Photo credit: Kevin Faingnaert

Emilie Cardon is a postdoctoral researcher at the University of Antwerp, Belgium. For her PhD, she explored the neural activity underlying Tinnitus perception. We asked her if she was interested in doing a written interview with us, and she agreed! While we realize that her research only focuses on tinnitus, the subject and contents of her research are too interesting not to explore further. Many of our readers also have tinnitus, and her research might eventually help in finding treatments for hyperacusis. Our questions and replies are bolded, Emilie’s answers are in normal text. You can also watch a video summary of this interview on our YouTube channel:

Thanks for chatting with us today!

No problem!

Wonderful. We’ll get right to it. What made you interested in studying tinnitus?

So, I’ve always been interested in a lot of things 😉 I actually have a background as a musician. I studied musicology and piano right after high school, and during those studies, I became more interested in how the brain interprets music, and other sounds around us. So I decided to go on and study neuroscience afterwards. I always knew that I wanted to go into research after getting my degree. So I started looking around for interesting research groups and stumbled across a PhD vacancy at my current group that was about tinnitus – which to me felt like bringing several of my interests together. I don’t have tinnitus myself, but I know a lot of people that do! Also, the aspect of getting to potentially help people/patients was very important to me in deciding which sort of research I wanted to conduct. Very interesting! With this study, what was the main goal/outcome that you were looking for?
Within our research group, we are really interested in trying to ‘objectify’ tinnitus research. I think this is also something a lot of other tinnitus researchers are interested in at the moment. One of the (many) challenging aspects of tinnitus research is that we are so reliant on all kinds of subjective measures: you can ask someone whether they have tinnitus or what their tinnitus sounds like, you can have them fill out some questionnaires, etc. But those subjective measures are not ideal for research purposes (for example, they might not be sensitive enough to pick up changes after a certain treatment) and they are also often quite difficult for people with tinnitus! It’s not easy to say, for example, how intrusive your tinnitus has been on average during the last 4 weeks… So we really wanted to find something you can measure objectively, that would also help us understand the way tinnitus develops. Our goal was to develop a model that was able to classify a large amount of data into either people with tinnitus or people without tinnitus. I was very happy that we succeeded in doing just that!

Having a way to measure it objectively is definitely a game-changer in so many ways!

I totally agree. This is obviously only a first step in developing such objective measures, but I think we’re on the right path.

It certainly wouldn’t cover all the detailed specifics, but how would you describe your methods and findings in lay terms?

Photo credit: Bart Vandersnickt

Basically, we recorded the brain’s activity while listening to certain sounds. We used EEG, which is a method of recording the brain’s electrical activity (you might know it from sleep research, for instance). We place a cap containing about 30 electrodes on the head of each participant, then give them headphones through which they hear certain sounds. You can use very complicated sound stimuli for these kinds of measurements, but we kept it pretty simple: people only heard 2 different tones. There was a ‘normal’ tone that occurred 80% of the time, and a higher tone 20% of the time. We asked people to pay attention to this tone specifically, and every time they heard it, they had to press a button. The fact that people have to pay attention to that one specific sound, elicits a very specific reaction in the brain at around 0.3 seconds after people hear the sound. The more you’re capable of paying attention to that sound (or, for instance, the more unexpected that sound is), the larger that response will be. We found that, if you have tinnitus, the brain’s response to that important sound is diminished! Specifically, we saw that some important brain areas (both auditory and non-auditory) did not respond as well to those sounds in people with tinnitus. We now think this is the case because those brain areas are already so preoccupied with the tinnitus (the ‘internal sound’), they do not have enough resources to also deal adequately with those external sounds. The difference between people with and without tinnitus was so big that we could accurately classify a new set of data – so we could objectively determine who had tinnitus and who didn’t!

