Chronic Tinnitus Treatment Challenges

Chronic tinnitus differs from acute tinnitus in several key areas. That's why we need drugs that address tinnitus in both its acute and chronic stages. Here's a study from 2011 based on neural networking that evidences how the dysfunction in brains of chronic tinnitus sufferers differs from those with acute tinnitus.


The neural network of phantom sound changes over time: a comparison between recent-onset and chronic tinnitus patients.
Vanneste S, van de Heyning P, De Ridder D.

Source
TRI Tinnitus Clinic, Brai²n, TRI & Department of Neurosurgery, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. sven.vanneste@ua.ac.be

Abstract
Tinnitus is characterized by an ongoing conscious perception of a sound in the absence of any external sound source. Chronic tinnitus is notoriously characterized by its resistance to treatment. In the present study the objective was to verify whether the neural generators and/or the neural tinnitusnetwork, evaluated through EEG recordings, change over time as previously suggested by MEG. We therefore analyzed the source-localized EEG recordings of a very homogenous group of left-sided narrow-band noise tinnitus patients. Results indicate that the generators involved in tinnitus of recent onset seem to change over time with increased activity in several brain areas [auditory cortex, supplementary motor area and dorsal anterior cingulate cortex (dACC) plus insula], associated with a decrease in connectivity between the different auditory and nonauditory brain structures. An exception to this general connectivity decrease is an increase in gamma-band connectivity between the left primary and secondary auditory cortex and the left insula, and also between the auditory cortices and the right dorsal lateral prefrontal cortex. These networks are both connected to the left parahippocampal area. Thus acute and chronic tinnitus are related to differential activity and connectivity in a network comprising the auditory cortices, insula, dACC and premotor cortex.

 

It's probably why my tinnitus originally started as a loud ringing in my left ear for 4 days and then turned into the more quiet high pitched hiss after that.

 

Mine has also changed from being in my ear and maskable to being in my head and utterly unmaskable. Everyone knows that tinnitus becomes more entrenched in your brain as time progresses. That's why I am that glad that acute tinnitus is being addressed in drug trials--ongoing and potential.

Chronic tinnitus is impossible to treat, but why? This is one study attempting to answer that question. De Ridder has done similar studies. And unless you're a medical research scientist, De Ridder's studies are difficult to read and understand. Highly technical and theoretical, De Ridder is trying to map out the tinnitus brain--focusing on its abnormal oscillatory patterns. This information may end up being critical for future treatment modalities or even in perfecting current ones, like rTMS or deep brain probes. The research may even have implications for drug development.

Here's another De Ridder study comparing the brain wave patterns and interconnectedness between tinnitus sufferers and those people with musical hallucinations. (Actually, some people with tinnitus also have this disorder--which is a variant of "ear worms," i.e., when you can't get a song out of your head.)

Examining this study in the context of De Ridder's work, I understand its raison d'etre. And, while I would rather him research something with more practical applications, like the study cited above, it's good to know he's determined to understand every part of the tinnitus brain.

Here's the musical hallucination and tinnitus study for anyone interested:

http://www.ncbi.nlm.nih.gov/pubmed/23732881

 

Do they? Serious question: is this a generally accepted phenomenon?

 

Yes. Sadly, the brain fails to compensate for the damage and plasticizes poorly. This is why people can leave a concert with ringing and in the next couple of days be back to normal, sans a little hearing. The brain is screwing up somewhere.

My dad's hearing is shitty, never wore hearing protection in his life, and he doesn't have tinnitus. He's had ringing after noise exposure, but never permanent.

We need to know why the majority of people don't develop chronic subjective tinnitus.

 

I would say that your brain most likely loses the ability to spontaneously adapt after a certain point to the tinnitus. But to say it becomes more entrenched as time goes by, I disagree with that. I don't think chronic tinnitus is impossible to treat, either. Science may not have the answer yet, but tinnitus does not just "happen" with no cause. Just becaue a doctor can't figure out what the cause is doesn't mean there isn't one. There's a definite biochemical pathway sustaining the hyperactivity seen in the brains of tinnitus sufferers. All processes in the body that take place have mechanisms to up-regulate and down-regulate the process. The question isn't whether it's treatable, it's more just finding what mechanism is sustaining that hyperactivity, and why isn't there something that naturally down-regulates that unneeded hyperactivity?

