Evidence of Cochlear Neural Degeneration in Normal-Hearing Subjects with Tinnitus

[WillBeNimble]

Nothing says they can't try the neurotrophins this study mentions. Wouldn't it be something if they just have to replicate Spiral Therapeutics and Rinri Therapeutics' pathways to the ear, get some neurotrophins in there and that speeds up the painfully slow nerve repair.

 

[UKBloke]

I had a couple of hours spare last night and read the study. Aside from perhaps some interesting and seemingly new ways of measuring signal waves I came away feeling thoroughly underwhelmed. By their own admission [my emphasis]:

It is also important to note that CND, irrespective of OHC loss, is unlikely to be sufficient to evoke the central changes necessary for the development of a tinnitus percept

The following statement impacted me more, however:

additional failures in central auditory pathways (e.g. failure of the thalamic gating) may be necessary for the development of an anomalous perception

Thus we swing back to the gating model discussed at length in Rauschecker's 2010 paper.

It's one thing to develop fresh and novel ways of measuring various brain-wave outputs but in terms of taking us a step closer to providing a sensible model of how and why tinnitus is generated I don't think this study cuts the mustard. CND instinctively just feels like another trigger mechanism and not the actual quirk within our brains that creates these noises.

 

[Nick47]

Thus we swing back to the gating model discussed at length in Rauschecker's 2010 paper.

Then why does a cochlear implant work well, even in a soundproof booth where external sounds are not present? As far as I'm aware, the implant bypasses many of the nerves. Does the gating just restore itself?

 

[UKBloke]

Then why does a cochlear implant work well, even in a soundproof booth where external sounds are not present? As far as I'm aware, the implant bypasses many of the nerves. Does the gating just restore itself?

I've been working on a hypothesis that the output of the (thalamic) gating mechanism is actually a control signal (voltage) for an upstream neural (tinnitus) filter.

Logical gating mechanisms (FWIW the model I'm in the process of developing is really simple and based on a logical 'AND' system) require a combination of input signals to provide a specific output signal. Importantly, if any of the input signals fail, the output will fall to zero, which in the case of a tinnitus model would result in there being a loss of control signal to power the upstream tinnitus filter.

A model like this doesn't care how much a person assaults their ears. If the gating system is robust, the person can beat up their ears relentlessly; the positive output of the gate will always power the upstream filter. At this point in time I believe those of us with tinnitus are born with a (potentially genetic) defect around the input of the gating system, which inevitably leads to tinnitus for the reason mentioned.

In direct answer to your question, I theorise that the electrical current from a cochlear implant raises the input voltage levels on the logical gates with the net effect of powering (or at least semi-powering) up the upstream neural filter that keeps tinnitus at bay. I also believe this is what Hamid Djalillian's work is leading towards, which is why I'm quite bullish about it.

Again, a system like this is the only explanation I've been able to think of as to why some people with hearing damage experience tinnitus, whilst others don't. The issue is neural in nature.

 

[Nick47]

I also believe this is what Hamid Djalillian's work is leading towards, which is why I'm quite bullish about it.

Yes, I'm bullish about it too. I'm pissed off, given the good results from probes that we are not pursuing this as research in the UK. It would also be ideal for companies like Cochlear UK and Med-El to pick up and develop this technology. It will have a much bigger client base than those who are cochlear implant candidates.

 

[gameover]

Okay, so here is my problem with it: what does "nerve loss" mean? Like you have totally fine outer hair cell & inner hair cell situation in cochlea, and all of a sudden the nerve bundle between the cochlea and the brain gets damaged? Is this what they mean? I find this extremely unlikely to be a common thing, I would equal this to basically something like having tumor growth on the nerve. And why is tinnitus the only symptom? Why not balance issues?

In my opinion (and of course I am not an MIT researcher), most of us have tinnitus simply because our hair cells got damaged and lost synapses which resulted in loss of signaling between the hair cells and brain, hence we got tinnitus.

Synapses are very important and this is what connects our hair cells to the nerve bundle.

I think that in order to cure most cases with tinnitus, we would need to regenerate hair cells + synapses, which would restore communication between sensor (hair cells) and main board (brain) and that would get rid of the check engine light (tinnitus).

