[Current diagnostics and treatment options for tinnitus]. / Diagnostiek en behandelopties voor tinnitus.

Tinnitus is a common condition with great variability in the intensity of symptomatology. In recent years, more and more insights have been gained into the mechanism of tinnitus and its relationship with hearing loss and other factors such as stress. Depending on the symptoms and clinical findings, a patient may be referred to an ENT specialist or audiologist. For the majority of patients, re-assurance and providing good information is sufficient. For others improving hearing and possibly cognitive behavioral therapy remains the most important pillars for treatment of tinnitus. A number of experimental treatments are currently underway which offer hope for the future.

Comparison between two self-guided tinnitus pitch matching methods.

Introduction: Tinnitus pitch matching is a procedure by which the frequency of an external sound is manipulated in such a way that its pitch matches the one of the tinnitus. The correct measure of the tinnitus pitch plays an important role in the effectiveness of any sound-based therapies. To date, this assessment is difficult due to the subjective nature of tinnitus. Some of the existing pitch matching methods present a challenge for both patients and clinicians, and require multiple adjustments of frequency and loudness, which becomes increasingly difficult in case of coexisting hearing loss. In this paper, we present the comparison in terms of reliability between two self-guided pitch matching methods: the method of adjustment (MOA) and the multiple-choice method (MCM). Methods: 20 participants with chronic tinnitus and hearing loss underwent the two assessments in two different sessions, 1 week apart. Measures of intraclass correlation (ICC) and difference in octaves (OD) within-method and within-session were obtained. Results: Both methods presented good reliability, and the obtained values of ICC and OD suggested that both methods might measure a different aspect of tinnitus. Discussion: Our results suggest that a multiple-choice method (MCM) for tinnitus pitch matching is as reliable in a clinical population as more conventional methods.

Carbamazepine induces upward frequency shifts of spontaneous otoacoustic emissions.

In three subjects, we measured spontaneous otoacoustic emissions (SOAEs) when they were using carbamazepine (CBZ), and compared this to the SOAE measurement when they were not using CBZ. We observed 14 SOAEs showing a consistent upward shift of center frequency, related to CBZ intake. On average, the magnitude of the frequency shift increased with increasing frequency. The magnitude of the shift was 30-104 Hz, at frequencies ranging from 1.3 to 2.3 kHz, corresponding to a shift between 2.3 and 4.5%. Compared to other causes and manipulations known to change SOAE frequency, these shifts are relatively large. The underlying mechanism is most likely an increased stiffness of the cochlear partition. This would also explain the downward pitch shift due to CBZ, which has been reported by subjects with absolute pitch.

Relationship between irregularities in spontaneous otoacoustic emissions suppression and psychophysical tuning curves.

The suppression of spontaneous otoacoustic emissions (SOAEs) allows the objective evaluation of cochlear frequency selectivity by determining the suppression tuning curve (STC). Interestingly, some STCs have additional sidelobes at the high frequency flank, which are thought to result from interaction between the probe tone and the cochlear standing wave corresponding to the SOAE being suppressed. Sidelobes are often in regions of other neighboring SOAEs but can also occur in the absence of any other SOAE. The aim of this study was to compare STCs and psychoacoustic tuning curves (PTCs). Therefore, STCs and PTCs were measured in: (1) subjects in which the STC had a sidelobe, and (2) subjects without STC sidelobes. Additionally, PTCs were measured in subjects without SOAEs. Across participant groups, the quality factor Q10dB of the PTCs was similar, independently from whether SOAEs were present or absent. Thus, the presence of an SOAE does not provide enhanced frequency selectivity at the emission frequency. Moreover, both PTC and STC show irregularities, but these are not related in a straightforward way. This suggests that different mechanisms cause these irregularities.

Investigating the relation between minimum masking levels and hearing thresholds for tinnitus subtyping.

