New University of Michigan Tinnitus Discovery — Signal Timing

[John Mahan]

Thanks.

Thanks Chris. I just took some time and read a couple of Shore's recent papers - her 2018 pre-clinical trial of bimodal stimulation, and her 2019 Neuron review (which is a tougher read, to be sure). I now have a much better understanding of her work, theory, technique, etc. It's promising for sure. Though the fact that the tinnitus percept comes back almost immediately upon stopping bimodal stimulation is a bit of a bummer. Particularly since the long-term effects of the technique are unknown (meaning it may or may not be suitable for lifetime use).

So, she's promoting LTD in the cochlear nucleus. I think her Neuron review implies how this is done. Has no one tried to recreate her pipeline? Test it out?

Even if we have to steal one of the machines and use it 30 minutes a day into perpetuity, it maybe worth it to keep the noise off our doorstep.

This made me think of something. I was cruising YouTube and there was this nice lady talking about her experience with Lenire which is now up and going as many know and there are quite a few positive testimonials on YouTube.

This lady said when the 12 weeks was up, she lied about not being home so she couldn't return the device and she said she kept it and used it for 2 more weeks.

Me personally...when asked to return the machine? Sorry but my dog ate it along with my homework. Bad Fido.

 

[Fabrikat]

I don't think this question has been covered before, but does anyone know if Susan Shore's device will have the same hearing loss limits for potential users as for Neuromod's device? Has she given any clues at all in this regard?

 

[ChrisBoyMonkey]

I don't think this question has been covered before, but does anyone know if Susan Shore's device will have the same hearing loss limits for potential users as for Neuromod's device? Has she given any clues at all in this regard?

From people that have emailed her regarding the trial hearing loss seems to be less of an issue for her device, but she hasn't been specific other than people should be able to hear the sounds of her treatment.

 

[Stefaniie]

I don't think this question has been covered before, but does anyone know if Susan Shore's device will have the same hearing loss limits for potential users as for Neuromod's device? Has she given any clues at all in this regard?

People have asked but she won't answer. I understand she most likely isn't allowed to discuss it while trials are still ongoing, but still. I wish they would just come out and say if they believe this treatment will work for those with more severe hearing loss. If it does, then it gives us hope. If it doesn't, at least we won't have to be devastated when the device finally comes out and it turns out we're ineligible. The not knowing is awful.

 

[Fabrikat]

at least we won't have to be devastated when the device finally comes out and it turns out we're ineligible. The not knowing is awful.

Yes! Lenire's exclusions hurt a lot. If Susan Shore's device has the same limits, then things are going to look pretty bleak for some us for a fair while longer.

 

[Bobbette]

 

[all to gain]

Thankfully, it seems post people's tinnitus is somatic.

Damn, mine isn't.

I didn't realise most people's is somatic.

 

[ChrisBoyMonkey]

Damn, mine isn't.

I didn't realise most people's is somatic.

Try clenching your teeth or moving your jaw around. If it gets louder or quieter, or pretty much changes in any way, it's somatic. I think there are more ways to check for it but that's the best I know that comes to mind because that's how mine is. She still hasn't confirmed if it does or doesn't work for non-somatic yet.

 

[Daniel Lion]

Damn, mine isn't.

I didn't realise most people's is somatic.

Me too, mine doesn't change, but that doesn't mean we are out of the game.
Let's stay positive... 2020s should bring something... if not... well that's another road we can deal with later.

 

[all to gain]

Me too, mine doesn't change, but that doesn't mean we are out of the game.
Let's stay positive... 2020s should bring something... if not... well that's another road we can deal with later.

Daniel, i haven't got the slightest bit of positivity in me! Life is torture. And saying the words 'should bring' gives me no hope. Sorry for the doom.

 

[Johnny Karate]

Mine goes way higher pitched when I open my mouth wide, does that mean it is somatic?

 

[GoatSheep]

Mine goes way higher pitched when I open my mouth wide, does that mean it is somatic?

yes

 

[linearb]

Me too, mine doesn't change, but that doesn't mean we are out of the game.
Let's stay positive... 2020s should bring something... if not... well that's another road we can deal with later.

If and when a UMich device emerges, I will be very curious to see it used by people who have clear noise trauma or HL involvement but no discovered somatic triggers.

I do not want to provide any false hope, but I think it's worth explaining something I don't have a good answer to (which would be a great question to ask one of the lab techs, for anyone who might be involved in a current trial and reading this).

In the animal studies which proceeded the development of the human protocols, as far as I know, no differentiation was made between "somaticly involved experimental animals" and not. Meaning, the study protocol was just:

• invoke noise trauma in animals with sustained ~90dB noise (don't remember exact number but it wasn't staggeringly over OSHA limits)
• differentiate between tinnitus animals and non tinnitus animals (complex; explained in publicly available information)
• treat tinnitus animals with experimental device and re-assess tinnitus over time

Selecting only a patient group / cohort with obvious somatic involvement, has been done I believe because there is a hypothesis that the device will work more reliably in this group based on how it works, and because the goal of a pre-market study is to use the cohort most likely to show a clear benefit with a high confidence.

