Hope for sufferers of ‘invisible’ tinnitus disorder

Researchers are gaining new insights into the “invisible” disorder tinnitus, whose phantom ringing, hissing, and other noises are often linked to hearing damage, but for which physicians have not had an objective measure, until now.

The advance, reported in late April in the journal Science Translational Medicine and funded by the National Institute of Deafness and Other Communication Disorders, has the potential to provide physicians and researchers with a way to gauge tinnitus severity beyond the subjective patient questionnaires in use today. In addition, it also may help develop more effective therapies.

In this edited conversation, Daniel Polley, director of the Eaton-Peabody Laboratories at Harvard-affiliated Massachusetts Eye and Ear and professor of otolaryngology head and neck surgery at Harvard Medical School, discusses research conducted with MEE colleagues that examines involuntary pupil dilation and facial movement in reaction to sound in patients with varying levels of tinnitus.

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What is tinnitus? Is it more than just ringing in the ears?

Most cases of tinnitus have one thing in common: the conscious awareness of a sound that doesn’t exist in the physical environment, a phantom sound.

I have tinnitus, and it’s like a 24/7 radio broadcast — a single note — that I usually can put out of mind. But it’s always there if I want to tune into it.

It’s exceedingly common, affecting about 12 percent of people. Among those 65 and older, those numbers jump to 25 percent and higher.

For most, this phantom sound is a mild nuisance, but for some it is debilitating. It’s not just an auditory problem, it’s a whole-life problem, a mental-well-being problem. Their tinnitus is not necessarily louder, because when most people match the loudness of their tinnitus to a physical sound, it is actually quite soft.

But what makes people with tinnitus disorder different is that it encroaches on systems that regulate mood and arousal level. A common complaint with severe tinnitus is that it takes longer to go to sleep and you wake up more easily.

Very often people with tinnitus disorder will have a hypersensitivity or aversion to sound. There’s high comorbidity with depression, anxiety, and social withdrawal, a spectrum of neurological and psychiatric issues that come along with it.

So, people who have real trouble, it’s not because it’s louder, but that they just can’t put it out of mind?

They can’t tune it out. Perhaps what makes the neurological signature of more severe tinnitus different than mild tinnitus is that the very systems in the brain responsible for tuning out irrelevant and uninformative things is co-opted in generating the tinnitus. That was the hypothesis that inspired the work that we did. That’s what got us going on this road.

And you believe your work could provide a way to understand this condition better, to study it better?

We need better therapies for tinnitus. That’s the top priority for the field — and for me as well. But taking shots at treatment without first laying the groundwork is unlikely to get us anywhere.

It’s not hard to claim a therapy works when success is measured only by subjective questionnaires and there’s no control for the placebo effect. To be convincing, future studies will need to show improvements in physiological signs of tinnitus distress — changes that are unlikely to come from placebo alone.

This study helps lay that groundwork. First, it offers a way to visualize different tinnitus subtypes. Second, it allows us to link those subtypes to an intervention and ask, “Did it work?” not just based on whether the patient says they feel better, but whether something objective in the body changed, too. That’s how we’ll know we’re truly making progress.

So, what’s different about tinnitus from the common cold or cancer is that, before now, we didn’t have a physiological way to identify what’s going on? It’s subjective and self-reported?

That’s right. It puts us back into the 19th century or 18th century. With any other neurological disorder, like epilepsy, you can measure a seizure or a stroke. With Parkinson’s, you have the neuroimaging and can do an objective measurement of motor behavior.

There aren’t many disorders that are truly hidden, where you can’t use outputs or inputs to shine light on the ghost in the machine. Chronic pain is first and foremost in that category — it’s even more common than tinnitus.

And for both of these conditions, you need an objective measure. For chronic pain, all they have is, “How bad is your pain today, on a scale of one to 10?” That’s the value of this metric: It predicts the individual severity scores that come from the questionnaire.

Can you describe the measure that you’ve documented?

The study provides a new way of thinking about what’s causing tinnitus. We wanted to come up with a measure that would relate to someone’s severity and not just distinguish them from someone without tinnitus.

We also wanted to avoid a measurement that could only be done in a specialized research hospital with expensive equipment. We want to measure these things with equipment that could feasibly wind up in a typical hearing health clinic.

Our idea is that when you or I go about our day, our brain is always surveilling the environment for possible threats so we can defend ourselves, flee, or freeze in place. Those systems are designed to get your conscious attention because you need to be aware of a possible threat.

If those systems are co-opted in the tinnitus-generation network, that would explain why you can’t put it out of mind: because you’ve incorporated the system that is designed to always elicit conscious awareness. If these networks identify a threat, they engage the sympathetic nervous system — fight, flight, or freeze — and you get, among other things, pupil dilation and increased galvanic skin response.

So, if people with severe tinnitus have their auditory threat evaluation system stuck in overdrive, then we could present emotionally evocative sounds that span a range: neutral sounds, like a typewriter; pleasant sounds, like a giggling baby; and sounds that almost everybody finds unpleasant, like an intense fit of coughing.

We expected that people with more severe tinnitus would have an overly robust response to a broad class of sounds, their sympathetic nervous system would report all of these sounds as possible threats.

How do you link that to an objective measure?

Obviously, we control our faces to communicate our emotional status, but our faces also involuntarily move to reflect our evaluation of events — pleasant or unpleasant — and our internal state of being — sad or happy. A lot of studies have examined facial movements when presented with images intended to cause happiness or fear, but nobody’s looked at facial movements when presented with sounds. We did and found that sounds do elicit facial movements.

If the sound is pleasant, in a neurotypical person there’s more facial movement around the mouth. If the sound is unpleasant, you get movement in the brow, squeezing the eyes.

When we looked at people with severe tinnitus and sound sensitivity, there was a very clear difference. Their faces didn’t move. They had a blunted affect across the board, from pleasant to neutral to unpleasant. There was a diminished response to all.

Nobody’s ever measured it before. Nobody’s ever thought about the face and its connection with tinnitus. But that ended up being far and away the most informative measurement to predict an individual’s tinnitus severity.

There was a pupil response, too?

Yes, the pupil is part of the sympathetic nervous system. It’s wired into the fight, flight, or freeze system. The pupil dilates when the sympathetic nervous system is activated and, in our work, the pupil over-dilated to the sounds that the face was under-moving to.

They’re mirror images of each other. They were providing different perspectives on someone’s severity. If you use them together, you can better predict somebody’s tinnitus severity than if you used just one. The face is by far the most informative.

How could this be used as a tool?

The first FDA-approved device for tinnitus is available for prescription, but there’s controversy about how effective it is. One of the issues is that they use the same subjective questionnaires to evaluate results. Every time a tinnitus intervention is identified, people ask, “Is it placebo?”

My lab is focused on developing new therapies, so these results are an important milestone. We can incorporate them into our interventional studies. We want to migrate to a video-based system so we can make high-quality measurements faster, with less specialized equipment. We might get it into clinical use if doctors can subtype a tinnitus patient as severe or mild in their office with an objective measure.