Dr. Konstantina Stankovic

So now there is mounting evidence for a strong link between hearing loss and dementia.

You partly answered your question because sound intensity is the key.

And as humans, we can produce only sounds of certain frequencies.

And throughout history, people have used horns.

Horns really work.

And so that would be the first thing that you do.

And you can even create it like this yourself.

Exactly, to project.

But if you have a longer horn, use that.

That really works.

In terms of our human ability to detect tones, in every species, it's a sensitivity curve.

Hearing loss is a huge problem.

So, when we test hearing in clinic, we tested only up to 8 kilohertz, but we can hear up to 20,000 hertz.

And it's because most of speech really lives below that frequency.

Lots of speech lives between 250 hertz and 4,000 hertz.

And if you speak at those levels, which we do because that's what we do as humans, women can have more high-pitched voices or children can have more high-pitched voices, but it's still in the range of optimal human hearing.

That's what you would need to do.

So then all you have to do when you're in a situation like that is speak as loudly as you can, and if you can, find a horn so that it amplifies.

Intuitively, exactly.

And that works too.

It absolutely works.

Our patients tell us it works.

Sometimes in the clinic, if people don't have a hearing aid and they are really hard of hearing and they don't

know how to lip read, and they don't want to be reading what's being written, that's what they do.

And it really makes a difference.

Exactly.

Yeah, it's vestigial.

Some people indeed can do it.

It's not common.

And as far as we know, it doesn't convey any advantage in modern world to human hearing.

I don't think that's been studied.

I certainly haven't come across data to support that.

In human body, things tend to be very proportional, and they grow with time.

Children tend to reach their adult ear size around age 10.

So, for example, those who are born without the outer ear altogether, that's called microtia, we can make it, but the timing of surgery has to be...

and conduct it appropriately so that you don't give them too small of an ear if you operate too early.

It currently affects one and a half billion people and disables half a billion of them.

Absolutely.

Really, the brain has evolved to perceive and manage sensory inputs.

And sound is one of these sensory inputs, and it's critical for emotional well-being.

We have thus far talked about the periphery, what happens in the inner ear and how those signals are then transmitted all the way to the brain.

Well, there are numerous relay stations from the ear to the brain, to the cortex, and they are in the brain.

brain stem and midbrain, all the way to the cortex.

And these auditory pathways have very strong links with emotional pathways and the limbic system.

And in fact, that's why music, hearing music, can really move us.

That's why remarkable speeches of impressive leaders can get people aroused and motivated to do something.

So that link between hearing and emotion is really strong, well-established, and sometimes can be detrimental, for example, for people with tinnitus.

So tinnitus, it's a phantom sound.

It's produced by the brain, typically in response to reduced input to the brain.

So the brain makes up the sound that it's normally not detecting.

It's similar to phantom limb pain where people don't have an arm or a leg, but they can still perceive pain in the limb that they don't have.

So now some people with tinnitus can just put it in the background.

They can ignore it.

They are reassured by knowing that it's not life-threatening and it's fine.

But there are people who can't handle it.

They are really severely disabled by it.

And some are suicidal, which is a huge spectrum.

And why is that?

So clearly, these circuits in the brain are differently connected for different people.

And in some, that emotional component is really amplified.

There is this phenomenon of hyperacusis or even phonophobia.

And when it comes to hyperacusis, it frequently accompanies hearing loss.

And really what happens in people with hearing loss is that sounds have to be loud enough for them to hear them, but if they are too loud, that can be painful, very uncomfortable.

So their dynamic range of hearing is reduced.

And pretty much everybody with hearing loss experiences that.

Now to have a real fear of sound, phonophobia, that's not common, and it's usually linked with some underlying mental health condition.

It's more common in people with obsessive-compulsive disorder or personality trait and other conditions.

You are correct.

And that can be true for both unpleasant and pleasant experiences.

And you are absolutely correct that it goes into our memory bank.

And how do we know that?

There are people who are profoundly deaf.

And if they have been profoundly deaf for many years and now they are becoming a candidate for having cochlear implant surgery, and that's surgery that bypasses any cells in the inner ear that could be missing or non-functional, and it directly electrically stimulates the auditory nerve,

Before they have that cochlear implant surgery, when they've been profoundly deaf, they can have memories of music that they used to listen to.

So these are auditory hallucinations, but they are different musical hallucinations.

They're not like auditory hallucinations that people with schizophrenia have.

They're not hearing voices.

They're hearing symphonies.

and concerts in their head, whatever music they used to listen to.

And what's fascinating is after they get the cochlear implant and now they can hear speech, those musical hallucinations go away.

Possibly.

And what I say possibly is that until maybe 10 years ago, we thought that if you go to a concert like that, you have ringing in your ears.

You may even feel like your ear is clogged.

And then it goes away, that that is temporary threshold shift.

But now we know that some forms of temporary threshold shift are in fact permanent.

Although your hearing may come back, and in fact we can see it on audiometric testing, we now know that

The wheel has been set in motion where synapses that connect these sensory cells to neurons that contact them have been damaged or destroyed by loud sound.