We don't know what we don't know, but I'll tell you what @Daniel Lion -- if I ever get one of these things, you should come visit my wooded wonderland for a few weeks and take it for a test ride. I think my family would allow it if you're cool sleeping in a tent on a platform.

 

[Daniel Lion]

If and when a UMich device emerges, I will be very curious to see it used by people who have clear noise trauma or HL involvement but no discovered somatic triggers.

I do not want to provide any false hope, but I think it's worth explaining something I don't have a good answer to (which would be a great question to ask one of the lab techs, for anyone who might be involved in a current trial and reading this).

In the animal studies which proceeded the development of the human protocols, as far as I know, no differentiation was made between "somaticly involved experimental animals" and not. Meaning, the study protocol was just:

• invoke noise trauma in animals with sustained ~90dB noise (don't remember exact number but it wasn't staggeringly over OSHA limits)
• differentiate between tinnitus animals and non tinnitus animals (complex; explained in publicly available information)
• treat tinnitus animals with experimental device and re-assess tinnitus over time

Selecting only a patient group / cohort with obvious somatic involvement, has been done I believe because there is a hypothesis that the device will work more reliably in this group based on how it works, and because the goal of a pre-market study is to use the cohort most likely to show a clear benefit with a high confidence.

We don't know what we don't know, but I'll tell you what @Daniel Lion -- if I ever get one of these things, you should come visit my wooded wonderland for a few weeks and take it for a test ride. I think my family would allow it if you're cool sleeping in a tent on a platform.

Thanks man, your words really mean a lot.

I am not looking for a "savior" as some have posted.

I've reconciled myself to a tough road but one still full of joy and wonder.
Such is life when your disabled, I am stupid but not naive.

Anyhoo, if some relief comes... great, if it doesn't, so be it.
Either way sleeping under the stars in Vermont is awesome and I will not be robbed of life's beauty... well ok robbed a little from time to time.

I am gonna continue to fight for me and my family.
I took them to a festival last night, boat racing, it's the end of Bhuddist Lent. It's loud.
I found a quiet spot and chilled away from the chaos and read and drank fruit shakes.
Two hours later my kids and wife came back exhausted and happy. My son said it was way too loud for me, even for him. I apologized I couldn't be with them, everyone was "we love you dad, it's cool"...

There you go, a day in the life of Daniel.

Appreciate our friendship... take care.

 

[Mitch]

Try clenching your teeth or moving your jaw around. If it gets louder or quieter, or pretty much changes in any way, it's somatic. I think there are more ways to check for it but that's the best I know that comes to mind because that's how mine is. She still hasn't confirmed if it does or doesn't work for non-somatic yet.

Thank you for posting this, I wasn't sure if my tinnitus is somatic or not, but I now notice it gets louder and higher pitch if I push my jaw forward or if I yawn or stretch.

 

[Mr.Drop]

I wonder if it will work if there are several different frequencies in tones and hisses.

 

[Daniel Lion]

I wonder if it will work if there are several different frequencies in tones and hisses.

I bought 200 kilos of terracotta clay yesterday. I am going to make a small sculpture of Dr. Shore. She is a genius and super hot, as in attractive. I will post on completion and of course send her a photo or copy. She is one of my heroes.

 

[Mitch]

I am curious why it matters at all whether the tinnitus is somatic or not for the purpose of Dr. Shore's treatment. If the source of tinnitus is the dorsal cochlear nucleus as she claims, why would bimodal stimulation not work for people with non-somatic tinnitus?

The most I could find on this was this interview with Dr. Shore:

What, then, does Shore's study mean? The key is in the word synchronicity. She found that fusiform cells in the dorsal nucleus fired together in animals that had tinnitus, and her study was based on years of studying these cells figuring out how to influence them to alter this process in a specific way that lessens (rather than increases, as is also possible) the tinnitus percept.

For years she studied these fusiform cells in the dorsal cochlear nucleus, discovering in the process that they not only respond to auditory inputs, but also somatic sensory ones – information inputted via the skin, skeletal muscle or sensory organs. This built on the work of Robert Aaron Levine MD, who first discovered the presence of a somato-sensory connection in some tinnitus, which can be momentarily modulated (for better or worse) by clenching the jaw, or pushing on their face. In other words, touch and movement can activate these neurons, just like sound can.

By presenting sound combined with a systematic sensory stimulation, Shore was able to induce long term changes in the neurons in the dorsal cochlear nucleus to change their firing rate. Shore and her team worked out the specific combination of auditory and somatic stimulation required to reduce synchronicity in animals, and then played that specific combination to humans whose tinnitus, they had already established, was capable of being modulated. In Levine's studies, Shore says, he shows that approximately two thirds of people are able to do this if shown how.

