Neural Plasticity in Tinnitus Mechanisms

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Systems Neuroscience".

Deadline for manuscript submissions: closed (1 August 2022) | Viewed by 19866

Special Issue Editors


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Guest Editor
Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
Interests: auditory system; neuromodulation; tinnitus models; biomarkers of tinnitus; tinnitus therapy

E-Mail Website
Guest Editor
Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
Interests: auditory system; neuromodulation; tinnitus models; biomarkers of tinnitus; tinnitus therapy

Special Issue Information

Dear Colleagues,

Despite more than 20 years of research, the underlying mechanisms and aetiological factors of tinnitus have yet to be properly understood. Tinnitus is associated with hearing loss and can be caused not only by damage to the cochlear nerve but also by altered somatosensory inputs from the head and neck region. Evidence of the changes in neurotransmitter function and spontaneous firing rates have been found in the dorsal and ventral divisions of the cochlear nucleus, with both showing an integration of auditory and somatosensory inputs that may be important in the generation of tinnitus. Bimodal integration also occurs in the cerebellum, inferior colliculus, and medial geniculate body as well as in various areas of the auditory cortex. In addition, other structures seem to be involved in tinnitus-related changes, such as the limbic system, which is thought to mediate activity related to emotional levels and stress.

By bringing together work from different approaches and a variety of different brain structures, this Special Issue aims to increase our understanding of the neural changes that occur during the initiation and development of tinnitus in both animal models and humans.

We invite you to submit innovative papers on the cellular changes in neuromodulators and neural activity linked to tinnitus in a variety of structures in the rodent brain as well as on functional alterations in rodent and human brains at a systems level.

Dr. Mark N. Wallace
Prof. Alan R. Palmer
Guest Editors

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Keywords

  • Neural mechanisms of tinnitus
  • Neuromodulators in tinnitus
  • Neural plasticity in tinnitus
  • Functional imaging in tinnitus
  • Bimodal interactions in tinnitus

Published Papers (9 papers)

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Editorial

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5 pages, 200 KiB  
Editorial
Neural Plasticity in Tinnitus Mechanisms
by Mark N. Wallace and Alan R. Palmer
Brain Sci. 2023, 13(12), 1615; https://doi.org/10.3390/brainsci13121615 - 22 Nov 2023
Viewed by 863
Abstract
Basic work into neuroplasticity mechanisms in both invertebrate and vertebrate brains, followed by the development of the first animal model of tinnitus, and coupled with clinical studies of tinnitus, meant that, by 1990, Jastreboff [...] Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)