I met the researcher (Dr. Maison) earlier this year, a few months after my acoustic trauma. Based on what I understood, he was saying that the nerve damage can happen alone in response to loud sound, as if the nerve connections themselves cannot withstand the force of high sounds levels. That's not intuitive.

Personally I wonder if a low frequency bone conducted noise plays a role in whacking these nerve connections. My exposure was to an air hammer in a close vicinity to my head that I hand held. An assault on all frequencies, not to mention physical vibrations through my hands/arms. Idiot, yes. Plus I was recovering form a sinus infection which probably inhibited healing or aggravated the injury.

I agree. Nerve repair should be on higher on the list of things to investigate rather than hearing repair. Not saying hearing restoration wouldn't be nice but I've been noticing more and more articles on nerve repair discussion and brain trimming than anything else.

Agree. I give little shit about ability to hear compared to tinnitus or hyperacusis. All I want is to not have tinnitus and hyperacusis. I guess being deaf or seriously haring impaired should render hyperacusis moot.

 

[Joe Cuber]

I've been working on a hypothesis that the output of the (thalamic) gating mechanism is actually a control signal (voltage) for an upstream neural (tinnitus) filter.

Logical gating mechanisms (FWIW the model I'm in the process of developing is really simple and based on a logical 'AND' system) require a combination of input signals to provide a specific output signal. Importantly, if any of the input signals fail, the output will fall to zero, which in the case of a tinnitus model would result in there being a loss of control signal to power the upstream tinnitus filter.

A model like this doesn't care how much a person assaults their ears. If the gating system is robust, the person can beat up their ears relentlessly; the positive output of the gate will always power the upstream filter. At this point in time I believe those of us with tinnitus are born with a (potentially genetic) defect around the input of the gating system, which inevitably leads to tinnitus for the reason mentioned.

In direct answer to your question, I theorise that the electrical current from a cochlear implant raises the input voltage levels on the logical gates with the net effect of powering (or at least semi-powering) up the upstream neural filter that keeps tinnitus at bay. I also believe this is what Hamid Djalillian's work is leading towards, which is why I'm quite bullish about it.

Again, a system like this is the only explanation I've been able to think of as to why some people with hearing damage experience tinnitus, whilst others don't. The issue is neural in nature.

I'm trying to understand the model you're working on. I might not entirely follow, but I'm wondering if you think such a model could explain why some folks such as myself experience intermittent tinnitus, where tinnitus is either switched on for the day or switched off. In my case in particular, I'll have one loud volume day, followed by 2-5 mild volume days, then a 1-2 quiet days before it repeats.

 

[gameover]

I think reactivity is caused by hair cells that are damaged/vulnerable but not yet broken. These hair cells are much more susceptible to noise trauma. Over time they either break down (worsening early on) or stabilize (less reactive/strengthened) but are still easy to break. They are essentially connecting/disconnecting continuously from the auditory nerve, or not catching the sound signals well causing fluctuations in tinnitus - like a bad phone charger plug in a phone.

Damaged hair cells could break easily from loud sounds or cause long spikes - one loud sound causes the same effect as going to a festival for 16 hours with normal ears.

It's my theory and not backed by science.

I really like your theory. It makes a lot of sense. Maybe a case or Occam's Razor. Stupid hair cells work as "mechanical devices". It makes sense that after damage they are compromised and do not react/convey signals as they do normally. And then you have the nerve damage that may or may not accompany this.

But then you have this:

OK, I had very reactive tinnitus with HORRIBLE sound distortions. And I mean horrible. This happened 18 days after I stopped Mirtazapine, after Fluoroquinolones damaged my brain. At the onset of this, I got back to using Mirtazapine for sleep (BIG MISTAKE). Over time it got worse and worse.

I was about to end it, before my father convinced me to go to a University Hospital to have my ears checked out.

Turned out, my hearing was perfect indeed with perfect DPOAEs. Can hear up to 20 kHz no problems... It wasn't ototoxicity that was the cause, it was neurological...

