Dr. Will Sedley Requesting YOUR Input — Predictive Brain Processing for Tinnitus

Thanks for your time, Will.

Is it still the prevailing consensus that tinnitus is primarily (save some outliers like auditory radiation) a function of hearing loss? If so...

Since hearing loss can be present at many untested frequencies (e.g. 8437 Hz, 12897 Hz) would curing the hearing loss by restoring the hair cells and their synaptic connections corresponding with such frequencies likely reduce or cure the tinnitus? Upon hearing restoration, might tinnitus reduction then depend on brain plasticity/elasticity to recognize that since the function has been restored, there is no need to keep inputting/outputting this aberrant signal?

 

I should mention that I realize this is not the focus of your research and that you may not be able to provide a picture of the opinion at large. I also should mention the theory that hearing losses below the regions of perceived tinnitus frequency might be the causative factor of increased central gain, and thus causative of perception of high frequency tinnitus even if there is no damage at the corresponding OHC's.

 

Maybe you can do an interview for the Tinnitus Talk Podcast?

 

Brilliant!

 

Thanks for pointing out those who sell expensive hearing aids for the snake oilists they are.

 

Hi Will,

As someone for whom neuromodulation sounds show some effect (reducing or eliminating tonal element of tinnitus), I am very excited about the direction of your research. Your theory seems compatible with my experience as my tinnitus is quite variable and when it's at a particular threshold (e.g., between hiss/crickets and tone) my expectations seem to have some (very minor) influence on what I hear.

Have you any idea at this stage when the online sound trials might occur? I'd love to take part in those!

 

I am interested in your study proposal. Combining detailed modeling with clinical data has a lot of potential and it seems you try to be clear about what is supporting a theory and what is proving a theory. As you have mentioned, this seems helpful for other areas as well and I hope the next step is examining hyperacusis. I’ll be excited to see the results.

I hope something below is useful.

Research Testing Questions/Thoughts

1. Given the exclusion criteria you seem to need for the experiment, I think it would be good to highlight that this experiment is studying a subtype of Tinnitus. Acknowledging heterogeneity and studying the subtypes of tinnitus is something that we all would like more emphasis on.
2. Despite attempts to exclude more reactive cases, how will you handle people with pain from sounds you generate or whose tinnitus changes or increases as a result of the sound?
   1. If they are already inside an MEG, it would be interesting to see what this expensive machine picks up when their tinnitus gets worse or if they feel pain. I imagine you would need to instruct them to let you know.
3. Comments about the fMRI that you may have already considered:
   1. MRI sounds will strongly overlap with your sounds even with hearing protection.
   2. MRI testing will likely activate global circuits including discomfort from confinement, visual processing alterations, and attention to MRI sounds in ways that the EEG and MEG will not.
   3. Hearing protection will change the frequency distribution of the sounds you are presenting, filtering high frequencies more than low frequencies.

Questions/Thoughts about the theory

1. Cochlear implants are an interesting case for studying time constants for reprogramming predictors I would imagine. People initially hear very harsh, robotic sounds and then adapt, presumably from changing the auditory predictors. Also cochlear implants have been shown to reduce tinnitus and hyperacusis after SSHL [Macias 2015, Mertens 2015].
2. SBUTTs (Sudden Brief Unilateral Tapering Tinnitus) last about 30 seconds and then fade away to nothing. It would be interesting if a subject experiences this during testing and you observe using the MEG. A side note, SBUTTs seem to be more frequent in tinnitus and hyperacusis patients [Oron 2011].
3. Why does playing a sound through headphones that resembles tinnitus not fade away? (Why is it not deemed imprecise relative to predicted sounds?). This seems like it may show limitations or barriers that need to be overcome. Especially if sound is used as the injection point to influence these feedback networks.
4. Cause and effect for brain waves. I wonder if it is easy to jump to conclusions about what is actually causing these waves (global or local influences) although i’m out of my depth here.

Works Cited

Macias, Angel Ramos, et al. “Cochlear Implants as a Treatment Option for Unilateral Hearing Loss, Severe Tinnitus and Hyperacusis.” Audiology and Neurotology, vol. 20, no. 1, 2015, pp. 60–66., doi:10.1159/000380750.

Mertens, Griet, et al. “Cochlear Implantation as a Long-Term Treatment for Ipsilateral Incapacitating Tinnitus in Subjects with Unilateral Hearing Loss up to 10 Years.” Hearing Research, vol. 331, 2016, pp. 1–6., doi:10.1016/j.heares.2015.09.016.

Oron, Yahav, et al. “Sudden Brief Unilateral Tapering Tinnitus.” Otology & Neurotology, vol. 32, no. 9, 2011, pp. 1409–1414., doi:10.1097/mao.0b013e3182355626.

