be explained by unspecific drug effects on motor activity, motivation, learning or hearing loss. The conditional paradigm is discussed in the context of its potential as a model for testing drugs that may have a therapeutic value in tinnitus research.

Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.

The most impressive property of outer hair cells (OHCs) is their ability to change their length at high acoustic frequencies, thus providing the exquisite sensitivity and frequency-resolving capacity of the mammalian hearing organ. Prestin, a protein related to a sulfate/anion transport protein, recently has been identified and proposed as the OHC motor molecule. Homology searches of 1.5 kb of genomic DNA 5' of the coding region of the prestin gene allowed the identification of a thyroid hormone (TH) response element (TRE) in the first intron upstream of the prestin ATG codon. Prestin(TRE) bound TH receptors as a monomer or presumptive heterodimer and mediated a triiodothyronine-dependent transactivation of a heterologous promotor in response to triiodothyronine receptors alpha and beta. Retinoid X receptor-alpha had an additive effect. Expression of prestin mRNA and prestin protein was reduced strongly in the absence of TH. Although prestin protein typically was redistributed to the lateral membrane before the onset of hearing, an immature pattern of prestin protein distribution across the entire OHC membrane was noted in hypothyroid rats. The data suggest TH as a first transcriptional regulator of the motor protein prestin and as a direct or indirect modulator of subcellular prestin distribution.