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Otonomy Now Recruiting Participants for Phase 2 Study of OTO-313 in Tinnitus [Update: New Locations Added]

Otonomy’s recently announced OTO-313 clinical trial was posted to ClinicalTrials.gov on April 2 and will enroll an estimated 140 participants.

Here is a link to the official study record (NCT03918109): A Randomized, Double-blind, Placebo-controlled Phase 2 Study of OTO-313 Given as a Single Intratympanic Injection in Subjects With Unilateral Subjective Tinnitus

OTO-313 Recruiting April 2, 2021Status: Recruiting

April 11 Update: As we predicted, the OTO-313 study has now expanded its study locations and is currently recruiting in seven states: California, Colorado, Florida, Louisiana, North Carolina, South Carolina, and Utah. (We expected all these locations, with the one surprise being South Carolina.)

The new OTO-313 study is currently recruiting in two locations: Florida and North Carolina.

However, we expect to see more recruitment sites added across the United States in the coming weeks.

Here are some likely states the trial will expand to (based on the previous OTO-313 study locations): California, Colorado, Illinois, Kentucky, Louisiana, New Jersey, New York, North Carolina, Texas, Utah, West Virginia.

International expansion?

It is unknown whether this phase of the trial will expand to other countries.

More updates to follow…

Remember to subscribe to the email newsletter for upcoming OTO-313 updates (and news about other experimental tinnitus treatments in development).

Activity of CaMKIIa+ dorsal cochlear nucleus neurons are crucial for tinnitus perception but not for tinnitus induction [Preprint]

https://www.biorxiv.org/content/10.1101/2021.04.06.438667v1.full

Activity of CaMKIIa+ dorsal cochlear nucleus neurons are crucial for tinnitus perception but not for tinnitus induction

https://doi.org/10.1101/2021.04.06.438667

Abstract

The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2α (CaMKIIα) positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. Mice were exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence) and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded two days before and two weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKIIα+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKIIα+ DCN units decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKIIα-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKIIα-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice). Our results suggest that CaMKIIα-hM4Di positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.

What’s the Buzz? The Neuroscience and the Treatment of Tinnitus [Thanos Tzounopoulos]

CATEGORY:
Research

TITLE:
What’s the Buzz? The Neuroscience and the Treatment of Tinnitus

DESCRIPTION:
Tinnitus is a pervasive public health issue that affects approximately 15% of the United States population. Similar estimates have also been shown on a global scale, with similar prevalence found in Europe, Asia, and Africa. The severity of tinnitus is heterogeneous, ranging from mildly bothersome to extremely disruptive. In the United States, approximately 10-20% of individuals who experience tinnitus report symptoms that severely reduce their quality of life. Due to the huge personal and…

CONTENT:
Physiol Rev. 2021 Mar 26. doi: 10.1152/physrev.00029.2020. Online ahead of print.

ABSTRACT

Tinnitus is a pervasive public health issue that affects approximately 15% of the United States population. Similar estimates have also been shown on a global scale, with similar prevalence found in Europe, Asia, and Africa. The severity of tinnitus is heterogeneous, ranging from mildly bothersome to extremely disruptive. In the United States, approximately 10-20% of individuals who experience tinnitus report symptoms that severely reduce their quality of life. Due to the huge personal and societal burden, in the last twenty years a concerted effort on basic and clinical research has significantly advanced our understanding and treatment of this disorder. Yet, neither full understanding, nor cure exists. We know that tinnitus is the persistent involuntary phantom percept of internally-generated non-verbal noises and tones, which in most cases is initiated, by acquired hearing loss and maintained only when this loss is coupled with distinct neuronal changes in auditory and extra-auditory brain networks. Yet, the exact mechanisms and patterns of neural activity that are necessary and sufficient for the perceptual generation and maintenance of tinnitus remain incompletely understood. Combinations of animal model and human research will be essential in filling these gaps. Nevertheless, the existing progress in investigating the neurophysiological mechanisms has improved current treatment and highlighted novel targets for drug development and clinical trials. The aim of this review is to thoroughly discuss the current state of human and animal tinnitus research, outline current challenges, and highlight new and exciting research opportunities.

PMID:33769102 | DOI:10.1152/physrev.00029.2020

SOURCE:
Physiological reviews

DATE – PUBLISHED:
2021-03-26T13:02:58Z

DATE – DOI: 2021-03-26T13:02:58Z
DATE – PUBMED: 2021 Mar 26
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 26 Mar 2021 06:00:00 -0400

DATE – RETRIEVED:
03/26/21 03:50PM
2021-03-26T15:50:44-04:00

IDENTIFIER:
pmid:33769102,doi:10.1152/physrev.00029.2020

PUBMED ID:
pubmed:33769102

DOI:
10.1152/physrev.00029.2020

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33769102/

LINK – DOI:
https://doi.org/10.1152/physrev.00029.2020

LINK – PUBLISHER:
https://journals.physiology.org/doi/10.1152/physrev.00029.2020

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-26T15:50:44-04:00, www.tinnitustreatmentreport.com.

Otonomy Initiates Phase 2 Clinical Trial of OTO-313 in Tinnitus

https://investors.otonomy.com/news-releases/news-release-details/otonomy-initiates-phase-2-clinical-trial-oto-313-tinnitus

Otonomy Initiates Phase 2 Clinical Trial of OTO-313 in Tinnitus
March 25, 2021 at 7:30 AM EDT
Phase 2 study design based on successful Phase 1/2 trial including use of Tinnitus Functional Index (TFI) responder analysis for primary efficacy endpoint
Patient enrollment criteria refined to enrich study population
Top-line results expected in mid-2022

MISSING: Day-90 Study Results on Impact of FX-322 on Tinnitus…

FX-322 tinnitus missing milk carton memeNotably absent from the recent FX-322 data readout: partial data on measures of FX-322 on tinnitus.

In fact, there is no mention of “tinnitus” at all.

None.

What’s going on?

Dear Frequency Therapeutics,

We understand that the timing and completeness of data readouts is subject to change. Such is the nature of forward looking statements.

But when things do change – things such as the availability of FX-322 day-90 tinnitus-related data – you ought to mention it.

Consider this:

Your clinical trials include tinnitus-related outcomes as a secondary outcome measure…

Your previous press releases mention tinnitus…

Your corporate presentations and event slides mention tinnitus.

In January, you listed “partial data on measures of FX-322 on tinnitus” as part of the anticipated phase 2a readout (planned for late Q1 2021)…

And yet, two days ago, on March 23, you released an update that did not even include the word “tinnitus” in the text.

Not even in the tiny text at the bottom. (We looked everywhere.)

Why not?

Until Frequency Therapeutics releases a statement or formal update on tinnitus study results, it is reasonable to assume there is no good news. There seems to be no other explanation as to why the word tinnitus was “scrubbed” from the ongoing list of talking points.

skeptical cat meme fx-322

Prove us wrong, Frequency Therapeutics.

Because we hope we’re wrong. We hope there’s promising tinnitus data somewhere that someone forgot to publish or mention. But, sadly, that seems unlikely.

To our readers: as soon as we have more information about FX-322 and tinnitus… we will be sending it out via the email newsletter. But it’s important to remember that FX-322 is NOT the only “horse in the race” toward effective tinnitus treatments. Others exist. And we will be posting information about them next week. (Note: these treatments have received far less mainstream attention and PR than “famous” upcoming drugs such as FX-322… yet some are surprisingly further along in their development than you might expect.)

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

CATEGORY:
Research

TITLE:
Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

DESCRIPTION:
Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable…

CONTENT:
Sci Rep. 2021 Mar 19;11(1):6470. doi: 10.1038/s41598-021-85871-6.

ABSTRACT

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06. PMID:33742053 | DOI:10.1038/s41598-021-85871-6 SOURCE: Scientific reports DATE - PUBLISHED: 2021-03-19T13:06:54Z DATE - DOI: 2021-03-19T13:06:54Z DATE - PUBMED: 2021 Mar 19 DATE OUTPUT MATCHED: True DATE - ADDED: Sat, 20 Mar 2021 06:00:00 -0400 DATE - RETRIEVED: 03/20/21 05:25PM 2021-03-20T17:25:35-04:00 IDENTIFIER: pmid:33742053,doi:10.1038/s41598-021-85871-6 PUBMED ID: pubmed:33742053 DOI: 10.1038/s41598-021-85871-6 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33742053/ LINK - DOI: https://doi.org/10.1038/s41598-021-85871-6 LINK - PUBLISHER: http://www.nature.com/articles/s41598-021-85871-6 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2021-03-20T17:25:35-04:00, www.tinnitustreatmentreport.com.

Effect of Highly Bioavailable Curcumin on Subjective Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Effect of Highly Bioavailable Curcumin on Subjective Tinnitus

DESCRIPTION:
Condition :   Tinnitus, Subjective

Interventions :   Biological: Curcumin-phosphatidylcholine;   Biological: Placebo capsule

Sponsor :   Ascension South East Michigan

Recruiting

GUID:
NCT04800107

ID:
NCT04800107

DATE – FIRST POSTED:
Tue, 16 Mar 2021 12:00:00 EDT

DATE – LAST UPDATED:
03/16/21 09:56AM

DATE – RETRIEVED:
03/16/21 09:56AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04800107?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F15%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04800107

Effectiveness of Intratympanic Dexamethasone With Lignocaine for Alleviation of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Effectiveness of Intratympanic Dexamethasone With Ligmocaine for Alleviation of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Intervention :   Drug: Dexamethasone

Sponsor :   Combined Military Hospital, Pakistan

Active, not recruiting

GUID:
NCT04798391

ID:
NCT04798391

DATE – FIRST POSTED:
Mon, 15 Mar 2021 12:00:00 EDT

DATE – LAST UPDATED:
03/15/21 10:41AM

DATE – RETRIEVED:
03/15/21 10:41AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04798391?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F14%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04798391

Otolith Labs Initiates Clinical Trial of OtoBand Device as a Treatment to Reduce Perceived Loudness of Tinnitus

A new clinical trial from Otolith Labs, a U.S. Defense Department-backed startup developing a device that could potentially extinguish the debilitating symptoms of vertigo, motion sickness, and now… lower tinnitus volume?

Otolith Labs Logo
Otolith Labs logo. Source: Otolith Labs (https://otolithlabs.com)

The study, titled Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus (NCT04787653) was posted to ClinicalTrials.gov on March 8, 2021 (a few hours ago, as of this writing).

Placebo-controlled study…

Unlike the Neuromod (Lenire) clinical trials, this OtoBand study involves a placebo device and group. (We here at Tinnitus Treatment Report applaud this decision.)

OtoBand study record screenshot
Here is a screenshot of the OtoBand clinical trial record… which was added to ClinicalTrials.gov *today* (March 8, 2021)

Here is a brief summary of how the study – which is an at-home study (conducted remotely and does not require travel to/from the clinic) – will work:

This proposed study is a blinded study in which the participant will wear the OtoBand when their tinnitus is present to determine if the OtoBand reduces the perceived loudness of their tinnitus. The Study will be placebo controlled with each participant using an effective device for half of the enrollment period and a placebo device for half of the enrollment period. The order of placebo and effective usage will be randomized, and the researchers will be blinded to which device a participant is using. Study participants will be instructed in an online telehealth conference on how to operate the OtoBand and how to wear the OtoBand. Participants will be enrolled for approximately 30 days from Informed Consent to Wrap-up call.

Great, but what does this “OtoBand device” look like?

Here is a photo from Otolith Labs company website:

Otoband Device Tinnitus
Source: Otolith Labs (https://otolithlabs.com)

We are unsure if this is the *exact* same model of the Otoband device that is being studied for its potential in reducing tinnitus loudness. The above photo might be an earlier version, a prototype. Plus, we do not know what design changes might be made during development. (It is not uncommon to see the design of novel devices like this evolve over time.)

As for the effectiveness of the device… we do not know anything yet. That’s what this clinical trial will hopefully tell us, in time…

Are we there yet are we there yet how about now? meme tinnitus treatment

Otoband clinical trial results… available when?

Not sure yet. The study was literally only added to the ClinicalTrials.gov database today. Too early to even guess. But here’s a good way to stay current with what’s happening:

For updates on the progress of OtoBand, I invite you to sign up for the Tinnitus Treatment Report email newsletter. It’s an easy way to get the very latest in tinnitus treatment development news and updates. For devices such as OtoBand, as well as pharmacological updates (e.g., FX-322, OTO-313, CS0022, and more). The email updates are 100% free and – importantly – your information is never shared with third parties, and you an unsubscribe with one click. Simple.

The first issue will begin sending soon (perhaps an exclusive update related to FX-322’s upcoming tinnitus study results)…

Got feedback? Send an email to michael@urgentresearch.com and speak your mind. Request an update!

Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Interventions :   Device: Otoband;   Device: Placebo

Sponsor :   Otolith Labs

Recruiting

GUID:
NCT04787653

ID:
NCT04787653

DATE – FIRST POSTED:
Mon, 08 Mar 2021 12:00:00 EST

DATE – LAST UPDATED:
03/08/21 06:05AM

DATE – RETRIEVED:
03/08/21 06:05AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04787653?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F07%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04787653

Effectiveness of photobiomodulation in the management of tinnitus remains debatable: A systematic review

CATEGORY:
Research

TITLE:
Efficacy of photobiomodulation in the management of tinnitus: A systematic review of randomized control trials

DESCRIPTION:
There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c)…

CONTENT:
Eur Ann Otorhinolaryngol Head Neck Dis. 2021 Mar 5:S1879-7296(21)00043-0. doi: 10.1016/j.anorl.2020.10.013. Online ahead of print.

ABSTRACT

There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c) low-level laser therapy; (d) photobiomodulation; (e) tinnitus; (f) medium-level laser; (g) photo-biomodulation; and (h) low-power laser; and RCTs performed on humans were included. Letters to the editor; case reports/series; commentaries; experimental studies and historic reviews were excluded. The risk of bias was assessed using the modified cochrane collaboration tool. The format of the current systematic review was personalized to summarize the appropriate information. Ten RCTs (2 single-blinded and 8 double-blinded) were included. One study reported 30% and 100% resolution of tinnitus using diode and Neodymium-doped Yttrium Aluminum Garnet lasers; respectively. One study reported that PBM was effective in relieving tinnitus for up to 3 months. Eight studies reported that PBM was ineffective in the management of chronic tinnitus. The risk of bias was high; medium and low in 4; 5 and 1 studies; respectively. The effectiveness of PBM in the management of tinnitus remains debatable. Further power-adjusted and well-designed RCTs with long-term follow-up are needed.

PMID:33685826 | DOI:10.1016/j.anorl.2020.10.013

SOURCE:
European annals of otorhinolaryngology, head and neck diseases

DATE – PUBLISHED:
2021-03-07T15:51:15Z

DATE – DOI: 2021-03-07T15:51:15Z
DATE – PUBMED: 2021 Mar 5
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 09 Mar 2021 06:00:00 -0500

DATE – RETRIEVED:
03/09/21 07:23AM
2021-03-09T07:23:35-05:00

IDENTIFIER:
pmid:33685826,doi:10.1016/j.anorl.2020.10.013

PUBMED ID:
pubmed:33685826

DOI:
10.1016/j.anorl.2020.10.013

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33685826/

LINK – DOI:
https://doi.org/10.1016/j.anorl.2020.10.013

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1879729621000430

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-09T07:23:35-05:00, www.tinnitustreatmentreport.com.

Increased Serum Lipid Levels in Patients with Subjective Tinnitus

CATEGORY:
Research

TITLE:
Increased Serum Lipid Levels in Patients with Subjective Tinnitus

DESCRIPTION:
CONCLUSION: The results indicated that TC, TRG and LDL levels were significantly higher in tinnitus group and this increase implicates the potential role of hyperlipidemia associated with altered lipid metabolism in the etiology of tinnitus. We suggest that serum lipid levels could be useful and conducive in the diagnosis and prognosis of tinnitus.

CONTENT:
Iran J Otorhinolaryngol. 2021 Jan;33(114):31-36. doi: 10.22038/ijorl.2020.43663.2442.

ABSTRACT

INTRODUCTION: The aim was to investigate the link between tinnitus and serum levels of total cholesterol (TC), triglyceride (TRG), low-density (LDL) and high-density lipoprotein (HDL) in the central anatolian Turkish population.

MATERIALS AND METHODS: The retrospective and case-control study included a total of 91 patients with subjective tinnitus and a control group of age- and sex-matched 65 healthy volunteers. A detailed otolaryngologic examination followed by pure tone audiometry, serum lipid values, and magnetic resonance imaging of the temporal bone was performed. The clinical characteristics of tinnitus were registered for all patients. The serum levels of TC, TRG, LDL and HDL were compared between the two groups.

RESULTS: Mean TC level was 200.57±41.06 mg/dL in the patient group and 179.0±39.03 mg/dL in the control group (P=0.001). Mean TRG level was 177.76±86.94 mg/dL in the patient group and 124.43±61.44 mg/dL in the control group (P=0.000). Mean LDL level was 115.88±32.56 mg/dL in the patient group and 101.31±34.42 mg/dL in the control group (P=0.008). Mean HDL level was 50.25±13.60 mg/dL in the patient group and 53.46±12.66 mg/dL in the control group (P=0.137). Among all the serum lipids, TC, TRG and LDL established a significant difference between the two groups.

CONCLUSION: The results indicated that TC, TRG and LDL levels were significantly higher in tinnitus group and this increase implicates the potential role of hyperlipidemia associated with altered lipid metabolism in the etiology of tinnitus. We suggest that serum lipid levels could be useful and conducive in the diagnosis and prognosis of tinnitus.

PMID:33654688 | PMC:PMC7897436 | DOI:10.22038/ijorl.2020.43663.2442

SOURCE:
Iranian journal of otorhinolaryngology

DATE – PUBLISHED:
2021-02-21T23:07:27Z

DATE – DOI: 2021-02-21T23:07:27Z
DATE – PUBMED:
DATE OUTPUT MATCHED: False

DATE – ADDED:
Wed, 03 Mar 2021 06:00:00 -0500

DATE – RETRIEVED:
03/03/21 08:03AM
2021-03-03T08:03:01-05:00

IDENTIFIER:
pmid:33654688,pmc:PMC7897436,doi:10.22038/ijorl.2020.43663.2442

PUBMED ID:
pubmed:33654688

DOI:
10.22038/ijorl.2020.43663.2442

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33654688/

LINK – DOI:
https://doi.org/10.22038/ijorl.2020.43663.2442

LINK – PUBLISHER:
https://ijorl.mums.ac.ir/article_17205.html

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-03T08:03:01-05:00, www.tinnitustreatmentreport.com.

The progression of chronic tinnitus over the years

CATEGORY:
Research

TITLE:
The progression of chronic tinnitus over the years

DESCRIPTION:
Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were…

CONTENT:
Sci Rep. 2021 Feb 18;11(1):4162. doi: 10.1038/s41598-021-83068-5.

ABSTRACT

Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers.

PMID:33602995 | DOI:10.1038/s41598-021-83068-5

SOURCE:
Scientific reports

DATE – PUBLISHED:
2021-02-20T09:59:22Z

DATE – DOI: 2021-02-20T09:59:22Z
DATE – PUBMED: 2021 Feb 18
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 19 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/21/21 02:03PM
2021-02-21T14:03:44-05:00

IDENTIFIER:
pmid:33602995,doi:10.1038/s41598-021-83068-5

PUBMED ID:
pubmed:33602995

DOI:
10.1038/s41598-021-83068-5

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33602995/

LINK – DOI:
https://doi.org/10.1038/s41598-021-83068-5

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-021-83068-5

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-21T14:03:44-05:00, www.tinnitustreatmentreport.com.

Pharmacological Evaluation of Drugs in Animal Models of Tinnitus

CATEGORY:
Research

TITLE:
Pharmacological Evaluation of Drugs in Animal Models of Tinnitus

DESCRIPTION:
Despite the pressing need for effective drug treatments for tinnitus, currently, there is no single drug that is approved by the FDA for this purpose. Instead, a wide range of unproven over-the-counter tinnitus remedies are available on the market with little or no benefit for tinnitus but with potential harm and adverse effects. Animal models of tinnitus have played a critical role in exploring the pathophysiology of tinnitus, identifying therapeutic targets and evaluating novel and existing…

CONTENT:
Curr Top Behav Neurosci. 2021 Feb 16. doi: 10.1007/7854_2020_212. Online ahead of print.

ABSTRACT

Despite the pressing need for effective drug treatments for tinnitus, currently, there is no single drug that is approved by the FDA for this purpose. Instead, a wide range of unproven over-the-counter tinnitus remedies are available on the market with little or no benefit for tinnitus but with potential harm and adverse effects. Animal models of tinnitus have played a critical role in exploring the pathophysiology of tinnitus, identifying therapeutic targets and evaluating novel and existing drugs for tinnitus treatment. This review summarises and compares the studies on pharmacological evaluation of tinnitus treatment in different animal models based on the pharmacological properties of the drug and provides insights into future directions for tinnitus drug discovery.

PMID:33590458 | DOI:10.1007/7854_2020_212

SOURCE:
Current topics in behavioral neurosciences

DATE – PUBLISHED:
2021-02-18T21:11:17Z

DATE – DOI: 2021-02-18T21:11:17Z
DATE – PUBMED: 2021 Feb 16
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 16 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/19/21 11:29AM
2021-02-19T11:29:00-05:00

IDENTIFIER:
pmid:33590458,doi:10.1007/7854_2020_212

PUBMED ID:
pubmed:33590458

DOI:
10.1007/7854_2020_212

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33590458/

LINK – DOI:
https://doi.org/10.1007/7854_2020_212

LINK – PUBLISHER:
http://link.springer.com/10.1007/7854_2020_212

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-19T11:29:00-05:00, www.tinnitustreatmentreport.com.

Transient Delivery of a KCNQ2/3-Specific Channel Activator [RL-81] 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

CATEGORY:
Research

TITLE:
Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

DESCRIPTION:
Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced…

CONTENT:
J Assoc Res Otolaryngol. 2021 Feb 11. doi: 10.1007/s10162-021-00786-3. Online ahead of print.

ABSTRACT

Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced tinnitus, assessed 1 week after trauma. Subsequently, we developed RL-81, a very potent and highly specific activator of KCNQ2/3 channels. Here, to test the timing window within which RL-81 prevents tinnitus in mice, we modified and employed an operant animal model of tinnitus, where mice are trained to move in response to sound but not move in silence. Mice with behavioral evidence of tinnitus are expected to move in silence. We validated this mouse model by testing the effect of salicylate, which is known to induce tinnitus. We found that transient administration of RL-81 1 week after noise exposure did not affect hearing loss but reduced significantly the percentage of mice with behavioral evidence of tinnitus, assessed 2 weeks after noise exposure. Our results indicate that RL-81 is a promising drug candidate for further development for the treatment of noise-induced tinnitus.

PMID:33575914 | DOI:10.1007/s10162-021-00786-3

SOURCE:
Journal of the Association for Research in Otolaryngology : JARO

DATE – PUBLISHED:
2021-02-11T18:11:11Z

DATE – DOI: 2021-02-11T18:11:11Z
DATE – PUBMED: 2021 Feb 11
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 12 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/12/21 12:44PM
2021-02-12T12:44:10-05:00

IDENTIFIER:
pmid:33575914,doi:10.1007/s10162-021-00786-3

PUBMED ID:
pubmed:33575914

DOI:
10.1007/s10162-021-00786-3

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33575914/

LINK – DOI:
https://doi.org/10.1007/s10162-021-00786-3

LINK – PUBLISHER:
http://link.springer.com/10.1007/s10162-021-00786-3

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-12T12:44:10-05:00, www.tinnitustreatmentreport.com.

Using cortical neuron markers to target cells in the dorsal cochlear nucleus: new means for treatment of bothersome tinnitus?

CATEGORY:
Research

TITLE:
Using cortical neuron markers to target cells in the dorsal cochlear nucleus

DESCRIPTION:
The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. Yet, lack of useful genetic markers for in vivo manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIα) promoter and a mouse line of nicotinic acetylcholine receptor alpha 2 subunit (Chrna2)-Cre can target specific DCN…

CONTENT:
eNeuro. 2021 Feb 8:ENEURO.0413-20.2020. doi: 10.1523/ENEURO.0413-20.2020. Online ahead of print.

ABSTRACT

The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. Yet, lack of useful genetic markers for in vivo manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIα ) promoter and a mouse line of nicotinic acetylcholine receptor alpha 2 subunit (Chrna2)-Cre can target specific DCN populations. We found that CaMKIIα cannot be used to target excitatory fusiform DCN neurons as labelled cells showed diverse morphology indicating they belong to different classes of DCN neurons. Light stimulation after driving Channelrhodopsin2 by the CaMKIIα promoter generated spikes in some units but firing rate decreased when light stimulation coincided with sound. Expression and activation of CaMKIIα -eArchaerhodopsin3.0 in the DCN produced inhibition in some units but sound-driven spikes were delayed by concomitant light stimulation. We explored the existence of Cre+ cells in the DCN of Chrna2-Cre mice by hydrogel embedding technique (CLARITY). There were almost no Cre+ cell bodies in the DCN; however, we identified profuse projections arising from the ventral cochlear nucleus (VCN). Anterograde labeling in the VCN revealed projections to the ipsilateral superior olive and contralateral medial nucleus of the trapezoid body (bushy cells); and a second bundle terminating in the DCN, suggesting the latter to be excitatory Chrna2+ T-stellate cells. Exciting Chrna2+ cells increased DCN firing. This work shows that cortical molecular tools may be useful for manipulating the DCN especially for tinnitus studies.Significance statement Cortical neuron markers could be used to label subcortical regions such as the dorsal cochlear nucleus (DCN) that integrates sound and somatosensory input. Here we examine if excitatory (CaMKIIα ) or inhibitory (Chrna2) neuron markers used in neo/paleo-cortex studies label unique DCN populations. We found CaMKIIα to be expressed by different DCN neuron populations (affecting sound sensitive and nonsensitive neurons). The Chrna2 promoter was specifically expressed in excitatory cells of the ventral cochlear nucleus and could drive indirect activity in the DCN. This study highlights novel ways of regulating DCN neuron activity, which can provide new means for treatment of bothersome tinnitus.

