Does Listening to Tinnitus Frequency-Filtered Music Relieve Tinnitus?

BACKGROUND AND OBJECTIVES: Tinnitus frequency-filtered music therapy aims to restore lateral inhibition to reverse tonotopic reorganization in the auditory cortex. Although the tinnitus-relieving effect of this therapy has been investigated, the results remain controversial. We performed a prospective, randomized, controlled double-blind study to determine the tinnitus-suppressing effect of tinnitus frequency-filtered music therapy. SUBJECTS AND METHODS: The study included 90 participants who were randomly categorized into an experimental group that listened to tinnitus frequency-filtered music and a control group that listened to music from which a random frequency was removed. The Tinnitus Handicap Inventory (THI) score and measures of tinnitus loudness, daily awareness, and tinnitus-induced annoyance were evaluated at the initial visit and at 3 and 6 months (final follow-up). The rates of improvement in THI scores in the two groups were also recorded. RESULTS: All measured variables showed significant improvement in both groups, except the matched tinnitus loudness and minimal masking level. However, no significant intergroup differences were observed in the amount of improvement in THI scores and any other variable. The rates of improvement in THI scores were higher in the control group at 3 and 6 months. CONCLUSIONS: Listening to tinnitus frequency-filtered music reduced tinnitus-induced handicaps; however, this approach was not significantly better than listening to music from which a random frequency was removed.

Direct and Transcutaneous Vagus Nerve Stimulation for Treatment of Tinnitus: A Scoping Review.

Recent animal research has shown that vagus nerve stimulation (VNS) paired with sound stimuli can induce neural plasticity in the auditory cortex in a controlled manner. VNS paired with tones excluding the tinnitus frequency eliminated physiological and behavioral characteristics of tinnitus in noise-exposed rats. Several clinical trials followed and explored the effectiveness of VNS paired with sound stimuli for alleviating tinnitus in human subjects. Transcutaneous VNS (tVNS) has received increasing attention as a non-invasive alternative approach to tinnitus treatment. Several studies have also explored tVNS alone (not paired with sound stimuli) as a potential therapy for tinnitus. In this review, we discuss existing knowledge about direct and tVNS in terms of applicability, safety, and effectiveness in diminishing tinnitus symptoms in human subjects. This review includes all existing clinical and neuroimaging studies of tVNS alone or paired with acoustic stimulation in tinnitus patients and outlines the present limitations that must be overcome to maximize the potential of (t)VNS as a therapy for tinnitus.

A double-blind, randomized controlled trial exploring the efficacy of frequency lowering hearing aids in patients with high-frequency hearing loss.

OBJECTIVE: Whether linear frequency transposition (LFT) assists individuals with hearing difficulties has been studied for years, but no reliable comparison between LFT hearing aids (HAs) and conventional compression-type HAs has been conducted. Herein, we report on the first, relevant, double-blind, randomized controlled trial on this topic using a large sample size. We compared the efficacies of LFT HAs to those of compression-type HAs in patients with high-frequency hearing loss (HFHL); we also reviewed the literature. METHODS: A total of 103 patients were randomized into three groups: conventional HAs featuring wide dynamic range compression (control group); HAs featuring LFT (LFT group); and HAs employing both LFT and wide dynamic range compression of high frequencies (combined group). Pure tone averages (PTAs), speech recognition thresholds (SRTs), word recognition scores (WRSs), and Abbreviated Profile of Hearing Aid Benefit (APHAB) inventories were assessed at the initial visit and after 3 months of HA use. Subject preferences in terms of continued use of their HAs were also evaluated. RESULTS: The PTA, SRT, and WRS scores significantly improved in all three groups. No significant among-group differences were evident. The APHAB score significantly improved only in the control group; HA future-use preference was also highest in this group. CONCLUSION: LFT did not provide an additional benefit for subjects with HFHL over conventional amplification and users preferred conventional HAs featuring wide dynamic range compression.

