Why Is Tinnitus So Hard To Understand And Treat?

SOPHIE BUSHWICK: This is Science Friday. I’m Sophie Bushwick, in for Ira Flatow. Tinnitus, a condition commonly described as a persistent ringing in the ears, affects millions of people around the world. In the US, the prevalence of tinnitus is estimated at around 11% of the population, with 2% affected by a severe form of the condition. But even though it’s so common, the exact causes of some tinnitus and how best to think about treating the condition are still unclear. In some cases it’s brought on by exposure to loud noise, while in others, an ear infection or even earwax might be to blame.

Joining me now to talk about research into tinnitus and possible ways to treat it is Dr. Gabriel Corfas. He’s the director of the Kresge Hearing Research Institute and the Lynn and Ruth Townsend professor of communication disorders at the University of Michigan in Ann Arbor. Welcome to Science Friday.

GABRIEL CORFAS: Thank you very much for having me.

SOPHIE BUSHWICK: Let’s start with some definitions. What is tinnitus?

GABRIEL CORFAS: A simple way to think about it is a phantom sensation of sound in the absence of an external sound.

SOPHIE BUSHWICK: And I’ve said ringing in the ears, but it can have other sounds, as well, right?

GABRIEL CORFAS: Yes. Some people feel it like a constant buzzing. Some people feel it like a chirping. It can be of different frequencies, as well as different intensities. And sometimes, they are constant, and for some people, they come up and go away intermittently.

SOPHIE BUSHWICK: And these phantom sounds, do we know where in the auditory system they’re being produce? Is it something in the ear or in the brain or somewhere in the connections between them?

GABRIEL CORFAS: All the evidence points out that tinnitus, or tinnitus, is created in the brain, most probably caused in response to changes in the periphery in the inner ear. But the sound itself, it is generated by activity most likely in the brainstem.

SOPHIE BUSHWICK: If we were talking about a mechanical system, something like a microphone, as you turn up the gain to try to get a stronger signal, you also get more noise. Could it be that tinnitus is the result of the brain acting like a mic– it’s trying to turn up a quiet signal, but turning it up too much?

GABRIEL CORFAS: That is pretty accurate, in some way. The way most researchers are thinking about is that when there is a significant hearing loss, and there is less input from the ear to the brain, some circuits in the auditory pathway respond to that by increasing the gain. And that can generate these phantom sounds.

SOPHIE BUSHWICK: So it sounds like hearing loss could be one of these causes of tinnitus. But apparently, there are a lot of other ones. Can you tell me about some of them?

GABRIEL CORFAS: Today, we consider hearing loss as the key cause, which could be working together with others. For example, some people may have the onset of their tinnitus after a stressful situation. The ear in that case would be that there was already a defect in hearing that was contributing to changes in the brain. But then the stressor could have been a second hit that enhance either the perception or the strength of the tinnitus.

SOPHIE BUSHWICK: So what are some causes of hearing loss that can end up resulting in tinnitus?

GABRIEL CORFAS: There are many reasons why people lose hearing. Aging is one of the most common. And the cause of age-related hearing loss is not yet clear, but there are several potential contributors. Of course, normal aging, during normal aging, our tissues and organs start getting significant damage through just regular life or insults like noise, antibiotics, other drugs that could affect the inner ear.

SOPHIE BUSHWICK: And some of your work involves studying how nerves can be regrown. How does that connect to tinnitus?

GABRIEL CORFAS: So in the inner ear, we have very specialized cells that are called hair cells. These are the cells that respond to the movement of waves within the ear. And they are activated through these mechanical processes. And they release neurotransmitters and activate the auditory neurons in the ear, that then they send the signals to the brain.

The connection between the inner hair cells and these very specialized auditory neurons, called spiral ganglion neurons, the synapses that connect them, which are critical for the information to move from the hair cells to the neurons, are very sensitive to noise, and they can be destroyed by noise exposure. For example, in animal models, we know that putting a mouse in conditions that would be similar to a rock concert, let’s say, two hours of sounds of about 100 decibels, is sufficient to cause the loss of these synapses. And this loss, unfortunately, in large part, cannot be repaired by itself.

By studying the mechanisms that regulate the formation of these synapses, we discover certain molecules, in particular, a neurotrophic factor called NT-3, or Neurotrophin-3, that is very critical in regulating the formation of these synapses. And then we were able to demonstrate that by increasing the amount of neurotrophin-3 in the ear after noise exposure, a very significant portion of the lost synopsis can be regenerated.

SOPHIE BUSHWICK: So normally, these cells wouldn’t regrow after damage. But you add this compound, and then you’re coaxing them to regrow?

GABRIEL CORFAS: To reconnect.

SOPHIE BUSHWICK: To reconnect.

GABRIEL CORFAS: Exactly. Yes, to reform the synapses. And therefore, the signals can move from the hair cells to the neurons.

SOPHIE BUSHWICK: And once you’ve regrown it, do you see changes in how the mice, for example, respond to sound? Yes

GABRIEL CORFAS: Yes. So we can test mice for their ability to hear by measuring the physiological responses to noise. And also, by using behavioral tests, that tells us if the animal is processing the auditory signals correctly. What we have found is that in mice that have been exposed to noise– and if we increase the amount of NT-3, the electrophysiological responses of the mouse to sounds are increased and go back to what it was normal, before the noise exposure.