It takes them a long time to degenerate.

And in fact, it's led to the concept of the so-called hidden hearing loss.

So there is obvious hearing loss that you can measure on audiograms, but now we have a new appreciation for the type of hearing loss that you are describing, and it's more common among young people.

And if they go through standard audiometric testing, it'll be perfect.

All of their audiometric thresholds are fine.

However, they report that

they cannot hear clearly in a noisy background, or they have this tinnitus that they didn't have before.

So what's now emerging from both animal and clinical data is that indeed there are anatomical correlates of this damage, and it typically involves synapses between sensory cells and neurons, or it may even involve hair cells and neurons themselves.

So what is the loud noise level?

That was one of your questions.

For example,

Right now, we are speaking at about 60 decibel in terms of sound pressure level.

And what does that mean?

Decibel, it's a logarithmic scale because we had to compress an enormous scale that's really million fold from the softest sound to the loudest sound that we can hear.

Thank you.

We compressed it to a linear scale.

That looks linear, it's not, but it's a logarithmic scale.

So that's what dB is.

And we can hear anywhere between 0 to 120 decibel and louder.

We can even hear a jet engine, and that's 140 decibel.

And to calibrate us, if I'm now speaking at around 60 decibel, to come here, I had to take a plane.

And the noise in the cabin is typically around 80 decibel.

If you drive a motorcycle, it's about 100 decibel.

If you go to a concert that you have referred to, it's not uncommon that it's between 110 and 120 decibel.

And jet engine is around 140 decibel.

And the loudest noise level ever achieved at a football stadium was in Kansas City, and it was 142 decibel.

That is deafening.

Literally deafening.

Because it's, again, a logarithmic scale.

So for every three decibel increase in sound intensity, you have to half the time exposure that's safe.

So now back to your question, what is safe?

Roughly speaking, 80 decibel is fine for eight hours, but for any three decibel increase, you have to half it, which means 83 decibel is okay for four hours, 86 for two hours.

And the World Health Organization estimates that another billion will be affected by 2050.

89 for one hour, 92 for half an hour, while most of music concerts that use amplified music are above 92 decibel.

But it's not that everyone develops hearing loss, and it's not that we have to stop enjoying music concerts at all.

It's just that we have to take precautionary measures.

First of all,

Why does music have to be that loud?

It's kind of a peer pressure phenomenon because most people don't even enjoy it when it's that loud, but they feel like they should because somehow it's a kind of being youthful.

There is something to it because it turns out that at loud enough sound intensities, the vestibular system is stimulated at all as well.

And there are experiments in animals that have shown this unequivocally.

So there are vestibular or balanced neurons that actually respond to loud sound.

So, yes, there is a component of that.

However, we talked about initially how delicate this organ is.

Again, it can detect sub angstrom displacements, and now you are literally hammering it with this blast noise.

It's like an elephant in a china shop.

And that is not good.

And that's what contributes to some hearing loss.

So what can you do to protect your hearing if you're going to a loud concert like that?

Definitely wear earplugs.

You can even measure sound intensities if you want to be very quantitative about it, because now you have a rough formula.

You can get a DB app on your phone.

It's free.

You can measure it.

And let's say if it's 120 decibel at the concert you're using, then wear earplugs that provide at least 30 decibel of attenuation.

When you buy these earplugs in a store, it tells you what degree of attenuation they provide, and it can be anywhere from 10 to 30.

Musicians' earplugs usually provide about 14 decibel of attenuation, so clearly that wouldn't be good enough for this event.

And you have to put them in correctly, because if they don't fit in, it doesn't matter what the number says.

They're not protecting you.

So that's one thing that you could do.

Another thing that you can do is take magnesium before going to a loud concert.

And this is because studies have shown that magnesium can protect against noise-induced hearing loss.

And the studies were done in countries where they have mandatory military service.

And they literally grouped people into those who received magnesium before those exercises and those who didn't.

And everybody was exposed to the same artillery and explosions as a part of preparation.

Those who took magnesium beforehand had less hearing loss.

Also, what measurements have shown in animal models is that after noise trauma is the levels of magnesium that change the most in the cochlea, in the organ of hearing, more than any other ion that's been studied.

And also what large-scale human population studies have shown is that those with higher magnesium serum levels or higher magnesium intake tend to have better hearing.

However, that needs to be further studied and replicated because the precise dose is really not known or the formulation.

Because as you know, there are many different kinds of magnesium and magnesium is good for your whole body, but depending on the formulation,

it may be better for the gut versus the musculoskeletal system versus the brain.

Absolutely.

And different formulations have been studied in different scenarios.

What we now think is that magnesium threonate is most efficient in crossing the blood-brain barrier, so we think it's probably the best for hearing protection, but that study is yet to be conducted.

So hearing loss is a huge problem.

It currently affects one and a half billion people and disables half a billion of them.

And the World Health Organization estimates that another billion will be affected by 2050.

I think it's probably both at both levels.

And by the way, going back to supplementation, really the best way is to have a healthy diet.