Does the tinnitus pitch correlate with the frequency of hearing loss?

BACKGROUND: The tonotopic model of tinnitus claims that the tinnitus pitch corresponds to the audiometric edge; the homeostatic model suggests that it falls within the hearing loss (HL) area. The existing evidence mostly supports the homeostatic model, but the relationship between the tinnitus pitch and the HL frequencies has been insufficiently explored. AIMS/OBJECTIVE: To investigate the association between the tinnitus pitch and the audiometric profile in the largest study population to date. MATERIALS AND METHODS: Three hundred and ninety-three patients with tonal or narrow-band tinnitus participated. HL frequencies included 30, 40, 50 (F50), 60 dB, and maximum HL. We defined edge frequencies in four different ways according to the existing studies. We assessed the association between all estimated frequencies and the tinnitus pitch using t-tests, Spearman's correlation, and multiple regression. RESULTS: All calculated frequencies differed significantly from the tinnitus pitch except for F50. None were correlated with the tinnitus pitch. F50 was the only significant predictor among the estimated frequencies in multiple regression. CONCLUSIONS: The tinnitus pitch fell within the HL area, and was mildly associated with F50. SIGNIFICANCE: Our results support the homeostatic tinnitus model, and provide reliable evidence that tinnitus pitch does not correspond to the audiometric edge.

What Makes Tinnitus Loud?

INTRODUCTION: Tinnitus loudness is a subjective measure, and it does not directly reflect either tinnitus severity or the impact on daily life. Nevertheless, loud tinnitus may be the most frequent clinical complaint of tinnitus patients. Factors contributing to the loudness of the phantom sound have rarely been studied. We evaluated both matched and self-rated loudness in a large sample of patients with tinnitus and analyzed the influencing factors among demographic, hearing, and tinnitus characteristics. METHODS: Two hundred ninety-nine patients with chronic tinnitus were enrolled. We evaluated the matched loudness, minimal masking level (MML), and visual analog scale (VAS) loudness. Stepwise multiple regression analyses were performed for each loudness measure using independent variables of age, sex, time since tinnitus onset, tinnitus laterality, pure-tone average, tinnitus pitch, tinnitus handicap inventory (THI) score, VAS annoyance, disturbance and daily tinnitus duration, and depression score. We calculated bivariate correlations between each loudness measure and all independent variables. RESULTS: The psychoacoustic loudness measures (matched loudness and MML) were highly correlated and were affected by the hearing deficit and tinnitus pitch (Pearson r > 0.5 for pure tone averages, and r > 0.3 for tinnitus pitch for both variables, p < 0.05), whereas the subjective measurement (VAS loudness) exhibited little to no correlation with the other two measures and was related to psycho-emotional factors such as the THI score, VAS variables, and depression (Pearson r > 0.6 for VAS annoyance, r > 0.4 for VAS daily duration and disturbance and THI score, r > 0.3 for the depression score, p < 0.05). CONCLUSION: The matched tinnitus loudness and MML values were influenced principally by the extent of hearing loss and related factors, suggesting that rehabilitation using hearing aids could help reduce perception of tinnitus loudness. A psycho-emotional approach might more effectively lessen self-perceived loudness.

Tinnitus Suppression Effect of Hearing Aids in Patients With High-frequency Hearing Loss: A Randomized Double-blind Controlled Trial.

