Tinnitus: Ringing in the Brain | Josef Rauschecker | TEDxCharlottesville

Translator: Tijana Mihajlović
Reviewer: Peter van de Ven I would like to talk with you
about a medical disorder that is incredibly common, and yet it gets often underestimated – misunderestimated, as one of our
former presidents would have said – (Laughter) in its impact on our psychology
and on the patients. The patients really suffer from it. And it's very pervasive;
about 50 million Americans suffer from it. I bet many of you in the audience
will have friends or family that suffer from it. What I'm talking about tinnitus, the ringing in the ears. It's often depicted in this painting
by Edvard Munch although we don't know for sure
whether he actually had tinnitus himself.

But the person in the painting
is sort of covering his or her ears, and it doesn't help because the ringing
is actually generated in the brain. It's not a real sound that is there
that a person hears; it's a phantom sound. So we often talk about it
as ringing in the brain rather than ringing in the ears. And of those 50 million Americans
that suffer from it, about 10 million of them
really suffer very badly – they go to the extent that they have
depression and suicidal thoughts.

I get emails every day from patients
that are asking, "Is there not a cure?" There is no cure,
unfortunately, at this point. And part of our research
is aiming for that, of course, that we're trying to find ways
to help these patients. And I can play some examples for you, (High-pitched tone) of what that sounds like. This is just a pure tone
of a single frequency, relatively rare. Usually, tinnitus sounds
more like the next one. (Hissing sound) You can imagine how annoying that is if you hear that all the time
in one of your ears or both of your ears. You can't turn it off,
you can't run away from it; it's always there. (Cricket sound) Sometimes, you get this more sophisticated
cricket sound that you hear. So, people suffer from it. There are groups that are more affected
or at risk than others. Musicians get it surprisingly often because they are exposed
to louder sounds than they realize.

I once remember being
at the Kennedy Center in Washington, DC., where we live, and went to a concert there, symphony concert by the National Symphony. They played Shostakovich's War Symphony. Very loud, of course. One of the violinists
in the first or the second row was sitting right in front
of the trombones behind her. The trombone was sort of blowing
right into her ear and she was reflexively covering
her ears to protect herself.

This is actually the right reaction;
you have to avoid loud noises in order to avoid
getting hair cell damage, and then hearing loss,
and ultimately tinnitus. So, loud noise exposure
is certainly one of the biggest risks. Then you take a group
like construction workers. If they don't wear hearing protection,
that can be very risky. The group most at risk
are our war veterans, of course. They are constantly exposed
to artillery fire, to bombs, explosives and so on, you know. In addition – this is
a very important factor, which I want to stress
in this presentation – stress is a very important factor. So, it's not just the loud noise exposure
that can give you tinnitus – it actually doesn't always do that – but if it combines
with a stressful situation, this is the most likely scenario
where you end up getting tinnitus. So, our veterans are much more likely to come home
from the battlefield with tinnitus.

In fact, the Veterans' Administration,
if you look up the statistics, they show that tinnitus
is the most frequent cause for benefits paid to veterans. Hearing loss is the second
most frequent one. Tinnitus has often been compared
with other phantom sensations like phantom limb pain,
which you might have heard about. In this case, somebody misses a limb
because of an accident or an explosion that damaged his arm or her leg. And it's a very similar thing.

In this case again,
the brain is the cause for this. Even though the leg may be missing, the neurons in the brain
that represent the brain are still there and they are firing along. On occasions, the person
might get the impression that his leg is still there. And you can actually feel
pain in that leg. Animal experiments have shown – that's shown on the right
of that slide here – that this is in fact what's happening.

In monkeys that have lost
a hand, for example, the hand representation
gets filled in with input from the face representation,
which is right next to it. Ramachandra and then
neuroscientists in California did studies on amputees, where he showed that if you touch
the face of an amputee, they actually feel their phantom hand,
in this case, more frequently than not. So, there's a profound reorganization
going on in the brain, both in a phantom limb and in tinnitus, which is the equivalent
in the auditory domain. People have referred to this often
as maladaptive plasticity. Plasticity, by definition,
should be something good, right? We are learning: this is plasticity;
memory is kind of a form of plasticity, so we associate this
with an adaptive function. But in this case, is it really adaptive? I would think so. It's not necessarily maladaptive,
because the brain has set out a plan how to deal with these
kinds of situations.

