Discordant Dysfunction Theory

Recently I have been reading a lot about "discordant dysfunction theory" for Tinnitus. It is quite an old theory, but still seems interesting (to me at least) as a potential etiology for Tinnitus. I have done some searching on this forum, but can only find some references to it in some other threads, mentioning it briefly. I think the topic is interesting enough to warrant it's own thread though.

I have recently done some audiometric testing on myself for the frequencies above 8Khz and found dips on low volume between 10500Hz and 11600Hz (the volume of the sound goes noticeably lower for these frequencies and goes up again around 11600Hz) and 9800hz to 10300hz. The "discordant dysfunction theory" might explain this.

The basic premise of the theory states that the Tinnitus might be caused by damage to the OHCs, while the IHC is left intact. The imbalance of the signalling between the IHC and the OHC for a certain frequency will create the perception of Tinnitus in the dorsal cochlear nucleus (DCN).

The proposed function of the OHCs is to register sounds at lower volume for a certain frequency (<50dB), the IHC takes over if sound intensity is raised beyond this treshold. The OHCs are first in line for acquiring noise damage (especially at the higher frequencies). For these reasons audiometric treshold testing is done with generally low-intensity sounds.



This theory might explain many Tinnitus questions, e.g. the following (among others):

• Why some people have normal audiograms while still reporting Tinnitus (partial damage to OHC, but IHC left intact).
• The absence of Tinnitus in the totally deaf (both OHC and IHC are destroyed or otherwise non-functional).

What happened to this theory? Is it still an accepted theory or are there new developments and/or shortcomings disproving this theory? Maybe we can discuss this some more.

Interesting read regarding this subject: https://books.google.nl/books?id=BqEq9Re3L5UC&pg=PA96&lpg=PA96&dq=discordant+theory&source=bl&ots=ekfqfTbAde&sig=zLl4e_E-VuFu4AGuLz0lqtzW9sI&hl=en&sa=X&ved=0ahUKEwiV9Kq3uYrQAhXF1RoKHb3aBR0Q6AEIGzAA#v=onepage&q=discordant theory&f=false

 

good stuff, seems to make sense

 

Is it symmetrical on both ears?
Can the used headphone be responsible? Can you match it tyour tinnitus frequency?

I recently did the same check and found a loss between 10.000Hz and 10.800Hz in my left ear only. Threshold is hard to determine but I guess 25db to 35db total and around 10db to 15db worse than my right ear. My tinnitus is in the left ear mainly and even though my tinnitus sound is quite complex this lost frequencies are definetly a part of it.

What I dont know is when I ve developed this loss. Is it really the trigger for tinnitus or just the longer existing prerequisite for tinnitus triggered by some other malady?
A question impossible to answer with introspection.

One remark to the mentioned theory:
Age related hearing loss rarely leads to tinnitus, even though hair cells are dying. I guess OHCs are more prone to die with age as well, right? Why then not more tinnitus cases with aging?

I think there must be more.

Currently I looking into the possible benefits of a hearing aid just amplifying my lost 10kHz to 11kHz range to equal it out. If tinnitus is about a maladaption to (spontaneous) hearing loss this should help.
What I could find out in literature is not promising though. If it was that easy, it should be known by now I fear.

 

Hello Marlino,

Thank you for your response. You raise some valid points. It could indeed have been the headphones not being able to replicate the sound correctly at such specific frequency and volume. I plan to repeat the test at the same volume with other headphones. It remains a crude way of measurement though.

The relative rarity of Tinnitus in age-related hearing loss is indeed interesting, if that is the case. I don't have numbers on how rare Tinnitus is in age-related hearing loss when compared to noise-induced hearing loss for example. Perhaps age-related hearing loss is triggered by a process resulting in synchronised cell apoptosis, where both the IHCs and OHCs die at the same time for a certain frequency. This wouldn't result in an imbalance in the dorsal cochlear nucleus (DCN) but just in a hearing loss for those frequencies. Maybe Tinnitus in age-related hearing loss only occurs when this process goes awry for some reason.

