Central Aspects of Tinnitus: Advances in Mechanisms and Neuromodulation

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropharmacology and Neuropathology".

Deadline for manuscript submissions: closed (29 March 2024) | Viewed by 11255

Special Issue Editors


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Guest Editor
Department of Ear Nose and Throat, Head and Neck Surgery, Zuyderland, 6419 PC Heerlen, The Netherlands
Interests: tinnitus; hearing disorders; neuromodulation

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Guest Editor
1. Department of Clinical Neurophysiology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
2. Mental Health and Neuroscience Research Insitute, Maastricht University, 6229 ER Maastricht, The Netherlands
Interests: deep brain stimulation; neuromodulation; neurophysiology; tinnitus; movement disorders
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Special Issue Information

Dear Colleagues,

The auditory pathway is a complex system that processes neural signals from the cochlea to the auditory cortex, where the actual perception of sound occurs. Within this pathway, a number of sophisticated processes take place, such as sound localization and the filtering of sounds. Pathology within this system can result in hearing loss (e.g., tumor or stroke) but also hyperacusis and tinnitus. While hearing loss is usually of a peripheral origin and tinnitus and hyperacusis are triggered by peripheral pathology, the brain plays a crucial role in these pathologies.

Although the prevalence and burden of persons with tinnitus is high, to date, none of the available tinnitus treatments have been proven to be effective for most tinnitus patients. Neuromodulation is currently gaining more interest as an avenue to explore for tinnitus treatment. Noninvasive neuromodulation has been shown to be effective in some tinnitus patients in the short term. Additionally, invasive techniques such as deep brain stimulation and auditory brain stem implants are currently being studied. A better understanding of the central auditory pathway supports further development of the objective measurement of hearing (e.g., auditory brainstem response) and may support further development of both non-invasive and invasive neuromodulation therapies such as auditory brainstem implants for hearing loss, deep brain stimulation, and transcranial magnetic stimulation for tinnitus.

This Special Issue of Brain Sciences aims to provide more insight into the central mechanism and therapeutics of hearing(-related) disorders. Authors are invited to submit research and reviews that address a broad range of topics, such as central aspect of hearing disorders, pathophysiology of tinnitus, hearing loss and hyperacusis, diagnostics related to the auditory pathways, invasive and non-invasive neuromodulation for (central) hearing loss, tinnitus, and hyperacusis.

Dr. Jasper V. Smit
Dr. Marcus L. F. Janssen
Guest Editors

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Keywords

  • tinnitus
  • hyperacusis
  • hearing disorders
  • auditory pathway
  • neuromodulation

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Published Papers (7 papers)

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Editorial

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3 pages, 140 KiB  
Editorial
Central Aspects of Tinnitus: Advances in Mechanisms and Neuromodulation
by Jasper V. Smit and Marcus L. F. Janssen
Brain Sci. 2024, 14(9), 889; https://doi.org/10.3390/brainsci14090889 - 31 Aug 2024
Viewed by 1026
Abstract
Tinnitus is a complex neuro-otologic disorder with a significant global impact, affecting approximately 14% of adults, with 2% experiencing severe forms [...] Full article