That sounds amazing! How did you come up with this specific idea to detect tinnitus? Is it based on older research? There’s actually a lot of earlier research that used this exact same method to compare people with versus without tinnitus (but not to detect tinnitus), so one of the first things I did in my research was to compile all of those earlier papers in a meta-analysis. Based on that meta-analysis, we already strongly suspected that that specific brain response was diminished if you have tinnitus, but we couldn’t know for sure, because a lot of earlier papers did not accurately correct for important factors that could have an effect on those kinds of findings. There’s so many things you have to take into account: hearing levels, age, anxiety levels, depression, … So what makes our study unique is that we really tried to match each person in the tinnitus group with their ‘match’ in the non-tinnitus group, like a sort of dating agency.
That way, we could be sure that any differences we found could be specifically attributed to tinnitus and not to any of those other factors. The idea to ‘detect’ tinnitus actually came from machine learning practices: developing a model that is able to detect the presence of tinnitus (in new data!) is so much more powerful than just comparing two groups.

In another article, we read that you say tinnitus leaves a signature in the brain. Does this lead you to believe that it originates in the brain too, and tinnitus is mainly a brain issue? Or do you believe (damage in) the ears plays a role too?

This is kind of tricky because the question of the ’cause’ of tinnitus is just so difficult to answer… Obviously, there’s a very strong link between hearing loss and tinnitus – hearing loss is the most common risk factor to develop tinnitus! But on the other hand, some people develop tinnitus without having any kind of (measurable) hearing loss. So there must be other factors at play as well. What I currently think is that the original cause of tinnitus might very well be hearing loss (that might be permanent or transient), but may also be other bodily problems (for instance, jaw/neck complaints) or psychological issues – but that regardless of the cause, we see some kind of pattern of brain activity that explains why tinnitus then becomes a problem or has an impact on daily life. For instance, we see altered activity in many regions that are important for the regulation of attention, which might explain why for some people, it is so difficult to direct their attention away from the tinnitus. And we also see altered activity / connectivity in regions that process emotions, which is possibly why in some people, tinnitus comes with that elevated emotional burden. And, if I may add to this: the cause is very often something that we cannot do anything about anymore (for instance, in the case of damage to the cochlea), but that altered brain activity might be something that we can target therapeutically. So I think that is also why it’s so important to investigate that further.

Is that what you mean by top-down vs bottom-up central gain? In your study, it was people with no identifiable hearing loss, but that may still be part of a cause? Could, for instance, cochlear damage, cause a snow-ball type of effect to alter how the brain reacts? Like people without previous attention or emotional problems might develop them because of tinnitus? Or is that still unclear… like the which came first, chicken or the egg scenario?

Yes, exactly! We did have people with normal hearing for their age in our study (which of course does not exclude age-related hearing loss, and we did have some participants with a bit of hearing loss in the study). It might also be that those ‘top-down’ processes determine how sensitive you are to develop tinnitus, which might also explain why we see a lot of people with hearing loss that do not have tinnitus. But at the moment, it’s not really possible to determine which came first.

Good to know! How could treatment options be created based on these findings?

There’s a couple of different ways in which our findings can help the development of new treatment options. The first thing that we want to look into in the future is whether we can use that objective measurement to ‘track’ changes in tinnitus severity after treatment (so if they correlate with those subjective measurements that I talked about earlier). This would be really important to be able to better evaluate novel treatment options in the future. Another thing we want to do is look at whether we can use that measurement to predict how people will respond to certain treatments. In that way, we could potentially further personalize tinnitus treatment plans (which is a really crucial challenge in current tinnitus research). Maybe in the future, we would be able to recommend certain treatments for everyone individually, based on that kind of brain measurement. And then lastly, of course: the more we know about that underlying brain activity, the more we might be able to use that activity itself as a target in novel treatments. So then I’m talking about non-invasive brain stimulation. There have already been some trials using different forms of brain stimulation for tinnitus, but the results have been very variable and not overall positive – I’m thinking that the more we learn about that underlying brain activity, the better we will be able to target with novel treatments. How are you planning on convincing researchers to use your method to detect a patient’s tinnitus?

Good question. I think that we have to do a bit of work ourselves first: for instance, look at whether our method does correlate with subjective tinnitus severity or loudness. Luckily, we are planning to further investigate just that. Once we are totally convinced that our method can do all those things, we really need to think about ways to implement it more easily. Maybe we can find a way to measure that brain response using only 1 electrode instead of the whole cap – you would then ‘sacrifice’ some interesting information but it would make it so much easier to implement it in the clinic. And something completely different: I really like to communicate about my research to a non-academic audience, as you’ve seen in the PhD Cup. I think it would be really important to think about ways to disseminate our findings to (for example) clinicians or people who themselves suffer from tinnitus, other than academic papers!!

