Advances in the Neurobiology of Tinnitus and Hyperacusis

Very interesting 2013 article on tinnitus and hyperacusis. The article's highlights are summarized as follows, quoted from the authors:

• Hearing disorders can be linked with cochlear damage without an elevation of hearing thresholds.

• Tinnitus and hyperacusis may be associated with various degrees of deafferentation not necessarily linked with an elevation of hearing thresholds

• Tinnitus may not necessarily be linked with cortical reorganization.

• Tinnitus and hyperacusis may be associated with differences in central gain.

• Tinnitus and hyperacusis may be associated with abnormal stress effects that may act in the periphery of the cochlea.

Here is the article's abstract:

Advances in the neurobiology of hearing disorders: recent developments regarding the basis of tinnitus and hyperacusis.

Knipper M1, Van Dijk P, Nunes I, Rüttiger L, Zimmermann U.
Author information

Abstract
The prevalence of hearing problems in the Western world has, due to aging of the population, doubled over the past 30 years. Thereby, noise-induced hearing loss is an important factor that worsens over time in addition to age-related hearing loss. Hearing loss is usually measured as an elevation of a person's hearing thresholds, expressed in decibel (dB). However, recent animal studies have unraveled a type of permanent cochlear damage, without an elevation of hearing thresholds. This subtle damage is linked to a permanent and progressive degeneration of auditory fibers that occurs in association with damage of the inner hair cell synapse. Afferent neuronal degeneration has been suggested to be involved in hyperacusis (over sensitivity to sound) and tinnitus (a phantom sound percept). Hyperacusis and tinnitus are potentially devastating conditions that are still incurable. The main risk factors to develop tinnitus or hyperacusis are hearing loss, social stress and age. Both tinnitus and hyperacusis have been discussed in the context of a pathological increased response gain in subcortical brain regions as a reaction to deprivation of sensory input. Novel studies confirm the involvement of peripheral deafferentation for tinnitus and hyperacusis, but suggest that the disorder results from different brain responses to different degrees of deafferentation: while tinnitus may arise as a failure of the brain to adapt to deprived peripheral input, hyperacusis may result from an 'over-adaptive' increase in response gain. Moreover, moderate and high stress levels at the time of acoustic trauma have been suggested to play a pivotal role in the vulnerability of the cochlea to acoustic damage and therefore for the development of tinnitus and hyperacusis.​

Of particular interest is a graphic the authors include that hypothesize differences between tinnitus and hyperacusis:



For explanation of the figure, please see the article.

References:

http://www.ncbi.nlm.nih.gov/pubmed/24012803/

http://www.sciencedirect.com/science/article/pii/S0301008213000804

 

So this is bad news?

 

Good to see some light being shed on that, it's as taken out of my t-story. Not sure whether it's good news all in all

 

That's a very positive way of seeing it

 

"Moreover, moderate and high stress levels at the time of acoustic trauma have been suggested to play a pivotal role in the vulnerability of the cochlea to acoustic damage and therefore for the development of tinnitus and hyperacusis."

This finding of links between stress and circuitry response is very interesting. From the paper's conclusions:

"Elevated cortisol levels (stress) may be regarded in the context of exhibiting an impact on the vulnerability of the IHC synapse and degree of deafferentation, thereby changing the risk for the generation of an either adaptive (hyperacusis) or non-adaptive (tinnitus) central circuitry response, including subsequent influence on the emotional/memory pathway."

 

Jazz...this is an incredible article! Sort of the "go to" for a comprehensive, technical, "how does it all work" for hearing and it's relationship to T and H. Not that I understand it all by any means! However, for those who like detail or want to see some very good schematics of the ear/hearing/neural/brain thing, this is very worth looking at.

Of course, we longer term T folk know enough by now to realize "scientific opinions" about T (and H) are as plastic and mobile as the brain appears to be. But I am bookmarking this article as one the to use as a basic reference to how 'hearing' and all that functions...Only the second link opened for me by the way - with a cut and paste.

http://www.sciencedirect.com/science/article/pii/S0301008213000804

For those more intrigued, but not wanting to wade through it, I have added some of the "sub conclusions" below, and then the "conclusion of conclusions" in full. You will get a fuller taste of the detail involved.