Research

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13 pages, 3683 KiB  
Article
Sound-Evoked Neural Activity in Normal-Hearing Tinnitus: Effects of Frequency and Stimulated Ear Side
by Shahin Safazadeh, Marc Thioux, Remco J. Renken and Pim van Dijk
Brain Sci. 2024, 14(6), 544; https://doi.org/10.3390/brainsci14060544 - 27 May 2024
Cited by 1 | Viewed by 1189
Abstract
Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, [...] Read more.
Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise normal hearing, but the results are not consistent across studies. Here, we aimed to investigate these differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis. Furthermore, there was an interaction between stimulation side and tinnitus in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation. Full article
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15 pages, 4550 KiB  
Article
Attention-Modulated Cortical Responses as a Biomarker for Tinnitus
by Matthew L. Richardson, Jiaxin Luo and Fan-Gang Zeng
Brain Sci. 2024, 14(5), 421; https://doi.org/10.3390/brainsci14050421 - 25 Apr 2024
Viewed by 1311
Abstract
Attention plays an important role in not only the awareness and perception of tinnitus but also its interactions with external sounds. Recent evidence suggests that attention is heightened in the tinnitus brain, likely as a result of relatively local cortical changes specific to [...] Read more.
Attention plays an important role in not only the awareness and perception of tinnitus but also its interactions with external sounds. Recent evidence suggests that attention is heightened in the tinnitus brain, likely as a result of relatively local cortical changes specific to deafferentation sites or global changes that help maintain normal cognitive capabilities in individuals with hearing loss. However, most electrophysiological studies have used passive listening paradigms to probe the tinnitus brain and produced mixed results in terms of finding a distinctive biomarker for tinnitus. Here, we designed a selective attention task, in which human adults attended to one of two interleaved tonal (500 Hz and 5 kHz) sequences. In total, 16 tinnitus (5 females) and 13 age- and hearing-matched control (8 females) subjects participated in the study, with the tinnitus subjects matching the tinnitus pitch to 5.4 kHz (range = 1.9–10.8 kHz). Cortical responses were recorded in both passive and attentive listening conditions, producing no differences in P1, N1, and P2 between the tinnitus and control subjects under any conditions. However, a different pattern of results emerged when the difference was examined between the attended and unattended responses. This attention-modulated cortical response was significantly greater in the tinnitus than control subjects: 3.9-times greater for N1 at 5 kHz (95% CI: 2.9 to 5.0, p = 0.007, ηp2 = 0.24) and 3.0 for P2 at 500 Hz (95% CI: 1.9 to 4.5, p = 0.026, ηp2 = 0.17). We interpreted the greater N1 modulation as local neural changes specific to the tinnitus frequency and the greater P2 as global changes to hearing loss. These two cortical measures were used to differentiate between the tinnitus and control subjects, producing 83.3% sensitivity and 76.9% specificity (AUC = 0.81, p = 0.006). These results suggest that the tinnitus brain is more plastic than that of the matched non-tinnitus controls and that the attention-modulated cortical response can be developed as a clinically meaningful biomarker for tinnitus. Full article
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10 pages, 412 KiB  
Article
Effect of the COVID-19 Pandemic on Resting-State Brain Activity in Individuals with Tinnitus
by W. Wiktor Jedrzejczak, Elżbieta Gos, Malgorzata Ganc, Danuta Raj-Koziak, Piotr H. Skarzynski and Henryk Skarzynski
Brain Sci. 2024, 14(2), 174; https://doi.org/10.3390/brainsci14020174 - 12 Feb 2024
Cited by 1 | Viewed by 1398
Abstract
This study looked at the possible effect of the COVID-19 pandemic on individuals who came to our clinic seeking relief from tinnitus. The performance of the subjects during the COVID-19 pandemic was compared with similar individuals who came to our clinic before the [...] Read more.
This study looked at the possible effect of the COVID-19 pandemic on individuals who came to our clinic seeking relief from tinnitus. The performance of the subjects during the COVID-19 pandemic was compared with similar individuals who came to our clinic before the pandemic began. The study involved 50 adults with chronic tinnitus, made up of a study group (24 subjects tested during the COVID-19 pandemic of 2020–2021) and a control group before the pandemic began (26 subjects tested from 2013 to 2017). None of the 24 reported having contracted COVID-19. Data collection involved the Tinnitus Handicap Inventory (THI) questionnaire, audiological tests, and quantitative electroencephalography (qEEG). In terms of THI scores, there were no statistically significant differences between the two groups. However, with regard to qEEG, some changes were observed, with significant decreases in alpha and beta band activity in the study group compared to the control group, particularly over the auditory cortex. We conclude that COVID-19 did not have a discernible impact on the general well-being of individuals with tinnitus. However, it did appear to alter brain activity, specifically in the alpha and beta bands over the auditory cortex, and these reults warrant further investigation. Full article
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14 pages, 1141 KiB  
Article
Changes in Tinnitus Characteristics and Residual Inhibition following Cochlear Implantation: A Prospective Analysis
by Ann Nancy Deklerck, Freya Swinnen, Hannah Keppler and Ingeborg Johanna Maria Dhooge
Brain Sci. 2023, 13(10), 1484; https://doi.org/10.3390/brainsci13101484 - 20 Oct 2023
Cited by 1 | Viewed by 1335
Abstract
This study aims to explore the effect of cochlear implantation on tinnitus perception. A prospective study was conducted on 72 adult hearing-impaired patients to evaluate tinnitus perception before and after cochlear implantation, using standardized tinnitus questionnaires (the tinnitus sample case-history questionnaire, tinnitus functional [...] Read more.
This study aims to explore the effect of cochlear implantation on tinnitus perception. A prospective study was conducted on 72 adult hearing-impaired patients to evaluate tinnitus perception before and after cochlear implantation, using standardized tinnitus questionnaires (the tinnitus sample case-history questionnaire, tinnitus functional index (TFI), and tinnitus handicap inventory (THI)). A large variety of demographic and hearing- and implant-related data was collected from patient hospital records to explore possible associations with the implantation effect. The prevalence of tinnitus complaints before implantation was 58.3%. The temporary induction or aggravation of tinnitus immediately after surgery was noted in 20% and 46.7% of patients, respectively. When evaluated 3 months after implantation, 60% of tinnitus patients experienced a clinically significant reduction in their complaints; most of the improvements were experienced immediately after activation of the implant. Only the scores for TFI and THI at baseline were found to be significantly correlated with a reduction in TFI scores after implantation. In 80% of tinnitus patients, the tinnitus remained suppressed for some time after taking off the device. The large subset of patients with residual inhibition supports the involvement of central pathophysiological processes in implantation effects on tinnitus, which are explored in this paper. Full article
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Other