Heterogeneity of tinnitus imposes a challenge for its treatment. Identifying tinnitus subtypes might help to establish individualized diagnosis and therapies. The minimum masking level (MML) is a clinical tool defined as the minimum intensity of a masking sound required to cover tinnitus. Understanding the differences among masking patterns in patients could facilitate the task of subtyping tinnitus. Here, we studied the variability of hearing thresholds and MMLs among patients with tinnitus to identify tinnitus subgroups. A population of 366 consecutive patients from a specialized tinnitus clinic were included in the analysis. Hearing thresholds and MMLs were determined for octave frequencies from 0.25 to 8kHz, as well as for 3 and 6kHz. Subjects were divided into two groups according to whether their tinnitus was maskable (M, 329 subjects) or non-maskable (NM, 37 subjects). Hearing thresholds and tinnitus loudness did not differ significantly between both groups. The dimensionality of the data was reduced by means of principal component analysis (PCA), and the largest resulting components were used for clustering the data. The cluster analysis resulted in five clusters with differences in tinnitus pitch, lateralization, hearing thresholds and MML, as well as on age and gender. Clusters differed in contours of hearing thresholds and MML, describing patterns of low or high thresholds in combination with low or high MML. The clustering solution presented a low silhouette value (0.45), implying that the clustering is weak and could be artificial. The analysis pointed out the diversity across tinnitus patients. Our results suggest that there might be a continuum of patients' characteristics rather than discrete subgroups.

Changes in Tinnitus by Cochlear Implantation: A Parametric Study of the Effect of Single-Electrode Stimulation.

INTRODUCTION: While cochlear implantation may have a positive effect on tinnitus, it is not effective in reducing tinnitus in all patients. This may be due to different patients requiring different strategies of electrical stimulation in order to obtain a positive effect on tinnitus. It is, therefore, important to identify the most effective stimulation strategies to reduce tinnitus. The simplest possible strategy is stimulation by only one electrode. In this study, we investigated tinnitus suppression by electrical stimulation via a single electrode of the cochlear implant. METHODS: We performed a listening experiment in 19 adult participants, who had received a unilateral cochlear implant (CI) because of severe bilateral hearing loss. All of these patients had indicated that they suffered from tinnitus. During a 300-s interval, patients listened to blocks of single-electrode stimulation and rated the loudness of the stimulus and any effects on their tinnitus. The 300-s interval included a block of single-electrode stimulation (duration 120 s). In consecutive intervals, the stimulus differed in its cochlear location (basal or apical), its pulse rate (720 or 725 Hz, 1,200 Hz, and 2,400 or 2,320 Hz), and amplitude (just above threshold or equivalent to moderate loudness). Thus, 2 × 3 × 2 = 12 stimulus conditions were tested in each participant, and each condition was presented only once. During the experiment, the participants promptly rated the loudness of the stimuli and the loudness of their tinnitus on a Visual Analogue Scale (10-point VAS). RESULTS: Significantly more tinnitus reduction was observed with stimuli at a moderate intensity level (30%) compared to stimuli at near-threshold level (18%) (χ2 [1, N = 222] = 14.115, p < 0.01). No significant differences in tinnitus levels resulted from the different pulse rates and stimulation sites. Eight participants reported an increase of tinnitus loudness under at least one stimulus condition. Changes in tinnitus loudness were generally minor, and never exceeded 3 points on the VAS. The overall effect of cochlear implantation on tinnitus, that is, the effect with full-array stimulation, was not correlated with the effectiveness of the single-electrode stimulation on tinnitus. CONCLUSION: In conclusion, the effect of single-electrode stimulation on tinnitus is relatively insignificant in comparison to the effect of full-array stimulation. However, in some individual cases, sustained single-electrode stimulation may be beneficial for tinnitus management.

Gray matter declines with age and hearing loss, but is partially maintained in tinnitus.