And numerous studies have shown is that what we absorb through a healthy diet is better than supplementation.

And supplements are not really strictly regulated in the way that other prescription medications are.

So what the label says on a box could be all over the map.

So this is an enormous issue.

What is known is that for some people with tinnitus in the setting of migraine,

magnesium supplementation really helps.

As you know, magnesium can do magic for people with migraines, along with healthy diets and coenzyme Q10 and B-complex or at least B12 vitamins.

And it's really underappreciated and stigmatized, and lots of people live in silence.

So that is the standard part of armamentarium to treat migraines.

And some people with migraines have tinnitus during their exacerbations, as well as auditory fluctuations, and some people get really dizzy.

And this is where thorough evaluation is really key, because someone may assume that the problem is in the inner ear, but the problem is really in the brain.

And then going back to pharmacology.

foods that are good for you, that are better than a supplement, given this unregulated nature of the supplements.

They include seeds and nuts and fish, especially salmon, and then green leafy veggies like spinach.

They are all rich in magnesium, but it's all common sense.

Basically, what's good for your body is good for your hearing.

For example, for those who have problems with their vision, they wear glasses, and glasses can restore their vision back to normal, to the point that people now wear glasses even if they don't need them.

That really hasn't been studied for any type of tinnitus.

It's been studied in the context of migraine, and there it really helps.

And tinnitus, it's an umbrella term.

Just like sensorineural hearing loss, it's an umbrella term.

It encompasses lots of different conditions.

When it comes to hearing loss, there are already more than 200 genes identified to cause hearing loss, and that's the genetic component.

But then there are environmental components to hearing loss, which includes noise trauma that we talked about, aging, infection.

Lots of different infectious diseases can cause hearing loss.

Not only viruses from the herpes family, like herpes simplex virus, which causes a cold sore, or cytomegalovirus, which is the most common congenital infectious cause of hearing loss.

Exactly.

It's a fashion statement.

Yes, indeed.

And some of these viruses, they stay dormant and live with us forever.

And then when the immune system gets weakened, then they can wreak havoc.

And some of the other viruses from the herpes family, like Epstein-Barr virus, CBV, it's actually linked to cancer, different cancer types, including nasopharyngeal cancer.

However, that's not the case for hearing loss.

So that's yet another cause of hearing loss, infectious hearing loss.

Then there is immunologic hearing loss when there is no infection, but it's an inflammation such as people with celiac disease or rheumatoid arthritis.

They may have higher predisposition to developing hearing loss, not only because the little tiny joints in the middle ear become fixed and don't vibrate as well, but also because the inner ear is injured.

And it's because hearing aids are aids, like the name says.

So when we now say sensory neural hearing loss, we actually cannot specifically say exactly what's wrong.

And the reason for that really goes back to the tiny size of the inner ear to the point that if you image it using the current state-of-the-art imaging tools that include computed tomography or a CT scan or MRI, which is magnetic resonance imaging, you don't see cells in the living human inner ear.

You just see a gray or white blob.

They don't restore hearing back to normal.

And the organ is too small to be detectable by technologies of that resolution.

Another issue is that you cannot biopsy it.

It's so tiny that if you did tissue biopsy, you would destroy it.

So that has really stimulated lots of very promising research in the area to improve diagnostics for hearing loss, which include both high resolution imaging of the inner ear and liquid biopsy as opposed to tissue biopsy.

So to answer your question, I think we really should review how hearing works.

And we have shown that if you take as little

as half a microliter of that fluid, perilymph, we can detect molecular differences between mice with or without hearing loss.

However, we have also collected this fluid from patients who undergo ear surgery.

It's either when we perform cochlear implantation for those who are profoundly deaf, or we literally have to drill through the inner ear to get to the brainstem because they have a tumor such as a vestibular schwannoma or an acoustic neuroma, which is a tumor that causes hearing loss.

So in these two instances,

we can actually get inner ear fluid and we can study it and we can see differences.

So I think that's a promising direction on the horizon.

Another diagnostic possibility is genetic testing.

So the way we hear is when sound comes and travels down the ear canal, it vibrates the eardrum.

That's relevant for people in whom there is a family history of hearing loss.

But today, when we test for known deafness-causing genes, it comes back with a definitive answer only in 50% of people.

And in another 50%, it often lists lots of variants of unknown significance.

They are so common that we even use an acronym, VUSs.

And some people will have tens, if not hundreds, of these variants of unknown significance.

So what do you make of that?

You just shrug your shoulders.

And at this point, we say, well, we don't know.

But now, one exciting research direction that we are pursuing with other investigators at Stanford and in collaboration with Google is to use AI to help us figure out which of these variants of unknown significance is actually significant.

And by using those tools, we can establish the diagnosis in 80% of people.

So...

Now that's for hearing loss, and you really asked about tinnitus.

The fancy term for it is the tympanic membrane.

But this is really to tell you that both of these terms are huge umbrella terms, and it's been super frustrating not having the ability to establish precise diagnosis to guide therapy.