Immediately after I dropped Mirtazapine cold turkey (still have problems to this day by doing it but I had to), the distortions were COMPLETELY gone, and the reactivity only happens after I get home and lie down on the bed. My tinnitus goes up for 5 minutes or so before settling down. But even that does not happen all the time these days.

Meaning, reactivity might have more than one cause.

Hearing up to 20 kHz no problems! Ha. I think when I did a home hearing test like maybe 10+ years ago when I was in my mid-30s I could not hear anything above 13-14 kHz if I remember correctly. Not sure exactly but something in that range. I know my wife could hear higher, and my kids could hear everything. I did not study the topic thoroughly, but remember reading it was deemed "normal".

So a pure brain malfunction in your case caused by meds, evidently. Or maybe something about the synapses, too, in a way that does not prevent them from conveying signals from apparently intact hair cells, but yet the nerves misfire resulting in reactivity?

Nobody knows. We are barely scratching the surface of understanding how the brain works, and when it comes to the auditory parts, it feels like we are barely out of the stone age. Long way to go.

 

[UKBloke]

I'm trying to understand the model you're working on. I might not entirely follow, but I'm wondering if you think such a model could explain why some folks such as myself experience intermittent tinnitus, where tinnitus is either switched on for the day or switched off. In my case in particular, I'll have one loud volume day, followed by 2-5 mild volume days, then a 1-2 quiet days before it repeats.

The model definitely outlines a description for intermittent tinnitus. Up until now though I've only really considered activation of the upstream filter in the binary sense, i.e. on or off.

If the filter behaved in a more analogue way, like a fader, then this could account for quiet days/loud days but that's not something I've specifically factored into the current model (that incidentally I hope to have ready for posting as soon as I can make some proper edits).

 

[BB23]

Hearing up to 20 kHz no problems! Ha. I think when I did a home hearing test like maybe 10+ years ago when I was in my mid-30s I could not hear anything above 13-14 kHz if I remember correctly. Not sure exactly but something in that range. I know my wife could hear higher, and my kids could hear everything. I did not study the topic thoroughly, but remember reading it was deemed "normal".

So a pure brain malfunction in your case caused by meds, evidently. Or maybe something about the synapses, too, in a way that does not prevent them from conveying signals from apparently intact hair cells, but yet the nerves misfire resulting in reactivity?

Nobody knows. We are barely scratching the surface of understanding how the brain works, and when it comes to the auditory parts, it feels like we are barely out of the stone age. Long way to go.

I mean, go on Visual Snow Syndrome (VSS) or HPPD boards. Some people, aged as young as 13, take a hit of weed, or LSD, and end up with PERMANENT HPPD (VSS with visual hallucinations), with tinnitus.

Are you going to tell me weed or LSD gave them hearing loss?

I believe hearing loss isn't a requirement for tinnitus.

OH AND HPPD FOLKS ARE LUCKIER THAN US. You know why? At least there was one doctor who tried to actually research and solve this condition, instead of some scammer like Jastreboff who basically just says to "deal with it" and gets critical acclaim for his work.

 

[Utdmad89]

OH AND HPPD FOLKS ARE LUCKIER THAN US. You know why? At least there was one doctor who tried to actually research and solve this condition, instead of some scammer like Jastreboff who basically just says to "deal with it" and gets critical acclaim for his work.

So Dr. Shore isn't researching tinnitus?

 

[gameover]

Are you going to tell me weed or LSD gave them hearing loss?

I am not saying that, maybe I did not write up my post coherently (screaming tinnitus does not help, you know). The damage can happen to many parts of the brain, including auditory nerves, or some other parts that interact with the auditory cortex or whatever creates perception of sound. It's very complex, and that's why we are so helpless.

Let's hope the Shore device finally comes out and maybe it helps some people. I am not sure I will be able to last till then, though I am trying.

 

[BB23]

So Dr. Shore isn't researching tinnitus?

The research should have started decades ago. Thanks to Jastreboff, it didn't.

I am not saying that, maybe I did not write up my post coherently (screaming tinnitus does not help, you know). The damage can happen to many parts of the brain, including auditory nerves, or some other parts that interact with the auditory cortex or whatever creates perception of sound. It's very complex, and that's why we are so helpless.

