Production and Perception of Speech and How Marmosets Are Helping to Advance the Future of Voice Therapy

By Aleksandra Golota

Would you introduce yourself and tell me what you do?

My name is Steven Eliades. I am an associate professor in the Department of Head and Neck Surgery & Communication Sciences and have been at Duke for a year and a half. I'm a physician-scientist—I see both patients in clinic and operate for about a third of my time and then the rest of my work is research. This basic science work is mostly in animal models, focused on questions related to hearing and vocal communication.

What was appealing to you about coming to Duke and doing your research here as opposed to other institutions?

This is my second faculty position. I was originally at University of Pennsylvania for almost nine years. Several things interested me and turned my eye toward Duke.
Dr. Howard Francis, whom I've known for many, many years, was certainly a large part of it. He was my residency program director but even before that, I knew him as a medical student from the classes I took in graduate school on hearing, etc. He was actually the preceptor on a term paper I had to write back in 2001. I knew that as part of becoming a department he really wanted to build the department’s research infrastructure and research credentials. It's not something that traditionally had been done before at Duke, being a much smaller, very clinically heavy division. Prior to this, I also knew Brad Goldstein so I kind of had a sense of what he was trying to build at Duke as well.

And as far as science, there are a lot of people at Duke, collaborators and researchers, with similar or at least complementary interests. Richard Mooney, who primarily works with songbird and now mice in Neurobiology. Jennifer Groh, who does hearing research, who is in Psychology as well as in Neurobiology. Mark Summer, who does a lot of sensory motor type research on other species. So there were a lot of people at Duke I already knew and that was a nice incentive.

What kind of patients do you see?

My clinical specialty is otology, meaning diseases of the ear. I see patients with problems with hearing imbalance, chronic ear infections, hearing loss, dizziness, balance issues, etc. Surgically, I'm still building my services, it is still early on. It takes several years after a transition to a new institution. I also do a lot of
cochlear implant surgeries.

What are marmosets?

Marmosets are small little monkeys. They are natively from Brazil. They were originally exported as a pet species to a lot of different countries, England, U.S., Europe, South Africa, etc. Marmosets are non-human primates, although they're very small. We typically think of bigger monkeys when it comes to research, like rhesus monkeys, which can weigh 20 kilos. Typical marmoset weighs about one pound. So they're little monkeys, but they do have a lot of advantages for the type of work I do.

First and foremost is they are very chatty. And since I study a lot of vocal communication, you want an animal that chats and you can't say that about a lot of the species that people do research on. Songbirds have traditionally been a very big model, but obviously are evolutionarily very removed from humans. So there's some debate about what's useful and what can be applied or not to humans. Bats have become a popular model as of late but also have their idiosyncrasies as well.

The other advantage of marmosets is because they are small, you can raise them and breed them and keep them in social settings. We can also study their social communication as a kind of a way of trying to understand the evolutionary basis of human social communication and how we interact in large groups and coordinate our timing and communicate information etc. Marmosets are very, very useful for that because they do have a lot of very human like social behaviors, including things like cooperative rearing of young, which is not typical in the primate community where usually it's all the mom and everyone else is off doing their thing, which I guess is not atypical in humans either. Marmosets are about the whole family participating in raising their young and that's very interesting and applicable social parallel thing to human behavior. Lastly, marmosets have become much more popular over the last several years. I've been working with them on and off over a decade or two and that allows us the potential to try some newer techniques for research that traditionally have only ever been done in mice and rats that are starting to show some benefits.

Tell me more about establishing the lab for them at Duke. Did you have a group of marmosets that you brought with you when you started?

Yes, we brought down about 20 animals that I had at Penn, I'd had a colony there for eight years or so. There are companies who specialize in transporting exotic animals, making sure they are comfortable and have heated or cooling trailers depending on what time of year they are transported. We were in temporary space while my lab space was renovated. We finally moved them over to their permanent home last month and they seem to be very happy.

How many do you have now?

We have 31 right now.

What is an average lifespan of a marmoset?

I'd say the average true lifespan, barring health and health issues—which are not uncommon in marmosets—is somewhere in the order of 10 to 12 years. I think the record is 18 in captivity, but a lot of them unfortunately will develop middle age health issues, which can be around age six or seven, which is middle age for them in the same way humans have middle age, and that can often be limiting.

Do you have a favorite one?

No, not one that is particularly a favorite. There are some I like better than others because some of them are just a little bit more socially interactive than others. Some of them are much better about being social with humans and some are very much like “I don't want to deal with you, humans, unless you have a treat in your hand.”