In noise-induced hearing loss however, the loss of hair cells may be asymmetrical in the sense that OHCs are damaged or lost (as they are first in line), while the IHC remains. This causes imbalance in the DCN, resulting in Tinnitus according to this theory.

I don't think amplification with a hearing aid will solve the issue (at least not as far as this theory is concerned), but rather mask it for the time being. If you consider that OHC's are responsible for the lower-intensity sounds (<50dB) and beyond that limit the IHC is triggered, it doesn't make sense to amplify sounds because beyond a certain point you will trigger the IHC instead of the OHC. If you go below that certain point, you just will not register the sound because that's where the OHCs would have responded, but they are lost or damaged. According to "discordant dysfunction theory", the Tinnitus-percept is triggered by the imbalance between input from OHC and IHC in the DCN. Wearing a hearing aid will not solve this imbalance, as the input from OHCs remains reduced due to damage. I think hearing aids will result in masking and some residual inhibition at best if there is truth to this theory.

 

An interesting question in the light of this theory would be the following; if you have hearing loss in the higher frequencies (>8Khz) and we take into account the natural age-related hearing loss process, would this mean that people with higher-pitched Tinnitus have a better chance of disappearance of their Tinnitus when they get old enough for the age-related hearing loss to set in and take away their remaining IHC, restoring balance in the DCN?

If you consider most people will continue to lose their high-frequency hearing above 8Khz over time, one would say any existing Tinnitus caused by imbalance in these frequencies between IHC and OHC has a chance to resolve when enough time passes. If there is any truth to both this theory AND synchronised cell apoptosis in age-related hearing loss, that is.

I wonder if there is any data on the perceived frequency of Tinnitus and Tinnitus resolution/softening over time... I highly doubt it, but it would be interesting to know...

 

I asked around for that a little and there seems to be no indication for that unfortunately. The contrary mightbe the case.

 

Agreed. I'm speculating on another theory which claims a maladaptive amplification of lost frequencies generates tinnitus. If so, the brain should reduce the amplification again after getting a proper stimulus for a while. But its too simple to be true,I know...

 

Btw I've just read an interesting retrospective study about the correlation between tinnitus pitch and gradient of hearing loss / T50 (where OHC are lost).

Unfortunately there seems to be no significant correlation. This makes the DD theory less likely, I guess.
Only clear result is, that tinnitus pitch is in the area of hearing loss.

If interested, Google for:
Relationship between tinnitus pitch and edge of hearing loss in individuals with a narrow tinnitus bandwith.

The study seems to be quite well done but also mentions the problems to match tinnitus pitch reliable.

What also wonders me is that this very basic study was done only last year, confirming my view of that we know nothing about tinnitus or are overlooking something.

 

Related to age and tinnitus frequency I wonder if there is one.
I get the impression there is.
I only see young people with high frequency tinnitus > 10 kHz.
Also, often I get the sensation of tinnitus, but not hear it particularly loud.
Is the tinnitus frequency to high for me to hear?

 

I just stumbled upon this study: https://www.ncbi.nlm.nih.gov/pubmed/17259699, where they say that "susceptibility to tinnitus in normal hearing subjects exposed to noise on a daily basis seemed to be clearly related to lower DPOAEs, bilaterally, in the 1500- to 2800-kHz range."
And further "This study provided evidence of outer hair cell dysfunctions in normal hearing subjects exposed to noise and susceptible to tinnitus."

Coincidentally I think that my T actually is exactly in this range.. around 1,5 khz on the right and 2,5 khz on the left..
Personally I think that the theory of imbalance of outer and inner hair cells seems quite logical, they also say that "no difference could be observed between groups on audiograms at the 2-kHz frequency range." So in deed this could be an explanation why the audiograms often seem "perfect" despite having Tinnitus.

 

Also interesting: https://www.ncbi.nlm.nih.gov/books/NBK11122/

"Thus, it seems likely that the outer hair cells sharpen the frequency-resolving power of the cochlea by actively contracting and relaxing, thus changing the stiffness of the tectorial membrane at particular locations. An active process of this sort is necessary in any event to explain the nonlinear vibration of the basilar membrane at low sound intensities. "

not sure if I understand this correctly.. but could an outer hair cell dysfunction lead to a constant contraction of the tectorial membrane? I also often get a vibrating sensation in my ears..

