Squeaking, humming, buzzing… in the Netherlands, an estimated two million people hear a sound that is not there. It is a phantom sound; it does not come from outside, the brain makes it itself. It's called tinnitus, or ringing in the ears.
“After 20 years of searching for solutions for tinnitus, nothing much has come of it. The question is why,” says Dirk de Ridder. “The approach may be completely wrong, so we went back to the drawing board. What is the fundamental thing we missed?”
De Ridder is professor of neurosurgery at the University of Otago in New Zealand and has been researching tinnitus for decades. Together with Wouter Serdijn, professor of bioelectronics at TU Delft, he designed a device to treat tinnitus via a different route than has been usual until now.
'The lunchbox', as they jokingly call the device during the interview, must teach the brain that the sound a tinnitus patient hears is not an important sound. Then the brain hopefully stops producing the signal.
Whether the Delft Tinnitus Device – as the device is really called – will indeed completely or partially eliminate tinnitus remains to be seen. Clinical tests will start in April in New Zealand, where De Ridder, originally from Belgium, lives and works.
A festival in Mali
The introduction between De Ridder and Serdijn took place through the desert in Mali. There, at a music festival, De Ridder started talking to an artist and researcher who knew that bioelectronicist Serdijn was working on medical implants. What he didn't know is that Serdijn also suffers from tinnitus. “Not a bad variant, fortunately,” Serdijn hastens to say. “It is approximately the sound of an idling washing machine, here in the ambient noise it almost disappears.” It did make Serdijn interested in the tinnitus approach that De Ridder had in mind: stimulating the autonomic nervous system with electrical pulses.
The causes of tinnitus are diverse: listening to loud music for a long time, banging noises, an ear infection, age-related deafness. Sometimes it starts spontaneously.
“Many only experience it as annoying, but others can no longer sleep or work because of it and for some it is completely maddening,” says Serdijn. “Now that our research has been publicized, I hear emotional stories. This week four people emailed me who are so desperate because of tinnitus that they want to end their lives. Four!”
For a long time, tinnitus was approached and treated as a problem of the ear. As brain science developed, it became clear that the problem lies in the brain. “It was only in 2000 that the step from the ear to the brain was taken,” says De Ridder. “Imaging techniques suddenly made it clear that tinnitus is located in the auditory cerebral cortex.” The treatment also progressed, with magnetic pulses through the skull attempting to address the auditory cerebral cortex. “We sometimes saw a temporary improvement with this. Then we knew that the brain must have something to do with it, but it was not the solution.”
Still later, 'networks' became popular. “The neurons in the brain form one large network. We understood that we had to view tinnitus as something that happens within a network,” says De Ridder. “The route sound takes from the ear to the auditory cortex is clear, but once within the auditory cortex there are many different possibilities.”
A major unknown factor is that there are probably different subtypes of tinnitus, but it is unclear how many and what properties they have. “That is an important basic problem that we still have and why finding treatments is so difficult,” says De Ridder. “In chronic pain, for example, we know that there are many different types, and that each requires a different treatment. If you test one medicine for all those different pains at the same time, the tests will yield nothing because it does nothing for too many people. If you can distinguish between subtypes, you discover that a drug works very well for one subtype.”
“It is currently accepted that there are at least two types of tinnitus: tinnitus with hearing loss, and tinnitus without hearing loss,” says De Ridder. “But it could also be six. Artificial intelligence is very good at distinguishing between subtypes, but in this case not much has come of it.”
But, De Ridder reasoned in his attempt to approach the whole problem freshly, ultimately all subtypes lead to sound perception that is not there. There must be some common denominator. “If you know it, you can treat it. And we believe there is.”
Fight or flight
“Our brain is a big prediction machine,” says De Ridder. “When you play tennis you have to predict the speed of the ball, otherwise you are too late. The brain is constantly interpreting the world and acting accordingly. If you ever heard well, your brain knows all frequencies between 20 and 20,000 hertz. Suppose you have a fireworks accident, this can lead to hearing damage between 4,000 and 6,000 hertz. Those tones then no longer reach your brain. The brain can then choose two solutions: either it is not important and then you simply no longer hear those tones, or it is important and the brain will produce it itself to be on the safe side.”
And then follows an important question in De Ridder's reasoning: why does your body say that something is important or not? “These types of reactions are controlled in the body by the autonomic nervous system,” says De Ridder. “That's what the fight or flightresponse, and the opposite remainder-and-digest-response, reactions over which you have little influence. We think that tinnitus, especially tinnitus that has existed for years, is linked to this autonomic process.”
