Hidden Hearing Loss, Tinnitus and Trouble Hearing Conversations in Noise

[HomeoHebbian]

@HomeoHebbian sorry I forgot to tag you in my question. Also when you are predicting attenuation via DNS and gaming do you think that will be lasting treatment effects after months of use or a daily routine treatment

If I had to guess, I would think that a treatment like this would be something like learning to ski. Fairly intensive training on the front end, followed by periodic refreshers to maintain. Reorganizing brain circuits is not like fixing a broken arm, where you can reset the bone and leave it be. At least for adult brains, reorganizing the brain to support newly learned skills etc. requires the proper "instructive signal" to start with and efficient strategies to maintain.

 

[Jim51042]

@HomeoHebbian I know you had mentioned drug would supplement this process. Do you know of any current drugs or can you speculate on which future drug would be helpful? Potassium channel modulators?

 

[HomeoHebbian]

The most effective therapies for cancer are cocktail approaches that bundle a set of tailored therapies. I think redundant, cocktail treatments will be key for treating T as well. My point here is that I am pessimistic that any one drug, in isolation, will prove terribly effective. With that said, I think there are good reasons to pursue K+ channel modulators, though the most promising variants are still in development. I think there are good reasons to purse cholinergic modulators, like cholinesterase inhibitors, but only if they are paired with corrective listening therapies.

 

[HomeoHebbian]

It seems a diagnostic test for hidden hearing loss has been developed. It's a so-called "binaural test". The binaural system is involved in sound localization and speech discrimination in noisy places.

Read more:
https://www.sciencedaily.com/releases/2016/12/161222143525.htm

Makes sense but not earth shattering. They just reheated a classic test - the binaural masking level difference [http://www.ee.columbia.edu/~dpwe/classes/e6820-2001-01/matlab/MAD/bmld/bmld.htm]- and provided a new spin. With that said, binaural processing could be a sensitive measure for neuropathy and excess central gain. There are newer, more informative tests of binaural phase detection that can be coupled with objective physiologic measurements. I think these will prove the better way to proceed. What any of this has to do with tinnitus is unclear, but is something we plan to investigate in my lab.

 

[Jim51042]

@HomeoHebbian Thanks for introducing cholinesterase inhibitors I had not hear of them before. As far as K modulators is 1OP-2198 the only one in development (RL-81 and SF-3400 have been shelved right)? With the latest news that come out this 1Quarter do you still think any form of hearing restoration is over 15 years plus away? Maybe the brain retraining and repair components will come together, especially the neurotrophic repair/regen trials, to provide the ultimate solution to tinnitus?

 

[Rubenslash]

@HomeoHebbian Thanks for introducing cholinesterase inhibitors I had not hear of them before. As far as K modulators is 1OP-2198 the only one in development (RL-81 and SF-3400 have been shelved right)? With the latest news that come out this 1Quarter do you still think any form of hearing restoration is over 15 years plus away? Maybe the brain retraining and repair components will come together, especially the neurotrophic repair/regen trials, to provide the ultimate solution to tinnitus?

Source?

 

[Jim51042]

@Rubenslash well I have contacted sciFlour and didn't hear back but this was a reply to one member (see thread) back in Feb of 2016 "We appreciate your interest in this compound. We have not begun human testing for the compound yet. We are not able to provide any forecast about when or if we will test this for tinnitus sufferers. We have a corporate policy that precludes us from sharing such information on an individual basis. I apologize but I cannot share more than that at this time. We wish you the best in your pursuits."
They still have it listed on their website under their pipeline but their recent news postings have been all about their ophthalmic compound SF0166. Again I think SF0034 would have an effect on T but the question is whether it will ever get to market.

In the RL thread it was mentioned that Dr. Tzounopoulos and everyone seemed pessimistic on human trials for a long time.

 

[Jim51042]

@Rubenslash did you know of any other K modulators in the works?

 

[Jim51042]

There is also a drug therapy under development that could be used in more spread out injuries

Was this a drug therapy, I read it was that they mentioned retro viruses so that would be gene therapy right? Has there been any updates on this research?

A more generic question is how many glial cells get damaged during noise?

