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  1. Hu S, Hall DA, Zubler F, Sznitman R, Anschuetz L, Caversaccio M, et al.
    Hear Res, 2021 10;410:108338.
    PMID: 34469780 DOI: 10.1016/j.heares.2021.108338
    Recently, Bayesian brain-based models emerged as a possible composite of existing theories, providing an universal explanation of tinnitus phenomena. Yet, the involvement of multiple synergistic mechanisms complicates the identification of behavioral and physiological evidence. To overcome this, an empirically tested computational model could support the evaluation of theoretical hypotheses by intrinsically encompassing different mechanisms. The aim of this work was to develop a generative computational tinnitus perception model based on the Bayesian brain concept. The behavioral responses of 46 tinnitus subjects who underwent ten consecutive residual inhibition assessments were used for model fitting. Our model was able to replicate the behavioral responses during residual inhibition in our cohort (median linear correlation coefficient of 0.79). Using the same model, we simulated two additional tinnitus phenomena: residual excitation and occurrence of tinnitus in non-tinnitus subjects after sensory deprivation. In the simulations, the trajectories of the model were consistent with previously obtained behavioral and physiological observations. Our work introduces generative computational modeling to the research field of tinnitus. It has the potential to quantitatively link experimental observations to theoretical hypotheses and to support the search for neural signatures of tinnitus by finding correlates between the latent variables of the model and measured physiological data.
  2. Wilson CA, Berger JI, de Boer J, Sereda M, Palmer AR, Hall DA, et al.
    Hear Res, 2019 03 15;374:13-23.
    PMID: 30685571 DOI: 10.1016/j.heares.2019.01.009
    A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species. In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS. Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.
  3. Bester C, Collins A, Razmovski T, Weder S, Briggs RJ, Wei B, et al.
    Hear Res, 2022 Dec;426:108353.
    PMID: 34600798 DOI: 10.1016/j.heares.2021.108353
    BACKGROUND: Preservation of natural hearing during cochlear implantation is associated with improved speech outcomes, however more than half of implant recipients lose this hearing. Real-time electrophysiological monitoring of cochlear output during implantation, made possible by recording electrocochleography using the electrodes on the cochlear implant, has shown promise in predicting hearing preservation. Sudden drops in the amplitude of the cochlear microphonic (CM) have been shown to predict more severe hearing losses. Here, we report on a randomized clinical trial investigating whether immediate surgical intervention triggered by these drops can save residual hearing.

    METHODS: A single-blinded placebo-controlled trial of surgical intervention triggered when CM amplitude dropped by at least 30% of a prior maximum amplitude during cochlear implantation. Intraoperative electrocochleography was recorded in 60 adults implanted with Cochlear Ltd's Thin Straight Electrode, half randomly assigned to a control group and half to an interventional group. The surgical intervention was to withdraw the electrode in ½-mm steps to recover CM amplitude. The primary outcome was hearing preservation 3 months following implantation, with secondary outcomes of speech-in-noise reception thresholds by group or CM outcome, and depth of implantation.

    RESULTS: Sixty patients were recruited; neither pre-operative audiometry nor speech reception thresholds were significantly different between groups. Post-operatively, hearing preservation was significantly better in the interventional group. This was the case in absolute difference (median of 30 dB for control, 20 dB for interventional, χ² = 6.2, p = .013), as well as for relative difference (medians of 66% for the control, 31% for the interventional, χ² = 5.9, p = .015). Speech-in-noise reception thresholds were significantly better in patients with no CM drop at any point during insertion compared with patients with a CM drop; however, those with successfully recovered CMs after an initial drop were not significantly different (median gain required for speech reception score of 50% above noise of 6.9 dB for no drop, 8.6 for recovered CM, and 9.8 for CM drop, χ² = 6.8, p = .032). Angular insertion depth was not significantly different between control and interventional groups.

    CONCLUSIONS: This is the first demonstration that surgical intervention in response to intraoperative hearing monitoring can save residual hearing during cochlear implantation.