Research

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12 pages, 271 KiB  
Article
Experiential Characteristics among Individuals with Tinnitus Seeking Online Psychological Interventions: A Cluster Analysis
by Eldre W. Beukes, Srikanth Chundu, Pierre Ratinaud, Gerhard Andersson and Vinaya Manchaiah
Brain Sci. 2022, 12(9), 1221; https://doi.org/10.3390/brainsci12091221 - 09 Sep 2022
Cited by 3 | Viewed by 1295
Abstract
Objective: This study was designed to gain insights regarding patterns of social representations (values, ideas, beliefs) of tinnitus and their relation to demographic and clinical factors. Method: A cross-sectional survey design was used including 399 adults seeking help and reporting interest in internet-based [...] Read more.
Objective: This study was designed to gain insights regarding patterns of social representations (values, ideas, beliefs) of tinnitus and their relation to demographic and clinical factors. Method: A cross-sectional survey design was used including 399 adults seeking help and reporting interest in internet-based cognitive behavior therapy for tinnitus. Data were collected using a free association task and analysis used qualitative (content analysis) and quantitative (cluster analysis and chi-square analysis) using the Iramuteq software. Results: The social representations identified the negative impact of tinnitus and included the way it sounded (descriptions of the way tinnitus sounds (18%), annoyance (13.5%), and persistence (8%)). Four clusters were identified representing four levels of tinnitus severity, namely debilitating tinnitus (24%), distressing tinnitus (10%), annoying tinnitus (46%), and accepting tinnitus (20%). Cluster identity was associated with demographic and clinical variables. Discussion: The identified clusters represented tinnitus severity experience in four stages, ranging from debilitating tinnitus to acceptance of tinnitus. These findings are important for clinical practice where tinnitus descriptions can indicate the stage of the tinnitus experience and which intervention pathway may be most appropriate. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
12 pages, 1163 KiB  
Article
The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway
by Faris Almasabi, Gusta van Zwieten, Faisal Alosaimi, Jasper V. Smit, Yasin Temel, Marcus L. F. Janssen and Ali Jahanshahi
Brain Sci. 2022, 12(8), 1099; https://doi.org/10.3390/brainsci12081099 - 18 Aug 2022
Cited by 2 | Viewed by 1701
Abstract
Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and [...] Read more.
Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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16 pages, 1313 KiB  
Article
Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Tinnitus in a Guinea Pig Model
by Farah Amat, Jack W. Zimdahl, Kristin M. Barry, Jennifer Rodger and Wilhelmina H. A. M. Mulders
Brain Sci. 2022, 12(8), 1096; https://doi.org/10.3390/brainsci12081096 - 18 Aug 2022
Cited by 4 | Viewed by 1690
Abstract
The auditory phantom sensation of tinnitus is associated with neural hyperactivity. Modulating this hyperactivity using repetitive transcranial magnetic stimulation (rTMS) has shown beneficial effects in human studies. Previously, we investigated rTMS in a tinnitus animal model and showed that rTMS over prefrontal cortex [...] Read more.
The auditory phantom sensation of tinnitus is associated with neural hyperactivity. Modulating this hyperactivity using repetitive transcranial magnetic stimulation (rTMS) has shown beneficial effects in human studies. Previously, we investigated rTMS in a tinnitus animal model and showed that rTMS over prefrontal cortex (PFC) attenuated tinnitus soon after treatment, likely via indirect effects on auditory pathways. Here, we explored the duration of these beneficial effects. Acoustic trauma was used to induce hearing loss and tinnitus in guinea pigs. Once tinnitus developed, high-frequency (20 Hz), high-intensity rTMS was applied over PFC for two weeks (weekdays only; 10 min/day). Behavioral signs of tinnitus were monitored for 6 weeks after treatment ended. Tinnitus developed in 77% of animals between 13 and 60 days post-trauma. rTMS treatment significantly reduced the signs of tinnitus at 1 week on a group level, but individual responses varied greatly at week 2 until week 6. Three (33%) of the animals showed the attenuation of tinnitus for the full 6 weeks, 45% for 1–4 weeks and 22% were non-responders. This study provides further support for the efficacy of high-frequency repetitive stimulation over the PFC as a therapeutic tool for tinnitus, but also highlights individual variation observed in human studies. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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15 pages, 4309 KiB  
Article
Post-Mortem Analysis of Neuropathological Changes in Human Tinnitus
by Faris Almasabi, Faisal Alosaimi, Minerva Corrales-Terrón, Anouk Wolters, Dario Strikwerda, Jasper V. Smit, Yasin Temel, Marcus L. F. Janssen and Ali Jahanshahi
Brain Sci. 2022, 12(8), 1024; https://doi.org/10.3390/brainsci12081024 - 01 Aug 2022
Cited by 2 | Viewed by 2128
Abstract
Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to [...] Read more.
Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients’ auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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20 pages, 653 KiB  
Article
Systematic Evaluation of the T30 Neurostimulator Treatment for Tinnitus: A Double-Blind Randomised Placebo-Controlled Trial with Open-Label Extension
by Deborah Ann Hall, Robert Henryk Pierzycki, Holly Thomas, David Greenberg, Magdalena Sereda and Derek James Hoare
Brain Sci. 2022, 12(3), 317; https://doi.org/10.3390/brainsci12030317 - 26 Feb 2022
Cited by 7 | Viewed by 2627
Abstract
Tinnitus is often triggered by cochlear damage and has been linked with aberrant patterns of neuronal activity. Acoustic Coordinated Reset (CR®) Neuromodulation is a sound therapy hypothesised to reduce tinnitus symptoms by desynchronising pathological brain activity using a portable acoustic device [...] Read more.
Tinnitus is often triggered by cochlear damage and has been linked with aberrant patterns of neuronal activity. Acoustic Coordinated Reset (CR®) Neuromodulation is a sound therapy hypothesised to reduce tinnitus symptoms by desynchronising pathological brain activity using a portable acoustic device (the T30 neurostimulator). We report results of a pivotal trial to test the efficacy of this intervention. This two-centre, double-blind randomised controlled trial with long-term open-label extension, was undertaken between February 2012 and February 2014 in the UK. Participants were 100 adults with tinnitus as a primary complaint, recruited through hearing clinics and media advertisements. Intervention was the device programmed either with the proprietary sound sequence or placebo algorithm, fit by one of five trained audiologists. Minimisation software provided group allocation (1:1 randomisation), with groups matched for age, gender, hearing loss and tinnitus severity. Allocation was masked from participants and assessors during the trial. The primary measure of efficacy was change in tinnitus symptom severity between groups, measured using the Tinnitus Handicap Questionnaire at 12 weeks. Secondary outcomes were other measures of tinnitus symptom severity, health-related quality of life, and perceptual characteristics (pitch, loudness, bandwidth) at 12 weeks, and Tinnitus Handicap Questionnaire at 36 weeks (open-label extension). A statistician blinded to the allocation conducted an intention-to-treat analysis that employed linear regressions on minimisation variables, trial centre and intervention group, with multiple imputations for missing data. The study was registered on clinicaltrials.gov (NCT01541969). We screened 391 individuals and assigned interventions to 100 eligible participants. The primary outcome was not statistically significant between groups (mean group = −0.45, 95% CI −5.25 to 4.35; p = 0.85), nor were any of the secondary outcomes. Four adverse events occurred during the trial. Analysis of tinnitus symptom severity data collected across the 24-week open-label extension showed no statistically significant within-group changes after 12, 24, or 36 weeks treatment with the proprietary sound sequence. While individual participants may benefit from sound therapy, Acoustic CR® Neuromodulation did not lead to group-mean reductions on tinnitus symptom severity or other measures compared to placebo, or over time. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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Review