I develop interesting relationships with them. If there's one that I'm actively doing work with, I get to know it very well. But they have their own personalities and quirks, trust me.

That's fun. What kind of observations do you conduct with these animals and what you learn from them?

We do a lot of different things with them. We're primarily focused on vocal communication, but it spans the whole range of the communication processes, from perception to how do you hear sounds? How do you encode sounds? How does your brain encode sounds of both artificial as well as natural sounds and your own production? How does the brain control what you say? And how do you change what you say? How do they decide who they are going to talk to and how do they say it this way versus that way?

In presentations of your work, you mentioned sound booths and studying marmoset brain activity to understand sound interpretations. Could you explain more about that?

Traditionally we look at sensory physiology to understand how the brain interprets sensory stimuli, or sounds specifically, the same way we do it with a human—through a hearing test. We put them in a quiet room, in a sound booth. These are rooms with a metal box that is built within the room, that attenuate outside sounds because we want to isolate you, so you don't hear anything in the hallway, etc.

We have these big metal boxes that weigh about two tons a piece, they're built by the same company that makes the sound booths that we use clinically with patients. Basically, what we do is sit an animal in a chair designed for a marmoset in one of the sound booths, where it's quiet. And you play sounds to it through a speaker and observe their brain function.

It's interesting to me to think about the sound booth being so big and these little animals being so little, sitting in these tiny chairs.

So there’s some discussion in the field: do we need such a big sound booth? It’s easier for us to go in and do our manipulations. If we can physically go in the room with marmosets to do things like get them in the chair, to get everything set up and things like that. It is easier. The inside of the sound booth is six by six by six feet, roughly a cube. The walls must have a certain thickness, and, in our case, these booths are actually a box in a box. There are two walls to really attenuate the sound even more. And that adds to the space too because you must have room for the inner room and then you must have the outer room around the inner room.

What is natural basis of vocal communication?

Natural basis is communication that's happening the way it's meant to happen, meaning in a natural or at least naturalistic context. There are ways of getting an animal to vocalize, which may or may not be ethologically relevant. Ethology is the study of natural behavior of a species and trying to study a species for what it's good at, as opposed to imposing your own expectations or your own notions about how the behavior should be used.

Some people have trained primates to vocalize on demand, but the behavior is not normal. You get very different neural responses when the animals vocalizing for reward, versus when they vocalize spontaneously, meaning just naturally, and so there's a bit of philosophical debate going on about what's the right way and what's natural and what's not.

I've always argued for doing things as naturally as possible, engage the system doing what it was shaped to do, shaped by evolution, by development and experience. And that is how we conduct our research in my lab.

Can you tell me how your research so far has translated into clinical/patient treatment?

It is still very early, and I can't say that it has truly translated into anything just yet. We know that being congenitally deaf or being born without any hearing affects speech, language, and ability to acquire language. We know that losing hearing does subtly affect speech and language in people. Some neurologic disorders, like people who have cerebellar dysfunction—where the parts of the brain that does coordination of things does not function properly—those patients have abnormal speech and voice. People who have strokes have abnormal speech and voice. People who have Parkinson's and others, have abnormal speech and voice too.

We can behaviorally test a lot of these patient populations, using very similar sorts of protocols as we do in the animals and see how these things are abnormal. We haven't learned to do anything with that yet. Eventually we would like to see how brain functions in people with hearing issues, understand why it happens and how to improve it.

Where do you hope to be with your work in five/10 years?

There are two branches I think about. Continuing to pursue the basic science, the animal work, as we start drilling down more and more precisely on mechanisms. For example, how does our brain calculate an error in speech when we hear ourselves say something wrong and corrects it?

The other direction is patient and human based testing, and that itself has two directions. One is trying to drill it down a little bit more precisely in humans, not necessarily from a therapeutic standpoint, but to understand aspects of the phenomenology of the neural basis. We can’t do that with animals, can’t ask questions about that was heard, how the sound was heard or what was noticed while studying them.

And on the other side of humans, is to start trying to identify potential therapeutic options for voice disorders. There are different ways we may be able to change voice therapy through more knowledge of the science or manipulations through devices that may be like some of the things we're doing in in research but might show a clinical benefit, and long term, are there even drugs?

But that's long term since I think that's going to require a detailed mechanistic understanding. I think we're not 10 years away. We're 20 years 30 years away from realistically understanding that.

That sounds exciting.

Well, there's a lot of work to be done.