And other things beginning with T.

And what, pray tell, is tinnitus? Well, have you ever had your ears ring? When it happens to me it sounds like a high-pitched electric tone. Around the E above high C. It only occurs in my left ear. In other people, it sounds like ringing, a whine, buzzing, or even crickets chirping. It’s called tinnitus, the perception of a phantom sound that isn’t actually there. It can occur in one or both ears, and up to 10% over the population has shown symptoms at one time or another.

Where does it come from and what causes it? Well, we know that it’s usually accompanied, or possibly caused by, hearing loss. I date mine to this SUPER LOUD concert my friend P dragged me to. I don’t remember the name of the band, but I DO remember trying to put the hood of my sweatshirt as far in my ears as possible. It was the first time that I had ever experienced sound as physically painful. After that, for several days, I heard ringing in my ears at a high pitch.

So we know what tinnitus is. We know it’s not really there. But HOW does it happen? Now, it looks like we might know.

Yang et al. “Homeostatic plasticity drives tinnitus perception in an animal model” PNAS, 2011.

There have been two hypotheses as to why tinnitus occurs. The first is that, when you kill in the hair cells in your ear using a high noise stimulus (like a rock concert), your brain areas which process sound will remap to make up the difference. This remapping could cause abnormal brain activity, and thus produce tinnitus. The other hypothesis is that losing hearing decreases the inhibition you normally have in your auditory cortex (because it’s not getting any sound stimulus to inhibit), and therefore you get more excitatory signals, more firing, and phantom perception of sound.

So which one is right? Turns out it’s a little of both, but the second hypothesis appears to be the main one responsible for making your ears ring.

(Side note: for more on hearing and how it works, see my SCIENCE: 101 post on the auditory system)

To figure this out, the authors took a bunch of rats, and gave them a rock concert. A very high pitched, irritating rock concert. They exposed them to 123 decibels of sound at greater than 4 kilohertz, for more than 7 hours.

(That’s 2 kHz. Turns out that is EXACTLY my tinnitus tone! Go figure)

You can imagine that was probably pretty rough. The net result of this was when they tested the rats to see if they reacted to tones a week later, they still had their low pitch hearing, but nothing in the high range. They did this by playing the tones and looking at the brainstem responses of the rats, do the auditory neurons fire? They were just fine for lower tones, but for higher tones they had to play the tones at a much higher volume to get any effects.

So ok, the rats are deaf in these ranges. They also looked at patterns of activity in the auditory cortex of the animals, and found that the deafened rats had undergone cortical reorganization, with a lot more of their brain taking over the low tones, and less available for the high tones. Work with what you’ve got, you know?

And at the bottom of that figure right there, you can see the brain responses in the auditory cortex to a 2KHz tone played at 50 dB. Both rats did respond, so the hearing lesioned rats are NOT deaf to those tones (which is important, usually even when we have hearing loss like this, it’s not total). And the interesting thing is that the deafened animals actually responded MORE to the test sound. When they probed this further, the authors were able to show that not only did the deafened animals have brains that responded more to a test tone, they had neurons that were more excitable to the tone, meaning they fired more in response. So it looks like they are lacking inhibition.

Of course…do the rats have tinnitus? And what TONE is it? I was pretty impressed that they managed to come up with a TEST for this! After all, you can’t just ask a rat if his ears are ringing. Instead, they did a modified version of something called conditioned place preference. And this test could also measure what tone the rats were hearing. It looks like from the other studies the tone should be high pitched, if the excited neuron firing which they detected was in the areas they thought it was.

In one test, the rats were encouraged to prefer the light side of two chambers (they usually prefer the dark) in response to a specific, higher than 4KHz tone. A lower tone (3KHz) taught them to prefer the dark side (this is called a conditioned place preference test with bias. Many scientists prefer to run these WITHOUT bias, but I think that would have been a lot harder to do in this particular test). Then they tested them with silent periods, interspersed with some tones. Generally, the rats preferred the dark side in the silent trials (no sound, no stimulus, and they like the dark, you know?), but rats that had been DEAFENED actually preferred the LIGHT side more during the silences, which suggests that they might be hearing things, and that they were hearing them at the high pitch they had been deafened at. It doesn’t actually prove it, but I think it’s is probably as close as they are going to get.

So. We know the rats’ brains remapped. We know that the individual neurons are more excitable. We know the rats have tinnitus. The question is, can they BLOCK the effect? The idea is that if individual neurons are more excitable, they lack inhibition. Inhibition is usually provided by the neurotransmitter GABA. So if, after hearing loss, you have less GABA signaling, you have excitatory signaling that is uninhibited, and you might get tinnitus. But you don’t KNOW this unless you block the effect.

And it worked! When the authors gave drugs to the deafened rats that increased GABA signaling and tested them on conditioned place preference again, the rats began to prefer the dark side, suggesting they weren’t hearing the high pitched tones in their head anymore.

It’s an interesting study, and it looks like, though the brain does remap itself in response to hearing loss, the cause of tinnitus lies in the LOSS of inhibition to auditory cortex neurons. They then fire spontaneously, and this can produce that ringing in your ears. It also lines up with reports in humans, who usually report ringing in their ears at high pitches, rather than low. It makes me wonder what would happen if they tried to lesion at a low pitch. Are we less sensitive to that?

But it also means something else. There are relatively few people who suffer from CHRONIC tinnitus, but for those who do it can really get you down. But as yet there was no established treatment. But if this study is right and tinnitus is caused by excited neurons firing without inhibition…well we’ve got drugs for that. And they already EXIST. We have drugs that can increase inhibitory signaling, GABA drugs which are usually marketed for treatment of anxiety. It’s possible that these drugs could be tried to treat chronic tinnitus in humans (though no proof on that one yet) and finally get rid of that awful ringing in your ears.

Yang S, Weiner BD, Zhang LS, Cho SJ, & Bao S (2011). Homeostatic plasticity drives tinnitus perception in an animal model. Proceedings of the National Academy of Sciences of the United States of America, 108 (36), 14974-9 PMID: 21896771