 

[Cam Cam]

anyone else hear have noticeable hearing loss but has no trouble hearing in loud noises? for example my music sounds different and i have t and h but i hear my friends fine in busy restaurants and when there's plenty of backgound noise. Goes to show how far behind this field of work has been until recently. Dear god, the hearing aid industry need to fuck off because they are hindering the entire process. im all for biological solutions !

 

[Reinier]

for example my music sounds different and i have t and h but i hear my friends fine in busy restaurants and when there's plenty of backgound noise.

Does your audiogram show a dip? Or is it sloping at higher frequencies?

 

[Cam Cam]

Does your audiogram show a dip? Or is it sloping at higher frequencies?

there's my audiogram. kinda weird how i have a sharp dip in 1 ear only when im 99% sure mine was caused by headphones

 

[Samir]

Was this a drug therapy, I read it was that they mentioned retro viruses so that would be gene therapy right? Has there been any updates on this research?

Yes, gene therapy. But they are developing a drug therapy. I posted a link to a paper in Cell Stem Cell. It's a 4 years old paper (2013), but it explains some of the things they have been working on relating to gene therapy. By "they" I am of course talking about professor Gong Chen and his team Penn State University.

Updates? I think there is a new paper from 2016. I don't have it in front of me now, so I can't comment. I know I read it briefly and it looked like a continuation of their previous work. I'm sorry, I don't keep track of these things. I should probably start bookmarking and organizing these things. There was also a recorded interview with professor Gong Chen that I listened to, where he talked about his work. Again, no link. Sorry! But I'm sure you can find it if you google his name.

I have to say I love the way this guy thinks!

"Reactive glial cells are like police vehicles, ambulances, and fire trucks immediately rushing in to help".

He's just like me! Always using these analogies! I love doing that as well. It makes it dead simple for people to understand complex problems. But it takes a lot of insight into the subject for you to be able to explain it well to others.

A more generic question is how many glial cells get damaged during noise?

That's an excellent question! But it's also one that I have no answer to.

I don't know if you realize this, but professor Gong Chen is more focused on degenerative diseases of the central nervous system. In fact, one of his goals in life is to try to cure Alzheimer's disease. That's one big challenge! To say the least. It's his professional and personal goal in life. When you decide you want to tackle a challenge like that, you know it has to be personal. He's been working at it for years now, at least since the 1990s. He has not given up yet. It's reasonable to assume that this is why he is now one of the foremost experts in the world in this area of research.

So what does this mean for peripheral nervous system injuries? Everything! The way I see it, any new insight, any new knowledge is a win for everyone. I won't go into details. Just as an example, I will mention CRISPR. This system was born out of studies of a certain type of bacteria. Now the scientists can use these new insights for gene editing, among other things.

 

[Reinier]

@Cam Cam
I understand this looks like typical NIHL. Around 3-4 Khz.

Perhaps before your NIHL you were able to hear people in loud noises even better. It is difficult to compare if or when it changes slowly.

 

[Samir]

Goes to show how far behind this field of work has been until recently. Dear god, the hearing aid industry need to fuck off because they are hindering the entire process. im all for biological solutions !

I can understand your frustration. Many of us feel the same way you do. I know I had no idea that it was so lacking in many respects. Because I never had to visit any ear doctors. Not until I started having problems myself.

The thing is though, the hearing aid industry has been around since the early telephones. While it was only in 1989 (if memory serves me) that scientists discovered that chickens can regenerate their sensory hair cells. A lot of research has been done so far, key insights have been revealed, but we are still very early in.

I also sometimes wish that not just hearing aid industry, but also the cochlear implant industry would take the back seat. For the GFC166 GenVec trial, they are stealing away possible trial candidates from us. Which stretches out the whole process for us. There may be other potential companies who are awaiting to see how the GenVec trial goes before they jump into this business. But everything takes time...

 

[Samir]

kinda weird how i have a sharp dip in 1 ear only

Are you referring to the 3 kHz dip in the left ear?

im 99% sure mine was caused by headphones

Do you have any previous audiogram to compare to?

How old is this diagram?

I had a 30 dB dip at exactly 6 kHz. After 2 months, I took another test (at a different audiologist) and it showed 15 dB dip at 6 kHz. As if it had improved! But I think it's my brain that has compensated for the loss by increasing central gain.

Here's another "cool" fact, I was previously exposed to a sudden, loud "PEEEEEP" noise coming out of my computer sound card, at around 6 kHz. It's interesting because my tinnitus frequency is around 6 kHz.