  4. Rahmat S, O'Beirne GA
    Hear Res, 2015 Dec;330(Pt A):125-33.
    PMID: 26209881 DOI: 10.1016/j.heares.2015.07.013
    Schroeder-phase masking complexes have been used in many psychophysical experiments to examine the phase curvature of cochlear filtering at characteristic frequencies, and other aspects of cochlear nonlinearity. In a normal nonlinear cochlea, changing the "scalar factor" of the Schroeder-phase masker from -1 through 0 to +1 results in a marked difference in the measured masked thresholds, whereas this difference is reduced in ears with damaged outer hair cells. Despite the valuable information it may give, one disadvantage of the Schroeder-phase masking procedure is the length of the test - using the conventional three-alternative forced-choice technique to measure a masking function takes around 45 min for one combination of probe frequency and intensity. As an alternative, we have developed a fast method of recording these functions which uses a Békésy tracking procedure. Testing at 500 Hz in normal hearing participants, we demonstrate that our fast method: i) shows good agreement with the conventional method; ii) shows high test-retest reliability; and iii) shortens the testing time to 8 min.
  5. Hall DA, Ray J, Watson J, Sharman A, Hutchison J, Harris P, et al.
    Hear Res, 2019 06;377:153-166.
    PMID: 30939361 DOI: 10.1016/j.heares.2019.03.018
    AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.
  6. Abdelatti ZAS, Hartbauer M
    Hear Res, 2017 11;355:70-80.
    PMID: 28974384 DOI: 10.1016/j.heares.2017.09.011
    In forest clearings of the Malaysian rainforest, chirping and trilling Mecopoda species often live in sympatry. We investigated whether a phenomenon known as stochastic resonance (SR) improved the ability of individuals to detect a low-frequent signal component typical of chirps when members of the heterospecific trilling species were simultaneously active. This phenomenon may explain the fact that the chirping species upholds entrainment to the conspecific song in the presence of the trill. Therefore, we evaluated the response probability of an ascending auditory neuron (TN-1) in individuals of the chirping Mecopoda species to triple-pulsed 2, 8 and 20 kHz signals that were broadcast 1 dB below the hearing threshold while increasing the intensity of either white noise or a typical triller song. Our results demonstrate the existence of SR over a rather broad range of signal-to-noise ratios (SNRs) of input signals when periodic 2 kHz and 20 kHz signals were presented at the same time as white noise. Using the chirp-specific 2 kHz signal as a stimulus, the maximum TN-1 response probability frequently exceeded the 50% threshold if the trill was broadcast simultaneously. Playback of an 8 kHz signal, a common frequency band component of the trill, yielded a similar result. Nevertheless, using the trill as a masker, the signal-related TN-1 spiking probability was rather variable. The variability on an individual level resulted from correlations between the phase relationship of the signal and syllables of the trill. For the first time, these results demonstrate the existence of SR in acoustically-communicating insects and suggest that the calling song of heterospecifics may facilitate the detection of a subthreshold signal component in certain situations. The results of the simulation of sound propagation in a computer model suggest a wide range of sender-receiver distances in which the triller can help to improve the detection of subthreshold signals in the chirping species.
  7. Mohamad N, Hoare DJ, Hall DA
    Hear Res, 2016 Feb;332:199-209.
    PMID: 26523370 DOI: 10.1016/j.heares.2015.10.001
    People with tinnitus report anecdotal difficulties in mental concentration and psychological treatments for tinnitus advise on concentration difficulties and how to manage them. Yet the literature lacks any coherent discussion about what precise theoretical cognitive constructs might be mediating reported concentration problems. This review addresses this gap by describing and critically appraising the behavioural evidence for the effects of tinnitus on cognitive performance (namely working memory and attention). Empirical evidence is somewhat limited, but there is some support that tinnitus interferes with executive attention, and mixed support that it impairs working memory and selective attention. We highlight a number of methodological considerations to help drive the field forward and we propose a putative model of the complex inter-relationships between tinnitus, cognition and confounding factors. This model provides a basis for hypothesis testing.
  8. Genitsaridi E, Partyka M, Gallus S, Lopez-Escamez JA, Schecklmann M, Mielczarek M, et al.
    Hear Res, 2019 06;377:353-359.
    PMID: 30871820 DOI: 10.1016/j.heares.2019.02.017
    BACKGROUND: The heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus.

    METHOD: Here we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This 'European School for Interdisciplinary Tinnitus Research Screening Questionnaire' (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration.

    CONCLUSIONS: With respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom.

  9. Biswas R, Lugo A, Gallus S, Akeroyd MA, Hall DA
    Hear Res, 2019 06;377:330-338.
    PMID: 30853349 DOI: 10.1016/j.heares.2019.02.008
    INTRODUCTION: Prevalence estimates depend largely on the nature of the question asked to define the presence of the health condition, and the literature on the population burden of tinnitus and hearing difficulties is no different in this respect. The lack of standardized questions for data collection limits comparison across studies and across countries. The purpose of this short Technical Note is to report the first attempt to establish a set of standard questions developed for use in population-based surveys, and their adaptation and translation from English into 11 European languages.

    METHODS: Four questions and their corresponding response options were adapted from existing population-based surveys to assess tinnitus prevalence, tinnitus symptom severity, use of healthcare resources for tinnitus and hearing difficulty. The translated versions (Bulgarian, French, German, Greek, Italian, Latvian, Polish, Portuguese, Romanian, Russian, and Spanish) were generated using recognized methods to achieve a "world-for-world" translation.

    RESULTS: Translated versions were produced with acceptable functional equivalence to the original English-language version, as judged by a small panel of bilingual speakers who participated in the online field testing.

    CONCLUSION: This work is the first of its kind to promote multi-national standardization by creating a set of tools that can readily be used across countries. These are currently being used in a European-wide study of tinnitus prevalence, and have wider application across English- and Spanish speaking countries including the Americas and Oceania.

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