INTRODUCTION: Hearing aids (HAs) with frequency lowering have been used for high-frequency hearing loss (HFHL), but their effects on tinnitus relief have not been studied extensively. This randomized double-blind trial was performed to investigate and compare tinnitus suppression effects of conventional type HAs and frequency-lowering HAs in patients with HFHL. METHODS: A total of 114 patients were randomized into three groups: conventional HA using wide dynamic range compression, HA with frequency translation, and HA with linear frequency transposition. Participants wore HAs for 3 months and then discontinued their use. The final evaluation was performed at 3 months after cessation of wearing HA (6 mo after the initial visit). The Tinnitus Handicap Inventory (THI) score and additional variables, such as matched tinnitus loudness and visual analog scale scores of subjectively perceived tinnitus loudness, daily awareness, and annoyance, were measured at the initial visit and at 3- and 6-month follow-ups. RESULTS: THI score and most of the additional outcomes were significantly improved at 3 and 6 months (3 mo after HA removal) compared with their initial values in all three groups. The incidence rates of patients with improvements in the THI score by 20% or more were 71.0, 72.7, and 74.3% at 3 months, and 54.8, 51.6, and 59.4% at 6 months for the three groups, respectively. There were no significant differences in primary or additional variables between hearing aid types at either 3 or 6 months. CONCLUSION: This is a consolidated standards of reporting trials-guided study providing direct evidence for tinnitus suppression effects of HA alone, without accompanying counseling or any other treatments, which lasted for at least 3 months after patients stopped using HAs. HAs effectively suppressed tinnitus in patients with HFHL regardless of the amplification strategy type.

Functional MRI evidence of the cortico-olivary efferent pathway during active auditory target processing in humans.

Auditory target detection has been explored by a number of studies, but none have demonstrated activity in the auditory subcortical centers evoked by the top-down attentional mechanism related to target detection in humans. We applied functional magnetic resonance imaging (fMRI) with sparse sampling to explore activity in the auditory centers, particularly in the subcortex, during an active auditory target detection task. Fourteen healthy subjects with normal hearing tapped the left index finger in response to target tonal stimuli presented among other (non-target) stimuli during continuous white noise stimulation. General linear model, region-of-interest, and connectivity analyses were performed. In the cortex, bilateral auditory cortices as well as the cingulate gyrus, thalamus, and supramarginal gyrus were activated to target stimuli and functionally connected to each other. In the subcortex, the superior olivary complex (SOC) and locus coeruleus were activated to the target but not to the non-target or background noise stimuli. The SOC was the only auditory subcortical center that displayed connectivity to the auditory cortical areas as well as the cingulate and supramarginal gyri during target presentation but not during other conditions. SOC activation appears to be the first fMRI evidence of direct cortico-olivary projections in the human brain as well as SOC participation in auditory target detection. Our results may be an initial step towards developing a noninvasive methodology to evaluate the functional integrity of the auditory efferent system in humans.

Sequential versus Combination Treatment Using Steroids and Diuretics for Acute Low-Frequency Sensorineural Hearing Loss: A Noninferiority Trial.

OBJECTIVE: Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. METHODS: A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. RESULTS: The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively. CONCLUSION: This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.

BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus.

OBJECTIVE: Vagus nerve stimulation (VNS) is a neuromodulation method used for treatment of epilepsy and depression. Transcutaneous VNS (tVNS) has been gaining popularity as a noninvasive alternative to VNS. Previous tVNS neuroimaging studies revealed brain (de)activation patterns that involved multiple areas implicated in tinnitus generation and perception. In this study, functional magnetic resonance imaging (fMRI) was used to explore the effects of tVNS on brain activity in patients with tinnitus. METHODS: Thirty-six patients with chronic tinnitus received tVNS to the inner tragus, cymba conchae, and earlobe (sham stimulation). RESULTS: The locus coeruleus and nucleus of the solitary tract in the brainstem were activated in response to stimulation of both locations compared with the sham stimulation. The cochlear nuclei were also activated, which was not observed in healthy subjects with normal hearing. Multiple auditory and limbic structures, as well as other brain areas associated with generation and perception of tinnitus, were deactivated by tVNS, particularly the parahippocampal gyrus, which was recently speculated to cause tinnitus in hearing-impaired patients. CONCLUSIONS: tVNS via the inner tragus or cymba conchae suppressed neural activity in the auditory, limbic, and other tinnitus-related non-auditory areas through auditory and vagal ascending pathways in tinnitus patients. The results from this study are discussed in the context of several existing models of tinnitus. They indicate that the mechanism of action of tVNS might be involved in multiple brain areas responsible for the generation of tinnitus, tinnitus-related emotional annoyance, and their mutual reinforcement.