So I don't have to relate my tinnitus frequency to an audiogram, I can relate it to the sudden noise I was exposed to by the stupid sound card, caused by some driver issue with the "latest and greatest" Windows 10.

Here's another fact! I was wearing earphones! I regret that now. But can't do anything about it, other than stop using earphones and headphones. I suggest you do the same.

Knowing what I know now, I can tell you that the audiogram is inadequate to assess inner ear damage. It's a subjective test and the brain plays its own tricks. It's good for detecting conductive hearing loss though, and middle ear pressure problems.

You seem to have normal middle ear pressure. Note that you have type A tympanogram. But one of your ears is little bit off, but not by much. I don't know what "Ad" tympanogram is. Near normal? I don't know.

Have you discussed the test results with your doctor or audiologist? You should discuss it with him or her.

It looks like you may have some conductive problem in the left ear. You can see that the bone conduction worked much better than air conduction. This may be caused by any pressure problem in the middle ear.

That's as much as I can tell you. It's not clear to me what is left ear and what is right ear tympanograf. If it's the left ear tympanograf that's off by a little, it may explain the air conduction fluctuation on the audiogram for the left ear.

These test results are not easy to read. Not only do you need to know how to read them, but this is one of those that is drawn by hand. The doctor or audiologist uses a printed template and plots the graph. So this can also depend on the penmanship of the doctor. Every place I have been to had these things plotted and printed by the computer. It makes it much easier to read. But this is not too bad either, but you should perhaps discuss it with the doctor.

I used to be obsessed by these audiograms! That's why I know how to read them. But as I said, they don't tell you much about the health of your inner ear.

Why do you think your headphones have caused your tinnitus?

 

[Cam Cam]

@Cam Cam
I understand this looks like typical NIHL. Around 3-4 Khz.

Perhaps before your NIHL you were able to hear people in loud noises even better. It is difficult to compare if or when it changes slowly.

is a dip at 3k an indication as well? just seems weird as it's only in one ear and the only loud noise came from headphones.

 

[Reinier]

is a dip at 3k an indication as well? just seems weird as it's only in one ear and the only loud noise came from headphones.

Yes to my knowledge this is a typical NIHL audiogram.
No way of knowing why one ear is more effected. My right ear is much worse than my left ear. The processes are so complex that it could very well be that one ear was more susceptible to NIHL.
By the way, I think your audiogram does not look so bad. Mine is much worse
And than there are people that have worse audiograms than my audiogram again.
It al is relative.

 

[Aaron123]

Could we get the discussion back to research related to hidden hearing loss? If people want to talk about audiograms, it would make more sense to start a thread in support.

 

[Jim51042]

More discussion of hidden hearing loss (note its in the second half of the interview).

 

[Reinier]

note its in the second half of the interview

19 minutes 35 seconds.

 

[Jim51042]

This is also the work of Gong Chen and his team. They showed that up to 90% of the glial cells were successfully converted into neurons

So I wanted to provide an update based on messaging between myself and Dr. Chen. Does anyone know if this transcription factor is under study for the ear at any labs or companies?

Dear Dr Chen,

Thank you for your many years of work and advances in the field of
neurology. I know your work has mainly been focused on Alzheimer's disease, ALS, etc. However within the past decade Dr. Liberman at Harvard Medical School and others have confirmed that damage to neural
connections within the ear plays a big role hearing loss and tinnitus. I know the Cochlear nerve is not technically part of the CNS but I was wondering whether your transcription factor NeuroD1 would be effective in noise damaged ears. I believe there are already safe delivery mechanisms which are self contained to the ear. Thank you for any insights and for all you've done to further health research.

Sincerely,
Jim

Dear Jim:
Thank you for your inquiry. I believe our technology should be useful for regenerating auditory neurons, either with NeuroD1 or with similar transcriptional factors. Someone should do it. I have shipped our NeuroD1 around the world. Hope it will produce positive results in the auditory field.