So tinnitus is an even bigger black box.

That sets in motion the smallest bones in the body.

They are called the malleus, incus, and stapes, which is Latin for the hammer, the anvil, and the stir bone.

As they vibrate, they set in motion fluids in the inner ear.

And this is where these incredibly delicate sensory cells reside.

They are called hair cells, but that has nothing to do with this hair.

And as they deflect their sensors on top of their surface, which are called stereocilia, that leads to flow of ionic current and release of neurotransmitter and excitation of the auditory nerve, which then sends signals all the way to the brain.

Yeah, it's the latter that they need to really be evaluated.

And what studies have shown and systematic reviews and meta-analysis that none of this supplementation makes a difference for tinnitus.

It's a shame.

And...

It's also potentially a methodological issue because, again, everything was lumped under the same umbrella.

But it is conceivable that different subtypes may respond to certain interventions.

But because we don't know how to identify these subtypes, we are lumping them all together.

So when you lump them all together and put all studies together that have ever been done and perform meta-analysis, then...

It sounds like none of them make a difference, so to the point that the American Academy of Otolaryngology Head and Neck Surgery really endorses two main interventions.

One is amplification with a hearing aid for those who need it, and two is cognitive behavioral therapy.

Those two interventions have actually shown to make a difference.

There are other things that have been tried.

Some people take things on their own.

There is anecdotal reports of potential benefit, but that hasn't panned out in large scale epidemiologic studies that have had the appropriate control group.

Exactly.

And in fact, that's what we recommend in the clinic as well.

And lots of people find it reassuring because we first have to do tinnitus.

So in the inner ear occurs this, it's called mechanoelectrical transduction, because we are converting a mechanical stimulus into an electrical one.

complete and thorough evaluation, which includes examination of the ears, examination of the whole head and neck, hearing testing to make sure that there is no asymmetry or difference between the two ears.

If there is a significant asymmetry, that triggers imaging or additional testing, like auditory brainstem evoked response testing.

And imaging, it's typically MRI, and this is where we are looking for these tumors that could cause hearing loss.

They are super rare, so I don't want people to be stressing out and thinking they have that, but it's important to rule out.

So, indeed, once we find that there is...

no tumor, then we do try to reassure patients and explain that tinnitus is indeed a phantom sound produced by the brain and why it makes it.

And the more you think about it, the more you reinforce that circuit, just like you said.

So if you are occupied by other things or you have background noise, it lessens it.

And we already know that this is true in terms of experiments that have been conducted.

And that has been shown by electrophysiology, by imaging, even in people.

In people with tinnitus with normal audiometric thresholds, you can see hyperactivity in auditory centers in the brain.

And in particular, the area that has been imaged is the inferior colliculus.

And so we know that there is hyperactivity.

Also, most of the brain works on the principle of inhibition.

Now, what has been shown in animal studies is that loud noise, which causes tinnitus, can lead to loss of that inhibition.

So that can lead to hyperactivity.

But tinnitus can also be due to increased synchrony.

And that informs different strategies going forward.

But at this day and age, really the best treatment option for tinnitus is a cochlear implant.

However, most people don't need a cochlear implant.

And there are two broad categories of hearing loss.

And why do I say that?

Because we know that 75% of people with tinnitus who undergo cochlear implantation because they have severe or profound hearing loss get better.

And in 10% of those, it goes away altogether.

So it tells you that if you improve function at the periphery, the brain recalibrates and takes care of it.

Which is great, indeed.

And that's why we are so enthusiastic about all the research that's happening at Stanford and across the world to regenerate and restore function in the inner ear, because that then facilitates

One is the so-called conductive hearing loss, and the other is sensorineural hearing loss.

the brain's adaptability to take care of itself.

The conductive hearing loss affects the ability of sounds to be conducted to the inner ear.

Yes, and it's so interesting that observation that you have made because these regulations are different in different countries.

So even the same manufacturer of phones will set up the threshold at a lower level for the European market than for the American market.

That can be if there is a hole in the eardrum or there is fluid behind the eardrum or these hearing bones don't vibrate, they are frozen because of a disease process.

Because the assumption is that Americans like it louder.

Yes.

And to your question, it's not really the headphone style.

It's really the sound level.

And you can measure it.

You can measure it on your dB meter that you can download on your phone if you don't have it already.

And again, the safe rule of thumb is 80 decibel is safe for eight hours.

However, and then for every three decibel increase in sound level, you have to half it.

What if I'm lazy and I... So then if anyone can hear what you are listening to who's standing by you, it's too loud.

So that's a good rule of thumb.

Exactly.

Take note.

If you can hear your child's music or podcast that they are listening to through the headphones that they are wearing, too loud.

There are surgical treatment options for that type of hearing loss and non-surgicals, which include amplification with hearing aids.

Not really, as long as it's at the safe sound levels.

It's really all about what is the sound level that's damaging.

And it's not the same level for all.

In fact, if you have a construction worker and you have two of them being exposed to exactly the same levels of noise, one may lose hearing very quickly and the other may work in that environment for 20 years and have really mild hearing loss.