So, if you have loud noise exposure, you kill some of your hair cells
in the inner ear, and they can't be replaced;
they don't grow back. So, what the brain does,
it kind of fills in that gap. Nature doesn't like gaps. So, the gap is filled in with neurons that normally respond
to other frequencies, like on the left or right of that gap. Another example
is the blind spot in your eye. You all know we have
a blind spot in our retina where there are no photoreceptors, so the blood vessels
go in and out from there. The optic nerve goes in from there. We don't see, but we
don't notice that hole because with the same mechanism
the brain fills in that hole. And the same thing happens – We call this lesion-induced plasticity. The same thing happens in tinnitus. So, it is per se an adaptive mechanism. But it has an unintended side effect, this hyperactivity
that I've been talking about, that we can actually visualize
with fMRI, for example.

And then, the next step is missing
in tinnitus patients. Normally, the brain is even more clever. It realizes there is this internal noise
being generated, so it puts its executive sentence in play and they would suppress that noise. So, most people actually
even after extensive loud noise exposure don't get tinnitus. You might have hearing loss
but you don't end up with tinnitus. You go to a loud noise concert,
for example, loud rock concert, and you have tinnitus maybe the next day,
but then it goes away after a few days. So, many people have
just temporary tinnitus which gets repaired by the brain;
there are mechanisms for that. But in those unfortunate people
where these mechanisms don't work, they are the ones that are becoming
the chronic tinnitus patients. So, in the next few slides, I'll show you the brain
and how it is organized, how it reacts to these events
and these situations.

Here's the brain as a whole, and you see the auditory cortex
somewhere in the middle there; it's been exposed. This is just a drawing. You see the tonotopic map, how the different frequencies are laid out
along the auditory cortex. And you see how – Normally this is pretty regular. All the frequencies are equally spaced, but after you lose
that yellow region there, then the green
and the orange region move in, and they are the ones
that are overrepresented and give you the tinnitus noise,
the tinnitus signal.

So, now we have a real picture. This is an old research scanner at NIH, where some of these techniques
have actually been established. Now you can do this with any MRI scanner that you've probably seen
and been in, yourself. And we can visualize the auditory cortex
in normal controls without tinnitus. You see a nice activation
in the auditory cortex. And in the patients
that constantly have tinnitus, this activation is doubled or tripled; it's very significantly increased. So this is the physical realization
of what people actually perceive. But this is not the whole story. The rest of the talk
will try to convince you that tinnitus is not
just an auditory disorder; it is more than that.

It has to do with the higher
brain functions in the frontal cortex, in the limbic system. If you think about it,
there's a good reason to assume that it's more than an auditory disorder, because not everyone, as I said,
ends up getting tinnitus, even if you have a hearing loss and have suffered from loud noise
exposures many times. A lot of people only have
intermittent tinnitus. If you're like me,
you often have stressful situations, like a deadline that you have to meet. You're working very hard,
you get less sleep during that period, and then your tinnitus suddenly appears. Even if you don't have it normally, you might get tinnitus
in a situation like this. Then you submit the grant or the project
that you've been working on. You're finished, you have a good feeling,
you get a good night's sleep. Next day the tinnitus is gone. That shows you
that it's not just auditory. There's something regulatory
higher up in the brain that can normally take care of this.

And there's also comorbidity
with depression. If you feel bad and you have sort of a – if you're sad or if you're stressed out, then your tinnitus is much more likely
to come up and get worse. So, there's clear comorbility
with these kinds of mechanisms which we refer to often
as the limbic system. So, on the left, the blue region
is the auditory system.

Every sensory system
has its representation in the brain. And then, in the frontal cortex,
sort of in the front part of the brain, there’s this green system, which we often
refer to as the limbic system; it regulates our emotions. And it has some very well-defined
building blocks in there, which I'll show you in a minute: ventral medial prefrontal cortex
and nucleus accumbets. They all play their role and they interact
with the sensory systems and are able like an operating system
in a way in a computer to emphasize or de-ephasize
what you hear, what you see, and sort of give you the actual percept,
experience of your daily lives. So, the upshot of all that is that tinnitus as a phantom sensation
depends on three things. First of all, in most cases
there is a peripheral auditory lesion; there's no way around it.