 

Exposing Pathological Sensory Predictions in Tinnitus Using Auditory Intensity Deviant Evoked Responses (see attached file) is the recently published study, which aimed to establish a biomarker of tinnitus.

 

I would gladly do the online sound part of the study. Scanning the brain seems like a good idea. We could certainly use a way to prove the presence of tinnitus. Just stop shoving TRT down our throats. Use animals, as long as it's ethical and good luck. I'll let other people do the smart talk.

 

It would be interesting to know if the reverse also applies. That listening to certain sounds can influence the default prediction of silence to tinnitus.

I am way out of my league with this material here, but there are a lot of people who have expected hearing loss for their age, no other identifiable cause and they just suddenly noticed tinnitus without any obvious triggers.

Also by the way I would be willing to participate in any possible test as long as it is feasible to do it remotely

 

Thanks again everybody for further comments and questions. As previously, please find a list of replies to specific points and questions below:

Sudden vs. gradual onset hearing loss and risk of tinnitus development: I think it is likely that, even if these are of the same amount, sudden hearing loss poses a higher risk of tinnitus. Possibly because of how sudden the change in neural activity in the hearing pathway is, and also likely the physical and psychological stress and the altered attention (for instance, blast injuries in soldiers are such a common cause of tinnitus, combining sudden hearing trauma with physical injury and massive psychological distress).

The potential for different structures in the cochlea to be damages in some cases of tinnitus than in others: Absolutely I agree. I think all that is needed is some sort of damage that causes hearing loss. There is a lot of ongoing research interest looking at inner hair cell loss versus damage to the ribbon synapse, or to the different types of nerve fibres (high and low activation thresholds). Of course, a few cases of tinnitus may not require hearing loss at all, though this is an ongoing area of debate.

Resolution of modern brain imaging methods being the limiting factor in being able to record the brain activity responsible for tinnitus: This is a good question, and is a plausible explanation for why we cannot 'see' tinnitus. The resolution of recordings possible in animals is essentially unlimited, so might be able to settle this issue, but the limiting factor in animals is knowing which ones actually have tinnitus, which is still controversial. Better biomarkers in animals (perhaps derived from better biomarkers in humans, as I am working on) might significantly help in this regard.

Whether tinnitus is "a function of hearing loss": Tinnitus is clearly strongly related to hearing loss, but there are other factors at play here, and it is common to have hearing loss (of any severity) with no tinnitus.

Would restoring hearing cure tinnitus: There is reason to think it might (and very strong reason to think it would at least quieten the tinnitus significantly). Restoring hearing should reduce spontaneous brain cell activity in the hearing pathway back down to normal levels (which are still above zero). The question is whether some tinnitus will remain because the brain has "learned" to find that sound pattern in the spontaneous cell firing. But, I still think this offers perhaps the best hope of a full tinnitus cure of all presently identified approaches.

The upcoming study of sound therapy to try and treat tinnitus: There are no specific dates for commencement yet, and a few logistics still to be worked out. We will aim to post details on Tinnitus Hub when this is ready to run.

In terms of the planned studies, the exclusion of certain subtypes: My plan is to be broad as possible in terms of who to recruit and include. The only restrictions really are looking to be profound hearing loss (because the investigative/treatment sounds would not get into the brain), tinnitus that is exacerbated by sound exposure (because it would be unsafe), or pulsatile tinnitus that is likely to be due to audible blood flow (and is therefore a different condition entirely). While there is an ongoing scientific debate about whether there are distinct tinnitus subtypes, or just a spectrum across various factors, I am aiming to target brain processes that I believe are likely to be common to all tinnitus subtypes if subtypes do exist.

Sound protection: For fMRI, the issue of how scanner noise and sound protection affects hearing is one that applies to all auditory research and has well-established workarounds, which include using ear plugs with a flat frequency spectrum (like used by many musicians). In terms of the risks of sounds to hearing, there are known safe sound exposure limits, which will be followed. The less predictable issue is people who might find sounds unpleasant due to hyperacusis, or find their tinnitus exacerbated by the sounds. To mitigate this, we first pre-screen by asking whether people's tinnitus is made worse by moderate or loud sounds and advise non-participation to people in whom that applies. Then, the sounds to be used in the experiments are tested in a pre-experiment session where the frequency and volume of the sounds is adjusted to the ideal value, with one of the main focuses being ensuring the sounds are not uncomfortable.

Short bursts of transient tinnitus: It would be great to study this, but to make anything of brain imaging studies we would have to capture literally hundreds of these in the same individual, so it is probably unfeasible.

Why we do not tune out (and stop hearing) a constant persistent sound presented through headphones: We actually might, and I am not sure that anyone has ever tested this (it would require listening to the sound constantly without any breaks, day or night, for perhaps weeks on end). Although, the closer analogy to tinnitus would be wearing the headphones for a long period anyway, and following that to very gradually introduce a constant sound, starting from inaudibly quiet and slowly building up. I had previously applied for funding to try this, but did not get funded.