So very roughly, we categorize them into those with tough versus tender ears.

That's super simplification.

But it tells you that there must be a genetic predisposition to their vulnerability because they had the same environmental exposure.

And now we are uncovering genes that are contributing to this vulnerability.

And it's not one.

It seems like it's several different genes that are working together to orchestrate this sensitivity.

What we have also learned from both human and animal studies is that children are definitely more vulnerable.

So another take-home lesson for the parents, what may be comfortable for an adult may be too loud for children.

So that's an easier type of hearing loss to have.

And it's another important message for how loud different events are in elementary schools.

or middle schools, because by the time they are high schoolers, auditory sensitivities are changing.

But there are numerous studies that have shown that younger people or younger animals are more vulnerable to noise levels.

But the more common type of hearing loss is the sensory neural hearing loss.

It's the one that originates from the inner ear.

And why it's been so challenging to study and to crack that nut is because it's tiny.

Yes, it's adding insult to injury.

And indeed, then the effect can be synergistic as opposed to additive.

It's a tiny organ.

They do.

It really depends on whether they are fitted properly and how much attenuation they are designed to provide.

Because some provide only 10 to 15 decibel of attenuation and others provide 30 decibel of attenuation.

It's encased in the densest bone in the body, and it's located deep in the base of the skull.

And depending on the ambient noise levels, one versus the other may work.

They are.

And the way we know that is from people who have hyperacusis that we alluded to before.

And they are just so uncomfortable being in loud environments or even what we consider normal auditor environments that they wear earplugs.

But then...

when they pull them out, everything is unbearably loud.

You may even ask, how tiny?

So in fact, the first thing in terms of counseling them, we say, well, take out your earplugs.

You have to get used to the normal listening environments.

And we already know that the brain is amazing.

It can get used to different stimuli.

And it's important that it gets natural input so that it can work normally.

Otherwise, indeed, it can

calibrate in ways that are unhealthy.

Yes.

In the second trimester.

If you take a penny, then you'll notice that Lincoln is on a penny.

Wow.

And the organ of hearing is fully formed in utero, fully formed.

Listening, ready to go.

And again, they hear in the womb.

It's amazing.

As you can imagine, challenging experiments to perform and some are based on electrophysiologic data and others are done based on imaging data.

And there's only so much you can do to pregnant women for safety reasons.

So it's actually hard to precisely answer your question.

So the human organ of hearing, which is called the cochlea, in cross-section is the size of Lincoln's upper face on a penny.

But what is clear that the fetus can hear the mother's voice.

So anything that's of that same intensity, the fetus can hear.

Of all animals, absolutely.

And the most striking example is actually sea animals like whales and dolphins.

All of that noise generated by big ships and motorized vehicles that are in the water.

damaging their hearing and modes of communication to astounding and scary ways.

It's really unfair that we are doing that to the world around us.

So now whales are getting lost because they communicate by sending and receiving these sound waves really long distances, miles away.

And now you find them lost.

They can't find their

crew, the rest of their family, if you call it that.

And if they're in a quiet environment, the way they used to communicate before the modern industrial world, they function completely differently.

Very real.

Yes.

It's actually messing their navigation.

Super small.

And that organ is filled with fluid.

It's hard because it's not even tightly regulated for people on land.

And there is a lot of room for improvement.

How much fluid?

For example, you have mentioned that you've traveled the world.

You have noticed that in Western Europe, amplified music is not allowed on the streets.

What's your guess?

But in the United States, and you mentioned New York, you can have any artist amp up the volume to any level they want.

What's the volume of this inner ear fluid?

Yes.

It's completely unregulated.

And when I have approached some people about this topic, then I was told, well, this is a free country.

People should be allowed to do whatever they want.

And if they choose one behavior, then it's up to them.

They know the consequences.

So there are pros and cons to that because as physicians and scientists, we also know what's good for people.

And if that

It even has a fancy term.

information is not widely disseminated or if it's not widely accessible, which our conversation today clearly illustrates it's not, then having some regulation in place to protect us all is a good thing.

It's called paralymph and endolymph.

There are two types of fluid, but that doesn't matter.

That directly links to what you mentioned before, the importance of hearing for emotional communication, for relational well-being, and for cognition.

What matters is the scale.

So now there is mounting evidence for a strong link between hearing loss and dementia.

It's not that everyone with hearing loss will develop dementia.

So I really want the listeners to feel reassured that they don't need to run home and

So how much fluid do you think there is?

purchase hearing aids right away.

It's just not the case.

However, we are trying to identify who is at risk.

And the standard tests are not that helpful in that regard because if you get just the standard audiometric testing where you're in a sound booth and they play different tones and you raise your hand if you hear it, and then you have a plot generated, it turns out that you can have 90% of neurons gone

and your audiometric thresholds could be normal.

And it's because the auditory system is so exquisitely sensitive that there is tremendous redundancy in it.

And we talked about sensory cells, how they are connected to the brain by the auditory nerve.

It turns out that 10 different nerve fibers contact a single sensory cell.