Here you go:

~ Tinnitus caused by short-term noise exposure, such as attending a loud concert, usually goes away. In contrast, long-term exposure to loud sound can cause permanent damage and thereby increase the risk of developing tinnitus.

~ In conclusion, hyperacusis and tinnitus both often occur in conjunction with a loss of threshold hearing sensitivity ( Dauman and Bouscau-Faure, 2005), but neither hearing threshold loss nor OHC loss is essential to develop either condition. This suggests that their etiologies may be related. However, evidence suggests that there are also important differences between the mechanisms involved in tinnitus and hyperacusis (see later in this review).

~ We conclude that in animal studies, deafferentation *[Interruption or stopping of nerve input = the normal conduction is screwed up...my translation! Zimichael] is linked to tinnitus, but may also occur without evidence of tinnitus. A larger extent of deafferentation appears to be correlated with tinnitus. A lesser extent of deafferentation may not lead to tinnitus, but rather be linked to hyperacusis. More evidence for this hypothesis that deafferentation primarily causes tinnitus and hyperacusis in humans, has to be accumulated by detailed audiometric assessments.

~ In conclusion, future studies in humans and animals may carefully consider the possibility that the central nervous system can respond in two different ways to auditory deprivation, depending on the degree of deafferentation. First, it can respond with an increase in response gain (synaptic strength) maintaining the stable neuronal circuit, and second, it can respond with a failure to appropriately adapt the central response gain, which may cause tinnitus or hyperacusis.

~ In conclusion, novel findings suggest that an over-adaptive compensating central gain that spreads from the brainstem toward ascending pathways may be associated with hyperacusis, but not with tinnitus.

~ We may conclude that cortical reorganization is not a prerequisite for the generation of tinnitus or hyperacusis, just like a loss of threshold sensitivity is not a necessary condition for either etiology. Functional cortical reorganization is possibly a concomitant phenomenon and a risk factor for tinnitus and hyperacusis, rather than part of its origin. *[In other words..."This is one helluva difficult beast to pin down!"...Ummmmmmmmmmmm, not so cool, but increased understanding of what is, and is not happening, can only help us! Zimichael].

And it goes on... And

here is a fuller summary of the "Conclusions of the Conclusions". Jazz posted some of them already...

Best, Zimichael


6. Conclusion
We outlined a possibly universal model for the pathomechanisms of tinnitus and hyperacusis. However, it has been repeatedly suggested that tinnitus may have a range of such mechanisms, leading to a number of tinnitus subtypes. Possibly, the peripheral pathology (deafferentiation) that is described in this review is caused by various phenomena besides acoustic trauma that could be classified as different tinnitus subtypes. In this case, the model would be universal. Alternatively, this review describes only one of the possible tinnitus subtypes and other causes of hearing loss besides acoustic trauma may trigger different pathological pathways and thereby different forms of tinnitus. Future studies will show whether the mechanisms proposed in this review are universal or constitute a subtype of tinnitus. Given the widespread presence of noise-induced hearing loss among hearing deficits, the clinical relevance of the mechanisms described in this review are expected to play a major role in tinnitus and hyperacusis.

The following conclusions can be drawn from our model and are discussed in this review:

(i)
Hearing disorders can be linked with cochlear damage without an elevation of hearing thresholds.

(ii)
Noise-induced cochlear damage can cause persistent and progressive deafferentation of auditory nerves without detectable elevation of hearing thresholds.

(iii)
A larger extent of deafferentation may trigger tinnitus. A lesser extent of deafferentation may rather be linked to hyperacusis.

(iv)
The central nervous system may respond in two different ways to auditory deprivation, depending on the degree of deafferentation. First, it can respond with an increase in response gain (synaptic strength) maintaining the stable neuronal circuit, a feature that may lead to hyperacusis. Second, it can respond with a failure to appropriately adapt the central response gain, which may cause tinnitus.