The impact of age-related hearing loss extends beyond the auditory pathway and impacts brain areas related to cognitive impairment and even dementia. The presence of tinnitus, a sensation of sound that frequently co-occurs with hearing loss, is additionally linked to cognitive decline. Interestingly, structural neuroimaging studies have reported that hearing loss may precede or modulate the onset of cognitive impairment. In this study, we aimed to disentangle the effects of age, hearing loss, and tinnitus on gray matter structure. In total, 39 participants with hearing loss and tinnitus, 21 with hearing loss but without tinnitus, and 39 controls were included in this voxel- and surface-based morphometry MRI study. Whole brain volume and surface thickness measures were compared between the groups. Age-related gray matter volume decline was observed in all groups. Several brain areas showed smaller gray matter volume and cortical surface thickness in hearing loss without tinnitus, relative to controls. This reduction was observed both within and outside of the auditory pathway. Interestingly, these reductions were not observed in participants with tinnitus, who had similar hearing loss and were of similar age. Since we have tools to improve hearing loss, hearing screening may aid in the battle against cognitive decline.

Frequency selectivity of tonal language native speakers probed by suppression tuning curves of spontaneous otoacoustic emissions.

Native acquisition of a tonal language (TL) is related to enhanced abilities of pitch perception and production, compared to non-tonal language (NTL) native speakers. Moreover, differences in brain responses to both linguistically relevant and non-relevant pitch changes have been described in TL native speakers. It is so far unclear to which extent differences are present at the peripheral processing level of the cochlea. To determine possible differences in cochlear frequency selectivity between Asian TL speakers and Caucasian NTL speakers, suppression tuning curves (STCs) of spontaneous otoacoustic emissions (SOAEs) were examined in both groups. By presenting pure tones, SOAE levels were suppressed and STCs were derived. SOAEs with center frequencies higher than 4.5 kHz were recorded only in female TL native speakers, which correlated with better high-frequency tone detection thresholds. The suppression thresholds at the tip of the STC and filter quality coefficient Q10dB did not differ significantly between both language groups. Thus, the characteristics of the STCs of SOAEs do not support the presence of differences in peripheral auditory processing between TL and NTL native speakers.

Intraocular and intracranial pressure in glaucoma patients taking acetazolamide.

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.

Associations between tinnitus and glaucoma suggest a common mechanism: A clinical and population-based study.

The purpose of this study was to determine if there is an association between tinnitus and glaucoma. We tested this by first completing a clinic-based cross-sectional questionnaire study in which we sent a series of tinnitus-related questions to glaucoma patients and healthy subjects, and then followed up with a large population-based cross-sectional study in which glaucoma and tinnitus were also assessed by questionnaire. For the clinical study, we received 209 responses from glaucoma patients and 109 responses from healthy subjects (primarily the spouses of the patients). For the population-based study, we evaluated 79,866 participants. Logistic regression models were used to test the relationship between glaucoma and tinnitus; the clinical study analysis was adjusted for age, gender, BMI, hypertension, and diabetes and the population-based study was adjusted for these same variables with the addition of socioeconomic status and subjective hearing loss. For the clinical study, glaucoma patients had an 85% increase in odds for tinnitus (adjusted OR 1.85, 95% CI 1.10 to 3.05). The effect did not depend on pretreatment intraocular pressure, and the associated symptoms were not pulsatile in nature. For the population-based study, glaucoma patients had a 19% increase in odds for tinnitus (adjusted OR 1.19, 95% CI 1.02 to 1.40). Overall, our results suggest that those with glaucoma are more likely to have tinnitus than those without glaucoma. These results provide hypotheses for a mechanism involved in both tinnitus and glaucoma. One possible mechanism could be vascular dysregulation due to impairment of nitric oxide production.

Suppression tuning of spontaneous otoacoustic emissions in the barn owl (Tyto alba).