Do you need all 10 of them to perceive sound?

No, you need one.

However, you need all 10 of them if you are in a noisy environment.

So going back then to the link between hearing loss and cognitive decline, we are now using different tests to identify people who are at risk and studies such as testing speech in noise or the ability to understand words in a noisy environment as opposed to in a quiet environment turns out to be helpful.

It's not so simple.

It's not there is one test that has perfect sensitivity and specificity, but the field has recognized the need to develop better hearing tests, which are being developed.

That's pretty close.

It's actually the equivalent of three raindrops, so about 140 microliters.

It's a brain thing, it's a circuit, and it's absolutely essential for understanding speech and noise.

In fact, people with hearing loss typically experience problems understanding speech and noise.

They have no problem in a quiet and facing you.

In fact, that's a big

message for everyone who is listening that it's more important to face someone and speak slowly if they have hearing loss than speaking loudly.

I mean, than yelling.

And so if someone has hearing loss,

It's not that everyone with hearing loss will develop dementia.

So this is an organ that's amazing.

and you are trying to talk to them with water running or TV on or you are trying to talk to them from a different room, forget about it.

You really have to face them and it has to be quiet and you have to slow down and then they can really understand so much more.

It is the most sensitive sensory organ.

It can detect displacements that are on the order of the diameter of a hydrogen atom.

We think that it's both.

However, the direct link has not been established yet.

Lots of studies are being done, both in people and in animal models, trying to really establish the direct link.

So there are

data supporting it and refuting it, so that's why it's an active area of research.

The indirect link is super well established because we know that hearing loss leads to social isolation, to depression, and cognitive decline.

In fact, the cost of unaddressed hearing loss

is the staggering nearly trillion dollars annually.

With a T. Absolutely.

Whoa.

Yes.

And it's because people have issues getting employed.

That's astounding.

They may not get the best jobs that they would like to be qualified for.

All of arrangements that have to be done to make them as fully functional as possible are very costly.

So indeed, it's an enormous problem that really needs more focus, more attention, and more research to develop new therapies.

If you just think in terms of electronic chips, the traces are now on the order of one nanometer, which is the size of five silicon atoms.

Some people are better than others and

As we've been discussing all along, it's not that one size fits all.

All of us are a little different, and some people are better at some things than others, and people lip read to different degrees depending on all sorts of things.

Their innate predisposition, their potential hearing loss that they may not even know,

artistic nature where they are analyzing a face all the time, their engagement and interest in what's being said.

but the ear can detect displacements that are one-tenth of that.

So going back to your question about the cocktail party environment, it's a problem that

for standard hearing aids in an environment like that because they tend to amplify everything including that background noise.

So that has led to a new generation of hearing aids that are AI informed and really are performing auditory scene analysis in real time to pick up signal from noise and

to reduce amplification of the noise and reduce feedback.

So that's an active area of research.

The latest data are very promising.

However, what's still needed is large-scale controlled studies comparing traditional versus AI-enhanced hearing aids.

And indeed, that auditory

scene analysis in a cocktail party environment is a problem.

For example, directional hearing aids can address it to a point.

I mean, hearing aids that have directional microphones, if you know who you want to be listening to, because then you face them.

Subangstrom level.

However, you may also want to be

hearing someone who's talking behind your back and you don't realize it until you hear the first sentence or two that they have said so if you have purely directional microphones you're not even aware that that's happening and that's why uh

Subangstrom level.

hearing aids with directional microphones are loved by some and not by others.

So again, really all of this highlights that we are all a little different and it calls for personalized approaches that are tailored to a given individual's makeup and needs and preferences.

It's really phenomenal.

And another example to really highlight the sensitivity of this organ, if you have a trained violinist, if they move their finger by only a micron, so that's a millionth of a meter, right?

It is incredible.

And you actually bring two really interesting points.

One about sleep.

So what studies have shown is that the ideal sleeping environment is what bears do when they hibernate.

It's three things.

It has to be quiet, dark, and cold.

And that's perfect for sleeping for months.

But then when it comes to not hearing ourselves, actually some people do, and that's very disturbing.

And that can occur if there are basically two things.

One, it can be that they are missing a part of the bone that covers the bony bone.

balanced canal, one of the canals.

We have focused on talking about the hearing part of the inner ear.

But the inner ear has one organ of hearing and five organs of balance.

the ear can perceive that as a change in pitch.

Two organs that detect linear acceleration, one in a horizontal and the other in the vertical plane.

And then there are three organs that detect angular acceleration.

And these are the three semicircular canals.

Yes.

So what can happen is that over that superior semicircular canal, that bone can be missing partly, and people can have superhuman hearing.

They can hear everything.

You can't see that with your naked eye, but the ear can perceive it.

They can hear their eyeballs moving.

They can hear their footsteps.

If they're taking a shower, it's deafeningly loud.

They really can't take it.

If an ambulance drives by, they start spinning.

If they are straining on the toilet, they start spinning and can pass out.

So that's called superior semicircular canal dehiscence.