Best wishes,
Gong

 

[Aaron123]

Interesting non-technical article on HHL and auditory testing by one of the authors of the paper mentioned in the original post: http://journals.lww.com/thehearingj..._the_Routine_Audiological_Test_Battery.3.aspx

 

[Jim51042]

More awareness on testing hearing within noise

http://www.npr.org/sections/health-...in-boot-camp-using-music-to-ease-hearing-loss

 

[Frédéric]

Two interesting articles about hearing in noise :
http://journals.lww.com/thehearingj...in_Noise___The_Brain_Health_Connection.2.aspx
http://journals.lww.com/thehearingj...a_Noisy_World___Problems_and_Solutions.3.aspx

 

[HomeoHebbian]

Not sure if this was brought up, but this is a paper from a very productive, reputable lab that is not at Mass. Eye and Ear that casts some doubt on the recent findings in human subjects from Maison and Liberman -

Tinnitus with a normal audiogram: Relation to noise exposure but no evidence for cochlear synaptopathy.
Guest H, Munro KJ, Prendergast G, Howe S, Plack CJ.
Hear Res. 2017 Feb;344:265-274. doi: 10.1016/j.heares.2016.12.002. Epub 2016 Dec 11.

Liberman and his colleagues have been pushing the idea that there are better audiological tests can be developed to measure the physiological basis for difficulties processing speech and noise: 1) The envelope following response, 2) a specific variant of the middle ear muscle reflex test that uses a Wideband elicitor, 3) the amplitude of ABR wave 1, or the ratio of the summating potential to wave 1 amplitude (see references below for each). The paper from Plack and colleagues had no trouble finding subjects with normal audiograms but complaints of tinnitus and difficulty following speech in noise. But they were unable to replicate previous findings that the envelope following response or ABR wave 1 amplitude could predict these deficits.

There are some reasons why the Liberman paper in PLoS One and the Plack paper might have come up with different results. But it is equally clear that cochlear synapse loss is far from a >direct< cause for difficulties processing speech in noise. A critical trigger, perhaps, but not a proximal cause. This is the perception of sound we are talking about here and the neural basis for sound perception is much further downstream, in auditory processing centers of the cerebral cortex.

Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses.
Shaheen LA, Valero MD, Liberman MC.
J Assoc Res Otolaryngol. 2015 Dec;16(6):727-45.

The middle ear muscle reflex in the diagnosis of cochlear neuropathy.
Valero MD, Hancock KE, Liberman MC.
Hear Res. 2016 Feb;332:29-38.

Toward a Differential Diagnosis of Hidden Hearing Loss in Humans.
Liberman MC, Epstein MJ, Cleveland SS, Wang H, Maison SF.
PLoS One. 2016

 

[Aaron123]

Nice question and answer with Sharon Kujawa about cochlear synaptopathy: http://www.audiologyonline.com/articles/20q-cochlear-synaptopathy-interrupting-communication-20946

 

[HomeoHebbian]

Massachusetts Eye and Ear just received a large award from the NIH to develop new functional tests to reveal the pathology underlying "hidden hearing loss". This award binds four research groups (one project per group) into a clinical research center.

Project Number: 1P50DC015857-01A1 Contact PI / Project Leader: KUJAWA, SHARON G
Title: COCHLEAR SYNAPTOPATHY: PREVALENCE, DIAGNOSIS AND FUNCTIONAL CONSEQUENCES Awardee Organization: MASSACHUSETTS EYE AND EAR INFIRMARY
Project Start Date: 2-AUG-2017 Project End Date: 31-JUL-2022

Cochlear synaptopathy is the loss of nerve connections between the sensory cells and the brain, which occurs in noise-damaged and aging ears. Although not detected by the threshold audiogram, this nerve damage is likely a major contributor to difficulties understanding speech in a noisy environment and may also instigate changes resulting in tinnitus and hyperacusis. Our Research Center aims to understand the prevalence of cochlear synaptopathy, measure/infer its consequences to suprathreshold sound processing, and to identify diagnostic markers. Therapies to reconnect nerves and sensory cells are on the horizon, and proper diagnostics are key to the design of clinical trials. The results are important to the public health, because noise- and ototoxic drug exposures may be damaging the ear well before the effects are seen in the threshold audiogram.