Changes in the regional shape and volume of subcortical nuclei in patients with tinnitus comorbid with mild hearing loss.

PURPOSE: Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. METHODS: The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. RESULTS: SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. CONCLUSION: Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.

The Effect of Primary Levels and Frequencies on the Contralateral Suppression of Distortion Product Otoacoustic Emission.

BACKGROUND AND OBJECTIVES: Changes in distortion product otoacoustic emission (DPOAE) caused by contralateral suppression (CS) allow the function of the auditory efferent system to be evaluated. Parameters affording maximum CS are preferred in terms of clinical application. Our objective was to evaluate the effects of primary levels and frequencies on DPOAE-mediated CS. SUBJECTS AND METHODS: Sixteen subjects with normal hearing participated. DPOAEs were recorded with and without contralateral acoustic stimulation; we delivered broadband noise of 65 dB SPL at f2 frequencies between 1,000 Hz and 6,727 Hz, at 8 pt/octave. The L2 was varied between 40 dB SPL and 80 dB SPL in 10-dB steps. RESULTS: L2 did not significantly affect DPOAE-mediated CS. Higher L2 levels significantly reduced the fine structure depth of both the baseline and suppressed DPOAE datasets. The amount of CS was greatly affected by the f2 frequency; lower and higher frequency ranges afforded significantly stronger suppression than did mid-frequencies within the studied range. CONCLUSIONS: Our findings suggest that DPOAE CS should be measured over a wide range of frequencies as the amount of CS seems to be highly dependent on f2. The use of a higher L2 level may be optimal when it is sought to evoke strong DPOAE-mediated suppression while simultaneously minimizing DPOAE fine structure. Our findings may assist in optimization of clinical procedures evaluating the integrity of the auditory efferent system.

Self-Administered Tinnitus Pitch Matching versus a Conventional Audiometric Procedure.

OBJECTIVE: Obtaining an accurate tinnitus pitch match is an initial and critical requirement for tinnitus evaluation and treatment, particularly for applying tailor-made notched music training. We investigated whether computer-based self-administered tinnitus pitch matching (CSTPM) is comparable with a conventional audiometric procedure (CAP). METHODS: In total, 82 patients (mean age 45.52 years; 42 females) with tonal tinnitus participated. The CAP was performed by the same audiologist using a 2-alternative forced choice method with a frequency range of 0.25-16 kHz. In the CSTPM, the subjects used personal computer software with a scrolling slider to select the sound closest to their tinnitus pitch. After each matching procedure, an octave challenge test was applied. A multivariate logistic regression was performed to determine factors associated with the difference between the CSTPM and CAP. RESULTS: The subjects' mean hearing threshold was 21.25 ± 17.61 dB HL; the mean tinnitus handicap inventory score was 35.56 ± 24.09. The mean pitches measured with the CSTPM and CAP were 6.29 ± 4.30 and 6.98 ± 5.33 kHz, respectively. In total, 57 (69.5%) subjects matched their tinnitus with less than half an octave difference between the procedures. The results of the 2 methods correlated significantly with each other (Pearson r = 0.793, p < 0.001). Octave confusion was a significant factor affecting the difference between the procedures (odds ratio 8.92, p < 0.05). CONCLUSIONS: The CSTPM appears to be as accurate as the standard audiological procedure, and may be used instead of the CAP when octave confusion is minimized.

Optimization of Transcutaneous Vagus Nerve Stimulation Using Functional MRI.