That is great! It’s something we hope to help with ourselves. Since our name is “Hyperacusis Central”, we are very interested in the impact this could have on hyperacusis. Do you believe the same or a similar method can be applied to detect Hyperacusis? Why (not)?

Difficult to say! I think that the research on underlying brain activity in hyperacusis has not yet reached the level it has in tinnitus research (although I have to admit I’m not as familiar with the literature myself). I know that there’s obviously a huge overlap between the two – people often experience both symptoms together, but also, there seem to be similar brain regions involved in both symptoms. I think we first need more research into underlying brain activity in hyperacusis which is accurately corrected for tinnitus – which I think is almost never done but super important. Intuitively, I think that the exact measurement that we used might not be as helpful in hyperacusis research, because it is so highly impacted by attention (which I think is the reason it’s so sensitive to detect tinnitus). But there are many different types of auditory stimuli that might be more useful in hyperacusis research, such as looking at comfortable/uncomfortable loudness levels etc.

Good point! Inhowfar is funding an issue with your tinnitus research? We know that there is very little funding for hyperacusis research, is more funding available for tinnitus research?

I do think that there’s more funding available for tinnitus research, simply because it’s more well-known! But I think the tricky thing is that no one really seems to agree on how to categorize tinnitus. For instance, for our Flemish research funding institute (FWO) we always submit our projects in the neuroscience category, but then you’re up against, for example, very important research into neurodegenerative disorders, etc. But tinnitus also doesn’t really seem to fit within the ‘traditional’ ear-nose-throat categories because of that strong influence of the brain…

That’s an interesting challenge which we assume hyperacusis researchers also face. Yes, you really have to think about where to position your research exactly!

Wonderful! Thank you so much! We were curious about the differences between CAEP, BAEP and MLAEP in how they apply to this study? *(See below for definitions)

So right now we’re only looking at CAEP – so only responses at the cortical level! My colleagues have also done some research into brainstem potentials in tinnitus and we recently did a systematic review on brainstem potentials and tinnitus: https://pubmed.ncbi.nlm.nih.gov/36071905/ There’s some evidence of alterations at the brainstem level, but again, based on the literature, it’s really hard to differentiate between effects of tinnitus and effects of (high frequency) hearing loss… And middle latency potentials are almost never investigated in this population, so it’s really hard to say something about that. Have you seen other areas of the brain involved in tinnitus? Some other studies, more recently an fMRI study, mentioned areas of the brain like the posterior cingulate gyrus and precuneus having a role in specifically the cause of tinnitus. We do not know about it definitively being a cause of tinnitus, similar to how you’ve been explaining, but have you seen other areas of the brain involved?

Yes, definitely! Both anterior and posterior cingulate gyrus seem to be heavily implied. It’s interesting that, as our research field is progressing, we’re seeing similar areas pop up in both EEG and fMRI studies. I think there’s definitely different networks that are important for different aspects of tinnitus. For example, we focus quite heavily on the salience network in our paper, but you could also find evidence for a tinnitus distress network, attention network, and so on. I agree with you that we’re not able to say that one region is the ’cause’ of the perception of tinnitus, at least not right now, but it would be interesting to see how the neuromodulation of those different areas might potentially impact the tinnitus itself. So much to do in our research field! It might also be very individualized! Which would give us more of a starting point for individualized/personalized treatment.

This has been very interesting and enlightening! We love your individualized approach, objective and goal-oriented work, and such attention to detail. Those were all of our questions, but we do hope to communicate with you again in the future. And we certainly look forward to your ongoing research.

Great to hear! I enjoyed chatting with you! It was my pleasure – and I’d love to speak with you again if we have more research out in the future!

Thank you Emilie!

You can read the full paper here: https://www.sciencedirect.com/science/article/pii/S0378595522000600

*AEP: Auditory Evoked Potentials A record of the time it takes nerves in the auditory system to respond to sound and electrical stimulation. Nerve signals are rapidly sent from parts of the ear to the brain and vice-versa.

CAEP (Cortical Auditory Evoked Potentials)

BAEP (Brainstem Auditory Evoked Potentials)

MLAEP (Middle Latency Auditory Evoked Potentials)