PMID:33563600 | DOI:10.1523/ENEURO.0413-20.2020

SOURCE:
eNeuro

DATE – PUBLISHED:
2021-02-09T18:52:33Z

DATE – DOI: 2021-02-09T18:52:33Z
DATE – PUBMED: 2021 Feb 8
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 10 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/10/21 11:52AM
2021-02-10T11:52:09-05:00

IDENTIFIER:
pmid:33563600,doi:10.1523/ENEURO.0413-20.2020

PUBMED ID:
pubmed:33563600

DOI:
10.1523/ENEURO.0413-20.2020

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33563600/

LINK – DOI:
https://doi.org/10.1523/ENEURO.0413-20.2020

LINK – PUBLISHER:
http://eneuro.org/lookup/doi/10.1523/ENEURO.0413-20.2020

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-10T11:52:09-05:00, www.tinnitustreatmentreport.com.

Novel Tinnitus Drug CS0022 Reduces Chronic Tinnitus in Preclinical Study

A pre-clinical tinnitus drug candidate from Cognosetta has shown promising results (and could soon be ready for human trials), according to new research.

Background:

CS0022 (formerly called BMS-191011) is a next generation BK channel opener designed to lower tinnitus volume by regulating the abnormal neural excitability in the central auditory system (CAS)… thereby restoring the proper “balance of excitation and inhibition” necessary for silence.

Cognosetta Inc logo
“Look, they even have a logo!” Image source: Cognosetta Inc

The small company behind CS0022 is Cognosetta, Inc. If you have been following our updates here at Tinnitus Treatment Report, that company name might sound familiar.

Just over a year ago, on January 14, 2020, we posted this: Cognosetta, Inc receives funding from NIH to test a novel therapeutic for treating tinnitus…

CS0022-Class Compounds for the Treatment of Tinnitus

Today, we finally have a follow-up about what is happening with that “novel therapeutic” and its development.

First, a quick primer on the company behind the drug. From the Cognosetta website:

Cognosetta is developing a first-in-market, brain targeted pharmaceutical solution for treating tinnitus […] Our priority is developing a first-in-market medication […] for those with moderate to severe tinnitus […] Our scientists have identified a drug target and drug candidates for improving neurophysiological and behavioral measures of tinnitus and age-related hearing loss. To support the clinical success of these drug candidates our scientists are also advancing quantitative methods for evaluating the efficacy of new drug candidates that can be shared across the preclinical and clinical development stages.

Here is a snapshot of their current pipeline, with CS0022 approaching human trials.

Cognosetta Tinnitus Pipeline
Source: Cognosetta, Inc

How close to human testing and safety trials is CS0022?

Too early to give an exact date.

But, according to a poster presentation from the upcoming 44th Annual ARO MidWinter Virtual Meeting, the drug continues to impress with promising results in preclinical (animal) studies.

Here is a “sneak preview” copy of the upcoming poster presentation – scheduled for Sunday, February 21, 2021:

The BK Channel Opener CS0022 Mitigates Chronic Tinnitus Following Acoustic Trauma

Background: Subjective tinnitus is an audiological and neurological condition that gives rise to a phantom perception of sound. The condition disproportionately impacts individuals with risky occupational or avocational noise exposure. Patients and animal models of tinnitus exhibit altered central auditory system (CAS) neural activity that is presumed to support the tinnitus percept. Broadly, these changes can be characterized by a dysregulation in the balance of excitation and inhibition that leads to neuronal hyperexcitability and synchrony. The large conductance calcium-activated potassium (BK) channel regulates neural excitability in the CAS and other brain regions. Our recent work suggests that systemic administration of a class of BK channel openers reduces salicylate-induced tinnitus in mice through action in the CAS. The main objective of the current study is to determine whether a similar low-exposure treatment also reduces behavioral and neural manifestations of tinnitus in a chronic tinnitus model induced by noise exposure.

Methods: Auditory brainstem response (ABR) thresholds and acoustic startle behavior were assessed in young adult CBA mice before and after acoustic trauma. For acoustic trauma, awake mice were placed in a small, sound transparent cage, and then exposed for 1 hour via free field to a 113 dB SPL, 1 kHz wide band noise centered at 16 kHz. Ten weeks after damaging noise exposure, mice began systemic treatment with a BK channel opener, CS0022. Gap-prepulse inhibition of the acoustic startle reflex (GPIAS) tracked the development of tinnitus and subsequent effects of treatment. A novel machine learning algorithm and computational analysis method was used to determine which mice displayed tinnitus from the GPIAS protocol.

Results: The acoustic trauma procedure caused limited permanent ABR threshold shifts, ranging from none to moderate (~50 dB) in the high frequencies above 16 kHz. Mice were selected for preliminary analysis if they exhibited minimal permanent hearing loss (< 10 dB) and GPIAS evidence of tinnitus at 16 or 32 kHz after acoustic trauma. Six out of the six selected mice showed less suppressed pre-pulse inhibition for the selected tinnitus frequencies following systemic treatment with a BK channel opener. In contrast, treatment did not influence acoustic startle amplitude functions. Pharmacokinetics studies confirmed low exposure in brain. As expected, improved startle selection via machine learning-enhanced computational analysis increased the power and accuracy for identifying tinnitus and treatment effects.

Conclusions: Ongoing neurophysiological and alternate behavioral measures continue to probe treatment outcomes in this model of acoustic trauma-induced chronic tinnitus. Thus far, preliminary outcomes support the idea that treatment with BK channel openers such as the one used in the current study may reduce evidence of tinnitus. There is currently no effective cure for chronic tinnitus, increasing the urgency for studies exploring the utility of promising drug candidates.

Credit to lead author Luisa Scott of Cognosetta Inc and her co-authors at the University of South Florida.

Thanks to their hard work, it looks like we now have another viable first-in-market tinnitus drug candidate to follow…

Plus, a shiny new meme to help spread the word:

Yoda There Is Another Meme

How to get CS0022 updates?

If you want to keep up with promising new tinnitus treatments that are currently in development (including CS0022)… I encourage you to sign up for Tinnitus Treatment Report email updates.

It’s an email newsletter with fresh links and updates (never junk), and… I believe there is no faster way to consistently stay on top of the very latest tinnitus treatment options and scientific breakthroughs.

(It is 100% free, no spam or advertorials, and your information is kept secure and private. Promise.)

Got questions? comments? requests?

Send an email to michael@urgentresearch.com and introduce yourself, say hello.

References and further reading:

  • https://braininitiative.nih.gov/funded-awards/developing-novel-therapeutic-treating-tinnitus
  • https://projectreporter.nih.gov/project_info_details.cfm?aid=9907138&icde=48273554
  • https://www.cognosetta.com
  • https://www.nature.com/articles/srep42433
  • https://aro.societyconference.com/conf/#sessions/conf10001

Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients

CATEGORY:
Research

TITLE:
Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients

DESCRIPTION:
CONCLUSION: Tinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

CONTENT:
Front Neurosci. 2021 Feb 4;14:623520. doi: 10.3389/fnins.2020.623520. eCollection 2020.

ABSTRACT

PURPOSE: Both tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.

METHODS: Sixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.

RESULTS: Tinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.

CONCLUSION: Tinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

PMID:33633528 | PMC:PMC7902065 | DOI:10.3389/fnins.2020.623520

SOURCE:
Frontiers in neuroscience

DATE – PUBLISHED:
2021-02-04T07:33:52Z

DATE – DOI: 2021-02-04T07:33:52Z
DATE – PUBMED: 2021 Feb 4
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 26 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/26/21 07:59AM
2021-02-26T07:59:11-05:00

IDENTIFIER:
pmid:33633528,pmc:PMC7902065,doi:10.3389/fnins.2020.623520

PUBMED ID:
pubmed:33633528

DOI:
10.3389/fnins.2020.623520

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33633528/

LINK – DOI:
https://doi.org/10.3389/fnins.2020.623520

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fnins.2020.623520/full

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-26T07:59:11-05:00, www.tinnitustreatmentreport.com.

Altering activity in the peripheral nerve may be a viable target for early pharmaceutical intervention in forms of tinnitus originating in the cochlea

Altering activity in the peripheral nerve may be a viable target for early pharmaceutical intervention in forms of tinnitus originating in the cochlea

Salicylate decreases the spontaneous firing rate of guinea pig auditory nerve fibres

Received 2 October 2020, Revised 26 January 2021, Accepted 29 January 2021, Available online 3 February 2021.

https://www.sciencedirect.com/science/article/pii/S0304394021000835

Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

https://www.sciencedirect.com/science/article/abs/pii/S0378595521000241

Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

Highlights

– The thalamus may play an important role in tinnitus generation.
– Patterns of neural activity were investigated in animals with and without tinnitus.
– Tinnitus leads to increased spontaneous firing but no change in burst firing.
– This supports theory of dysfunctional sensory gating in tinnitus.

The BDNF Val66 Met polymorphism regulates vulnerability to chronic stress and phantom perception

CATEGORY:
Research

TITLE:
The BDNF Val66 Met polymorphism regulates vulnerability to chronic stress and phantom perception

DESCRIPTION:
Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not…

CONTENT:
Prog Brain Res. 2021;260:301-326. doi: 10.1016/bs.pbr.2020.08.005. Epub 2021 Jan 22.

ABSTRACT

Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not bothered by their tinnitus. BDNF Val66 Met polymorphism (rs6265) is a known risk factor for affective disorders due to its common frequency and established functionality. To elucidate, we explore the neural activation pattern of tinnitus associated with the BDNF Val66 Met polymorphism using electrophysiological data to assess activity and connectivity changes. A total of 110 participants (55 tinnitus and 55 matched control subjects) were included. In this study, we validate that the BDNF Val66 Met polymorphism plays an important role in the susceptibility to the clinical manifestation of tinnitus-related distress. We demonstrate that Val/Met carriers have increased alpha power in the subgenual anterior cingulate cortex that correlates with distress levels. Furthermore, distress mediates the relationship between BDNF Val66 Met polymorphism and tinnitus loudness. In other words, for Val/Met carriers, the subgenual anterior cingulate cortex sends distress-related information to the parahippocampus, which likely integrates the loudness and distress of the tinnitus percept.

PMID:33637225 | DOI:10.1016/bs.pbr.2020.08.005

SOURCE:
Progress in brain research

DATE – PUBLISHED:
2021-01-22T09:14:30Z

DATE – DOI: 2021-01-22T09:14:30Z
DATE – PUBMED: 2021 Jan 22
DATE OUTPUT MATCHED: True

DATE – ADDED:
Sat, 27 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/27/21 08:23AM
2021-02-27T08:23:52-05:00

IDENTIFIER:
pmid:33637225,doi:10.1016/bs.pbr.2020.08.005

PUBMED ID:
pubmed:33637225

DOI:
10.1016/bs.pbr.2020.08.005

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33637225/

LINK – DOI:
https://doi.org/10.1016/bs.pbr.2020.08.005

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S007961232030131X

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-27T08:23:52-05:00, www.tinnitustreatmentreport.com.

Daily Bitemporal Low-frequency Transcranial Random Noise Stimulation in Tinnitus (tRNS2-tin)

CATEGORY:
Clinical Trials

TITLE:
Daily Bitemporal Low-frequency Transcranial Random Noise Stimulation in Tinnitus (tRNS2-tin)

DESCRIPTION:
Condition :   Chronic Tinnitus

Intervention :   Device: lf-tRNS

Sponsor :   University of Regensburg

Recruiting

GUID:
NCT02615600

ID:
NCT02615600

DATE – FIRST POSTED:
Thu, 26 Nov 2015 12:00:00 EST

DATE – LAST UPDATED:
01/20/21 07:32AM

DATE – RETRIEVED:
01/20/21 07:32AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT02615600?type=Intr&cond=Tinnitus&phase=012345&lupd_s=01%2F19%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT02615600

Noise Exposure Alters Glutamatergic and GABAergic Synaptic Connectivity in the Hippocampus and Its Relevance to Tinnitus

CATEGORY:
Research

TITLE:
Noise Exposure Alters Glutamatergic and GABAergic Synaptic Connectivity in the Hippocampus and Its Relevance to Tinnitus

DESCRIPTION:
Accumulating evidence implicates a role for brain structures outside the ascending auditory pathway in tinnitus, the phantom perception of sound. In addition to other factors such as age-dependent hearing loss, high-level sound exposure is a prominent cause of tinnitus. Here, we examined how noise exposure altered the distribution of excitatory and inhibitory synaptic inputs in the guinea pig hippocampus and determined whether these changes were associated with tinnitus. In experiment one,…

CONTENT:
Neural Plast. 2021 Jan 14;2021:8833087. doi: 10.1155/2021/8833087. eCollection 2021.

