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

This looks like an interesting piece of research. A couple of points I would make, quotes are taken from the summary of your research plan.

I've highlighted your remark about once this occurs because I think a crucial part of any research into tinnitus is to try to determine early interventions which can prevent tinnitus experienced, for example with SSHL, becoming a chronic, long-term condition. For example, some countries recommend particular medications/steroids being taken immediately after SSHL and tinnitus following a noise exposure incident because of evidence that they can reduce the probability of permanent hearing loss and tinnitus. The UK medical establishment however specifically tries to prevent GPs from prescribing any kind of intervention.

A useful development of your research would therefore be to determine a time period following SSHL during which tinnitus becomes permanent and what interventions could prevent that from happening

What is determined as a comfortable volume and what evaluation has been made of the potential for either the ERG or the noise delivered through headphones for worsening the tinnitus of those volunteers with tinnitus?

This all seems rather similar to the current projects of for example Neuromod in Ireland and Susan Shore in the United States - to what extent is your work distinct from these other projects?

 

How about people whose tinnitus came on gradually, and had previous instances of their ears ringing after loud noise exposure, only for it to go away?
How come the brain suddenly latches onto it?
What about people whose tinnitus changes in pitch, tones or loudness versus those who have constant tinnitus?

If what we hear is background neural activity, how is it that most people hear the exact frequencies they've lost on an audiogram?

Just some thoughts.

 

Thank you for insightful comments so far. I will reply to these below, and do my best to answer further questions raised.

Regarding early interventions for tinnitus, I fully agree that this is a potentially very important area. As raised, firstly there is the potential to prevent tinnitus in cases of sudden hearing loss, which is worthy of exploration. Also, we have previously wondered whether simply treating tinnitus (whether or not due to sudden hearing loss) early on in its course (e.g. in the first few weeks) might be more effective than leaving it later.

Regarding comfortable volume and the potential for tinnitus exacerbation: I did not mention this in the previous description, but we screen potential volunteers for noise exacerbation by asking if they have a history of their tinnitus being made worse by moderate or loud sound exposure, and advise against taking part where this has been a feature. In the experiments themselves, 'comfortable volume' is determined by the volunteer, who controls the loudness of the sound to get it to a comfortable level before the experiment begins.

For the sound-based intervention, the similarity to the work of Neuromod and Shore is worth noting. There are two main differences: 1) They are bimodal (as in, they stimulate both with sound and touch) whereas I am testing something using sound alone. The sounds I will use are a unique design, which has never been tested in tinnitus before. 2) Because what I am testing is sound alone, it would not require any specialised hardward, and so could be made much more widely available if it worked

The point about tinnitus being intermittent in some cases before becoming chronic is good. The reason for this is not known. Some instances may be explained if there is temporary hearing loss (e.g. from loud noise exposure) then the tinnitus may come on with that but disappear when the hearing loss resolves. However, there are clearly many cases where this does not apply. In these cases, one possible explanation is that the brain has not yet 'learned' the tinnitus as its default state of hearing, hence it can still disappear, whereas once present for weeks on end it learns the tinnitus signal and therefore can no longer ignore it.

In terms of the brain picking up on spontaneous activity in the auditory pathway. It is a good point that it is no coincidence that it is the frequencies on the audiogram affected by hearing loss in which the tinnitus is heard. Most researchers accept that spontaneous activity is selectively increased in precisely the frequencies affected by hearing loss, as a way of compensating for the reduced input they receive from the ear.

Many thanks once again to all who have commented, or have yet to do so.

Best wishes,
Will

 

A warm welcome Will, great to have you here. I'd be more than happy to volunteer when the time comes.

Do you have a view with regards to the central gain theory? Very shortly after my onset of tonal tinnitus I started hearing my pulse in both ears at night, never noticed it beforehand, so from personal experience it seems like internal volume has gone up.

 

Hi Will,

I've recently been watching a number of your videos online so reading your input here is most encouraging.

I'm particularly interested by the reference in your document to tinnitus and hyperacusis sharing many similarities with chronic pain. Are you familiar with the work of V S Ramachandran and his mirror box device used to treat phantom limb pain in amputees? I'm not a scientist but I've long had this hunch that a similar mechanism that creates the sensation of pain in a phantom limb creates the tinnitus sensation in our heads/ears.