Spontaneous otoacoustic emissions (SOAEs) have been observed in a variety of different vertebrates, including humans and barn owls (Tyto alba). The underlying mechanisms producing the SOAEs and the meaning of their characteristics regarding the frequency selectivity of an individual and species are, however, still under debate. In the present study, we measured SOAE spectra in lightly anesthetized barn owls and suppressed their amplitudes by presenting pure tones at different frequencies and sound levels. Suppression effects were quantified by deriving suppression tuning curves (STCs) with a criterion of 2 dB suppression. SOAEs were found in 100% of ears (n = 14), with an average of 12.7 SOAEs per ear. Across the whole SOAE frequency range of 3.4-10.2 kHz, the distances between neighboring SOAEs were relatively uniform, with a median distance of 430 Hz. The majority (87.6%) of SOAEs were recorded at frequencies that fall within the barn owl's auditory fovea (5-10 kHz). The STCs were V-shaped and sharply tuned, similar to STCs from humans and other species. Between 5 and 10 kHz, the median Q10dB value of STC was 4.87 and was thus lower than that of owl single-unit neural data. There was no evidence for secondary STC side lobes, as seen in humans. The best thresholds of the STCs varied from 7.0 to 57.5 dB SPL and correlated with SOAE level, such that smaller SOAEs tended to require a higher sound level to be suppressed. While similar, the frequency-threshold curves of auditory-nerve fibers and STCs of SOAEs differ in some respects in their tuning characteristics indicating that SOAE suppression tuning in the barn owl may not directly reflect neural tuning in primary auditory nerve fibers.

Noninvasive intracranial pressure assessment using otoacoustic emissions: An application in glaucoma.

The theory that glaucoma patients have a lower intracranial pressure (ICP) than healthy subjects is a controversial one. The aim of this study was to assess ICP noninvasively by determining the relationship between distortion product otoacoustic emission (DPOAE) phase and body position and to compare this relationship between patients with primary open angle glaucoma (POAG), patients with normal tension glaucoma (NTG), and controls. The relationship was also calibrated using published data regarding invasive measurements of ICP versus body position. DPOAEs were measured in 30 controls and 32 glaucoma patients (17 POAG, 15 NTG) at the following body positions (assuming 90° as upright): 45, 30, 20, 10, 0 (supine), -10, and -20°. DPOAE phase had a clear, nonlinear relationship with body position. The mean DPOAE phase shifts between the two most extreme body positions (45 to -20°) were 73.6, 80.7, and 66.3° for healthy, POAG, and NTG, respectively (P = 0.73), and the groups showed the same, nonlinear behaviour. This indicates that there is no evidence that glaucoma patients have a reduced ICP. When calibrated with invasive data, ICP and DPOAE phase were linearly related over an ICP of 3 mmHg. This suggests that, more broadly, DPOAEs could be used in the future to monitor changes in ICP in a clinical setting and to measure dynamic changes in ICP such as diurnal fluctuations or changes induced by certain medications.

Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.

INTRODUCTION: In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of patients with severe mental distress. The goal of this study was to identify subgroups in a large group of tinnitus patients. METHODS: Data were collected from patients with severe tinnitus complaints visiting our tertiary referral tinnitus care group at the University Medical Center Groningen. Patient-reported and physician-reported variables were collected during their visit to our clinic. Cluster analyses were used to characterize subgroups. For the selection of the right variables to enter in the cluster analysis, two approaches were used: (1) variable reduction with principle component analysis and (2) variable selection based on expert opinion. RESULTS: Various variables of 1,783 tinnitus patients were included in the analyses. Cluster analysis (1) included 976 patients and resulted in a four-cluster solution. The effect of external influences was the most discriminative between the groups, or clusters, of patients. The "silhouette measure" of the cluster outcome was low (0.2), indicating a "no substantial" cluster structure. Cluster analysis (2) included 761 patients and resulted in a three-cluster solution, comparable to the first analysis. Again, a "no substantial" cluster structure was found (0.2). CONCLUSION: Two cluster analyses on a large database of tinnitus patients revealed that clusters of patients are mostly formed by a different response of external influences on their disease. However, both cluster outcomes based on this dataset showed a poor stability, suggesting that our tinnitus population comprises a continuum rather than a number of clearly defined subgroups.