ABSTRACT

Accumulating evidence implicates a role for brain structures outside the ascending auditory pathway in tinnitus, the phantom perception of sound. In addition to other factors such as age-dependent hearing loss, high-level sound exposure is a prominent cause of tinnitus. Here, we examined how noise exposure altered the distribution of excitatory and inhibitory synaptic inputs in the guinea pig hippocampus and determined whether these changes were associated with tinnitus. In experiment one, guinea pigs were overexposed to unilateral narrow-band noise (98 dB SPL, 2 h). Two weeks later, the density of excitatory (VGLUT-1/2) and inhibitory (VGAT) synaptic terminals in CA1, CA3, and dentate gyrus hippocampal subregions was assessed by immunohistochemistry. Overall, VGLUT-1 density primarily increased, while VGAT density decreased significantly in many regions. Then, to assess whether the noise-induced alterations were persistent and related to tinnitus, experiment two utilized a noise-exposure paradigm shown to induce tinnitus and assessed tinnitus development which was assessed using gap-prepulse inhibition of the acoustic startle (GPIAS). Twelve weeks after sound overexposure, changes in excitatory synaptic terminal density had largely recovered regardless of tinnitus status, but the recovery of GABAergic terminal density was dramatically different in animals expressing tinnitus relative to animals resistant to tinnitus. In resistant animals, inhibitory synapse density recovered to preexposure levels, but in animals expressing tinnitus, inhibitory synapse density remained chronically diminished. Taken together, our results suggest that noise exposure induces striking changes in the balance of excitatory and inhibitory synaptic inputs throughout the hippocampus and reveal a potential role for rebounding inhibition in the hippocampus as a protective factor leading to tinnitus resilience.

PMID:33510780 | PMC:PMC7822664 | DOI:10.1155/2021/8833087

SOURCE:
Neural plasticity

DATE – PUBLISHED:
2021-01-16T00:50:09Z

DATE – DOI: 2021-01-16T00:50:09Z
DATE – PUBMED: 2021 Jan 14
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 29 Jan 2021 06:00:00 -0500

DATE – RETRIEVED:
01/29/21 07:02AM
2021-01-29T07:02:51-05:00

IDENTIFIER:
pmid:33510780,pmc:PMC7822664,doi:10.1155/2021/8833087

PUBMED ID:
pubmed:33510780

DOI:
10.1155/2021/8833087

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33510780/

LINK – DOI:
https://doi.org/10.1155/2021/8833087

LINK – PUBLISHER:
https://www.hindawi.com/journals/np/2021/8833087/

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-01-29T07:02:51-05:00, www.tinnitustreatmentreport.com.

Acoustic and Electrical Stimulation for the Treatment of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Acoustic and Electrical Stimulation for the Treatment of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Interventions :   Other: Electrical;   Other: Acoustic

Sponsor :   University of California, Irvine

Recruiting

GUID:
NCT03511807

ID:
NCT03511807

DATE – FIRST POSTED:
Mon, 30 Apr 2018 12:00:00 EDT

DATE – LAST UPDATED:
01/14/21 07:10AM

DATE – RETRIEVED:
01/14/21 07:10AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT03511807?type=Intr&cond=Tinnitus&phase=012345&lupd_s=01%2F13%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03511807

Towards personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses [Preprint]

https://www.medrxiv.org/content/10.1101/2021.01.11.21249600v1.full-text

Towards personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses
View ORCID ProfileStefan Schoisswohl, View ORCID ProfileBerthold Langguth, View ORCID ProfileTobias Hebel, Mohamed A. Abdelnaim, View ORCID ProfileGregor Volberg, View ORCID ProfileMartin Schecklmann
doi: https://doi.org/10.1101/2021.01.11.21249600
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

BREAKTHROUGH: NAC/HPN-07, also known as the Hough Ear Institute’s NHPN-1010, significantly reduced the incidence of tinnitus, study finds…

Hough Ear Institute tinnitus treatment update:

New research suggests that NAC/HPN-07 treatment (development code name: NHPN-1010) could potentially “reduce, or perhaps reverse, both primary neurodegeneration and excitotoxic trauma in cochleae and prevent or attenuate maladaptive neural plasticity in central auditory pathways.”

In other words, this drug could possibly reduce or even REVERSE tinnitus. At least, that’s what this study is suggesting.

Some more context: this was studied in a blast-induced model of tinnitus. However, the results are no less remarkable… and seem to have broader implications…

Here is a link to the study (which was published moments ago, on January 7, 2021):

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

NAC/HPN-07 is also known by its code name, NHPN-1010 (the much anticipated Hough Ear treatment). The lead author of this paper is Dr. Richard Kopke, CEO of Hough Ear Institute.

More information about this study and the drug (NHPN-1010) will follow soon. Including some answers about when the treatment mentioned in this paper could be offered in human clinical trials. Hmmm…

A strong start to tinnitus science in 2021. Lots happening 🙂

P.S. Keep an eye on this reddit thread for some discussion, opinion, and unfiltered speculation.

P.P.S. For more NAC/HPN-07 updates and breaking tinnitus treatment and science-related developments… please remember to sign up for email updates (it’s free and first issue will be sent out soon). Even better, share TinnitusTreatmentReport.com with others who might find this information helpful, too…

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243903

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus
Jianzhong Lu,Matthew B. West,Xiaoping Du,Qunfeng Cai,Donald L. Ewert,Weihua Cheng,Don Nakmali,Wei Li,Xiangping Huang,Richard D. Kopke
Published: January 7, 2021https://doi.org/10.1371/journal.pone.0243903

Low-Level Laser Therapy as a Therapeutic Strategy for Patients With Tinnitus: Not Yet Proven

CATEGORY:
Research

TITLE:
Effects of Low-Level Laser Therapy as a Therapeutic Strategy for Patients With Tinnitus: A Systematic Review

DESCRIPTION:
Purpose This systematic review aimed to analyze the effects of low-level laser therapy (LLLT) on the severity of tinnitus when compared to no therapy or other modalities of therapies. Method A systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the Registration Number CRD42019119376. A search was performed in each of the following databases: EMBASE, LILACS, PubMed, Science Direct, Scopus, Web of Science, Google Scholar, and…

CONTENT:
J Speech Lang Hear Res. 2020 Dec 29:1-20. doi: 10.1044/2020_JSLHR-20-00066. Online ahead of print.

ABSTRACT

Purpose This systematic review aimed to analyze the effects of low-level laser therapy (LLLT) on the severity of tinnitus when compared to no therapy or other modalities of therapies. Method A systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the Registration Number CRD42019119376. A search was performed in each of the following databases: EMBASE, LILACS, PubMed, Science Direct, Scopus, Web of Science, Google Scholar, and ProQuest. The inclusion criteria consisted of studies in adults over 16 years of age, randomized clinical trials in which subjects presented chronic (≥ 6 months) and subjective tinnitus (unilateral or bilateral) as well as with or without bilateral sensorineural hearing loss, and studies that used only LLLT for treatment of tinnitus compared to no-therapy group or other modalities of therapy. No language or time restrictions were stipulated. The references were managed by Endnote Web and Rayyan QCRI. Results After the screening process, seven studies remained that attained the eligibility criteria. Regarding the risk of bias, only one study was categorized as low risk of bias; the six remaining studies were classified as moderate risk of bias. The seven included studies mainly assessed the LLLT effects on tinnitus by Visual Analogue Scale, Tinnitus Handicap Inventory, pitch and loudness matching, minimum masking level, and pure-tone audiometry. All the seven selected studies found different degrees of significant results regarding tinnitus severity; however, there was no consensus among the results. Conclusion Even though the LLLT showed positive effects in the tinnitus severity in some studies, it is not possible yet to make any recommendation over its uses for the treatment of tinnitus severity.

PMID:33375822 | DOI:10.1044/2020_JSLHR-20-00066

SOURCE:
Journal of speech, language, and hearing research : JSLHR

DATE – PUBLISHED:
2020-12-30T02:46:47Z

DATE – DOI: 2020-12-30T02:46:47Z
DATE – PUBMED: 2020 Dec 29
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 30 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/30/20 11:58AM
2020-12-30T11:58:50-05:00

IDENTIFIER:
pmid:33375822,doi:10.1044/2020_JSLHR-20-00066

PUBMED ID:
pubmed:33375822

DOI:
10.1044/2020_JSLHR-20-00066

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33375822/

LINK – DOI:
https://doi.org/10.1044/2020_JSLHR-20-00066

LINK – PUBLISHER:
http://pubs.asha.org/doi/10.1044/2020_JSLHR-20-00066

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-30T11:58:50-05:00, www.tinnitustreatmentreport.com.

ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem

CATEGORY:
Research

TITLE:
ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem

DESCRIPTION:
KEY POINTS: Cartwheel neurons provide potent inhibition to fusiform neurons in the dorsal cochlear nucleus (DCN). Most cartwheel neurons fire action potentials spontaneously, but the ion channels responsible for this intrinsic activity are unknown. We investigated the ion channels responsible for the intrinsic firing of cartwheel neurons and the stable resting membrane potential found in a fraction of these neurons (quiet neurons) Among the ion channels controlling membrane potential of…

CONTENT:
J Physiol. 2020 Dec 28. doi: 10.1113/JP280233. Online ahead of print.

ABSTRACT

KEY POINTS: Cartwheel neurons provide potent inhibition to fusiform neurons in the dorsal cochlear nucleus (DCN). Most cartwheel neurons fire action potentials spontaneously, but the ion channels responsible for this intrinsic activity are unknown. We investigated the ion channels responsible for the intrinsic firing of cartwheel neurons and the stable resting membrane potential found in a fraction of these neurons (quiet neurons) Among the ion channels controlling membrane potential of cartwheel neurons, the presence of open ATP-sensitive potassium channels (KATP ) is responsible for the existence of quiet neurons. Our results pinpoint KATP channel modulation as a critical factor controlling the firing of cartwheel neurons. Hence, it is a crucial channel influencing the balance of excitation and inhibition in the DCN.

ABSTRACT: Cartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, DCN’s principal excitatory neuron. Most cartwheel neurons present spontaneous firing (active neurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a small fraction of these neurons do not fire spontaneously (quiet neurons). Hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Because of its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons in DCN slices from rats. We found that quiet neurons presented an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP ) antagonist. After inhibition with tolbutamide, quiet neurons start to fire spontaneously, while the active neurons were not affected. On the other hand, in active neurons, KATP agonist diazoxide activated a conductance similar to quiet neurons’ KATP conductance and stopped spontaneous firing. According to the effect of KATP channels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Our results reveal a role of KATP channels in controlling the spontaneous firing of neurons not involved in fuel homeostasis. This article is protected by copyright. All rights reserved.

PMID:33369743 | DOI:10.1113/JP280233

SOURCE:
The Journal of physiology

DATE – PUBLISHED:
2020-12-28T20:55:32Z

DATE – DOI: 2020-12-28T20:55:32Z
DATE – PUBMED: 2020 Dec 28
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 28 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/29/20 12:19AM
2020-12-29T00:19:56-05:00

IDENTIFIER:
pmid:33369743,doi:10.1113/JP280233

PUBMED ID:
pubmed:33369743

DOI:
10.1113/JP280233

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33369743/

LINK – DOI:
https://doi.org/10.1113/JP280233

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1113/JP280233

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-29T00:19:56-05:00, www.tinnitustreatmentreport.com.

Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus

CATEGORY:
Research

TITLE:
Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus

DESCRIPTION:
Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing…

CONTENT:
PLoS One. 2020 Dec 17;15(12):e0243785. doi: 10.1371/journal.pone.0243785. eCollection 2020.

ABSTRACT

Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing systematically between tinnitus patients and controls. Results from this model indicate that amplitude of the P300 component is lower in tinnitus patients (standardized mean difference (SMD) = -0.83, p < 0.01), while latency of this component is abnormally prolonged in this population (SMD = 0.97, p < 0.01). No other investigated LAEP components were found to differ between tinnitus and non-tinnitus subjects. Additional sensitivity analyses regarding differences in experimental conditions confirmed the robustness of these results. Differences in age and hearing levels between the two experimental groups might have a considerable impact on LAEP outcomes and should be carefully considered in future studies. Although we established consistent differences in the P300 component between tinnitus patients and controls, we could not identify any evidence that this component might covary with tinnitus severity. We conclude that out of several commonly assessed LAEP components, only the P300 can be considered as a potential biomarker for subjective tinnitus, although more research is needed to determine its relationship with subjective tinnitus measures. Future trials investigating experimental tinnitus therapies should consider including P300 measurements in the evaluation of treatment effect. PMID:33332414 | DOI:10.1371/journal.pone.0243785 SOURCE: PloS one DATE - PUBLISHED: 2020-12-17T19:56:22Z DATE - DOI: 2020-12-17T19:56:22Z DATE - PUBMED: 2020 Dec 17 DATE OUTPUT MATCHED: True DATE - ADDED: Thu, 17 Dec 2020 06:00:00 -0500 DATE - RETRIEVED: 12/17/20 06:44PM 2020-12-17T18:44:08-05:00 IDENTIFIER: pmid:33332414,doi:10.1371/journal.pone.0243785 PUBMED ID: pubmed:33332414 DOI: 10.1371/journal.pone.0243785 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33332414/ LINK - DOI: https://doi.org/10.1371/journal.pone.0243785 LINK - PUBLISHER: https://dx.plos.org/10.1371/journal.pone.0243785 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2020-12-17T18:44:08-05:00, www.tinnitustreatmentreport.com.