And it was actually discovered by our dean, dean of the School of Medicine, Lloyd Minor, when...

He was at Hopkins University.

So these examples really highlight how delicate this organ is.

Because he was such an astute physician where he listened to a patient.

Because before him, when patients like that would come to our office, I mean, what would be your knee-jerk reflex?

Come on.

Exactly.

But what Lloyd heard and paid attention to is that the patient said, when I hear a loud sound, I feel that my eyes are moving and my vision becomes blurry.

And so Lloyd thought, really?

So let me put loud sound in your ear, which he did.

And he noticed that the patient's eyes started moving in the vertical direction.

So there is this vestibular ocular reflex.

And he figured, well, then...

And another absolutely stunning thing about the ear is that there are these cells, they are sensory cells that we talked about, but they're called inner and outer hair cells.

The superior semicircular canal must be involved.

And that led to imaging that had to be really developed so that it's fine cuts through the appropriate plane.

And then you could really see the missing bone.

And then he developed surgery to fix the problem.

And now we can help people like that who actually do hear their bodily sounds that are too disturbing to them.

However, we don't do that surgery lightly because clearly it has some risks like any surgery.

There are two ways of doing this.

One is through the middle cranial fossa, which entails lifting of the brain to identify the dehiscence and then plugging it or resurfacing it and then letting the brain fall down again.

Or we can approach it through the ear, so drilling from behind the ear.

But normally, that surgery is really reserved for those with intractable vestibular symptoms.

They just can't

function in the normal world because if someone yells next to them or an ambulance drives by, they just start spinning.

And what's special about these outer hair cells, they actually move.

They both sense vibration, and vibration is such a fundamental phenomenon.

but they move at audio frequencies.

If you think about it in terms of the universe, it's these vibrations that are everywhere around us, electromagnetic vibrations.

We're talking about sound vibrations, but now we can even convert these electromagnetic vibrations

vibrations from the depths of the universe to sound so that we can hear gravitational waves, which is really interesting.

So this idea of being able to detect vibration is very deeply fundamental.

And even bacteria can detect vibration.

So what does that mean?

They have those little flagella that allow them to move around.

And fish, for example, we talked about fish and other species that live in the seas and oceans.

To put it in perspective, let's say that the heart beats at 60 beats per minute, which is one hertz.

They have this lateral line organ along their side that detects vibration.

And it's very similar to the sensory cells in the inner ear.

to the point that we sometimes use, for example, zebrafish as animal models because they are transparent, you can see through them, and you can literally see these hair cells in the lateral line organ and test for drugs that may be toxic to the ear, although they also have the ear.

So yes, there is this profound, deep connectedness, and in the human body,

auditory versus vestibular system, those cells look very similar.

We talked about inner versus outer hair cells in the auditory system.

Inner hair cells are flax-shaped, and outer hair cells are more like cylinder or cigar-shaped.

Similarly, in the vestibular system, there is type 1 and type 2 hair cells.

And they detect vibration at different frequencies.

The vestibular system is a lower frequency system compared to the auditory system.

But what's fascinating is that there are some data showing that even stimulation that's non-auditory can still be very impactful on auditory.

If the heart starts beating at two hertz, 120 beats per minute, that's arrhythmia that could be life-threatening.

our functioning and perception.

And there are some data showing that people who live close to windmills have described some disturbances that they initially couldn't really explain.

And then it turns out that that can stimulate stimulation of the vestibular system, and it's all connected.

I mean, the whole body is connected.

Convenience, we have decided to sub-specialize in ear physiology and surgery versus eye versus liver.

But really, it's all interconnected.

Well, these cells in the inner ear move in humans up to 20,000 hertz and in bats up to 100,000 hertz.

So this is to tell you how incredible this system is, and it's designed to let us detect sounds.

It is fascinating because really vibration is around all of us.

We are exposed to vibration all the time.

Different things do happen at different time points.

And there seems to be this really fascinating connection.

frequency pattern to it.

We already know that circadian rhythm exists even in the inner ear.

We know that certain drugs are more effective if they are given at certain times of the day.

So, yeah, there is something to be studied even more.

But keeping within the realm of what's manageable at this point in time, I will say that von Beckesche

who was a physicist, and he studied the auditory system because he worked for a telephone company, and he was charged by making better devices for communication.

And he said he reached a limit in terms of what he can do as a physicist.

So he needed to understand how the system worked.

And he started performing these experiments in human temporal bones.

So they are...

And it's evolved so that we can detect sounds at any point in a day or night.

collected when people die of unrelated causes and they donate their ears for study.

And he was playing sounds of different frequencies and noticed that those of high frequencies stimulated the basal portion of the cochlea and those of low frequencies stimulated the high end.

So because of his seminal contributions to understanding how the auditory system and description of this place frequency map, plus other things that he did, such as discovering that there is a biological battery in the inner ear,

uh where you have hundred millivolts of positive potential which is really unheard of everywhere else in the body cells are bathed in fluid and the potential of that fluid outside of them is typically around zero yeah we should explain first sorry to interrupt but just very briefly and we're talking about membrane potential some people will know what that is we're essentially talking about

Sound travels through any media.