Our problem is that the brain and auditory system remain poorly understood in comparison to the rest of the body. The brain is an incredibly complex system.

 

Hi Hudson,

I do believe tinnitus is treatable. I need to be more cautious with my phrasing. And I think that "entrenched" was the wrong word. It sounds too dire, and I didn't mean that. Perhaps, a better word would be "sticky." Your brain adjusts to the tinnitus, and these the maladaptive changes become the new normal. The reason why I say this is that rTMS studies point out that the longer one has tinnitus, the less responsive it becomes to treatment. De Ridder also talks about how tinnitus duration affects the responsiveness to treatment. (I believe he was citing his brain probe studies.) But being more difficult to treat does not mean tinnitus is untreatable! Curing chronic tinnitus will probably be more challenging than curing acute tinnitus. And so I worry that medical researchers--if they fail on the first or second attempt at drug development--will give up and move on. Merz, for example, didn't exactly fail in their drug, but the results weren't successful enough to continue development. I wouldn't want Autifony to abandon all efforts if their drug disappointed. These stories are my biggest fear. (Venture capital funding for drug development has also declined over the past several years. That's because money can be made more quickly in other areas, like software and the cloud.)

I like to think of the following analogy, which is imperfect but applicable: If two people break their legs, one get it set immediately and the other waits a year. The one who waits can still be cured. But it will be more difficult because the bone has healed the wrong way. This is the same for chronic vs acute tinnitus: we can be fixed, but it may be more complex. And since medical science has a poor understanding of all neurological disorders (unlike orthopedists who have things figured out), it may take a while for a cure.

Because the brain is so complex and so poorly understood, I do believe in supporting tinnitus research and will support the TRI. Bigger studies, like the US's proposed mapping of the brain, are also needed. It's about time the government devoted it's efforts to brain studies. Progress in tinnitus is slow because researchers are still figuring out the basic science.

 

This is just a gut feel based on 55 years of life and seeing how things work. I doubt that chronic tinnitus is something that becomes harder to treat the longer it exists. I'm guessing that there is that sense only because whatever success that has been achieved with T treatments like rTMS are at least partially biased by improvements that would have come from just habituation. Since many people with acute T will see spontaneous improvement within the first 6 -12 months this shows up as treatment success that may have in fact been habituation. The quantity of spontaneous improvers among the population of chronic T suffers is bound to be lower than amoung acute suffers, so this makes it appear as if acute T is easier to treat.

The other reason that I don't think the passage of time makes any difference is that for most people tinnitus happens quickly (at least that is my sense of things from reading all the stories in this forum). One minute its not there, and the next it is. It typically is not a gradual progression. My experience in life indicates that physical changes that happen abruptly typically can be resolved abrubtly. If tinnitus came on slowly - started faintly then the volume increased over time - then I would be more inclined to believe that it becomes more entrenched with time - that it is the result of some malfunction that grows with time. While the results of fMRI studies suggest that tinnitus is the result of auditory neurons reaching into parts of the brain that they normally do not, I'm not convinced this is some neuronal growth thing. I suspect the reaching out is more of a chemical signalling thing rather than a rogue nerve growing where it normally doesn't. If it were the latter, then it would seem to me to that it would be a gradual thing - symptoms worsening gradually.

Of course, I'm just having fun hypothesizing for the sake of hypothezising. I've nothing more to hang my hat on than my gut feel and very unrefined heuristics from a lifetime of observations. I think the odds are that tinnitus is entirely a neuro chemistry thing. Something is not clearing the presence of some molecule (or correcting the absence of some molecule) and it is that imbalance that is interfering with normal neuron function. Once we figure out how to reset things chemically, the problem will go away. I'm not convinced that acute and chronic tinnitus are all that different, but I concede that there may be something more going on in the acute phase that instigates the whole affair, and if that something is interrupted early then less damage is done and the problem is more likely to correct itself spontaneously.

 

Thanks Hudson and mick for your insights! It's important to stay positive and well informed.

 

Mick I completely agree with everything you said. My tinnitus is the same since day 1 it's now 9 months later. I also agree that it's chemical

 

then how can people suddenly lose their T after years?

 

Because not everyone's tinnitus is due to hearing loss. Many could be neck problems, drugs, chemical imbalances, etc.

 

yes, but does the brain care what causes the sound? if it gets "stuck" in the brain, why wouldn't it stay for people who got T due to neck issues?