Best wishes,
Will

 

Hello Will,

If I were to compare your theory of tinnitus using Predictions, how would it be similar and how would it differ from Josef Rauschecker's model of explaining tinnitus?

Are you both saying that the tonotopic map in the auditory cortex reorganizes and begins to fill in for frequencies that have been lost as a result of cochlear damage? And, are you saying this is the source of random activity in the hearing pathway?

Then, using the Prediction Model, the brain begins to assign more weight to this random activity. This, in effect, is the brain learning to hear the random noise and so it becomes tinnitus? Is it possible to explain this a little more in terms of synaptic transmission and by identifying where in the brain this is taking place?

I also have read that the tonotopic map reorganizes and fills in frequencies after hearing loss in those individuals who do not experience tinnitus. Using the Prediction Model, is not experiencing tinnitus explained as the brain not assigning weight to this random activity and not learning, hence no tinnitus?

In Rauschecker’s model, the gating system that usually stops the random activity from reaching conscious perception is not working properly and that produces tinnitus. I believe he theorizes this takes place in the limbic system.

So then is it correct to say - according to the Prediction Model it’s the weighting and learning mechanisms that are faulty in the tinnitus brain while in the model Rauschecker is using it's the gating mechanism that is faulty?

Are there other models of brain function and is Rauschecker using one of them? Which, if any, is in more widespread use or more widely accepted?

My apologies for all the questions, but many thanks for your time and willingness to interact with us!

TC

 

Hi TC,

Thanks for the well-considered questions.

With respect to filling in from missing frequencies, and auditory cortex reorganisation, these processes might contribute to tinnitus, but I think they are, if relevant, secondary to the more fundamental origins of spontaneous activity in the auditory pathway, which in my mind are:
1) Everyone has spontaneous activity, as it is just a fundamental property of the nervous system
2) Hearing loss, of any cause, increases spontaneous activity. So, I consider this to be a risk factor for tinnitus, as the stronger the activity is the more likely it will end up being consciously perceived.

So far, Rauschecker's and my models agree with each other. However, where they differ is that Rauschecker proposes this particular circuit that suppresses activity being relayed up from thalamus to cortex. He thinks that if it functions normally it is sufficient to stop spontaneous activity getting through to reach cortex, but if it fails then the activity gets through and tinnitus is perceived.

My model is different, in that I think the activity probably gets through to cortex anyway, whether tinnitus is perceived or not. Rauschecker's process may or may not be relevant, but is not the key determinant of whether tinnitus occurs. In my model, spontaneous activity is weight up against the brain's default auditory prediction, which is of silence (or other sounds in the environment). It is the precision of the spontaneous activity that determines how strongly it competes against the default prediction, and if precision gets high enough then the spontaneous activity gets perceived as tinnitus.

The second part to my model is the resetting of default predictions, whereby once tinnitus has been there a while, it becomes part of the brain's default prediction. Once this occurs, tinnitus continues even if the precision of the spontaneous auditory activity reduced again (though the tinnitus might still quieten to a degree).

In terms of what is 'faulty' in the tinnitus brain, I would consider tinnitus as a state of the system, rather than a disease or deficiency. However, for pretty much everyone it is a state they would rather not enter and get stuck in. But what I am meaning is it doesn't necessarily mean anything is 'wrong' with someone's brain if they get tinnitus. In fact, some recent work by a collaborator's group (Nathan Weisz, paper available as preprint on BioRxIv while awaiting publication) has looked at the formation and use of auditory predictions in peple with tinnitus and controls (but used low to medium frequencies with normal hearing, well away from tinnitus frequencies). They found brain responses that suggested people with tinnitus formed predictions that better represented the structure and predictability of the stimuli they were presented than controls; i.e. if anything, people with tinnitus formed better, or more accurate, predictions. These are still tentative conclusions for now, but this line of work may go on to prove very illuminating about why some people get tinnitus and others don't under apparently the same circumstances.

Best wishes,
Will

 

Thanks Will for your efforts. I read your paper.