Abstract Text:
Overall Project Summary New insights from animal studies of noise-induced and age-related hearing loss suggest that the most vulnerable elements in the inner ear are the synaptic connections between hair cells and sensory neurons. This primary neural degeneration, also called cochlear synaptopathy, does not elevate thresholds. Thus, it can be widespread in ears with intact hair cell populations and normal audiograms, where it has been called "hidden" hearing loss. It likely contributes to difficulties understanding speech in a noisy environment and may be an instigating factor in the generation of tinnitus and hyperacusis. Cochlear synaptopathy may also be widespread in acquired sensorineural hearing loss of other etiologies and degrees of hair cell damage. Thus, it may be a major contributor to the well-known differences in auditory performance among people with identical audiometric patterns of "overt" hearing loss. Our Research Center aims to take these paradigm-shifting ideas from animal models to human subjects. Based on the synthesis of many research threads from the study of overt and hidden hearing loss, we have devised a set of physiological, electrophysiological and psychophysical tests of hearing and cochlear function that we believe are most powerful in the diagnosis and understanding of cochlear synaptopathy in human subjects. In Project 1, we apply this test battery to gerbils exposed to noise or ototoxic drugs and test their diagnostic power by directly measuring the underlying cochlear histopathology in cases of overt or hidden hearing loss. In Project 2, we use immunostaining to directly assess the prevalence of cochlear synaptopathy in human temporal bones from subjects with overt or hidden hearing loss with a range of etiologies. In Project 3, we study hidden hearing loss in college students by applying the test battery to subjects with normal audiograms but a broad range of reported and measured sound exposures. In Project 4, we assess older adults with overt hearing loss by applying the tests to a subject pool with carefully matched down-sloping audiograms and by characterizing training-based improvements in speech-in-noise performance as reflected at different peripheral, brainstem, midbrain and cortical levels. Our preliminary studies of young adults show clear signs of hidden hearing loss in a group with repeated exposure to high-level music, suggesting the importance of this phenomenon to the public health. The success of neurotrophin-based approaches to the treatment of cochlear synaptopathy in animal models suggests that therapies may be on the horizon. Thus, the need for better understanding of the prevalence, diagnosis and functional consequences of cochlear synaptopathy is clear.

 

[Reinier]

This is very good news, I think.
Goodbye subjective, welcome objective!
I specially like this:

The success of neurotrophin-based approaches to the treatment of cochlear synaptopathy in animal models suggests that therapies may be on the horizon. Thus, the need for better understanding of the prevalence, diagnosis and functional consequences of cochlear synaptopathy is clear.

 

[Aaron123]

Interesting paper that finds some pretty significant increases in ability to understand speech in noise as a result of auditory training. Importantly, it is randomized, placebo controlled - with what seems to be a clever control group, and double-blind. Unfortunately, the results were not durable though obviously additional training over time might address that.

Audiomotor Perceptual Training Enhances Speech Intelligibility in Background Noise

Highlights

• Elderly subjects trained for 8 weeks on a computerized audiomotor interface
• Speech-in-noise intelligibility in challenging listening conditions improved by 25%
• Generalized training benefits were compared to and exceeded placebo effects
• Inhibitory control ability and game strategy predicted individual training benefits

Summary
Sensory and motor skills can be improved with training, but learning is often restricted to practice stimuli. As an exception, training on closed-loop (CL) sensorimotor interfaces, such as action video games and musical instruments, can impart a broad spectrum of perceptual benefits. Here we ask whether computerized CL auditory training can enhance speech understanding in levels of background noise that approximate a crowded restaurant. Elderly hearing-impaired subjects trained for 8 weeks on a CL game that, like a musical instrument, challenged them to monitor subtle deviations between predicted and actual auditory feedback as they moved their fingertip through a virtual soundscape. We performed our study as a randomized, double-blind, placebo-controlled trial by training other subjects in an auditory working-memory (WM) task. Subjects in both groups improved at their respective auditory tasks and reported comparable expectations for improved speech processing, thereby controlling for placebo effects. Whereas speech intelligibility was unchanged after WM training, subjects in the CL training group could correctly identify 25% more words in spoken sentences or digit sequences presented in high levels of background noise. Numerically, CL audiomotor training provided more than three times the benefit of our subjects' hearing aids for speech processing in noisy listening conditions. Gains in speech intelligibility could be predicted from gameplay accuracy and baseline inhibitory control. However, benefits did not persist in the absence of continuing practice. These studies employ stringent clinical standards to demonstrate that perceptual learning on a computerized audio game can transfer to "real-world" communication challenges.

Link to paper: http://www.cell.com/current-biology/fulltext/S0960-9822(17)31178-8