Happy to participate in the trial by the way if I can get in at UCL with the EEG.

 

Will, will your treatment have any effect on Visual Snow?

 

Why does the character of tinnitus change in terms of pitch and tonality? Upon loud noise exposure, acoustic trauma- and noise exposure-induced tinnitus more clearly has a distinct “eeeee” tone but tends to fade into a lower volume, higher frequency hissing.

Why would tinnitus be lowest upon waking, only to grow as the day continues?

 

I’ve been told by several people that it’s possible that you can’t hear the beep of the pure tone audiometry because your tinnitus sound interferes or matches the beep frequency (more or less). So you are led to think that you have damage at frequency x, but in fact you don’t, you just can’t properly make out the beep because your tinnitus sound has the same frequency.

I’ve discussed this with some audiologists. They said my main tinnitus sound is likely at 8kHz, but you probably have no significant damage at 8kHz, even though you have a 25dB notch in the audiogram. I highly doubted this, but did a DPOAE test and this confirmed or should confirm that my hair cells are not damaged at 8kHz. My hair cells were perfectly echoing the sound back to the recording device they inserted in my ears.

 

FYI neither test accounts for inner hair cell damage or synaptic damage.

 

That is very true. They didn’t tell me that in the hospital, but when I later checked DPOAE specifics on the Internet, I found that they only talk about OHCs. I don’t know why. I guess this technique is not capable of picking up echoes from IHCs? I don’t know at all and never figured out this point.

You’re also right about cochlear synaptopathy, there’s absolutely no objective test for that. Only word in noise can give an indication thereof, which shamefully I haven’t done. My audiologist in a specialised tinnitus clinic didn’t even suggest it to me. I’ve been thinking about this for a while, to go back and do one. Maybe it will tell me something I’m not aware of.

 

I'm not sure if you don't have widespread synaptopathy in the speech range if you will have much speech in noise issues but it's definitely worth a try imo.

 

Good luck with inventing a therapy only based on sounds. There have been many. They cost 1000s of €, non of them worked even the tiniest bit.
I'm afraid that it's not possible to treat tinnitus just with sounds. Many tried, all failed.
But if you can convince me that it's possible, I will pay 10.000€ for that treatment.
Actually I also don't think that the brain remembers the tinnitus sound somehow. The upper brain just reacts to what's coming from the brain stem. There is a nerve damage, most probably in the cochlear/DCN area. The rest of the brain works fine, it's processing the input like a computer.

 

So it's actually the reverse happening? One doesn't hear because of the tinnitus interference? I kind of doubt this can be the case, but who knows right?

Dr. Rauschecker believes the tonotopic map can be reorganised if the neighbouring frequencies are damaged with adjacent brain cells taking over. So maybe you could check out 7 and 9 kHz to shed some light?

Today I had an audiogram done and asked for an extended one. I posted them on here. For the first time I got diagnosed and the ENT used the term "hearing loss" to describe my case. All the audiograms before that were a-okay because they didn't go any higher than 8kHz.

So it's not a relief, but at least it's worth something to get some palpable evidence something isn't right. I'm still wondering why it's not standard procedure in the case of tinnitus. Granted, it doesn't have any value for further treatment because, well, there's only hearing aids and counseling on offer really...

But still, there's some evidence suggesting that everyone with tinnitus has some form of hearing loss and it'd be good for future research if we could just get the message across to every ENT once and for all. It's a patient's right to be properly diagnosed and know the cause of his/her tinnitus, even if it doesn't give any way to further treatment at the present time.

 

I wish there was a way to educate ENTs about this need for extended audiograms on a national level.

 

Well I honestly don’t know because everybody has their theories on tinnitus and in the end it becomes all confusing and simply confirms we really haven’t figured it out yet for non pulsatile and non somatic tinnitus. I simply explained what several audiologists told me, but they could all be wrong of course. Their education could be outdated, but they are supposed to be the experts, no? Brai3n also told me I had no hearing damage. When I challenged a senior ENT in a university hospital, she simply said that it cannot be objectified.