So in the past sound therapies (notched noise, notched music and ACRN) the idea is that 1st tinnitus frequency is discover and 2nd sounds are created that are around that frequency. However, once the sequence is set the brain can predict those sounds so it does not work? Instead you think the brain should be surprised as in MMN there is the element of surprise. So tinnitus sound therapy should be at or very near the tinnitus frequency not around it and the surprise would be either volume or duration?

https://en.wikipedia.org/wiki/Mismatch_negativity

My personal experience supports this at least in masking. Tinnitus maskers where my brain can find the sound pattern do not work because once my brain finds the sound pattern then it also can find my tinnitus sound. But if I run multitude of high frequency sounds then the brain cannot find any pattern and tinnitus is more easily masked. Like when running ACRN, and couple of myNoise sounds, e.g. Summer Night, Aural Scane, at same time and my tinnitus is completely masked even with low volumes.

http://generalfuzz.net/acrn/
https://mynoise.net/NoiseMachines/magicLocustsGenerator.php
https://mynoise.net/NoiseMachines/auralScannerNoiseGenerator.php

 

Hi Will,

Thanks very much for answering my questions. I have a couple more and do hope I'm not taking too much of your valuable time away from solving the tinnitus riddle!

1. Could you say a little more about what is meant by precision in the context of your model? Is this the synchronized firing of neurons that occurs with tinnitus?

2. I understand when you say that you consider tinnitus a state of the system rather than a disease or deficiency in the brain. Yet, something must have caused the brain to enter into the tinnitus state. There's been a change and it can't just be due to hearing loss because not everyone with hearing loss develops tinnitus. What something is driving the spontaneous activity towards precision in a brain that develops tinnitus? Would you say that same something must not be present or is not occurring in a brain that does not develop tinnitus? And, is this still to be uncovered perhaps by the future work that you mentioned by yourself and others?

Many thanks, TC

 

First thank you a lot for your interesting answers will.

This is less of a question but more of an anecdote:

Quite a few users here developed visual snow after getting tinnitus, others got increased floaters right after getting tinnitus. Some also seem to dream very vividly every night after onset. It seems that in a subset of tinnitus patients there seems to be some sort of a spillover to the visual processing. Maybe it's those who were susceptible to tinnitus from the beginning? Or as you said: people with brains which perform over-average predictions of sounds. Maybe these predictions also happen with visual processing?

 

My tinnitus was sudden onset with my first dose of Tamiflu on January 15, 2018 and has been constant since that day. I was told after a hearing test that I don't have hearing loss, though I don't know all of the parameters of my test. Will your study include medication-induced tinnitus?

 

Really looking forward to this.

 

Dr. Rauschecker's paper mentioned tinnitus patients had less grey matter in certain brain regions, as compared people without tinnitus.

Would you care to speculate as to why that may be so? Would less grey matter be indicative that something is wrong???

Are you implying that tinnitus is incurable?
Would hearing regeneration drugs eliminate tinnitus or quieten it to a large degree in your opinion?

 

Did you submit these questions via the link? I hope so, would like to hear Will Sedley's response to them.

Re whether or not his statement implies that tinnitus is incurable; this is not what I personally took it to mean. I thought the implication was that in his model of tinnitus there are at least two causal factors; auditory excitement and then the brain's default prediction. My understanding of his comment is that, even if the auditory excitement diminishes, we may still experience the tinnitus precept if the brain's default prediction is not reset. It's the resetting, which I believe he is aiming to achieve, that he believes may open the pathway to a cure, or at least more effective treatment.

Again, this is only my understanding. Would be good to have Will provide some clarity on this point so I hope your question gets through to him.

 

Thanks for the link, I submitted my questions.

 

Hello, my name is Ray Osorio and I read your research and i agree with part of it but i hope to be able to help a bit, please reach me at my Email raymundo22454675@gmail.com. and maybe get a bit of help as well.
I got tinnitus 7 yrs ago and i thinknit was noise induced after a noght at the bar dtanding beside a loud speaker. I was avle to lower my ringingat a point that o could hardly hear it, but now i am back at square one and o will try to lower it again and hopefully it works! I am hopefull anf have faith, sound therapies i believe work dependingbon the ringing and the sensitivities on the drums, hypercusis make it a bit harder but its managable i BELIEF!

 

I believe chronic inflamation is part od the problem, if we take carenof tge inflamation i believe we can lower the beep sound considerably, just my opinion.

 

❤ thank you Hazel!

 

Maybe an acoustic trauma causes tinnitus (and pain) because of a damaged TTM.

I have been exposed to noise all of my life, just like my father. My father is almost completely deaf (87) but has no tinnitus (or hyperacusis).

But I had an acoustic trauma in 2004, this felt like my ear broke or like the TTM just snapped, a very sharp pain. I think this event triggered all my problems (first mild tinnitus) that escalated in 2018 (into severe tinnitus and hyperacusis).

 

Thanks for the insight. I see you're a compatriot. How are you dealing with it after so long?

 

After the trauma in 2004 it took me only a few months to adapt, allthough initially I thought I wasn't going to be able to live with it. It was a mild tinnitus on the left (cat 0 Jastreboff). In 2018 this escalated suddenly to cat 4. Severe tinnitus and hissing in both ears and severe hyperacusis. Now, 2 years later I accepted it but when I have an onset it is still very, very difficult and hard to endure (earpain).