Let's hope the Shore device finally comes out and maybe it helps some people. I am not sure I will be able to last till then, though I am trying.

No, I was trying to make a general statement with the use of the question, it wasn't aimed at you.

One of the theories of HPPD is, serotonergic activity leads to glutamate excitotoxicity, leading to the loss of GABAergic interneurons. The healing that takes place after is due to neuroplasticity.

Of course nothing has been proven.

There might be some loss in the brain indeed with tinnitus as well. If there is loss, I don't know what needs to be done...

BHV-7000 is my last hope...

 

[EatMoTacos]

I honestly don't think you need to have noise exposure to have tinnitus. The use of daily chemicals, medicines, and even fumes can lead to neural issues.

Look at some of the safety labels for chemicals we might use daily, or just paint fumes! Some state being able to cause neural issues which makes me believe is the reason people with "normal" hearing hearing can still have tinnitus.

Drugs, including recreational drugs, can alter neural pathways in the brain, and thus affect the DCN. The entire brain is all interconnected. I've read that stroke patients, when going through physical therapy, basically regain movement using different parts of their brains. That's why meditation alone can alter the brain in a sense. The brain is very plastic.

 

[NikoD]

Nothing says they can't try the neurotrophins this study mentions. Wouldn't it be something if they just have to replicate Spiral Therapeutics and Rinri Therapeutics' pathways to the ear, get some neurotrophins in there and that speeds up the painfully slow nerve repair.

Spiral Therapeutics' drug delivery system to the cochlea which lasts a controllable time, in my opinion, will be one of the biggest breakthroughs and progress in hearing therapy.

Yes, it's no cure but it's a key step. We could see trials using Spiral Therapeutics' system that delivers drugs in a proven, repeatable, reliable way which has never happened before. Imagine trials where you know with a degree of certainty the drug actually made its way to the therapy site, and was in situ for x period of time vs. what right now is a guessing game, hoping the drug made contact with the RWM, stayed there long enough and didn't drain into the Eustachian tube

I firmly believe fixing this part of the process (delivery) will be a key step to solving tinnitus and hearing loss. The round membrane route is possibly the only way to the cochlea / perilymphatic system in humans, and is non-invasive and most direct.

I wish they'd hurry up or release more information so I could support them.

 

[gameover]

I honestly don't think you need to have noise exposure to have tinnitus. The use of daily chemicals, medicines, and even fumes can lead to neural issues.

Look at some of the safety labels for chemicals we might use daily, or just paint fumes! Some state being able to cause neural issues which makes me believe is the reason people with "normal" hearing hearing can still have tinnitus.

Drugs, including recreational drugs, can alter neural pathways in the brain, and thus affect the DCN. The entire brain is all interconnected. I've read that stroke patients, when going through physical therapy, basically regain movement using different parts of their brains. That's why meditation alone can alter the brain in a sense. The brain is very plastic.

Of course you don't, but noise is clearly #1 issue. It can cause tinnitus alone or be a contributing factor. There is the question of hearing deterioration happening gradually over a long period of time that "primes" you for tinnitus/hyperacusis. I've had misophonia for a long time. Was it hyperacusis lurking in there?

Or it is a combination of factors at the given moment. I had self-inflicted acoustic trauma while I was recovering from some nasty cold/sinus infection. Was it a factor? I believe it was, but I have no proof. If nothing else, it muffled my hearing so the noise I was exposing myself to, did not seem that loud.

 

[EatMoTacos]

Spiral Therapeutics' drug delivery system to the cochlea which lasts a controllable time, in my opinion, will be one of the biggest breakthroughs and progress in hearing therapy.

This right here is key. How it's delivered.

 

[Utdmad89]

The research should have started decades ago. Thanks to Jastreboff, it didn't.

No, I was trying to make a general statement with the use of the question, it wasn't aimed at you.

One of the theories of HPPD is, serotonergic activity leads to glutamate excitotoxicity, leading to the loss of GABAergic interneurons. The healing that takes place after is due to neuroplasticity.

Of course nothing has been proven.