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

CATEGORY:
Research

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

DESCRIPTION:
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,…

CONTENT:
Sci Rep. 2020 Dec 11;10(1):21801. doi: 10.1038/s41598-020-78571-0.

ABSTRACT

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.

PMID:33311548 | DOI:10.1038/s41598-020-78571-0

SOURCE:
Scientific reports

DATE – PUBLISHED:
2020-12-11T12:06:06Z

DATE – DOI: 2020-12-11T12:06:06Z
DATE – PUBMED: 2020 Dec 11
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 14 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/15/20 01:37AM
2020-12-15T01:37:27-05:00

IDENTIFIER:
pmid:33311548,doi:10.1038/s41598-020-78571-0

PUBMED ID:
pubmed:33311548

DOI:
10.1038/s41598-020-78571-0

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33311548/

LINK – DOI:
https://doi.org/10.1038/s41598-020-78571-0

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-020-78571-0

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-15T01:37:27-05:00, www.tinnitustreatmentreport.com.

Purinergic signaling controls spontaneous activity in the auditory system throughout early development

https://www.jneurosci.org/content/early/2020/12/09/JNEUROSCI.2178-20.2020

Purinergic signaling controls spontaneous activity in the auditory system throughout early development
Travis A. Babola, Sally Li, Zhirong Wang, Calvin J. Kersbergen, Ana Belén Elgoyhen, Thomas M. Coate and Dwight E. Bergles
Journal of Neuroscience 10 December 2020, JN-RM-2178-20; DOI: https://doi.org/10.1523/JNEUROSCI.2178-20.2020

Otonomy expects to start Phase 2 trial of OTO-313 in tinnitus in first quarter of 2021

https://investors.otonomy.com/news-releases/news-release-details/otonomy-provides-update-otividexr-and-oto-313-programs

https://www.globenewswire.com/news-release/2020/11/30/2136417/0/en/Otonomy-Provides-Update-on-OTIVIDEX-and-OTO-313-Programs.html

Otonomy expects to start Phase 2 trial of OTO-313 in tinnitus in first quarter of 2021

Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity

CATEGORY:
Research

TITLE:
Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity

DESCRIPTION:
CONCLUSION: While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

CONTENT:
Neuroreport. 2020 Nov 27. doi: 10.1097/WNR.0000000000001561. Online ahead of print.

ABSTRACT

OBJECTIVE: Tinnitus, phantom sound perception, arises from aberrant brain activity within auditory cortex. In tinnitus animal models, auditory cortex neurons show increased spontaneous firing and neural synchrony. In humans, similar hyperactivation in auditory cortex has been displayed with functional near-infrared spectroscopy (fNIRS). Resting-state functional connectivity (RSFC) or increased connectivity between brain regions has also been shown in tinnitus using fNIRS. However, current fNIRS technology utilizes infrared (IR)-sources and IR-detectors placed on the scalp that restricts (~3 cm depth IR penetration) signal capture to outer cerebral cortex due to skin and skull bone. To overcome this limitation, in this proof of concept study, we adapted fNIRS probes to fit in the external auditory canal (EAC) to physically place IR-probes deeper within the skull thereby extracting neural signals from deeper auditory cortex.

METHODS: Twenty adults with tinnitus and 20 nontinnitus controls listened to periods of silence and broadband noise before and after 5 min of silence to calculate RSFC. Concurrent scalp probes over auditory cortex and an adapted probe placed in the right EAC were utilized.

RESULTS: For standard probes, left and right auditory cortex in tinnitus showed increased RSFC to each other and to other nonauditory cortices. Interestingly, adapted fNIRS probes showed trends toward increased RSFC.

CONCLUSION: While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

PMID:33252478 | DOI:10.1097/WNR.0000000000001561

SOURCE:
Neuroreport

DATE – PUBLISHED:
2020-11-30T19:37:58Z

DATE – DOI: 2020-11-30T19:37:58Z
DATE – PUBMED: 2020 Nov 27
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 30 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/30/20 03:14PM
2020-11-30T15:14:28-05:00

IDENTIFIER:
pmid:33252478,doi:10.1097/WNR.0000000000001561

PUBMED ID:
pubmed:33252478

DOI:
10.1097/WNR.0000000000001561

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33252478/

LINK – DOI:
https://doi.org/10.1097/WNR.0000000000001561

LINK – PUBLISHER:
https://journals.lww.com/10.1097/WNR.0000000000001561

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-30T15:14:28-05:00, www.tinnitustreatmentreport.com.

Switching Tinnitus-On: Maps and source localization of spontaneous EEG

CATEGORY:
Research

TITLE:
Switching Tinnitus-On: Maps and source localization of spontaneous EEG

DESCRIPTION:
CONCLUSIONS: The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together…

CONTENT:
Clin Neurophysiol. 2020 Nov 23;132(2):345-357. doi: 10.1016/j.clinph.2020.10.023. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify the spectrotemporal changes and sources in patients that could “turn on” tinnitus with multichannel electroencephalography (EEG) system.

METHODS: Multichannel EEG was recorded from six patients during the Tinnitus-On and Tinnitus-Off states. The EEG power spectrum and eLORETA-based sources were measured.

RESULTS: There was a global increase in delta and theta during Tinnitus-On plus large changes in alpha 1 and alpha 2. During the Tinnitus-On state, many new sources in delta, theta, alpha 1 and gamma bands emerged in the opposite hemisphere in the inferior temporal gyrus (Brodmann area, BA 20), middle temporal gyrus (BA 21), lateral perirhinal cortex (BA 36), ventral entorhinal cortex (BA 28) and anterior pole of the temporal gyrus (BA 38).

CONCLUSIONS: The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together contribute to tinnitus severity.

SIGNIFICANCE: The sudden appearance of new sources of activity in the opposite hemisphere within the inferior temporal gyrus, middle temporal gyrus and perirhinal cortex may initiate the perception of tinnitus perception.

PMID:33450557 | DOI:10.1016/j.clinph.2020.10.023

SOURCE:
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

DATE – PUBLISHED:
2020-11-23T17:15:55Z

DATE – DOI: 2020-11-23T17:15:55Z
DATE – PUBMED: 2020 Nov 23
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 15 Jan 2021 06:00:00 -0500

DATE – RETRIEVED:
01/16/21 01:04AM
2021-01-16T01:04:05-05:00

IDENTIFIER:
pmid:33450557,doi:10.1016/j.clinph.2020.10.023

PUBMED ID:
pubmed:33450557

DOI:
10.1016/j.clinph.2020.10.023

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33450557/

LINK – DOI:
https://doi.org/10.1016/j.clinph.2020.10.023

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1388245720305575

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-01-16T01:04:05-05:00, www.tinnitustreatmentreport.com.

Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

CATEGORY:
Research

TITLE:
Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

DESCRIPTION:
Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is…

CONTENT:
Front Neurol. 2020 Nov 23;11:505995. doi: 10.3389/fneur.2020.505995. eCollection 2020.

ABSTRACT

Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is affected also by anxiety, memory, and attention circuits where cannabinoid effects are well described. Available studies on animal models of tinnitus suggest that cannabinoids are not likely to be helpful in tinnitus treatment and could even be harmful. However, the pharmacology of cannabinoids is very complex, and most studies focused on neural CB1R-based responses. Cannabinoid effects on the immune system (where CB2Rs predominate) are increasingly recognized as essential in understanding nervous system pathological responses, and data on immune cannabinoid targets have emerged in the auditory system as well. In addition, nonclassical cannabinoid targets (such as TRP channels) appear to play an important role in the auditory system as well. This review will focus on neuroimmunological mechanisms for cannabinoid effects and their possible use as protective and therapeutic agents in the ear and auditory system, especially in tinnitus.

PMID:33329293 | PMC:PMC7719758 | DOI:10.3389/fneur.2020.505995

SOURCE:
Frontiers in neurology

DATE – PUBLISHED:
2020-11-23T06:22:31Z

DATE – DOI: 2020-11-23T06:22:31Z
DATE – PUBMED: 2020 Nov 23
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 17 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/17/20 01:41PM
2020-12-17T13:41:18-05:00

IDENTIFIER:
pmid:33329293,pmc:PMC7719758,doi:10.3389/fneur.2020.505995

PUBMED ID:
pubmed:33329293

DOI:
10.3389/fneur.2020.505995

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33329293/

LINK – DOI:
https://doi.org/10.3389/fneur.2020.505995

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fneur.2020.505995/full

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-17T13:41:18-05:00, www.tinnitustreatmentreport.com.

Objective measurement of tinnitus using functional near-infrared spectroscopy and machine learning

CATEGORY:
Research

TITLE:
Objective measurement of tinnitus using functional near-infrared spectroscopy and machine learning

DESCRIPTION:
Chronic tinnitus is a debilitating condition which affects 10-20% of adults and can severely impact their quality of life. Currently there is no objective measure of tinnitus that can be used clinically. Clinical assessment of the condition uses subjective feedback from individuals which is not always reliable. We investigated the sensitivity of functional near-infrared spectroscopy (fNIRS) to differentiate individuals with and without tinnitus and to identify fNIRS features associated with…

CONTENT:
PLoS One. 2020 Nov 18;15(11):e0241695. doi: 10.1371/journal.pone.0241695. eCollection 2020.

ABSTRACT

Chronic tinnitus is a debilitating condition which affects 10-20% of adults and can severely impact their quality of life. Currently there is no objective measure of tinnitus that can be used clinically. Clinical assessment of the condition uses subjective feedback from individuals which is not always reliable. We investigated the sensitivity of functional near-infrared spectroscopy (fNIRS) to differentiate individuals with and without tinnitus and to identify fNIRS features associated with subjective ratings of tinnitus severity. We recorded fNIRS signals in the resting state and in response to auditory or visual stimuli from 25 individuals with chronic tinnitus and 21 controls matched for age and hearing loss. Severity of tinnitus was rated using the Tinnitus Handicap Inventory and subjective ratings of tinnitus loudness and annoyance were measured on a visual analogue scale. Following statistical group comparisons, machine learning methods including feature extraction and classification were applied to the fNIRS features to classify patients with tinnitus and controls and differentiate tinnitus at different severity levels. Resting state measures of connectivity between temporal regions and frontal and occipital regions were significantly higher in patients with tinnitus compared to controls. In the tinnitus group, temporal-occipital connectivity showed a significant increase with subject ratings of loudness. Also in this group, both visual and auditory evoked responses were significantly reduced in the visual and auditory regions of interest respectively. Naïve Bayes classifiers were able to classify patients with tinnitus from controls with an accuracy of 78.3%. An accuracy of 87.32% was achieved using Neural Networks to differentiate patients with slight/ mild versus moderate/ severe tinnitus. Our findings show the feasibility of using fNIRS and machine learning to develop an objective measure of tinnitus. Such a measure would greatly benefit clinicians and patients by providing a tool to objectively assess new treatments and patients’ treatment progress.

PMID:33206675 | DOI:10.1371/journal.pone.0241695

SOURCE:
PloS one

DATE – PUBLISHED:
2020-11-18T18:26:43Z

DATE – DOI: 2020-11-18T18:26:43Z
DATE – PUBMED: 2020 Nov 18
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 18 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/18/20 06:49PM
2020-11-18T18:49:54-05:00

IDENTIFIER:
pmid:33206675,doi:10.1371/journal.pone.0241695

PUBMED ID:
pubmed:33206675

DOI:
10.1371/journal.pone.0241695

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33206675/

LINK – DOI:
https://doi.org/10.1371/journal.pone.0241695

LINK – PUBLISHER:
https://dx.plos.org/10.1371/journal.pone.0241695

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-18T18:49:54-05:00, www.tinnitustreatmentreport.com.

Tinnitus impairs segregation of competing speech in normal-hearing listeners

CATEGORY:
Research

TITLE:
Tinnitus impairs segregation of competing speech in normal-hearing listeners

DESCRIPTION:
Many tinnitus patients report difficulties understanding speech in noise or competing talkers, despite having “normal” hearing in terms of audiometric thresholds. The interference caused by tinnitus is more likely central in origin. Release from informational masking (more central in origin) produced by competing speech may further illuminate central interference due to tinnitus. In the present study, masked speech understanding was measured in normal hearing listeners with or without tinnitus….