I’ve already done an extended audiogram and plenty other tests a long time ago. My hearing is truly excellent above 8kHz all the way up to 16kHz. On average 10dB threshold above 8kHz. Below 8kHz everything is within range for my age. I only have a 25dB notch at 8kHz on the left side and 15dB on the right side. Yet I have a three different tinnitus sounds. Low, Mid and a High frequency.

The only possibility for me seems to be cochlear synaptopathy if my tinnitus is related to hearing damage or perhaps some issue higher up along the auditory pathway.

Although there is also the theory about other adjacent hair cells being triggered for the missing frequencies.

I’ve argued with all ENTs and audiologists that they need to do extensive testing and that the extended audiogram must become standard. They didn’t even do one in a specialised tinnitus clinic. It’s not because they will be able to do something about it, but to show that there really is no damage across the entire spectrum. I don’t consult them for hearing damage in the speech spectrum, I want to know if there is any damage anywhere that could have resulted in tinnitus. Consequently, people should not claim to have hidden hearing loss without having done all the tests.

I really wanted to find some clear cut hearing damage as that would have given me hope that this can be fixed in the coming decade with some first generation hearing regeneration solution.

 

@Will Sedley

Thanks so much for interacting with our community.

I have read your document. It refers to the theory of auditory memory, right?




Do you have any publications or articles of any kind that go into more detail about above referenced theory / hypothesis of “predictive auditory memory” in general or specifically in relation to tinnitus?

Could you tell us what you mean with ‘random brain cell activity’?

Edit: Found your publications on:
https://www.researchgate.net/profile/William_Sedley

 

What is your opinion on why this happens for some people with hearing loss and not for others? Some people have very serious sudden hearing loss, yet no tinnitus whatsoever. Could there be an additional factor in play or is it a matter of how the damage happened?

Do you suspect that tinnitus can come from any point in the auditory pathway or is it more likely related to cochlear specific damage?

Do you believe that idiopathic tinnitus is always related to (hidden) hearing loss or could it be something else?

Thanks in advance for sharing your opinion.

 

Have you managed to find out what frequency your tinnitus is at? Will Sedley's confirmed that he believes audiogram and tinnitus frequencies are linked, even though you spoke to ENTs who believe the opposite.

 

If it’s directly linked to what you see in an audiogram then it should be (around) 8kHz for the high frequency. The other two sounds I cannot identify in terms of frequency. I find this incredibly hard to do and I’ve tried many times to put a frequency on it. I really don’t understand people who claim to have a tinnitus on an exact frequency like 8247Hz.

 

I'm assuming it's a noise rather than a pure tone? This makes it harder to identify indeed. I can't pinpoint mine either and I've had a lot of formal musical training but when it's a narrowband noise it's hard. I know it's where my hearing cuts off.

 

A loud very low frequency humming, some mid frequency noise and then a loud classic high pitch eeee tone. That is what I can distinguish.

Anyhow this is off-topic.

 

With regards to matching tinnitus frequency / pitch. What if like many of us, you have more than one sound?

 

Wow, thanks everybody for a lot of great questions and comments.

Hearing pulse:
I know people often try to categorise tinnitus as 'pulsatile' (i.e. hearing blood flowitself ) or 'non-pulsatile' (what we usually mean by 'tinnitus'). However I have long been convinced that there is overlap in some cases. My tinnitus is in most respects typical and non-pulsatile, but I certainly hear it go in time with my pulse a lot of the time. All the different senses in the head, neck and ears communicate, and things like blood vessel stretching with the pulse could easily modulate tinnitus. It also seems plausible that once the brain has tuned in to tinnitus, it might also tune in and hear blood flow where it didn't before, and hence get both kinds of tinnitus.

Central gain:
Most researchers think that central gain is at least part of the process of tinnitus. However, personally I don't think it offers a compelling full explanation. I wrote an article on this last year 'Tinnitus: does gain explain?' which is free online. There is some even more evidence coming out that suggests central gain may be increased in tinnitus with hyperacusis, but reduced in tinnitus without hyperacusis. But whether this 'reduction' is because some of the auditory pathway is taken up with encoding the tinnitus, hence not responding so much to other sounds, is a possibility. This is a fascinating and important area which researchers have yet to reach a consensus on. Watch this space...