Also what about the 8th cranial nerve and microvascular compression? They say "stimulation of the crossed olivocochlear bundle, which supplies efferent input to the outer hair cells, can broaden eighth nerve tuning curves.", not sure what this sentence exactly means but as I understand it the "speed of communication" can be altered somehow and this has to do with the 8th nerve?! .. maybe this is complete nonsense, not sure.

But I wonder if I could have microvascular compression.. does anybody by chance know if this is possible when T is bilateral?!

 

It seems that the study only included pilots with no or fleeting tinnitus. I could read only the abstract.
@Emmi Do you have access to the full study?

 

I did today another test about my lost frequency range and I've to say its probably much worse than 35db. Could easily be 50db.
Another interesting observation:
While hearing 10.400Hz via headphone only on the right with increasing volume I heard it also increasingly from the left again. On loud volume it was symmetrical again. This makes it logical to me, that I've lost mainly OHC, because they are only amplifying on lower volumes.
Also it could explain why my tinnitus is loud, since difference between IHC / OHC is really high in my case.
Fuck! My left ear is messed, the ENT overlooked it, now its permanent and T is killing me.

 

I think it's not fleeting T, but temporary T after noise exposure (from flying the airplane).. and they found that those pilots, who developed temporary T and thus were seemingly more prone to developing the condition have lower values in their DPOAEs. But unfortunately I don't have full access to the study either.

 

This seems in deed quite logical. Did you do a high-frequency hearing test? If so, I don't get how the ENT could not see this..
Do you think that by restoring the balance, through numbing of the IHC, the T would theoretically go away?

 

Maybe. Even if i dared, I couldn't successfully kill only the right IHCs by loud noise

 

I was wondering if a botox injection of the afferent axons would have this effect.. but no idea how you would find out where the afferent axons from the IHC at 10,4 khz go along..

 

Aside from the problem you mentioned, I'm afraid botox injections are a method way too crude to reach something as small as the specific afferent axons you are referring to. Considering the cochlea is pea-sized and the sensory cells microscopic, the risk of undesired collateral damage to other nearby cells will unfortunately be immense.

 

Let's keep in mind that this is a theory. No one can say if your condition is permanent or not. In fact, if this theory is true, it might be that your Tinnitus isn't permanent when your IHC dies due to the natural ageing process. However, that isn't sure, but an interesting question in the light of this theory. There are still people around who get rid of Tinnitus after years, for one reason or another.

This theory indicates a purely peripheral etiology for Tinnitus, which would indicate that severing the auditory nerve would solve the Tinnitus perception in this case (while that only appeared to help in a relatively small amount of cases). I wonder how viable this theory really is.

 

Very rare unfortunately, right?

I dont dare to hope for that. Many long term sufferers seem to be profoundly deaf at their t frequency. Probably they weren't all deaf though when t started.

Also I wouldn't rule out to have a dead area of IHCs at my t frequency. Unfortunately its almost impossible to say for sure.

 

It appears so. There is little data on it and people do not appear to talk about it much, but it is not impossible if you consider some anecdotal stories and the study about the long-term followup of military conscripts with noise-induced Tinnitus. Other than that study, not much research has been performed in this area as far as I know. There's still a lot to do in this field.

Agreed, that is one of the problems with this theory. Peripheral sustenance of Tinnitus doesn't make much sense in the light of this theory. Perhaps hidden hearing loss can offer some peripheral explanations, but other than that it seems entirely a brain/CNS-thing with hearing loss as a trigger.

 

I think this theory fell out of favor because it doesn't really make sense.

Outer hair cells are mechanical amplifiers. They 'focus' movement in the basilar membrane to create enhanced specificity and enhanced sensitivity. They are predominantly innervated by nerve fibers that come FROM the brain, not nerve fibers that convey signals to the brain. It's true, outer hair cells are more likely to die after noise exposure than inner hair cells. When outer hair cells die there is an immediate shift in the audiogram, i.e., there is a change in sensitivity to faint sounds and you lose your ability to control the excitability of the cochlea through brainstem reflexes.