CONTENT:
Sci Rep. 2020 Nov 16;10(1):19851. doi: 10.1038/s41598-020-76942-1.

ABSTRACT

Many tinnitus patients report difficulties understanding speech in noise or competing talkers, despite having “normal” hearing in terms of audiometric thresholds. The interference caused by tinnitus is more likely central in origin. Release from informational masking (more central in origin) produced by competing speech may further illuminate central interference due to tinnitus. In the present study, masked speech understanding was measured in normal hearing listeners with or without tinnitus. Speech recognition thresholds were measured for target speech in the presence of multi-talker babble or competing speech. For competing speech, speech recognition thresholds were measured for different cue conditions (i.e., with and without target-masker sex differences and/or with and without spatial cues). The present data suggest that tinnitus negatively affected masked speech recognition even in individuals with no measurable hearing loss. Tinnitus severity appeared to especially limit listeners’ ability to segregate competing speech using talker sex differences. The data suggest that increased informational masking via lexical interference may tax tinnitus patients’ central auditory processing resources.

PMID:33199782 | DOI:10.1038/s41598-020-76942-1

SOURCE:
Scientific reports

DATE – PUBLISHED:
2020-11-16T11:14:10Z

DATE – DOI: 2020-11-16T11:14:10Z
DATE – PUBMED: 2020 Nov 16
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 17 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/17/20 12:27PM
2020-11-17T12:27:23-05:00

IDENTIFIER:
pmid:33199782,doi:10.1038/s41598-020-76942-1

PUBMED ID:
pubmed:33199782

DOI:
10.1038/s41598-020-76942-1

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33199782/

LINK – DOI:
https://doi.org/10.1038/s41598-020-76942-1

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-020-76942-1

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-17T12:27:23-05:00, www.tinnitustreatmentreport.com.

Reversing Synchronized Brain Circuits With Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

CATEGORY:
Clinical Trials

TITLE:
Reversing Synchronized Brain Circuits With Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

DESCRIPTION:
Condition :   Tinnitus

Interventions :   Device: Burst-SCS/sham SCS;   Device: Sham SCS/Burst-SCS

Sponsors :   University of Michigan;   National Institute of Mental Health (NIMH)

Enrolling by invitation

GUID:
NCT03621735

ID:
NCT03621735

DATE – FIRST POSTED:
Wed, 08 Aug 2018 12:00:00 EDT

DATE – LAST UPDATED:
11/13/20 06:38AM

DATE – RETRIEVED:
11/13/20 06:38AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT03621735?type=Intr&cond=Tinnitus&phase=012345&lupd_s=11%2F12%2F2020&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03621735

Increased central gain caused by reduced auditory input is a major mechanism of tinnitus but may originate from other pathophysiologic factors rather than from cochlear synaptopathy

CATEGORY:
Research

TITLE:
Within-Subject Comparisons of the Auditory Brainstem Response and Uncomfortable Loudness Levels in Ears With and Without Tinnitus in Unilateral Tinnitus Subjects With Normal Audiograms

EDITED TITLE:
Increased central gain caused by reduced auditory input is a major mechanism of tinnitus but may originate from other pathophysiologic factors rather than from cochlear synaptopathy

DESCRIPTION:
CONCLUSION: Based on these results for UCL, increased central gain is a major mechanism of tinnitus in humans with normal audiograms. However, this compensatory mechanism for reduced auditory input may originate from other pathophysiologic factors rather than from cochlear synaptopathy.

CONTENT:
Otol Neurotol. 2020 Nov 10. doi: 10.1097/MAO.0000000000002867. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether cochlear synaptopathy is a common pathophysiologic cause of tinnitus in individuals with normal audiograms.

STUDY DESIGN: Prospective study.

SETTING: Tertiary referral center.

METHODS: We enrolled 27 subjects with unilateral tinnitus and normal symmetric hearing thresholds, and 27 age- and sex-matched control subjects with normal symmetric hearing thresholds. We measured 1) the amplitudes of waves I and V with 90 dB nHL click stimuli in quiet conditions; 2) the latency shift of wave V with 80 dB nHL click stimuli in background noise, varying from 40 dB HL to 70 dB HL; and 3) uncomfortable loudness levels (UCLs) at 500 Hz and 3000 Hz pure tones.

RESULTS: There were no significant differences in the wave V/I amplitude ratio or the latency shift in wave V with increasing noise levels among the tinnitus ears (TEs), nontinnitus ears (NTEs), and control ears. There were no significant differences in UCLs at 500 Hz or 3000 Hz between TEs and NTEs, but the UCLs were lower in TEs (mean 111.3 dB or 104.1 dB) and NTEs (mean 109.4 dB or 100.6 dB) than in control ears (mean 117.9 dB or 114.1 dB, p < 0.017). No subject met our criteria for cochlear synaptopathy or increased central gain in terms of all three parameters. CONCLUSION: Based on these results for UCL, increased central gain is a major mechanism of tinnitus in humans with normal audiograms. However, this compensatory mechanism for reduced auditory input may originate from other pathophysiologic factors rather than from cochlear synaptopathy. PMID:33177407 | DOI:10.1097/MAO.0000000000002867 SOURCE: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology DATE - PUBLISHED: 2020-11-11T19:59:34Z DATE - DOI: 2020-11-11T19:59:34Z DATE - PUBMED: 2020 Nov 10 DATE OUTPUT MATCHED: True DATE - ADDED: Thu, 12 Nov 2020 06:00:00 -0500 DATE - RETRIEVED: 11/12/20 06:38AM 2020-11-12T06:38:14-05:00 IDENTIFIER: pmid:33177407,doi:10.1097/MAO.0000000000002867 PUBMED ID: pubmed:33177407 DOI: 10.1097/MAO.0000000000002867 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33177407/ LINK - DOI: https://doi.org/10.1097/MAO.0000000000002867 LINK - PUBLISHER: https://journals.lww.com/10.1097/MAO.0000000000002867 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2020-11-12T06:38:14-05:00, www.tinnitustreatmentreport.com.

Tinnitus Symptoms Improve With Sound and Tongue Stimulation

CATEGORY:
Research

TITLE:
Tinnitus Symptoms Improve With Sound and Tongue Stimulation

DESCRIPTION:
No abstract

CONTENT:
JAMA. 2020 Nov 10;324(18):1818. doi: 10.1001/jama.2020.21628.

NO ABSTRACT

PMID:33170224 | DOI:10.1001/jama.2020.21628

SOURCE:
JAMA

DATE – PUBLISHED:
2020-11-10T20:47:34Z

DATE – DOI: 2020-11-10T20:47:34Z
DATE – PUBMED: 2020 Nov 10
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 10 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/10/20 08:01PM
2020-11-10T20:01:46-05:00

IDENTIFIER:
pmid:33170224,doi:10.1001/jama.2020.21628

PUBMED ID:
pubmed:33170224

DOI:
10.1001/jama.2020.21628

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33170224/

LINK – DOI:
https://doi.org/10.1001/jama.2020.21628

LINK – PUBLISHER:
https://jamanetwork.com/journals/jama/fullarticle/2772741

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-10T20:01:46-05:00, www.tinnitustreatmentreport.com.

What Makes Tinnitus Loud?

CATEGORY:
Research

TITLE:
What Makes Tinnitus Loud?

DESCRIPTION:
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.

CONTENT:
Otol Neurotol. 2020 Nov 6. doi: 10.1097/MAO.0000000000002932. Online ahead of print.

ABSTRACT

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. PMID:33165158 | DOI:10.1097/MAO.0000000000002932 SOURCE: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology DATE - PUBLISHED: 2020-11-08T23:02:00Z DATE - DOI: 2020-11-08T23:02:00Z DATE - PUBMED: 2020 Nov 6 DATE OUTPUT MATCHED: True DATE - ADDED: Mon, 09 Nov 2020 06:00:00 -0500 DATE - RETRIEVED: 11/10/20 12:41AM 2020-11-10T00:41:45-05:00 IDENTIFIER: pmid:33165158,doi:10.1097/MAO.0000000000002932 PUBMED ID: pubmed:33165158 DOI: 10.1097/MAO.0000000000002932 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33165158/ LINK - DOI: https://doi.org/10.1097/MAO.0000000000002932 LINK - PUBLISHER: https://journals.lww.com/10.1097/MAO.0000000000002932 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2020-11-10T00:41:45-05:00, www.tinnitustreatmentreport.com.

Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus

CATEGORY:
Research

TITLE:
Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus

DESCRIPTION:
The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap…

CONTENT:
PLoS One. 2020 Nov 5;15(11):e0241136. doi: 10.1371/journal.pone.0241136. eCollection 2020.

ABSTRACT

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

PMID:33152745 | DOI:10.1371/journal.pone.0241136

SOURCE:
PloS one

DATE – PUBLISHED:
2020-11-05T18:37:20Z

DATE – DOI: 2020-11-05T18:37:20Z
DATE – PUBMED: 2020 Nov 5
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 05 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/06/20 06:06AM
2020-11-06T06:06:54-05:00

IDENTIFIER:
pmid:33152745,doi:10.1371/journal.pone.0241136

PUBMED ID:
pubmed:33152745

DOI:
10.1371/journal.pone.0241136

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33152745/

LINK – DOI:
https://doi.org/10.1371/journal.pone.0241136

LINK – PUBLISHER:
https://dx.plos.org/10.1371/journal.pone.0241136

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-06T06:06:54-05:00, www.tinnitustreatmentreport.com.

Investigating Accelerated Learning in Tinnitus Participants Implanted With Vagus Nerve Stimulation [Suspended]

CATEGORY:
Clinical Trials

TITLE:
Investigating Accelerated Learning in Tinnitus Participants Implanted With Vagus Nerve Stimulation

DESCRIPTION:
Condition :   VNS Implanted Tinnitus Patients

Intervention :   Device: Vagus Nerve Stimulation

Sponsors :   The University of Texas at Dallas;   Defense Advanced Research Projects Agency

Suspended

GUID:
NCT03143842

ID:
NCT03143842

DATE – FIRST POSTED:
Mon, 08 May 2017 12:00:00 EDT

DATE – LAST UPDATED:
11/04/20 07:16AM

DATE – RETRIEVED:
11/04/20 07:16AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT03143842?type=Intr&cond=Tinnitus&phase=012345&lupd_s=11%2F03%2F2020&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03143842

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

CATEGORY:
Research

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

DESCRIPTION:
CONCLUSIONS: The tinnitus pitch fell within the HL area, and was mildly associated with F50.

CONTENT:
Acta Otolaryngol. 2020 Nov 4:1-8. doi: 10.1080/00016489.2020.1837394. Online ahead of print.

ABSTRACT

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.

PMID:33146043 | DOI:10.1080/00016489.2020.1837394

SOURCE:
Acta oto-laryngologica

DATE – PUBLISHED:
2020-11-04T10:32:57Z

DATE – DOI: 2020-11-04T10:32:57Z
DATE – PUBMED: 2020 Nov 4
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 04 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/04/20 12:36PM
2020-11-04T12:36:42-05:00

IDENTIFIER:
pmid:33146043,doi:10.1080/00016489.2020.1837394

PUBMED ID:
pubmed:33146043

DOI:
10.1080/00016489.2020.1837394

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33146043/

LINK – DOI:
https://doi.org/10.1080/00016489.2020.1837394

LINK – PUBLISHER:
https://www.tandfonline.com/doi/full/10.1080/00016489.2020.1837394

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-04T12:36:42-05:00, www.tinnitustreatmentreport.com.

Identification of an inhibitory neuron subtype, the L-stellate cell of the cochlear nucleus

https://elifesciences.org/articles/54350

Identification of an inhibitory neuron subtype, the L-stellate cell of the cochlear nucleus

Abstract
Auditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages in the ventral cochlear nucleus (VCN). Remarkably, to date only a single subtype of inhibitory neuron has been documented in the VCN, a projection neuron termed the D-stellate cell. With the use of a transgenic mouse line, optical clearing, and imaging techniques, combined with electrophysiological tools, we revealed a population of glycinergic cells in the VCN distinct from the D-stellate cell. These multipolar glycinergic cells were smaller in soma size and dendritic area, but over ten-fold more numerous than D-stellate cells. They were activated by auditory nerve and T-stellate cells, and made local inhibitory synaptic contacts on principal cells of the VCN. Given their abundance, combined with their narrow dendritic fields and axonal projections, it is likely that these neurons, here termed L-stellate cells, play a significant role in frequency-specific processing of acoustic signals.