 

http://anet.ua.ac.be/acadbib/irua/07690/E a collection of all de ridder studies for those interested

 

About half of T patient's T gone after cut off their hearing nerve and half still stay there. My guess is that 50% of T is caused by inner ear problems which could be caused by acoustic trauma, ototoxic medication, physical damage & etc, 25% due to TMJ, neck, blood vessels, allergy problems, 25% due to stress and the brain together which is inter related imo.

I believe all kind of T can be cure or at least can be treated/control. It's just a matter of time and it won't be too far away. These days medical research progress like Moore's law!

And by the way, in a year's time my T has been changing from 8/10 when it started then came down to 0.5-4/10 for almost 9 months and last month it bounced back to 7-8/10 and then last two week one day i wake up in the morning and my T has gone for half a day! But then came back and stay at 0.5-4/10 again.

Also many of us here who had T for years can still reduced their T with various methods like
https://www.tinnitustalk.com/threads/acoustic-cr®-neuromodulation-do-it-yourself-guide.1469/page-9

All these just means that T can be change (now) and can be stop (one day)!

 

I have a question. If this article states that chronic tinnitus means that different parts of the brain are involved in creating the sound, then how could regenerating hair cells help? Isnt the only possibility for chronic tinnitus stimulating the brain?

 

From my understand, yes. That's unfortunately the case. I'm guessing that Chronic Tinnitus suffers have damage to the nerves behind the hair cells in the inner ear, where as someone with Noise Induced hearing loss has damaged the hair cells. I would say people who have undergone laser radiation surgery to remove a Brain tumor, would have this issue (if the surgery was unsuccessful of course). Again it's just a wild guess.

 

Im sorry, what excactly are nerves "behind the hair cells in the inner ear"? Are they also related to hearing? And couldnt it simply be that they are not damaged but overactive?

 

Sorry, I meant the nerves that connect the hair cells to the brain. These would send the signal from the hair cells, to the brain. Hopefully they wouldn't be damaged, but I think radiation can damage these nerves.

 

It is all to complex for me to understand Is anyway working on recreating the nerves that connect the hair cells to the brain? Then again if chronic T originates from the brain then maybe it is possible that it could go away with stimulating the brain but without regenerating the nerves?

 

tell your T to calm down ...when you need to

 

Here's another thing to consider imo: If your T is so bad that you do the DRASTIC thing; To cut the audotory nerveM sacrifice hearing; then the the odds of the T having "settled" in the brain are a lot bigger than for.. me for exmpale, whose T is super low, I'm just easily annoyed. Which is why I still think AM101 will help me!

 

theres going to be a cure soon ...everyones T will settle down theres no need in cutting your ear off ..it just takes time to heal ,nueroplasicity is a good way to start ...

 

@Erlend: if i understand correctly he article states that in chronic T (which is maybe, after 1-2 years?) there are changes in different parts of the brain. I also understand that these changes dont necessarily mean that the ringing will get louder. I think that Am101 is more localized in one part of the brain which is why it is used on acute patients (it was also stated on Auris Medical's website). Of course if Am101 will come to the market, in lets say a year it would probably work. But not for the people who have had it for years and years.
@kenji Im simply interested in the subject It is nice to think what treatments would work. I really thought that regenerating the hair cells would work until I realized that if it is a brain problem I should probably take interest in the treatments focused on the brain. Not planning on cutting my ears off or smth;D

 

Well one condition i think it's worth to try is when someone's hearing is about 80-90% lost. So sacrificing the remaining 10/20% could potentially stop the T is a good bet! The brain is plastic if anything can bet recorded there it can be erased too

My guess is that AM101 will still work as long as your T is due to excitotoxicity which to my understanding is over active auditory nerve. Might be more repeated dosage of AM101 is needed to calm down the nerve again.

 

I think as research progresses, we will discover different treatments work for different patients. It will depend on how you got your tinnitus, as well as if you have other underlying medical or neurological conditions.

My hopes, at least for my type of tinnitus (induced by barometric pressure trauma that probably damaged some inner ear hair cells) is for electrical brain stimulation of the auditory nerves, similar to deep brain stimulation for Parkinson's. Regenerating hair cells via stem cell transplants is an interesting idea. But I see it as being very complicated, given it requires major surgery. And stem cell therapy research in general seems to be moving very, very slowly. Electric stimulation is less invasive.