So, there is no 'balance' in the signals transmitted between outer hair cells and inner hair cells to the brain. The inner hair cells provide 95% of the signal from the ear to the brain and the synapses between inner hair cells and those nerve fibers are more sensitive to noise exposure than outer hair cells. When inner hair cells die, there is no change in sensitivity until >80% of them are gone (hence hidden hearing loss).

Furthermore, the perception of sound and tinnitus reflect the processing of the brain. In fact, it reflects processing that is many synapses downstream of the cochlea and hair cells. Nowadays we know that the only way to understand the cause of tinnitus is through careful studies of brain plasticity, because it is the direct cause. The brain reacts to cochlear damage but has no access to whether that damage arises from inner hair cells, outer hair cells, synaptopathy, changes in the endocochlear potential, punctures in the tectorial membrane etc. etc. etc. The brain only sees the level of activity coming up the auditory nerve into the brainstem.

This is a terrific thread and I enjoyed reading the conversation but it's pretty clear that this theory has been tested and recent findings do not support this idea. If you want to understand tinnitus you need to understand brain plasticity, not the micro-anatomy of the inner ear.

 

Exactly right, Vinnitus. Disconnecting the cochlea from the brain by severing the auditory nerve almost always makes the tinnitus far worse. Let's not repeat that unfortunate discovery again!

The best way to cause tinnitus is a very sudden, very extreme loss of input from a restricted region of the cochlea. That will do it most every time and is a reasonably good description of what intense noise exposure does to the high frequency base of your cochlea. That's why intense noise is enemy #1 followed by high doses of ototoxic drugs. Aging, with its gradual loss of hair cell function, endocochlear potential and mechanical motility of the middle ear is not as direct a precipitator of tinnitus as noise exposure, but it is certainly on the list. Of course, you can also acquire tinnitus by taking high doses of drugs that act on the GABA receptor (e.g., benzodiazepines). More evidence that tinnitus arises from an imbalance of excitation and inhibition in the brain, not from the pathology within the ear.

 

That is exactly what I believe happened in my situation. One loud bang wiped hair cells at the base of my cochleas out of existence.
Hopefully the "imbalance" in the brain originating from the inner ear will one day be able to be reversed.
Reversed in the inner ear and not in the brain

 

Absolutely my opinion as well.
I assume trigger for the brain can be deprivation and overstimulation. If it tunes into a t sensation by being triggered depends on vulnerability.

What I just don't understand is how t loudness can be so different. My t changes between low moderate to quite severe periodically within several days independent from any other variable.
Very very weird.

 

Hello @HomeoHebbian

At first, thank you for your input. I always look forward to reading your input as it's often very informative and educational.

Yes, I noticed the discordant dysfunction theory has quite some shortcomings and questions that just cannot be answered using this theory. I know this is quite an old theory, I couldn't find info about the "how's and why's" of this theory being discarded by the scientific community. Thanks for clarifying on that.

The story still told to patients by ENT's (and also to me) is the age-old story of the "oscillating damaged hair cells" being the cause for the Tinnitus, which makes you think this theory might still have something to it. I think that story is ripe for a new revision. The loss of hair cells indeed plays a role in the origin of Tinnitus, but it is merely a trigger I suppose.

I wonder; could malformed auditory input to the brain caused by cochlear damage actually sustain the Tinnitus? I noticed neuromodulation rarely has the effect of totally being able to remove the Tinnitus; a soft hiss always remains in my case. Could the actual damage be able to permanently malform the input and hence sustain the maladaptive changes in the brain causing and sustaining the Tinnitus? Also, could the aural fullness sensations often accompanying Tinnitus be purely neurological in origin?

 

If noise-damage related tinnitus was purely due to damaged hair cells not getting enough input then this clinical study in which the missing frequencies were artificially boosted should have had a positive effect on tinnitus: http://duteela.et.tudelft.nl/~wout/documents/hearing2012.pdf

The fact that it did not suggests to me that one of the following three theories must be true:

1. Your discordant dysfunction theory in which input from the inner hair cells must match the outer hair cells, would make this clinical trial fail because the inner and the outer would be boosted equally and still not match.
2. Another theory is that damaged hair cells are actually sending the tinnitus signal. They are effectively stuck in the "on" position by their damage instead of "off". Boosted frequency inputs would not change this.
   