An indication of this is the link with stress. “The chance that tinnitus will persist is much greater if it has been acquired in a stressful situation, a situation in which the fight or flightresponse is active,” says De Ridder. “People also notice that their tinnitus gets worse when they experience stress.”
The circuit in the body that provides the non-important signal is the vagus nerve, the vagus nerve. Coming from the brain stem, this nerve runs via both sides of the neck to the chest, the abdomen, and via various side branches to the organs. This nerve is used in more treatments, including depression and epilepsy.
“We were looking for a place where it comes to the surface,” says Serdijn. “The tragus, the bulge at the front of your ear, in front of the ear canal, is such a place. By giving electrical pulses and simultaneously playing the tinnitus sound, so-called bi-modal stimulation, we link the sound to the activation of the nerve. Because it only sends a signal when it is quiet and safe, we teach the brain that the tinnitus sound is not important and that it should be ignored.”
Activating a nerve is not difficult, says Serdijn. “Nerves talk to each other via electrical pulses. What I never realized as an electrical engineering student is that electronics also allow you to interact very well with nerves. I can just talk to it perfectly.”
'Talking' is done via a clamp on the tragus. On both sides of the clamp there is a metal plate, the electrodes, that conduct electrical pulses to the nerve. The pulses are generated in 'the bread bin', which is connected to the clamp with a wire. The lunch box also contains headphones, which simultaneously emit the specific tinnitus sound of a patient along with the pulses.
A patient does not have to constantly travel with a lunch box and clamp. The learning effect is expected to occur with daily short use for several weeks. “Compare it with physiotherapy,” says Serdijn.
The difficulty lies in finding the right strength and pattern of pulses. This varies per patient. “From a biological point of view, the brain uses two 'languages' to fire the electrons in the brain, says De Ridder. “You have the tonic firing pattern as standard, and you have burst-fire. If someone further along mentions your name, your brain responds to it. They automatically know that this is where attention needs to be paid. That happens through it burstfiring pattern, which is stronger than the tonic. Mentioning your name doesn't do anything for me. So if we want to force the vagus to listen, we need the right one burst to create.”
The Delft Tinnitus Device does not make this plug and play. Adjustment is currently manual and must be done with the patient's exact tinnitus sound. Serdijn hopes that it will eventually become a consumer device, but it may also be used in a clinical environment.
Flow over the tongue
More researchers have turned to bi-modal stimulation as a treatment for tinnitus. Since last year, a device called Lenire has been on the market in the United States, which runs a current over the tongue while the tinnitus sound is played. And the University of Michigan developed a device that runs a current to the cheek or neck at the same time as the sound. They have already successfully completed some clinical tests.
“If you have to compare our lunch box with anything, it is these devices,” says De Ridder. “The difference is, they link another nerve to the sound, a sensory nerve. That doesn't come out of the blue. We know that 70 percent of patients can influence their tinnitus by moving the neck or jaw, where the nerve is located, and it can help in that group. This has been studied in great detail on both animals and humans. The essence of their systems is that if you link those two things, the sound is experienced as less disturbing. But the disadvantage of that is that you don't solve the fundamental problem; the brain does not learn that the sound is not important and that it no longer needs to be produced.”
The Delft Tinnitus Device must now prove itself in a clinical test. A modest number of thirty patients participate, divided into three groups of ten. “If a device works well, a clear difference can be seen in only a few patients,” says De Ridder. “We go for a well-functioning device, otherwise it makes no sense to us.”
Sound and pulses
The patients are selected according to the nature of their tinnitus: they must experience it as a pure tone (one tone, so that it can be easily imitated) and the severity is determined as grade two or higher on a scale of four. One group receives paired simulation: sound and pulses at the same time. The second group gets the sound and pulses disconnected. The third group will also receive the sound and pulses linked, and on top of that they will also stimulate the brain with electrical pulses at the terminal of the vagus nerve in the brain.
“We expect little results from group 2, because no learning capacity will occur due to the disconnection,” says De Ridder. “We both expect results from group 1 and group 3. If group 1 works sufficiently, then group 3 is unnecessary. But if you only see partial improvement in group 1, it may work better in group 3.” De Ridder expects the first results in October or November.
It is certain for De Ridder that the device can address the vagus nerve. “I tested it on myself at the same time as measuring my heart activity, because the vagus nerve also affects the heart. It calmed down in the right way.” And Serdijn, with his washing machine tinnitus, has it helped him yet? “I haven't treated myself, but I tried the device a while ago. I had the feeling it did something. I could still hear the washing machine, but my experience of stress seemed to decrease somewhat.”
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