Innovations in Doctoral Training and Research on Tinnitus: The European School on Interdisciplinary Tinnitus Research (ESIT) Perspective.

Tinnitus is a common medical condition which interfaces many different disciplines, yet it is not a priority for any individual discipline. A change in its scientific understanding and clinical management requires a shift toward multidisciplinary cooperation, not only in research but also in training. The European School for Interdisciplinary Tinnitus research (ESIT) brings together a unique multidisciplinary consortium of clinical practitioners, academic researchers, commercial partners, patient organizations, and public health experts to conduct innovative research and train the next generation of tinnitus researchers. ESIT supports fundamental science and clinical research projects in order to: (1) advancing new treatment solutions for tinnitus, (2) improving existing treatment paradigms, (3) developing innovative research methods, (4) performing genetic studies on, (5) collecting epidemiological data to create new knowledge about prevalence and risk factors, (6) establishing a pan-European data resource. All research projects involve inter-sectoral partnerships through practical training, quite unlike anything that can be offered by any single university alone. Likewise, the postgraduate training curriculum fosters a deep knowledge about tinnitus whilst nurturing transferable competencies in personal qualities and approaches needed to be an effective researcher, knowledge of the standards, requirements and professionalism to do research, and skills to work with others and to ensure the wider impact of research. ESIT is the seed for future generations of creative, entrepreneurial, and innovative researchers, trained to master the upcoming challenges in the tinnitus field, to implement sustained changes in prevention and clinical management of tinnitus, and to shape doctoral education in tinnitus for the future.

Unilateral tinnitus: changes in connectivity and response lateralization measured with FMRI.

Tinnitus is a percept of sound that is not related to an acoustic source outside the body. For many forms of tinnitus, mechanisms in the central nervous system are believed to play a role in the pathology. In this work we specifically assessed possible neural correlates of unilateral tinnitus. Functional magnetic resonance imaging (fMRI) was used to investigate differences in sound-evoked neural activity between controls, subjects with left-sided tinnitus, and subjects with right-sided tinnitus. We assessed connectivity patterns between auditory nuclei and the lateralization of the sound-evoked responses. Interestingly, these response characteristics did not relate to the laterality of tinnitus. The lateralization for left- or right ear stimuli, as expressed in a lateralization index, was considerably smaller in subjects with tinnitus compared to that in controls, reaching significance in the right primary auditory cortex (PAC) and the right inferior colliculus (IC). Reduced functional connectivity between the brainstem and the cortex was observed in subjects with tinnitus. These differences are consistent with two existing models that relate tinnitus to i) changes in the corticothalamic feedback loops or ii) reduced inhibitory effectiveness between the limbic system and the thalamus. The vermis of the cerebellum also responded to monaural sound in subjects with unilateral tinnitus. In contrast, no cerebellar response was observed in control subjects. This suggests the involvement of the vermis of the cerebellum in unilateral tinnitus.

Plasticity in tinnitus patients: a role for the efferent auditory system?

HYPOTHESIS: The role of the corticofugal efferent auditory system in the origin or maintenance of tinnitus is currently mostly overlooked. Changes in the balance between excitation and inhibition after an auditory trauma are likely to play a role in the origin of tinnitus. The efferent auditory system can be expected to be involved in such changes. BACKGROUND: The goal of this article was to investigate the current knowledge of the functional efferent auditory system in humans, mostly based on animal research, and to look for new possibilities to try to answer the question of the specific role(s) of the corticofugal efferent auditory system in tinnitus. METHODS: Literature review. RESULTS: Several suggestions for future research are made, for studies in humans as well as in animals. CONCLUSION: We think that it will be worthwhile to investigate the efferent auditory system and its relations to tinnitus in the near future. With this article, we hope to inspire such work.

Tinnitus-related dissociation between cortical and subcortical neural activity in humans with mild to moderate sensorineural hearing loss.