 

[Instant_exit]

Im sitting here looking at this https://stm.sciencemag.org/content/10/422/eaal3175/tab-figures-data and https://stm.sciencemag.org/content/scitransmed/suppl/2017/12/27/10.422.eaal3175.DC1/aal3175_SM.pdf and trying to figure out what they are actually doing here.

For me, the actual timings between audio and electrical stimulations are very unclear. What is the reference of the timings? Is it the start of the auditory stimulation, the middle, the end? Looking at this (attached) picture of a guinea pig from earlier research from the team, you can see on the left side where tone stimulus is 50ms long that the reference is always the start of the auditory stimulation, but on the right side for the 10ms it is not. On the 10ms side, all electrical stimulation preceeding audiotory seems to have the start of the audio as reference, and all stimulation after the audio seems to have the end as reference.

If you were to use the same logic on the 10ms side as for the 50ms side, -5ms stimulation would come in the middle of the tone, and not with a 5ms gap after the audio has ended, as shown in the picture. Its pretty unclear to what reference the timings in relation to the 10ms audio file are refering to. There seems to be an error of logic here in the picture, and im trying to figure out what reference to timing is the correct. See picture of guinea pig to understand what I mean.


In the human/guinea-pig study in 2018 they used 10ms tones paired with -5ms bimodal stimulation (audiotory stimulation preceeding electric stimulation by 5ms). Is that 5ms after the 10ms tone has ended, or 5ms after the start of the tone? (Which would put the electric stimulus in the middle of the 10ms tone) See my Illustration for clarity.

I should probably just email them and ask, but I figured someone here might know the answer.
It is not very clear to me at least.

Cheers,
J

 

[Autumnly]

In case anyone missed it, she said (starting at 04:15min) they're expecting the results from Phase 2 by the middle of 2020.

 

[vttbx]

Does anyone know if her study is listed on the clinical trials website?

https://clinicaltrials.gov/ct2/home

 

[ChrisBoyMonkey]

Does anyone know if her study is listed on the clinical trials website?

https://clinicaltrials.gov/ct2/home

https://clinicaltrials.gov/ct2/show/NCT03621735

 

[Rb86]

https://clinicaltrials.gov/ct2/show/NCT03621735

So it began over a year ago and zero updates. Ok.

 

[ee9892]

So it began over a year ago and zero updates. Ok.

Participants sign an NDA to not disclose information while the trial is underway. This makes sense.

 

[linearb]

Participants sign an NDA to not disclose information while the trial is underway. This makes sense.

Maybe they did in the phase II, but we definitely didn't get NDA'd in the phase I and I posted a bunch on here before and right after.

So it began over a year ago and zero updates. Ok.

With a study completion date 3 years in the future I am not quite sure what you're expecting here.

There has not been a lack of expected business-as-usual press releases from the lab in the meantime, and I believe Dr. Shore has been interviewed about current status within the next few months?

Compared to drug trials, this is all moving astoundingly quickly. The lab is not going to have anything useful to say about a blinded study which is still in process; if you could make meaningful observations about what was happening before data aggregation and unblinding.... it would mean that your blinding process doesn't work and so the data you're producing is useless anyway.

There's nothing unusual about relative information darkness from research institutions while said research is actively being conducted in RCTs. Contrast this with venture-backed capitalist endeavors, which necessarily have a group of financially invested stakeholders that they might try to appease by putting out frequent PR with colorful infographics showing their own analysis of their data, without publishing full data sets, and even more damningly without using placebo control at all in their methodologies...

...not that I am calling out any specific entities or organizations, of course.

 

[ee9892]

I'm in the phase 2 trial. There's an NDA section in the initial papers you sign now.

 

[linearb]

I'm in the phase 2 trial. There's an NDA section in the initial papers you sign now.

It's entirely possible I signed something to and promptly forgot. My short term memory isn't what it used to be, thanks in no small part to the trifecta of chemicals I use to suppress the noise...

 

[ChrisBoyMonkey]

So it began over a year ago and zero updates. Ok.

Did you seriously miss the interview we have with her posted about a month ago?



Cured in mice is Dr. Bao's cautionary warning on his research. He has to verify safety of the pill before starting human trials. It could be the full on cure cure though. I have no idea why you'd use such a ridiculous and irrelevant analogy to compare his research to. He's been looking into tinnitus for quite a few years too.

It's kinda funny how you're mocking the research that's probably gonna save you. It's almost like you want to hurt.

 

[GoatSheep]

It's kinda funny how you're mocking the research that's probably gonna save you. It's almost like you want to hurt.

He's just frustrated and suffering. We all are. @Rb86 is normally all about positivity and success stories.

 

[ChrisBoyMonkey]

He's just frustrated and suffering. We all are. @Rb86 is normally all about positivity and success stories.

Could be, but taking it out on the world is selfish. Also, I just can't stand the spreading of misinformation.