Extracellular.

Extracellular.

So normally cells have some resting potential, which is usually negative.

60, 80.

Exactly.

But now on top of it, you have 100 millivolts of extracellular potential.

So there's a difference that really drives ionic current through these sensory cells is really large.

Sound travels around obstacles.

And that contributes to this exquisite sensitivity of the inner ear.

He discovered the endocochlear potential.

He was the first to measure it.

So for these contributions, he actually won a Nobel Prize.

It's really essential for survival.

So by studying frequency, because you started talking about frequency and how there may be a whole...

Hearing-to-body frequency map, I think it's a fascinating phenomenon because at least the auditory system is all functioning based on frequency.

There are species that don't even...

And in fact, understanding that place frequency map has been essential for the introduction and success of cochlear implants because cochlear implants

rely on that cochlear implants, pick up sound from the environment via microphone, and then process it into different frequency bands.

And then that is delivered to the intracochlear electrode that directly electrically stimulates the auditory nerve.

So if you're hearing high frequencies, then it's only the electrodes that are

encoding high frequencies that are transmitting that information and so it all ties it together and really highlights how important it is to do fundamental research that is sometimes even curiosity driven to really lead to major advancements in terms of therapies for people and many times that

have vision, they are blind, and they are surviving superbly well because of their incredibly astute sense of hearing, like bats or moles.

curiosity-driven research and its potential impact on therapies for humans is unknowable.

There are really strong ties and it's a very active area of research.

And like you said, hearing is such an essential sense and it's hypersensitivity and sensory hypersensitivity or dysfunction beyond hearing

can be a part of both mental health disorders as well as on the other end of the spectrum, developmental disorders.

And I think it really calls for, first of all, greater awareness.

And a part of what we are doing today is really bringing it up to the known because so many people are really stigmatized

Because you don't have a label on your forehead that you have hearing loss.

It's invisible.

And people are afraid to admit that they have hearing loss because they are concerned about how they'll be perceived.

And for a long time, it's been linked automatically to losing your marbles.

And it's a part of why people...

in a social situation where they don't hear and they are having a gathering with friends and then they're initially just nodding their head and then they feel isolated because they're just nodding their head and then they respond to what they think was said and then it turns out it was something completely tangential and then they decide, I don't even want to be a part of this anymore.

And that's how they become withdrawn and isolated, at least a part of the reason.

And similarly, if you are hypersensitive to everything around you, you want to avoid that kind of situation.

And I think we definitely need better education.

We need better ways to measure these things and quantify them.

We talked about tinnitus.

We don't really have a way to quantify tinnitus, to measure it.

precisely, objectively, in a robust fashion.

And we need these types of tests for all of sensory perceptions that we are discussing, because senses are really essential for function of the brain.

And like I said before, the brain has really evolved to perceive and manage senses.

And it also provides a tremendous therapeutic potential because it's easier to fix sensory dysfunction than to fix brain function.

But the brain will take care of it if it's given corrected input.

And we already know that from the tremendous success of cochlear implants, which are the most successful neural prosthesis out there.

There are more people with cochlear implants than all other neural prosthesis combined.

Yes, it does.

And out the same day.

It takes only an hour or two.

By now, it's become routine.

Yes.

Yes, you're up and back.

You're down and back.

It's very delicate.

It's done under the microscope.

it was ear surgeons who were the first to introduce a microscope in the operating room.

And that was 100 years ago.

And it's for a reason.

Exactly.

And in fact, you were kind of considered a lesser surgeon if you used a microscope when it was introduced because the thinking was, well, your vision is not good enough or you are not good enough.

So interestingly enough, there was some backlash before widespread adoption.

And now, of course, you can't imagine doing anything precise.

without the use of a microscope, whether it's ear surgery or brain surgery or microvascular tissue transfer.

What we know is that women tend to have better hearing pre-menopausally.

But post-menopausally, they catch up to men.

So there are data showing that estrogen contributes to better hearing.

Now, larger-scale epidemiologic studies are being conducted.

As you know, for the longest time, women were not really studied in lots of clinical trials.

Most of clinical trials decades ago involved only men.

We already know from those studies that, for example, for a heart attack, how a woman presents with a heart attack could be very different than a man, where the classical description of a... Pain down the left arm.

They may not have discomfort, but no elephant pressing, no pain in the arm.

And so we are only now starting to understand all these differences, how different diseases manifest in men versus women and how they respond to different medications and different treatments.

And

Back to your question, what do we know about auditory sensitivity?

We do know that women tend to have better hearing premenopausally.

Now, does that have to do with environmental exposure?

That has to be factored in because traditionally men have been more involved in occupations that entail large noise exposures such as

military or construction.

But these days, everybody is exposed to recreationally loud music and noise levels.

So I think these studies need to be conducted with proper controls and proper sample sizes to really answer some of the questions you're asking.

Diverge, yeah.

Such that men have... Higher thresholds, which means worse hearing.

On average.