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21 pages, 2818 KiB  
Systematic Review
Neuromodulation Treatments Targeting Pathological Synchrony for Tinnitus in Adults: A Systematic Review
by Derek J. Hoare, Gillian W. Shorter, Giriraj S. Shekhawat, Amr El Refaie, Bas Labree and Magdalena Sereda
Brain Sci. 2024, 14(8), 748; https://doi.org/10.3390/brainsci14080748 - 26 Jul 2024
Viewed by 1352
Abstract
(1) Background: Tinnitus involves the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source. For many people, tinnitus is a disorder associated with symptoms of emotional distress, cognitive dysfunction, autonomic arousal, behavioural changes, and [...] Read more.
(1) Background: Tinnitus involves the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source. For many people, tinnitus is a disorder associated with symptoms of emotional distress, cognitive dysfunction, autonomic arousal, behavioural changes, and functional disability. Many symptoms can be addressed effectively using education or cognitive behavioural therapy. However, there is no treatment that effectively reduces or alters tinnitus-related neurophysiological activity and thus the tinnitus percept. In this systematic review, we evaluated the effectiveness of neuromodulation therapies for tinnitus that explicitly target pathological synchronous neural activity. (2) Methods: Multiple databases were searched for randomised controlled trials of neuromodulation interventions for tinnitus in adults, with 24 trials included. The risk of bias was assessed, and where appropriate, meta-analyses were performed. (3) Results: Few trials used acoustic, vagal nerve, or transcranial alternating current stimulation, or bimodal stimulation techniques, with limited evidence of neuromodulation or clinical effectiveness. Multiple trials of transcranial direct current stimulation (tDCS) were identified, and a synthesis demonstrated a significant improvement in tinnitus symptom severity in favour of tDCS versus control, although heterogeneity was high. (4) Discussion: Neuromodulation for tinnitus is an emerging but promising field. Electrical stimulation techniques are particularly interesting, given recent advances in current flow modelling that can be applied to future studies. Full article
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11 pages, 469 KiB  
Systematic Review
Deep Brain Stimulation for Primary Refractory Tinnitus: A Systematic Review
by Landon Basner, Jasper V. Smit, Daniel M. Zeitler, Seth R. Schwartz, Katie Krause, Aiyush Bansal and Farrokh Farrokhi
Brain Sci. 2024, 14(5), 452; https://doi.org/10.3390/brainsci14050452 - 30 Apr 2024
Cited by 1 | Viewed by 2380
Abstract
Background: tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show [...] Read more.
Background: tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. Methods: a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. Results: seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). Conclusions: DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice. Full article
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