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18 pages, 3106 KiB  
Review
Tinnitus Perception in Light of a Parietal Operculo–Insular Involvement: A Review
by Chloé Jaroszynski, Agnès Job, Maciej Jedynak, Olivier David and Chantal Delon-Martin
Brain Sci. 2022, 12(3), 334; https://doi.org/10.3390/brainsci12030334 - 01 Mar 2022
Cited by 1 | Viewed by 2872
Abstract
In tinnitus literature, researchers have increasingly been advocating for a clearer distinction between tinnitus perception and tinnitus-related distress. In non-bothersome tinnitus, the perception itself can be more specifically investigated: this has provided a body of evidence, based on resting-state and activation fMRI protocols, [...] Read more.
In tinnitus literature, researchers have increasingly been advocating for a clearer distinction between tinnitus perception and tinnitus-related distress. In non-bothersome tinnitus, the perception itself can be more specifically investigated: this has provided a body of evidence, based on resting-state and activation fMRI protocols, highlighting the involvement of regions outside the conventional auditory areas, such as the right parietal operculum. Here, we aim to conduct a review of available investigations of the human parietal operculo–insular subregions conducted at the microscopic, mesoscopic, and macroscopic scales arguing in favor of an auditory–somatosensory cross-talk. Both the previous literature and new results on functional connectivity derived from cortico–cortical evoked potentials show that these subregions present a dense tissue of interconnections and a strong connectivity with auditory and somatosensory areas in the healthy brain. Disrupted integration processes between these modalities may thus result in erroneous perceptions, such as tinnitus. More precisely, we highlight the role of a subregion of the right parietal operculum, known as OP3 according to the Jülich atlas, in the integration of auditory and somatosensory representation of the orofacial muscles in the healthy population. We further discuss how a dysfunction of these muscles could induce hyperactivity in the OP3. The evidence of direct electrical stimulation of this area eliciting auditory hallucinations further suggests its involvement in tinnitus perception. Finally, a small number of neuroimaging studies of therapeutic interventions for tinnitus provide additional evidence of right parietal operculum involvement. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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31 pages, 1194 KiB  
Review
Systematic Review on Intra- and Extracochlear Electrical Stimulation for Tinnitus
by Kelly K. S. Assouly, Max J. Dullaart, Robert J. Stokroos, Bas van Dijk, Inge Stegeman and Adriana L. Smit
Brain Sci. 2021, 11(11), 1394; https://doi.org/10.3390/brainsci11111394 - 24 Oct 2021
Cited by 7 | Viewed by 2037
Abstract
Several electrical stimulation patterns of the auditory nerve have been described for tinnitus relief, but there is no consensus on the most effective stimulation pattern. Therefore, we aim to systematically review the literature on the effect of intra- and extracochlear electrical stimulation patterns [...] Read more.
Several electrical stimulation patterns of the auditory nerve have been described for tinnitus relief, but there is no consensus on the most effective stimulation pattern. Therefore, we aim to systematically review the literature on the effect of intra- and extracochlear electrical stimulation patterns as a treatment option for patients with tinnitus. Only studies on intra- and extracochlear electrical stimulation for patients with tinnitus were included if the stimulation used did not concern standardized CI stimulation patterns to primarily rehabilitate hearing loss as intervention. A total of 34 studies met the inclusion criteria, with 10 studies (89 patients) on intracochlear electrical stimulation and 25 studies on extracochlear electrical stimulation (1109 patients). There was a high to medium risk of bias in 22 studies, especially due to lack of a non-exposed group and poor selection of the exposed group. All included studies showed subjective tinnitus improvement during or after electrical stimulation, using different stimulation patterns. Due to methodological limitations and low reporting quality of the included studies, the potential of intra- and extracochlear stimulation has not been fully explored. To draw conclusions on which stimulation patterns should be optimized for tinnitus relief, a deeper understanding of the mechanisms involved in tinnitus suppression is needed. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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Other