When we take animals that are at middle age– for a mouse, that would be one year old– if we increase the amount of NT-3 in the ear, that following week, their hearing is improved. And by the end of their lives, their ears look much younger functionally and structurally that they’re no longer counterparts. So we believe that the evidence indicates that increasing NT-3 or other molecules could help us not only restore hearing after noise exposure, in some cases, but as well as improve hearing in middle age and preserve hearing as we age.

SOPHIE BUSHWICK: I think it’s fascinating that you’re able to reverse hearing loss in this way. But I’m also curious about how this impacts tinnitus. And are there even animal models of tinnitus? How can we tell if a mouse is experiencing ringing in its ears?

GABRIEL CORFAS: That is a great question. And it’s challenging. But people have done many studies to do this. And primarily, there are two approaches that most laboratories use.

In one case, you train animals to be able to recognize a short gap of silence when there is a background noise. So the mice have to either respond to the gap in the background noise by performing a specific behavior. And the idea is that if the animals have tinnitus, that basically, fills the gap because there is a sound in their brains. Then they fail in the behavior. That’s primarily the way we can interrogate this.

We cannot ask the animal, are you hearing the sound? But we are using the lack of ability to report behaviorally that there was a gap in the background noise as a surrogate for measuring the tinnitus.

SOPHIE BUSHWICK: And when it comes to measuring tinnitus in people, are there ways to tap into the brain signals, using an MRI or other imaging methods? Can you see this constant buzz signal in their auditory systems?

GABRIEL CORFAS: Today, the most common way to test it is to put the patient in a sound chamber and let the patient move dials of sound in order to create the kind of a sound that they are hearing in– that the tinnitus has. So I have to say, I have tinnitus, and I have done that myself. And I’ve been able to identify the frequency and the intensity of my tinnitus by using that approach.

SOPHIE BUSHWICK: Tinnitus seems like a really tough condition to deal with. And it’s understandable that researchers are looking around for a lot of different kinds of treatments. So there’s also researchers who are working on using different types of electrical stimulation to try to treat tinnitus. Can you tell us about that technique?

GABRIEL CORFAS: Yes, absolutely. And part of that work was the pioneering work of Dr. Susan Shore, who until recently, was a professor in our institute. And her work identified some of the key mechanisms in the brainstem that subserve the tinnitus. What she discovered is that in animals that were exposed to noise that produced this mild hearing loss, they develop an increased excitability in specific nuclei in the brainstem. And she discovered this particular mechanism in which these overexcitation could be quiet down by the specific presentation of sound, as well as stimulation to the skin in the face or the neck.

And these protocols were very effective to quiet down the behavior that she used to measure tinnitus in animals. And then she developed a specific device and already run two clinical trials in humans that showed remarkable effects. A similar approach was developed by a company in Ireland, and the only difference is that instead of doing this very subtle stimulation to the skin of the neck or face, they use a stimulation of the tongue.

SOPHIE BUSHWICK: Wait, how does that work?

GABRIEL CORFAS: So the idea is that the specific presentation of the sound and the electrical stimulation produces what is called a sensory adaptation or quieting of specific connections between somatosensory stimuli and the auditory circuit, which are the ones that have been increased in response to the hearing loss and are believed to be the cause of the tinnitus.

SOPHIE BUSHWICK: I mean, is it like how one sense can damp down another, like feeling heat or cold might affect how someone feels pain, and in this case, they’re doing something with stimulating the tongue to affect how the ears are processing information?

GABRIEL CORFAS: Not exactly. The way we think about this is that because of the hearing loss, these somatosensory signals have invaded the auditory circuits. And by stimulating them in a very particular timing, these misconnections become quiet down by a process that is called synaptic plasticity.

So this is not something that occurs instantaneously, but is through repetition, that this synapses in the brainstem are changing, and these changes are not going to be permanent, but they are long-lasting. So when patients use these devices chronically and keep using them, these effects can be very significant and can persist even after you stop using the machine for a while.

SOPHIE BUSHWICK: So you’re, essentially, retraining that part of the brain?

GABRIEL CORFAS: Absolutely. That would be a very good way to put it.

SOPHIE BUSHWICK: This technique is a lot less scientific, but I’ve seen some posts on social media that talk about pressing on your head a certain way as a technique to temporarily relieve tinnitus symptoms. Is there anything to that? And if so, why would something like that work?

GABRIEL CORFAS: Well, this is the basis for the concept of this somatic tinnitus, which, according to the literature, may be 70% of the patients, which is where– and this is my case. When I move my jaws, the intensity of my tinnitus changes. And this is because these somatosensory systems, the nerves that take care of the sensation in my face, are misconnected now to the auditory system. And by stimulating both the somatosensory and the auditory systems at the same time with this particular timing, what we are doing is inducing a decrease in the effectiveness of that connection and thus, reducing the tinnitus.

SOPHIE BUSHWICK: What’s the cutting edge in this field? What do you really want to know?

GABRIEL CORFAS: Well, we need to understand exactly what about the hearing loss is triggering this plasticity. Because there may be ways eventually in which drugs could be used, as well, to treat tinnitus. One of the really interesting questions remaining is why some people develop tinnitus, while others with similar hearing loss do not. Are there genetic predispositions that we could identify and try to help people with that knowledge?

SOPHIE BUSHWICK: Dr. Gabriel Corfas is director of the Kresge Hearing Research Institute and the Lynn and Ruth Townsend professor of communication disorders at the University of Michigan in Ann Arbor. Thank you so much for taking the time to talk with me today.

GABRIEL CORFAS: Thank you very much.

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