(v)
Tinnitus and hyperacusis often occur within a single individual. As the proposed mechanisms for tinnitus and hyperacusis are different, it must be assumed that these occur in closely-spaced frequency band. Moreover, parallel pathways within an octave frequency band possibly cause tinnitus and hyperacusis, respectively. Detailed future studies of the physiology and psychoacoustic characteristics of tinnitus and hyperacusis need to provide support for this hypothesis.

(vi)
Cortical reorganization may not be an essential prerequisite for the generation of tinnitus or hyperacusis, just like a loss of threshold sensitivity is not a necessary condition for either etiology. Functional cortical reorganization is possibly a concomitant phenomenon and a risk factor for tinnitus and hyperacusis, rather than part of its origin.

(vii)
Increased sound-evoked or spontaneous firing rates in the auditory cortex may occur after moderate deafferentation as a result of increased subcortical response gain and may be linked to hyperacusis. A failure to increase central gain after a critical degree of deafferentation may be discussed in the context of increased cortical bEPSP and the epileptic-like, highly synchronous cortical activity that follows unscaled postsynapses within the sound-deprived cortical region during tinnitus.

(viii)
Elevated cortisol levels (stress) may be regarded in the context of exhibiting an impact on the vulnerability of the IHC synapse and degree of deafferentation, thereby changing the risk for the generation of an either adaptive (hyperacusis) or non-adaptive (tinnitus) central circuitry response, including subsequent influence on the emotional/memory pathway.

(ix)
The disturbance of central homeostatic adaptation and the influence of cortisol (stress) at the input side of a functional combined circuitry may also be a model for other brain disorders.

 

I have to be honest, this science stuff is all jibberish to me, especially when it's in english (not my first language).
@bill 112 What's your take on this? You usually describe stuff like this in a way that dummies like me can understand.

 

@Zimichael Thanks for the additional cut-and-paste! Very informative.

@lapidus There is a lot of information in the article. And it's all very technical. I will attempt to explain one part of the information that applies specifically to people with tinnitus and hyperacusis. @bill 112 will also contribute his insight, I'm sure.

Here goes:

The authors believe tinnitus and hyperacusis are related diseases. Specifically, they see the main difference between the two as the amount of damage done to the inner ear (cochlea).

In tinnitus, the damage is more severe and actually results in the sounds being disconnected from the ear to the brain (deafferentiation). Because the brain no longer hears those damaged frequencies, it attempts to compensate by increasing noise in surrounding frequencies. This increase is what we hear as tinnitus.

In hyperacusis, the damage to the inner ear is less severe. But it is still severe enough for the brain to notice. As a result, the brain turns up the volume on the damaged frequencies. It’s like an old analog radio. When a station had a weak signal, you would turn up the volume in order to hear it.

Many people have both disorders, tinnitus and hyperacusis. The authors look at this too. They believe both disorders represent a different degree of damage in frequencies that are close to each other. So, let’s say, you have severe damage in your inner ear at 6,000 Hz; you might less damage—but still significant—at 5,000 Hz. The result would be tinnitus at 6,000 Hz but hyperacusis at 5,000 Hz.

Finally, stress levels may determine if someone develops tinnitus or hyperacusis or both. Severe stress weakens the inner ear's ability to recover from damage.

I hope this helps.

 

Thank you @jazz

Yes I think I get it now. But it still doesnt answer how people can recover from hyperacusis (some even "cured") by TRT or other sound therapies. If the damage is permanent like tinnitus, it would not be able to get less hyperacustic? And in the past scientist has said that tinnitus and hyperacusis is two sides of the sam coin, does this still apply? Let's say that Autifony will work on reducing or even removing T, would it work on H too? If this theory that's stated in the article is correct, what would be the potential cure/treatment for H?

 

@lapidus I'll try to answer your questions; of course, with tinnitus and hyperacusis little is known for certain. Hopefully, this will change in the near future.