Tinnitus and phantom limb pain:
Great comparison. Lots of parallels, and some evidence of shared mechanims in the brain.

Visual snow:
I hope to do some studies directly on visual snow in future, but I have a few other things to get through on my list first. I think anything that sheds light on tinnitus will help shed light on VS, and vice versa.

Changes in tinnitus due to noise, time of day, etc.:
Good questions. Why do some peoople get a constant unchanging sound, whereas in others it is much more dynamic and responds either to various other factors, or changes for no clear reason? Hard to say really. Some people talk of tinnitus as a barometer of how they are doing in their general health/stress/wellbeing. There are brain mechanisms by which our level of activity and alertness turns up or down gain in the brain, so these could affect tinnitus. Also, for at least 20% muscle activity or posture of the head or neck modulates tinnitus.

Not hearing audiometry beeps due to the tinnitus or the hearing loss?:
We see this conundrum all the time. And it is so hard to tell which is it. The tinnitus always occurs in the area of hearing loss, so we just can't tell. In principle one could do a study where we temporarily suppress tinnitus and see how the sensitivity to the beeps changes in that period.

Cochlear synaptopathy:
The evidence of this (reduced ABR wave 1 etc.) underlying tinnitus has not been replicated in a large proportion of studies, so it seems like it is proably there in some cases but not others. Though the studies coming through recently do seem to be showing changes in the middle ear muscle reflex in tinnitus, which is another possible marker of synaptpathy. But, there is no practical benefit to testing for synaptopathy in routine practice, as it won't change treatment. It is very much a rersearch tool at present for understanding mechanisms of tinnitus.

Doubt over whether sound therapies can work:
I fully agree the odds are not wonderful. Indeed, many therapies have been tried, and most do not work better than placebo. A couple have shown some benefit in trials, and it has always saddened me how these have been commercialised with a huge price tag. The approaches I am planning to try are new, and would work via a different mechanism, so there is still a chance. Oh, and if they work then I have no intention of trying to make lots of money out of them.

Tonotopic map changes:
All the initial studies that suggested that these map changes were responsible for tinnitus compared people with tinnitus plus hearing loss to people with no tinnitus and no hearing loss. All the more recent studies that controlled for hearing loss found no difference. In fact, one is just coming out now showing that, once you account for hearing loss, tinnitus is associated with less tonotopic map change. I believe similar things were found for phantom limb pain (i.e. the map plasticity indicates the amputation, not the pain).

Underlying theory of predictive processing and auditory memory in tinnitus:
For further info, you can read my paper entitled 'An integrative tinnitus model based on sensory precision' which is free online. It is fairly heavy-going in places, but I have tried to make it understandable in others. It tries to explain how there can be various different contributory mechanisms, but how they all culminate in a single process whereby the brain stops ignoring spontaneous cell firing in the auditory pathway, and starts experiencing it as sound.

Tinnitus matching where there is more than one sound:
Good question. In terms of investigating mechanisms, I tend to ask the volunteer to focus on their dominant tinnitus sound, or even just pick one. Though, it may be slightly moot, because tinnitus pitch matching is so notoriously difficult and unreliable in most people (compared to loudness matching, which is very reliable) that we are probably only just 'in the ballpark' most of the time, rather than spot on. Thankfully, for my ongoing line of research, this doesn't seem to matter, and we seem to be able to tap into tinnitus mechanisms by just being close.

Going 'off-topic':
I don't mind that at all It is always nice to learn and be reminded of what is important to people living with tinnitus. It is you we are all doing this for, after all.

Thanks again everyone.

P.S. I really must try and do some new up-to-date research videos. The ones online are getting outdated now. Not that they are necessarily incorrect, but there have been advances in our understanding of tinnitus since then.

 

What do you think of the assumption that a sudden hearing loss like an acoustic trauma will give rise to tinnitus whereas very slow hearing loss like age-related hearing loss doesn't cause a huge change in the brain so no big groups of brain cells can start showing synchronized firing?