OBJECTIVE/HYPOTHESIS: Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, depression, and a number of other disorders. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) has been considered as a non-invasive alternative. Several functional magnetic resonance imaging (fMRI) studies on the effects of tVNS used different stimulation parameters and locations in the ear, which makes it difficult to determine the optimal tVNS methodology. The present study used fMRI to determine the most effective location for tVNS. MATERIALS AND METHODS: Four stimulation locations in the ear were compared: the inner tragus, inferoposterior wall of the ear canal, cymba conchae, and earlobe (sham). Thirty-seven healthy subjects underwent two 6-min tVNS stimulation runs per electrode location (monophasic rectangular 500 µs pulses, 25 Hz). General linear model was performed using SPM; region-of-interest analyses were performed for the brainstem areas. RESULTS: Stimulation at the ear canal resulted in the weakest activation of the nucleus of solitary tract (NTS), the recipient of most afferent vagal projections, and of the locus coeruleus (LC), a brainstem nucleus that receives direct input from the NTS. Stimulation of the inner tragus and cymba conchae activated these two nuclei as compared to sham. However, ROI analysis showed that only stimulation of the cymba conchae produced a significantly stronger activation in both the NTS and LC than did the sham stimulation. CONCLUSIONS: These findings suggest that tVNS at the cymba conchae properly activates the vagal pathway and results in its strongest activation, and thus may be the optimal location for tVNS therapies applied to the auricle.

Effects of scanner acoustic noise on intrinsic brain activity during auditory stimulation.

INTRODUCTION: Although the effects of scanner background noise (SBN) during functional magnetic resonance imaging (fMRI) have been extensively investigated for the brain regions involved in auditory processing, its impact on other types of intrinsic brain activity has largely been neglected. The present study evaluated the influence of SBN on a number of intrinsic connectivity networks (ICNs) during auditory stimulation by comparing the results obtained using sparse temporal acquisition (STA) with those using continuous acquisition (CA). METHODS: Fourteen healthy subjects were presented with classical music pieces in a block paradigm during two sessions of STA and CA. A volume-matched CA dataset (CAm) was generated by subsampling the CA dataset to temporally match it with the STA data. Independent component analysis was performed on the concatenated STA-CAm datasets, and voxel data, time courses, power spectra, and functional connectivity were compared. RESULTS: The ICA revealed 19 ICNs; the auditory, default mode, salience, and frontoparietal networks showed greater activity in the STA. The spectral peaks in 17 networks corresponded to the stimulation cycles in the STA, while only five networks displayed this correspondence in the CA. The dorsal default mode and salience networks exhibited stronger correlations with the stimulus waveform in the STA. CONCLUSIONS: SBN appeared to influence not only the areas of auditory response but also the majority of other ICNs, including attention and sensory networks. Therefore, SBN should be regarded as a serious nuisance factor during fMRI studies investigating intrinsic brain activity under external stimulation or task loads.

Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging.

INTRODUCTION: The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. METHODS: Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR=8 s) was used. RESULTS: In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. CONCLUSIONS: These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders.

Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis.

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the "classic" default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.

Prevalence and factors associated with neck and jaw muscle modulation of tinnitus.

Forceful contractions of neck and jaw muscles have consistently been shown to modulate tinnitus and can be used to screen patients who are responsive to somatic stimulation and, therefore, optimal candidates for somatosensory-based treatment. To identify the factors associated with somatic modulation of tinnitus, 163 patients underwent 19 neck and jaw maneuvers after an extensive physiological and audiological profile was compiled. Overall, tinnitus was modulated in 57.1% of ears tested. Unilateral tinnitus showed greater prevalence of modulation. Neck maneuvers generally decreased tinnitus loudness, whereas jaw maneuvers increased loudness. Female gender and buzzing tinnitus were associated with a high prevalence of modulation and a decrease in tinnitus loudness. Loud tinnitus and low-pitched tonal tinnitus were associated with exacerbation of the condition as a result of somatic testing. Use of these characteristics to select optimal candidates for somatosensory-based tinnitus therapies may be essential for the development of an effective approach for tinnitus treatment.