The role of prediction and gain in tinnitus

https://www.entandaudiologynews.com/features/audiology-features/post/the-role-of-prediction-and-gain-in-tinnitus

The role of prediction and gain in tinnitus

Frequency Therapeutics Will Report FX-322 Phase 2a Study Data in Late Q1 2021

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-announces-expanded-fx-322-clinical

Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis
Company Will Report Data from Phase 2a Sensorineural Hearing Loss (SNHL) Study in Late Q1 2021

First Patient Dosed in Phase 1b Study of Age-Related Hearing Loss; Additional Phase 1b Study for Severe SNHL Patients to Start This Quarter

Dietary Factors and Tinnitus among Adolescents

CATEGORY:
Research

TITLE:
Dietary Factors and Tinnitus among Adolescents

DESCRIPTION:
The number of people suffering from constant tinnitus is ever-increasing and has spread to all age groups, including adolescents. The etiology of tinnitus is multifactorial, but dietary factors have been rarely investigated. The purpose of this study is to examine the relationship between dietary factors and constant tinnitus among adolescents from an urban environment. A population-oriented cross-sectional study was carried out during the 2019/2020 school year in 12 Belgrade secondary schools….

CONTENT:
Nutrients. 2020 Oct 27;12(11):E3291. doi: 10.3390/nu12113291.

ABSTRACT

The number of people suffering from constant tinnitus is ever-increasing and has spread to all age groups, including adolescents. The etiology of tinnitus is multifactorial, but dietary factors have been rarely investigated. The purpose of this study is to examine the relationship between dietary factors and constant tinnitus among adolescents from an urban environment. A population-oriented cross-sectional study was carried out during the 2019/2020 school year in 12 Belgrade secondary schools. There were 1287 school children aged from 15 to 19 years who participated in the study. There were 1003 respondents who completed a questionnaire on tinnitus (response rate 77.9%; 31% male). We used the standardized Tinnitus Screener questionnaire and a food frequency questionnaire specially designed for this study and adapted to Serbian adolescents. A logistic regression analysis revealed a strong negative correlation between fresh vegetables and fruits and tinnitus presence. On the other hand, the risk of constant tinnitus increased with the increased intake of white bread, carbonated beverages, and fast food. In conclusion, we show that fresh fruit and vegetable intakes may be negatively related to tinnitus frequency, while sweetened sodas, fast food, and white bread may raise the odds for tinnitus.

PMID:33121120 | DOI:10.3390/nu12113291

SOURCE:
Nutrients

DATE – PUBLISHED:
2020-10-27T14:02:33Z

DATE – DOI: 2020-10-27T14:02:33Z
DATE – PUBMED: 2020 Oct 27
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 30 Oct 2020 06:00:00 -0400

DATE – RETRIEVED:
10/30/20 10:18AM
2020-10-30T10:18:27-04:00

IDENTIFIER:
pmid:33121120,doi:10.3390/nu12113291

PUBMED ID:
pubmed:33121120

DOI:
10.3390/nu12113291

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33121120/

LINK – DOI:
https://doi.org/10.3390/nu12113291

LINK – PUBLISHER:
https://www.mdpi.com/2072-6643/12/11/3291

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-10-30T10:18:27-04:00, www.tinnitustreatmentreport.com.

The Prevalence of Different Types of Headache in Patients with Subjective Tinnitus and Its Influence on Tinnitus Parameters: A Prospective Clinical Study

CATEGORY:
Research

TITLE:
The Prevalence of Different Types of Headache in Patients with Subjective Tinnitus and Its Influence on Tinnitus Parameters: A Prospective Clinical Study

DESCRIPTION:
Both tinnitus and headache are very prevalent conditions in the general population, with bidirectional co-occurrence of them. A number of studies revealed a high prevalence of headache in tinnitus patients; however, most of them used self-reported symptoms, questionnaires, or health databases and were retrospective. The aim of this study was to evaluate the prevalence of different types of headache in a cohort of tinnitus patients and to assess the influence of headache on tinnitus parameters,…

CONTENT:
Brain Sci. 2020 Oct 24;10(11):E776. doi: 10.3390/brainsci10110776.

ABSTRACT

Both tinnitus and headache are very prevalent conditions in the general population, with bidirectional co-occurrence of them. A number of studies revealed a high prevalence of headache in tinnitus patients; however, most of them used self-reported symptoms, questionnaires, or health databases and were retrospective. The aim of this study was to evaluate the prevalence of different types of headache in a cohort of tinnitus patients and to assess the influence of headache on tinnitus parameters, focusing on appropriate headache and tinnitus diagnosis verified by clinical examination. This prospective study involved 286 patients diagnosed with subjective non-pulsating tinnitus. Patients’ clinical information was thoroughly assessed by the multidisciplinary team, including tinnitus characteristics and severity according to the Tinnitus Handicap Inventory (THI), loudness assessed by the Visual Analogue Scale (VAS), audiometry, type of headache diagnosed according to the third edition of the International Classification of Headache Disorders, severity of headache assessed by the Numeric Rating Scale (NRS), and impact of headache using the Headache Impact Test (HIT). In total, 141 (49.3%) tinnitus patients were diagnosed with headache, most of them with tension-type headache or migraine. They were significantly younger; mostly women; had bilateral tinnitus, vertigo, and depression more frequently; and had hearing loss less frequently as compared with the non-headache group. In total, 82 (58.16%) patients had the same localization of tinnitus and headache. Younger age, female gender, higher tinnitus burden measured by THI, and coexistence of hearing loss were independent variables connected with the occurrence of headache in the tinnitus group. According to our study, headaches impact tinnitus on many different levels and may be an important co-factor for tinnitus subtyping. We recommend screening for headache coexistence in all tinnitus patients.

PMID:33114375 | DOI:10.3390/brainsci10110776

SOURCE:
Brain sciences

DATE – PUBLISHED:
2020-10-26T06:44:22Z

DATE – DOI: 2020-10-26T06:44:22Z
DATE – PUBMED: 2020 Oct 24
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 29 Oct 2020 06:00:00 -0400

DATE – RETRIEVED:
10/29/20 06:41AM
2020-10-29T06:41:32-04:00

IDENTIFIER:
pmid:33114375,doi:10.3390/brainsci10110776

PUBMED ID:
pubmed:33114375

DOI:
10.3390/brainsci10110776

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33114375/

LINK – DOI:
https://doi.org/10.3390/brainsci10110776

LINK – PUBLISHER:
https://www.mdpi.com/2076-3425/10/11/776

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-10-29T06:41:32-04:00, www.tinnitustreatmentreport.com.

Novel Tinnitus Implant System for the Treatment of Chronic Severe Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Novel Tinnitus Implant System for the Treatment of Chronic Severe Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Intervention :   Device: Tinnitus Implant System

Sponsor :   Matthew L. Carlson, M.D.

Not yet recruiting

GUID:
NCT03988699

ID:
NCT03988699

DATE – FIRST POSTED:
Mon, 17 Jun 2019 12:00:00 EDT

DATE – LAST UPDATED:
10/19/20 09:19AM

DATE – RETRIEVED:
10/19/20 09:19AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT03988699?type=Intr&cond=Tinnitus&phase=012345&lupd_s=10%2F18%2F2020&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03988699

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus

CATEGORY:
Research

TITLE:
Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus

DESCRIPTION:
The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy…

CONTENT:
Hum Brain Mapp. 2020 Oct 13. doi: 10.1002/hbm.25238. Online ahead of print.

ABSTRACT

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.

PMID:33090584 | DOI:10.1002/hbm.25238

SOURCE:
Human brain mapping

DATE – PUBLISHED:
2020-10-13T17:36:17Z

DATE – DOI: 2020-10-13T17:36:17Z
DATE – PUBMED: 2020 Oct 13
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 22 Oct 2020 06:00:00 -0400

DATE – RETRIEVED:
10/22/20 07:02PM
2020-10-22T19:02:20-04:00

IDENTIFIER:
pmid:33090584,doi:10.1002/hbm.25238

PUBMED ID:
pubmed:33090584

DOI:
10.1002/hbm.25238

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33090584/

LINK – DOI:
https://doi.org/10.1002/hbm.25238

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/hbm.25238

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-10-22T19:02:20-04:00, www.tinnitustreatmentreport.com.

Noise Induced Hearing Loss and Tinnitus-New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention

CATEGORY:
Research

TITLE:
Noise Induced Hearing Loss and Tinnitus-New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention

DESCRIPTION:
Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and…

CONTENT:
Brain Sci. 2020 Oct 13;10(10):E732. doi: 10.3390/brainsci10100732.

ABSTRACT

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.

PMID:33066210 | DOI:10.3390/brainsci10100732

SOURCE:
Brain sciences

DATE – PUBLISHED:
2020-10-13T13:30:21Z

DATE – DOI: 2020-10-13T13:30:21Z
DATE – PUBMED: 2020 Oct 13
DATE OUTPUT MATCHED: True

DATE – ADDED:
Sat, 17 Oct 2020 06:00:00 -0400

DATE – RETRIEVED:
10/19/20 06:34PM
2020-10-19T18:34:21-04:00

IDENTIFIER:
pmid:33066210,doi:10.3390/brainsci10100732

PUBMED ID:
pubmed:33066210

DOI:
10.3390/brainsci10100732

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33066210/

LINK – DOI:
https://doi.org/10.3390/brainsci10100732

LINK – PUBLISHER:
https://www.mdpi.com/2076-3425/10/10/732

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-10-19T18:34:21-04:00, www.tinnitustreatmentreport.com.

Heavy metals could play important role in development of tinnitus, study finds

Quick research update…

New paper outlines how elevated levels of manganese, cadmium, chromium, and selenium could potentially be the cause of subjective tinnitus.

Authors conclude that supplementation or reduction of these heavy metal elements “could be considered as novel therapeutic goals” for treating tinnitus.

Further studies are necessary. For now, here is the abstract for the study, The Role of Manganese, Cadmium, Chromium and Selenium on Subjective Tinnitus, published October 9, 2020:

Elevated levels of heavy metals like cadmium (Cd) and manganese (Mn) are known to lead to oxidative damage-related oto-toxicity and decreased levels of chromium (Cr) and selenium (Se) are known to lead to oto-toxicity due to reduced anti-oxidant activity. The aim of the present study was to evaluate serum levels of Cd, Mn, Cr, and Se and their relationship with tinnitus. A total of 48 patients with tinnitus (Group 1) and 40 healthy controls (Group 2) were included in the study. All participants were applied audiology tests. Severity of tinnitus was measured with Tinnitus Severity Index Questionnaire (TSIQ) in group 1. Serum Mn, Cd, Cr, and Se measurements were done by using The Agilent ICP-MS system consisted of a 7700 coupled plasma mass spectrometry (ICP-MS). Serum Cd, Mn, and Cr levels were higher in group 1 and Se level was lower in group 1 than that of group 2. We may conclude that Cd, Mn, Cr, and Se levels could play an important role in etio-pathogenesis of tinnitus, and thereby supplementation or reduction of these elements could be considered as novel therapeutic goals.

Source:

https://link.springer.com/article/10.1007/s12011-020-02420-4

Further reading:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201364/

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The Role of Manganese, Cadmium, Chromium and Selenium on Subjective Tinnitus

https://link.springer.com/article/10.1007/s12011-020-02420-4

https://doi.org/10.1007/s12011-020-02420-4

https://pubmed.ncbi.nlm.nih.gov/33037493/

TITLE:
The Role of Manganese, Cadmium, Chromium and Selenium on Subjective Tinnitus

ALTERNATIVE TITLE:
None

DATE:
Sat, 10 Oct 2020 06:00:00 -0400

AUTHORS:
Nihal Efe Atila,Alptug Atila,Zülküf Kaya,Yunus E Bulut,Fatih Oner,Kübra Topal,Zafer Bayraktutan,Ebubekir Bakan

SOURCE:
Biological trace element research

DESCRIPTION:

Elevated levels of heavy metals like cadmium (Cd) and manganese (Mn) are known to lead to oxidative damage-related oto-toxicity and decreased levels of chromium (Cr) and selenium (Se) are known to lead to oto-toxicity due to reduced anti-oxidant activity. The aim of the present study was to evaluate serum levels of Cd, Mn, Cr, and Se and their relationship with tinnitus. A total of 48 patients with tinnitus (Group 1) and 40 healthy controls (Group 2) were included in the study. All participants…

CONTENT:

Biol Trace Elem Res. 2020 Oct 9. doi: 10.1007/s12011-020-02420-4. Online ahead of print.

ABSTRACT

Elevated levels of heavy metals like cadmium (Cd) and manganese (Mn) are known to lead to oxidative damage-related oto-toxicity and decreased levels of chromium (Cr) and selenium (Se) are known to lead to oto-toxicity due to reduced anti-oxidant activity. The aim of the present study was to evaluate serum levels of Cd, Mn, Cr, and Se and their relationship with tinnitus. A total of 48 patients with tinnitus (Group 1) and 40 healthy controls (Group 2) were included in the study. All participants were applied audiology tests. Severity of tinnitus was measured with Tinnitus Severity Index Questionnaire (TSIQ) in group 1. Serum Mn, Cd, Cr, and Se measurements were done by using The Agilent ICP-MS system consisted of a 7700 coupled plasma mass spectrometry (ICP-MS). Serum Cd, Mn, and Cr levels were higher in group 1 and Se level was lower in group 1 than that of group 2. We may conclude that Cd, Mn, Cr, and Se levels could play an important role in etio-pathogenesis of tinnitus, and thereby supplementation or reduction of these elements could be considered as novel therapeutic goals.