TRT works specifically on your reaction to tinnitus and hyperacusis. Your emotions. In TRT, the goal is to retrain your brain to reclassify your tinnitus and hyperacusis from something fearful to something neutral. If you perceive tinnitus and hyperacusis as something neutral, you won't generate a fear response. If you are no longer afraid, your brain will learn to lower the sounds, and eventually they may disappear from your awareness. But the sounds will still be there; the damage is still there. You will just be unaware or less aware of them.

In other words, TRT is all about desensitizing your emotions to something you fear. If you are afraid of spiders, you can loose that fear by slowly exposing yourself to them. Of course, spider phobia is not the same as tinnitus and hyperacusis, but your reaction (fear) is the same.

Other sound therapies may work the same way: to desensitize your brain to the sounds. As your brain looses its fear, the sounds diminish.

This would explain why several different sound therapies exist--which supposedly affect your brain differently--and they all work for some people. Perhaps, these therapies really affect only one aspect of your brain--its reaction to your noise and sound sensitivities.

Yes. In fact, the article provides an interesting explanation why they are "two sides of the same coin." The main difference being the amount of damage done to your ear.

It might very well work for both.

In addition, if this explanation of tinnitus and hyperacusis is accurate, hair cell regeneration may also cure both conditions.

 

@Zimichael

Your observation is spot on! This is the first time I've seen new research contradict the cortical reorganization hypothesis as being a direct response to deafferentation.

 

@jazz
Thank you for your answers. Much appreciated. One thing you wrote leaves me very confused though.
You wrote:

"So, let’s say, you have severe damage in your inner ear at 6,000 Hz; you might less damage—but still significant—at 5,000 Hz. The result would be tinnitus at 6,000 Hz but hyperacusis at 5,000 Hz."

I don't have hyperacusis at a specific frequency, I'm sensitive to all frenquencies.

 

My guess is that you have damage at all frequencies. That's interesting. Don't you also have multiple tinnitus sounds? If so, and if the authors are correct, then your ear has been disconnected from your brain at multiple frequencies.

I'll re-read the article tonight and hopefully will find an explanation.

 

Yes I also have multiple T sounds, but I've had more than one sound in my head long before I got H. But I think that almost anyone with H would agree when I say that we're not just sensitive to a specific frequency, where sensitive to sounds in general. But of course some frequencies in the higher pitch are more bothersome. I guess that's the norm from what I've read.

 

Good luck figuring it out Jazz!...And @lapidus I can sympathize with your 'consternation', as it's not just the science that is difficult, but the T and H seem to be in a unique class of ability that could really tax the NSA's super-computers for "stealth" and "evasion". Unfortunate for us, though articles like this one show that people are drilling away at the thing, and chip by chip it will be exposed one day.

On a more personal note, I thought my H. was just kind of "overall volume sensitive" but after reading this stuff I am wondering if maybe it is also related to frequency, as indeed some frequencies seem easier to handle (maybe) than others at louder volumes. I'd need a Db meter to be sure though as after the amount of "jumps up" I have had I kind of err on the side of caution!!! I will pay more attention to this aspect though in future.

All four levels (volume increases) in my T. have been the same "note" (pitch, tone, sound, ringing) EEEEEEEEEEEEEEEEEEEEEEEEEE...and indeed a musical 'E flat'. Apparently around the 7,000 Hz range so maybe in reading this my H. is "close by" and not super divergent...How comforting (sic).
It will be hard to tell as I must have extensive "other" hearing damage at higher frequencies as no way I can hear anything over 10, 000 Hz like some people can. Those example sounds that some folks have posted, at the higher frequencies...I just plain don't hear a thing. One less area to have to habituate to maybe???!!!

Best, Zimichael

 

Is this implying that stress inhibits recovery? And if you're very stressed to begin with and around loud noise it can cause more or easier damage?

 

Stress is an important factor in developing tinnitus. While stress alone probably doesn't cause tinnitus initially--though some researchers may disagree--it does make tinnitus more likely to develop if your cochlea is injured through sound exposure and ototoxic drugs and chemicals.