Some people say there is tinnitus
without hearing loss, but it's very rare. It may happen sometimes with accidents. But in regular cases,
there's a lesion there. And there's central auditory organization,
as I've shown you, the fMRI, and then there's this
non-auditory gating system, and the rest of the talk
is only about this. About 10 years ago,
we had a crucial finding. That was, again, a brain imaging study that we did in collaboration
with the German MIT. He just said
in the introduction, in Munich. And we found that in tinnitus patients there's a very significant
shrinkage in one region. We call it a volume decrease because the MRIs determine
the volume of a part of the brain, of the brain tissue. And this was in the ventral medial
prefrontal cortex, which normally is there for the perception
of unpleasant sounds, say. There was a study before that showed
if we hear unpleasant sounds, the same region lights up. So, it makes sense
that this region was affected, but we didn't know at the time
how crucial it was. Another finding that helped us
understand what was going on is that this region
in the ventral striatum in the basal ganglia,
right in the middle there – You see this red spot there.
This is called the nucleus accumbens.

It's a small center
that regulates our emotions. It's often being called
the pleasure center. It's actually involved
in giving you addictions and has all kinds of roles
in terms of emotional regulation. And surprisingly, this region
was highly hyperactive. This was increased in its activity
in tinnitus patients. A very significant effect, as you can see on the right
if you understand statistics. So, those two regions together form
an internal noise cancellation system. It's what we figured. You've all had
noise cancellation headphones on the airplane. And what this does is it can't make
this noise really go away; the noise is still there but the system adds
another form of noise to a signal. And that's the negative form
of the original noise and that cancels out – there's some noise
and therefore you don't hear anything or you get sort of much milder effect.

And that system normally,
with the red box there, inhibits the internal noise signal
and you don't have tinnitus. But if that system is broken,
then you end up having tinnitus. So, here in a close-up, you see that the nucleus accumbens
is part of that evaluation system and the medial prefrontal cortex
does the volume control; it turns down the gain
when the nucleus accumbens tells it so. And then together,
this works or it doesn't work. So, where do we go from here? We have hints from this last slide. You see the boxes on the right.
That's dopamine and serotonin. These are two transmitters. They have to be high for you
to feel good and feel happy. If they are low, then you
get depression, for example, and you get tinnitus. So, this may be opening an avenue
for drug treatment in the long term. But there's another form of treatment that we might be able
to use in the future.

This is called Deep-Brain Stimulation, and it's been established
for Parkinson's disease and major depression. I'll show you in a brief video a patient
that actually undergoes this treatment. It may be shocking for you at first, but it's become routine in many disorders. The patient actually lies there awake.
She's slightly sedated. She's able to talk to the surgeon
and report her feelings. (Video) Mayberg: Does it have
any mental qualities to it or is it still mostly physical? Patient: Actually,
that time it kind of was – there was a lighterness of my mood that went with the lighterness
of my feeling. Voice-over: The transformation was dramatic:
a sudden remission from despair in a person who has spent years
in a nearly vegetative depression. Happiness felt like a possibility again. Josef Rauschecker:
So, I hope I've been able to tell you that we're getting closer
to understanding what tinnitus is, and with these considerations
that I've just said, we may be able to ultimately find a cure, and I may be able to respond
to those emails that I'm getting and say, "Well, help is on the way.

We're not there yet,
but help is on the way, though. I'll have something for you soon." (Applause) Master of ceremonies:
Thank you, doctor Josef. One quick question for you
before you leave the stage. So, with the leaps and bounds
in brain research, what do you see as the impact
going forward for society? JR: Oh, I think it's immeasurable. I think the impacts
for society are incredible because our brain is us, and we have to realize
that this is where we feel, where we dream, where we plan.

So, the more we understand
about the brain, we understand about human beings
as such and about humanity. This is how I look at it. MC: Thank you. JR: And if we have
disorders like this one, which seem so intractable, you first have to understand the brain
and then we can maybe help people. So I think it has
a lot of deep impact for our society. MC: Well, thank you so much
for sharing your knowledge with us today. (Applause).

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