PMID:33037493 | DOI:10.1007/s12011-020-02420-4

PUBMED ID:
pubmed:33037493

OTHER ID:
pmid:33037493,doi:10.1007/s12011-020-02420-4

PUBLICATION DATE:
Sat, 10 Oct 2020 06:00:00 -0400
2020-10-10

RETRIEVAL DATE :
10/11/20 02:01AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33037493/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20201011020136&v=2.12.3

LINK – DOI:
https://doi.org/10.1007/s12011-020-02420-4

LINK – FULL TEXT:
Pending

NOTES:
None

New Tinnitus Treatment Alleviates Annoying Ringing in the Ears: A noninvasive device [Lenire] designed to rewire brain circuits reduced symptoms of tinnitus in a large, exploratory clinical trial

https://www.scientificamerican.com/article/new-tinnitus-treatment-alleviates-annoying-ringing-in-the-ears1/

New Tinnitus Treatment Alleviates Annoying Ringing in the Ears
A noninvasive device designed to rewire brain circuits reduced symptoms of tinnitus in a large, exploratory clinical trial

Phenotyping chronic tinnitus patients using self-report questionnaire data: cluster analysis and visual comparison

https://www.nature.com/articles/s41598-020-73402-8

https://doi.org/10.1038/s41598-020-73402-8

https://pubmed.ncbi.nlm.nih.gov/33009468/

TITLE:
Phenotyping chronic tinnitus patients using self-report questionnaire data: cluster analysis and visual comparison

ALTERNATIVE TITLE:
None

DATE:
Sat, 03 Oct 2020 06:00:00 -0400

AUTHORS:
Uli Niemann,Petra Brueggemann,Benjamin Boecking,Wilhelm Mebus,Matthias Rose,Myra Spiliopoulou,Birgit Mazurek

SOURCE:
Scientific reports

DESCRIPTION:

Chronic tinnitus is a complex, multi-factorial symptom that requires careful assessment and management. Evidence-based therapeutic approaches involve audiological and psychological treatment components. However, not everyone benefits from treatment. The identification and characterisation of patient subgroups (or “phenotypes”) may provide clinically relevant information. Due to the large number of assessment tools, data-driven methods appear to be promising. The acceptance of these empirical…

CONTENT:

Sci Rep. 2020 Oct 2;10(1):16411. doi: 10.1038/s41598-020-73402-8.

ABSTRACT

Chronic tinnitus is a complex, multi-factorial symptom that requires careful assessment and management. Evidence-based therapeutic approaches involve audiological and psychological treatment components. However, not everyone benefits from treatment. The identification and characterisation of patient subgroups (or “phenotypes”) may provide clinically relevant information. Due to the large number of assessment tools, data-driven methods appear to be promising. The acceptance of these empirical results can be further strengthened by a comprehensive visualisation. In this study, we used cluster analysis to identify distinct tinnitus phenotypes based on self-report questionnaire data and implemented a visualisation tool to explore phenotype idiosyncrasies. 1228 patients with chronic tinnitus from the Charité Tinnitus Center in Berlin were included. At baseline, each participant completed 14 questionnaires measuring tinnitus distress, -loudness, frequency and location, depressivity, perceived stress, quality of life, physical and mental health, pain perception, somatic symptom expression and coping attitudes. Four distinct patient phenotypes emerged from clustering: avoidant group (56.8%), psychosomatic group (14.1%), somatic group (15.2%), and distress group (13.9%). Radial bar- and line charts allowed for visual inspection and juxtaposition of major phenotype characteristics. The phenotypes differed in terms of clinical information including psychological symptoms, quality of life, coping attitudes, stress, tinnitus-related distress and pain, as well as socio-demographics. Our findings suggest that identifiable patient subgroups and their visualisation may allow for stratified treatment strategies and research designs.

PMID:33009468 | DOI:10.1038/s41598-020-73402-8

PUBMED ID:
pubmed:33009468

OTHER ID:
pmid:33009468,doi:10.1038/s41598-020-73402-8

PUBLICATION DATE:
Sat, 03 Oct 2020 06:00:00 -0400
2020-10-03

RETRIEVAL DATE :
10/04/20 02:15AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33009468/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20201004021523&v=2.12.3

LINK – DOI:
https://doi.org/10.1038/s41598-020-73402-8

LINK – FULL TEXT:
Pending

NOTES:
None

How can sound generating devices support coping with tinnitus?

https://www.tandfonline.com/doi/full/10.1080/14992027.2020.1827307

How can sound generating devices support coping with tinnitus?
Shameela Munir &Helen Pryce ORCID Icon
Received 15 Jun 2020, Accepted 16 Sep 2020, Published online: 01 Oct 2020
Download citation https://doi.org/10.1080/14992027.2020.1827307

Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

https://clinicaltrials.gov/ct2/show/NCT03336398?type=Intr&cond=Tinnitus&phase=012345&lupd_s=09%2F15%2F2020&lupd_d=14

Condition :   Tinnitus

Interventions :   Drug: Ketamine Hydrochloride in saline;   Drug: Saline

Sponsor :   New York State Psychiatric Institute

Recruiting

Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

NCT03336398

Wed, 08 Nov 2017 12:00:00 EST

Last Update Posted:

09/29/20 06:51AM

A New Buzz for Tinnitus—It’s in the Genes!

https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2770968

September 24, 2020
A New Buzz for Tinnitus—It’s in the Genes!
Christopher R. Cederroth, PhD1,2,3; Natalia Trpchevska, MD3; Berthold Langguth, MD, PhD4
Author Affiliations
JAMA Otolaryngol Head Neck Surg. Published online September 24, 2020. doi:10.1001/jamaoto.2020.2919

Individualized Treatment of Tinnitus during Sleep Using Stimulation of the Auditory and Limbic Systems

https://www.karger.com/Article/Abstract/509981

https://doi.org/10.1159/000509981

https://pubmed.ncbi.nlm.nih.gov/32966989/

TITLE:
Individualized Treatment of Tinnitus during Sleep Using Combined Tinnitus Signal and Music

ALTERNATIVE TITLE:
None

DATE:
Wed, 23 Sep 2020 06:00:00 -0400

AUTHORS:
Huseyin Deniz,Yildirim Ahmet Bayazit,Elif Tugba Sarac

SOURCE:
ORL; journal for oto-rhino-laryngology and its related specialties

DESCRIPTION:

CONCLUSION: Stimulation of the auditory and limbic systems during sleep by the tinnitus signal combined with individualized musical melodies seems an alternative, effective, and cheap method in the treatment of tinnitus.

CONTENT:

ORL J Otorhinolaryngol Relat Spec. 2020 Sep 23:1-6. doi: 10.1159/000509981. Online ahead of print.

ABSTRACT

INTRODUCTION: Tinnitus is a widely seen otological symptom that interferes with daily activities and causes discomfort. Tinnitus treatments can be classified into 4 main groups: pharmacological treatments, cognitive and behavioral therapy, psychological treatments, and combined treatment approaches made up of at least 2 of these 3 treatment methods.

OBJECTIVE: The aim of this study was to assess whether it would be possible to develop an individualized treatment method of tinnitus by application of a combined tinnitus signal and music during sleep.

METHODS: Forty-three ears of 30 patients who had subjective tinnitus were included. The patients were evaluated using Tinnitus Handicap Inventory, Visual Analogue Scale, and Beck Depression Inventory. The psychoacoustic parameters of tinnitus, such as tinnitus frequency and loudness, and minimal masking levels, were determined. The patients were asked to select musical melodies that they liked. The tinnitus frequency of each patient was taken as the central frequency according to ANSI 2004. All sound files were prepared as stereo channels, with 16-bit resolution and 44,100 Hz sampling rate. The root mean square power value of the music and the band noise’s average root mean square power value were equalized with the “Amplification” command, and 70% of the music and 30% of wide/narrow-band noise were mixed as a stereo channel by the “Mix Paste” command. The patients were instructed to listen to that individualized music/narrow-band noise (tinnitus signal) for 2 h during sleep for a duration of 6 months.

RESULTS: Tinnitus frequencies of the patients measured prior to treatment and at the second, fourth, and sixth months of follow-up were not significantly different. A statistically significant decrease was seen in tinnitus loudness, minimal masking levels, and residual inhibition during the follow-up. Tinnitus Handicap Inventory scores decreased significantly during follow-up, and the number of patients who complained of tinnitus decreased (p < 0.05). The Visual Analogue Scale scores significantly decreased during follow-up (p < 0.05). Beck Depression Inventory scores decreased significantly during follow-up (p < 0.05). CONCLUSION: Stimulation of the auditory and limbic systems during sleep by the tinnitus signal combined with individualized musical melodies seems an alternative, effective, and cheap method in the treatment of tinnitus. PMID:32966989 | DOI:10.1159/000509981

PUBMED ID:
pubmed:32966989

OTHER ID:
pmid:32966989,doi:10.1159/000509981

PUBLICATION DATE:
Wed, 23 Sep 2020 06:00:00 -0400
2020-09-23

RETRIEVAL DATE :
09/24/20 12:32AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32966989/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20200924003250&v=2.11.5

LINK – DOI:
https://doi.org/10.1159/000509981

LINK – FULL TEXT:
Pending

NOTES:
None

Frequency Therapeutics Completes Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss

https://www.businesswire.com/news/home/20200922005309/en/Frequency-Therapeutics-Completes-Enrollment-of-FX-322-Phase-2a-Study-for-Sensorineural-Hearing-Loss

Frequency Therapeutics Completes Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-completes-enrollment-fx-322-phase-2a

Using cortical neuron markers to target cells in the dorsal cochlear nucleus: novel tools for studying tinnitus mechanisms [Preprint]

https://www.biorxiv.org/content/10.1101/2020.09.19.304550v2.full.pdf

https://www.biorxiv.org/content/10.1101/2020.09.19.304550v2

Using cortical neuron markers to target cells in the dorsal cochlear nucleus
Thawann Malfatti, Barbara Ciralli, Markus M. Hilscher, Steven J. Edwards, Klas Kullander, Richardson N. Leao, Katarina E. Leao
doi: https://doi.org/10.1101/2020.09.19.304550

Together, these results opens up for more detailed control of DCN circuit output in vivo and novel tools for studying tinnitus mechanisms.

Perceptual Dimensions Underlying Tinnitus-Like Sounds

https://doi.org/10.1044/2020_JSLHR-19-00327

https://pubmed.ncbi.nlm.nih.gov/32946329/

TITLE:
Perceptual Dimensions Underlying Tinnitus-Like Sounds

ALTERNATIVE TITLE:
None

DATE:
Fri, 18 Sep 2020 06:00:00 -0400

AUTHORS:
Jennifer J Lentz,Yuan He

SOURCE:
Journal of speech, language, and hearing research : JSLHR

DESCRIPTION:

Purpose The goal of this study was to establish the perceptual underpinnings of the terms that are commonly used by patients when describing the quality of their tinnitus. Method Using a free-classification method, 15 subjects with normal hearing placed 60 different tinnitus-like sounds into similarity clusters on a grid. Multidimensional scaling, hierarchical clustering, and acoustic analyses were used to determine the acoustic underpinnings of the perceptual dimensions and perceptual…

CONTENT:

J Speech Lang Hear Res. 2020 Sep 18:1-7. doi: 10.1044/2020_JSLHR-19-00327. Online ahead of print.

ABSTRACT

Purpose The goal of this study was to establish the perceptual underpinnings of the terms that are commonly used by patients when describing the quality of their tinnitus. Method Using a free-classification method, 15 subjects with normal hearing placed 60 different tinnitus-like sounds into similarity clusters on a grid. Multidimensional scaling, hierarchical clustering, and acoustic analyses were used to determine the acoustic underpinnings of the perceptual dimensions and perceptual similarity. Results Multidimensional scaling revealed three different perceptual dimensions (pitch, modulation depth + spectral elements, and envelope rate). Hierarchical clustering revealed five explicit similarity clusters: tonal, steady noise, pulsatile, low-frequency fluctuating noise, and high-frequency fluctuating. Conclusions Results are consistent with tinnitus perceptions falling into a small set of categories that can be characterized by their acoustics. As a result, there is the potential to develop different tools to assess tinnitus using a variety of different sounds.

PMID:32946329 | DOI:10.1044/2020_JSLHR-19-00327

PUBMED ID:
pubmed:32946329

OTHER ID:
pmid:32946329,doi:10.1044/2020_JSLHR-19-00327

PUBLICATION DATE:
Fri, 18 Sep 2020 06:00:00 -0400
2020-09-18

RETRIEVAL DATE :
09/18/20 06:26PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32946329/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20200918182634&v=2.11.5

LINK – DOI:
https://doi.org/10.1044/2020_JSLHR-19-00327

LINK – FULL TEXT:
Pending

NOTES:
None

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