And so it is important to get your stress levels under control. You can do this through medications; if, for example, you are depressed, you might try an antidepressant to improve your mood and help you better manage stress. Or you can manage stress with counseling, CBT, meditation, mindfulness, etc.

Since your tinnitus is recent, why don't you try the AM-101 trial? That is your best bet to prevent your tinnitus from becoming chronic. Of course, not everyone with tinnitus becomes chronic; my understanding is that most do not. But still why take a chance when you can be cured?

 

After discussing my situation with the ent, i didnt fit the criteria. I thought am101 was over or had poor results?

 

Well, after re-reading the article, I don't know the answer to your question. Sorry. I only understand that tinnitus and hyperacusis can coexist near similar sound frequencies.

 

No, I believe the studies are still occurring. Check the AM-101 thread for details. I've not kept track lately since I don't qualify.

Here is the link of study centers in the US:

http://www.tinnitus-study.info/us-en-study-centers

If your ENT said you didn't qualify, however, then you probably don't. There's still much you can do--especially in the early stages--by maintaining a positive attitude, keeping yourself in sound enriched environment that will help you tune out your tinnitus, etc. And make sure you get enough sleep. Sleep is very important for all people with tinnitus--whether acute or chronic.

 

That's okay @jazz I'm grateful for what you've explained so far. But I wonder one thing though. You said earlier:

"In addition, if this explanation of tinnitus and hyperacusis is accurate, hair cell regeneration may also cure both conditions"

I can't really see how. If the damage is in the auditory nerve and/or the nerve fibers, then fixing just the hair cells will do nothing. Also, my doctors have already said that I have no damage at all on my hair cells, since I don't have any hearing loss. This just doesnt add up. Wouldnt DBS be by far a more promising cure than hair cell generation? Since it actually already exists and have cured (not treated, cured) a few patients from their T that got the procedure for something else.

And yes @Zimichael I totally agree

 

@lapidus Of course, no one knows this. But there is a belief it is possible--especially if the tinnitus is still recent. Equally important, hair cell regeneration should halt any progression of tinnitus. Below are the ideas from the Hearing Health Foundation how hair cell regeneration may help tinnitus:

There is certainly evidence that the restoration of hearing can alleviate tinnitus. For example, tinnitus can be induced by exposure to loud sounds that result in the temporary loss of hearing, which is experienced by many after attending a loud event like a rock concert. In most such cases, the tinnitus disappears as the hearing recovers.

Another example is the response of patients for whom otosclerosis (an abnormal bone growth in the middle ear) has induced a conductive hearing loss. Many such patients with this hereditary condition experience tinnitus. However, when their hearing is restored through a stapedectomy, a surgical procedure, many report an improvement in tinnitus (see “About Otosclerosis”).

Finally, there have been several reports that patients, after receiving a cochlear implant, experience a significant reduction in their tinnitus. Interestingly, in some cases this tinnitus suppression continues for several hours after the implant is turned off. Though the mechanism by which cochlear implants may suppress tinnitus is not clear, these observations all suggest that restoring function to the auditory system may be very helpful for tinnitus in a variety of ways.

Hearing restoration may be especially helpful for tinnitus of recent origin. It has been suggested that while tinnitus begins in the cochlea due to hair cell damage, over time it appears to set up circuits in the brain which can be independent of the inner ear. Such long-term tinnitus may not be reduced in apparent intensity by repair of the organ of Corti.

That said, we cannot conclusively know the effects of repairing the hair cells in the organ of Corti that restore hearing until mammalian restoration of inner ear hair cells is achieved. It is even possible that the central auditory system can be retrained over time, leading to a reduction in long-standing tinnitus. The potential for masking long-term tinnitus or reducing its annoyance factor will still be a positive benefit from hearing restoration.​

That said, as you note, therapies like DBS appear more likely to help with tinnitus. They won't cure tinnitus, but they should lower the sound, maybe even eliminate it from your awareness. So you're correct. And Autifony also looks very promising for alleviating chronic tinnitus.