Thanks for doing this and being on here to answer our questions. It's unique and much appreciated.

 

Faith in humanity restored.

 

Thanks so much for doing this! A few more questions, I hope you don't mind...

Is cochlear injury believed to be the inciting cause of most tinnitus and hyperacusis? If so, is why one single structure has not yet been implicated because there isn't likely a single unified cochlear structure responsible (e.g., might by synapse in one person, hair cells in another etc etc)?

What about people who get tinnitus from things like antidepressants? Does the neuroexcitability start in the neurotransmitter receptors in the cochlea or does it seem to affect the brain directly? How does it decide what frequency to use if it's the latter?

 

So I read (with more or less attendance I must admit) your publication "An integrative tinnitus model based on sensory precision". I particularly remembered the sentence : "This means that observable neuronal activity is a signature of disequilibrium, rather than of perception per se."

So I guess, you are looking to prove your theory by the facts. I just hope that, for your study, you will get the most advanced technology (MRI strength*, EEG and MEG resolution) to screen this neuronal activity and then to confirm your theory.

* like this one : http://www.cea.fr/english/Pages/News/Iseult-MRI-Magnet-Record.aspx
Feel free to disturb the CEA, this MRI must be used for something.

If I undertood correctly, your theory involves Psychoacoustic treatment and Residual Inhibition. I just would like to know if you are in contact with Arnaud Norena, from CNRS Marseille, who is working on the same fields of tinnitus.

Many thanks for spending your time to answer to our questions and to collect our thoughts.

 

In my opinion the current state of imaging technology is the main reason why we can’t figure out tinnitus, hyperacusis, visual snow and so many other neurological disorders and conditions. We are simply not capable of seeing what happens in the brain on the neuronal level. We just can’t see where the neuronal paths are interrupted, overexcited, where the inhibitory neurons are failing to do their work or where neurons are out of synch et cetera. We have a very low resolution view on what happens in the brain. We only have a macro understanding and need to evolve to the pico level and beyond. This will unfortunately still take a very long time until we have the imaging technology that is capable of seeing brain activity in such precise detail. MRIs and so on are mainly used to see strokes, aneurysms, lesions, decreased or increased brain matter and large scale over or underactivity. Things you can see on a low resolution image.

I’ve come to the understanding that tinnitus can probably arise from abnormal neuronal activity anywhere along the auditory pathway, starting at the cochlea, all the way through the brainstem (cochlear nuclei, superior olives) along the midbrain (inferior collicili) and the thalamus (medial geniculate nuclei) to the auditory cortices. It can be an issue in the nuclei or in the internuclei pathways. It can even come from failing non-auditory pathway neuronal activity which is supposed to interact with the auditory pathway and modulate the auditory signal, for example in the thalamic reticular nuclei.

And likely a lot more that my broken brain is incapable of understanding.

An additional problem is the current state of pharmacological “technology”. As far as I know we are not capable of targeting specific neurotransmitters in specific parts of our body. If we would know which neurotransmitters were failing or are doing something abnormal, we would still not be able to really treat the problem directly. Current neurochemicals have a broad application and affect all receptors in the brain, instead of just the failing GABA receptors in the thalamus for example. So you get all kinds of side effects as these chemicals affect other GABA receptors in your brain which do not have a problem. When you use serotinergic or glutamergic chemicals they will affect all serotonin and glutamate receptors, et cetera, as far as I know. Please do correct me if my understanding is wrong or inadequate.

The problem here is that this approach is outdated or primitive in my opinion and the medical field needs to move ahead to neuroregeneration. Broken or dead neurotransmitters cannot be fixed with these chemicals. We need brain regeneration small molecules ;-)) Unless you are lucky enough to have tinnitus that directly stems from a problem in the cochlea itself. The rescue team seems to be on the way for you people.

 

Extended audiograms don’t evaluate your hearing at the many thousands of untested notches. Therefore blanket therapies that restore hearing in the upper registers should indiscriminantly restore hearing to all of these little notches that are likely the main contributors to HF tinnitus.