3. Finally it could be that although the initial trigger for the tinnitus might be loss of input from the ear, after a period of time it becomes "set" in the brain and will continue even if the ear problem is corrected by artificially boosting the missing noise frequencies.

An interesting experiment to see if #3 is true would be to do the same clinical trial on people who's tinnitus is very new (the trial used people who had T for years). If #3 is true then tinnitus could be stopped if that type of sound therapy was started right away. It also means that for people with longer term tinnitus the only way we will find a cure is using a drug that affects the brain. The ear will not offer a solution by itself.

 

It's a great question. We know that cochlear damage is almost always the initiator of tinnitus. We also know that a compensatory plasticity process in the brain that has run amok is almost certain the direct cause of tinnitus. But you are wise to question the gray area in between. Does the haywire plasticity process that generates the phantom tinnitus percept depend on the ongoing abnormal input from the ear or, once initiated, is it sustained independent of the ear? A) we don't really know for sure. B) Alas, the answer is almost certainly both. C) we researchers should really figure that out ASAP.

Most research findings suggest the following scenario: when the input coming through the auditory nerve suddenly drops, neurons in the auditory brainstem (e.g., the dorsal cochlear nucleus) detect the loss of input as a drop in intracellular calcium. This drop initiates a sequence of HOMEOstatatic changes that allow those brainstem neurons to become more sensitive to whatever input remains. The excitability of neurons at these earliest stages of auditory processing is so tightly linked to input from the cochlear nerve that if the damage is severe enough they may never ever be able to recover to their set point of intracellular calcium. They keep turning their amplifiers up and up and up but there just isn't enough drive from the cochlear nerve that would allow them to fully recover to their set point. In that sense, yes, the central pathology is sustained by the abnormal input from the ear.

The situation is different at higher stages of central auditory processing (e.g., the auditory cortex), where the activity of neurons more directly sculpts our perception of sound (both real or imagined). The loss of input from the ear initiates the same homeostatic processes, but these neurons receive a far greater set of inputs than do neurons at the earliest stages of processing. Unlike the brainstem centers, which are more 'hardwired' it is possible to supplant the missing input from the damaged region of the cochlea with other viable inputs through HEBBIAN plasticity mechanisms. This is what companies like MicroTransponder are trying to do with their vagus nerve trial. In effect, we should be able to reprogram the activity set point of higher auditory neurons and effectively turn off the cellular "distress signal" that causes the tinnitus sound. Even when the input from the ear remains abnormal. At least that is the hope.

 

Keep in mind that their acoustic stimulation does not replace the missing input. Yes, it directs an acoustic signal towards the region of the cochlea with presumptive synapse loss and missing hair cells but by no means does that replace what has been lost.

So, I wouldn't read too much into that study (though admittedly I need to read it more carefully myself) except to say that acoustic enrichment like all other "therapies" based on passive listening are never ever going to be a highly effective treatment. One doesn't tap into the remarkable plasticity of higher auditory processing centers of the adult brain through passive exposure to anything. It requires engaging other mechanisms through learning, training (or perhaps through vagus nerve stimulation or other forms of direct brain stimulation).

Regardless, yes, it seems that there is value in interventions that are initiated shortly after intense noise exposure. Before the auditory nerve retracts from the inner hair cell and while the central auditory neurons are adjusting their sensitivity.

 

Quite right. Think of it like steering your car on an icy road. Your brain reaches a tenuous 'steady state' in compensating for a deprivation of input from the ear. The loudness is stable and your car more or less points in the same direction. Neurons have undergone some pretty extreme changes to compensate for the loss of input from the ear and, as a result, their network activity is inherently unstable. One little shove, the siren of a passing ambulance, a leaf blower without ear protection etc. and your car begins to 'fishtail'. Excitation and inhibition are shifting up and down rather abruptly as those networks seek to recover their steady state. This is probably there reason the subjective loudness scales up and down. Take good care of those remaining hair cells and nerve fibers (i.e., keep a steady hand on the wheel!).