Reference:

https://www.tinnitustalk.com/threads/advances-in-the-neurobiology-of-tinnitus-and-hyperacusis.5410/

 

Not to try and add more confusion, but there are indeed a lot of grey areas in trying to interpret too much from this article and data. For sure it's for a good one to ponder if so inclined, as the graphics and general knowledge about hearing and damage and nerves and all that is pretty impressive...even if it has these multiple "grey zones".

I mean just think about it (IF I am even interpreting some of it correctly!)...One conclusion in there really puts a clear spike into the whole "multi-connected-multi-scheming-multi-mistaken multi-whatever-the-hell-auditory interpretation of brain causal function" for T theory.
That's a pretty "rock the boat" idea as far as I can tell, as there has been tons of stuff about how the brain (consciousness???) INTERPRETS afferent/firing nerve impulses in a T inducing situation in an 'erroneous way' and then over-does it, or under-does it, regarding appropriate response, that then can set up a phantom excitation or suppressive loop, that then results in tinnitus!!! Ummmmm...loud noise is easiest for me to get my head around the possibility of this...but ototoxic drugs??? Errrrggghhh...that gets even more "HTF???" for me.

Hey sorry for all the "quotes" and hesitation in that, but I have hard enough time following my own thinking with this. But bottom line in the paragraph above is: This challenge against the "cortical reorganization" theory is a major one. To me it may lead to more emphasis on trying to verify that, and/or look to at the 'physical damage' aspects more acutely...and thus regeneration or 'damage amelioration' therapies??? (As against neural plasticity targeting, which to me may be closer to what actually happens with things like TRT or self habituation).

In this same vein, and trying to use this model...How on earth does hyperacusis "go down/decrease" with time??? It took me about 5 to 6 years to be about 60% to maybe 70% re-tolerant of fairly loud sound (e.g that dance performance in 2012 - before my stage 4 damage)...yet I had habituated the the 'static', single tone, but louder 2006 T within maybe a year or two.
The T, yeah, I can see "brain conspiracy" and "plasticity" dealing a distorted deck in there pretty easily...but H.???? No way. It's MUCH more "physical" in my experience...So was there some form of nerve, or OTC (outer hair cell) regeneration that made my drop in sensitivity happen??? For sure I don't buy that it was "learned behaviour" or "adaption of consciousness" behaviour in my brain. I just don't. I have too much personal experience and time under my belt with this stuff.

Questions. Questions. Questions... But the only way this T and H is going to get figured out is if questions keep being asked and researchers of all stripes (which includes 'us') keep asking them. Thus I find this article 'encouraging' even though it has no "cure prognosis attached" unfortunately.

Best, Zimichael

 

Well said Jazz...You posted a lot of my thoughts while I was still typing!
Of course, you do see I presume the double contusion/confusion there of "restoration" being somewhat akin to "regeneration"...yet the on the inverse, the continued suppression of T with switched off cochlear implant, gives strong ammo to the "plastic memory brain" clan! Geez Louise.

I think I'm just going to shake my head here and keep mulling.

Best, Zimichael

 

I'm just going to ask an ENT to drop some ROGAINE inside my ears!

 

Not convinced that all tinnitus stems from cochlea damage. I think damage to the central auditory cortex, or auditory nerve in the more medial periphery may also be the case. Many sudden onsets not related to noise exposure exist that may bypass the cochlea and hit the central nervous system directly to trigger t.

 

Totally agree @Lisa88
And even in noise induced T I'm not that sure if hair cells play that big of a role. It does not explain why some people with a lot of hearing loss don't get T and some people with T havent got any hearing loss at all (like me).

 

@Zimichael Agreed!

 

Yeah I also second that @Zimichael
The thing is that the theories that pop up here on this board by "laypersons" like us arent that bad at all. Some stuff I've seen here make total sense to me. I would not underestimate the scientific discussions going on here on this part of the site. Discussions like these may even play a crucial part in solving this torturing puzzle.

Altough I'm not sure if you would count as a layman @jazz , you seem awfuly knowledgeable about this science stuff. Do you have som kind of medical education?