23 pages, 1684 KiB  
Systematic Review
Determining the Effects of Transcranial Direct Current Stimulation on Tinnitus, Depression, and Anxiety: A Systematic Review
by Bas Labree, Derek J. Hoare, Lauren E. Gascoyne, Polly Scutt, Cinzia Del Giovane and Magdalena Sereda
Brain Sci. 2022, 12(4), 484; https://doi.org/10.3390/brainsci12040484 - 08 Apr 2022
Cited by 8 | Viewed by 2987
Abstract
(1) Background: Tinnitus is the awareness of a sound in the absence of an external source. It affects around 10–15% of people, a significant proportion of whom also experience symptoms such as depression or anxiety that negatively affect their quality of life. Transcranial [...] Read more.
(1) Background: Tinnitus is the awareness of a sound in the absence of an external source. It affects around 10–15% of people, a significant proportion of whom also experience symptoms such as depression or anxiety that negatively affect their quality of life. Transcranial direct current stimulation (tDCS) is a technique involving constant low-intensity direct current delivered via scalp electrodes. It is a potential treatment option for tinnitus, as well as tinnitus-related conditions such as depression and anxiety. This systematic review estimates the effects of tDCS on outcomes relevant to tinnitus. In addition, it sheds light on the relationship between stimulation parameters and the effect of tDCS on these outcomes; (2) Methods: Exhaustive searches of electronic databases were conducted. Randomised controlled trials were included if they reported at least one of the following outcomes: tinnitus symptom severity, anxiety, or depression. Where available, data on quality of life, adverse effects, and neurophysiological changes were also reviewed. GRADE was used to assess the certainty in the estimate; (3) Results: Meta-analyses revealed a statistically significant reduction in tinnitus (moderate certainty) and depression (low certainty)-but not anxiety-following active tDCS compared to sham control. Network meta-analyses revealed potential optimal stimulation parameters; (4) Conclusions: The evidence synthesised in this review suggests tDCS has the potential to reduce symptom severity in tinnitus and depression. It further narrows down the number of potentially optimal stimulation parameters. Full article
(This article belongs to the Special Issue Neural Plasticity in Tinnitus Mechanisms)
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