There might be some loss in the brain indeed with tinnitus as well. If there is loss, I don't know what needs to be done...

BHV-7000 is my last hope...

Dr. Shore did start decades ago. She has therapy that others are researching as well. It's not true that no one is researching treatment/cure for tinnitus. It isn't helpful to state otherwise.

 

[UKBloke]

I honestly don't think you need to have noise exposure to have tinnitus.

There was a chap who posted here recently that I meant to converse with because his story was so curious. His tinnitus (that is chronic if I remember correctly) had started after he cracked his head on a wooden beam in his house.

Conversely there was also an account some years ago of a fella's tinnitus (that he'd experienced for decades) disappearing completely after he suffered a stroke.

Both of these cases point towards (I believe) a fundamentally neural contribution to the generation/de-generation of tinnitus.

 

[dan]

My father has profound hearing loss, with no tinnitus.

Most people have hearing loss with no tinnitus.

I have NO detectable hearing loss. Yet I got tinnitus.

Yes, because tinnitus is a brain filtering pathology, otherwise 95% of adults would have tinnitus! But they don't!

 

[Nick47]

My father has profound hearing loss, with no tinnitus.

Yes, but was it sudden hearing loss?

 

[WillBeNimble]

I wish these tests were ready and sort of fast tracked. Mainly because this might actually help me the best.

 

[BB23]

Yes, but was it sudden hearing loss?

I have thought a long time on how I should answer your question. During that time I also came up with some questions for you, I want to pick your brain on some stuff...

As you know, many people even on Tinnitus Talk, developed tinnitus WITHOUT an immediate trigger. Either they developed it one night during sleep or sitting in silence reading a book etc.

As for my father, he is practically deaf IMO. Sudden hearing loss isn't the case with him. He has trouble understanding speech in noisy environments, he can't hear low decibel sounds, he can't hear high frequency sounds (I tested this myself) and he has trouble understanding normal speech as well at times. On the other hand, he takes lots of meds that should act as triggers for tinnitus induction (heart meds, Aspirin etc.), yet they don't. He has had multiple heart surgeries (stent insertions, bypass). He has other health issues, he can't get proper sleep at night due to his chronic acid reflux, and he has lived a life full of stress. He hears complete silence.

My questions for you are:

• Why does tinnitus heal in some patients, even when the hearing loss remains? Spontaneous recovery of potassium channels? Healing of the nerves?
  
  
• Why does it get worse for some people without any more triggers like another acoustic trauma?

I have started to believe this stupid condition might be another form of a progressive neurodegenerative disease like Parkinson's or could be a result of mitochondrial damage/loss of inhibitory neurons, in other terms, a brain disease. I mean, people with hearing loss, who got tinnitus from benzos, heal, when they shouldn't, since they had prior hearing loss.

As I said. XEN1101 is my last hope. If it doesn't work, not sure what else to do, I don't think I'll stick around with this pain and constant electrical brain torture.

 

[NikoD]

I wish these tests were ready and sort of fast tracked. Mainly because this might actually help me the best.

I think we need an activism thread so US / UK / EU members can reach out to their political representative's with a templated letter, something about funding and research, fast tracking. Maybe there's already a thread?

It would be good if all politicians were aware of how widespread the issue is, designate funding and maybe even help fund outreach forums and programmes such as Tinnitus Talk, which do an amazing job at helping members like us understand!

 

[Nick47]

My questions for you are:

• Why does tinnitus heal in some patients, even when the hearing loss remains? Spontaneous recovery of potassium channels? Healing of the nerves?
  
  
• Why does it get worse for some people without any more triggers like another acoustic trauma?

I'm far from the front of all knowledge. All I know is from studies I've read.

For those that heal it will be down to either nerve repair or reorganizing of the brain to filter it out.

As for it getting worse, well you can protect hearing all you like. However, age, infection and stress all cause damage to us in general. There's also lifestyle factors like smoking, alcohol, processed foods and environmental factors. Then there are genetics, a new area of research in general.

It seems damage to the inner ear is a prerequisite most of the time and something like stress of medication can then be the trigger, but not the direct cause.