Tinnitus is a phantom sound percept that is strongly associated with peripheral hearing loss. However, only a fraction of hearing-impaired subjects develops tinnitus. This may be based on differences in the function of the brain between those subjects that develop tinnitus and those that do not. In this study, cortical and sub-cortical sound-evoked brain responses in 34 hearing-impaired chronic tinnitus patients and 19 hearing level-matched controls were studied using 3-T functional magnetic resonance imaging (fMRI). Auditory stimuli were presented to either the left or the right ear at levels of 30-90 dB SPL. We extracted neural activation as a function of sound intensity in eight auditory regions (left and right auditory cortices, medial geniculate bodies, inferior colliculi and cochlear nuclei), the cerebellum and a cinguloparietal task-positive region. The activation correlated positively with the stimulus intensity, and negatively with the hearing threshold. We found no differences between both groups in terms of the magnitude and lateralization of the sound-evoked responses, except for the left medial geniculate body and right cochlear nucleus where activation levels were elevated in the tinnitus subjects. We observed significantly reduced functional connectivity between the inferior colliculi and the auditory cortices in tinnitus patients compared to controls. Our results indicate a failure of thalamic gating in the development of tinnitus.

Can the tinnitus spectrum identify tinnitus subgroups?

The tinnitus spectrum is a psycho-acoustic metric of tinnitus. Previous work found a tight relation between the spectrum and the tone audiogram. This suggests that the spectrum and the audiogram provide essentially the same information, and the added value of the spectrum is limited. In order to test whether the spectrum shows tinnitus characteristics that cannot be inferred from the audiogram, we re-examined the relation between the tinnitus spectrum and the tone audiogram, in a group of 80 tinnitus patients. We defined three subgroups of patients, using the shape of their tinnitus spectrum: (1) patients with a spectrum, monotonously increasing with frequency (2) patients with a distinct peak in their spectrum, (3) all other patients. Patients in group 3 typically showed low frequency tinnitus spectra. In all three groups, the largest hearing loss was at high frequencies (>2 kHz). The mean audiograms of group 1 and 2 were remarkably similar; group 3 had an additional hearing loss for the lower frequencies (<2 kHz). The three groups did not differ with respect to age, sex, or tinnitus questionnaire outcomes. In subgroups 2 and 3, the shape of the spectrum clearly differed from that of the tone audiogram. In other words, the spectrum technique provided information that could not have been obtained by tone audiometry alone. Therefore, the spectrum measurement may develop into a technique that can differentiate between classes of tinnitus. This may eventually contribute to the effective management of tinnitus, as various classes of tinnitus may require different therapeutic interventions.

Gray matter in the brain: differences associated with tinnitus and hearing loss.

Tinnitus, usually associated with hearing loss, is characterized by the perception of sound without an external sound source. The pathophysiology of tinnitus is poorly understood. In the present study, voxel-based morphometry (VBM) was employed to identify gray matter differences related to hearing loss and tinnitus. VBM was applied to magnetic resonance images of normal-hearing control subjects (n = 24), hearing-impaired subjects without tinnitus (n = 16, HI group) and hearing-impaired subjects with tinnitus (n = 31, HI + T group). This design allowed us to disentangle the gray matter (GM) differences related to hearing loss and tinnitus, respectively. Voxel-based VBM analyses revealed that both HI and HI + T groups, relative to the controls, had GM increases in the superior and middle temporal gyri, and decreases in the superior frontal gyrus, occipital lobe and hypothalamus. We did not find significant GM differences between both patient groups. Subsequent region-of-interest (ROI) analyses of all Brodmann Areas, the cerebellum and the subcortical auditory nuclei showed a GM increase in the left primary auditory cortex of the tinnitus patients compared to the HI and control groups. Moreover, GM decreases were observed in frontal areas and mainly GM increases in limbic areas, both of which occurred for hearing loss irrespective of tinnitus, relative to the controls. These results suggest a specific role of the left primary auditory cortex and the additional involvement of various non-auditory brain structures in tinnitus. Understanding the causal relation between these GM changes and tinnitus will be an important next step in understanding tinnitus mechanisms.