Qui mana al nostre cervell?

First of all, we wanted to ask you to tell us a bit about your career and what made you decide to start this study.

Morten: The short story here is that Gustavo and I have been working together for many years, and we are very interested in trying to find out how the brain really works and find the true truth. And we do this by using these whole-brain models. So, what normally happens is that you put somebody in a scanner and you have a signal that goes up and then something happens and that also goes up and you do a correlation between the two situations and you get those blobs that you see in a lot of newspaper articles. “Look, there’s a blob that I like children, there’s a blob that I like wine, and so on”.

We got very frustrated by that and we thought: “Why don’t we do it in a more physical, realistic way?” Use the mathematics from physics to do this.Gustavo basically pioneered this by making what is known as whole brain models. And after he’d done that, I joined him in trying to make these things tell us something about how the brain is working. I’m sitting in Oxford and Gustavo is in Barcelona, but we try to meet every day virtually, and sometimes also actually physically. So that’s kind of the short story of where I’m coming from. 

Gustavo Just to complement that, on top of the whole brain modeling idea, I mean, in that particular paper, we also used the very elegant theoretical framework that we developed together recently during the pandemic. It is a pretty novel thermodynamic framework that combined the idea of modeling not only those correlations as Morten was mentioning but also the direction of time that we can measure in the experimental signals and, of course, is a much more detailed description of the data. We were able to capture in the model mechanistically, also this directionality of the time and because we were able to do that, we concluded what we concluded in that paper and what Morten said. Very strong hierarchical organization, that’s the brain. And, basically, hierarchical organization is basically orchestrating or controlling or biased by a couple of regions around the prefrontal cortex area. 

Morten  Almost like, and if I can add to that, we’ve also done a lot of work on what is hierarchical. So what are the conductors in the brain? And so there’s a famous theory called the Global Workspace Theory, where we also published a paper some time ago to show that it is sort of like the administrator of the brain. There are a number of different regions that are making sure everything is running smoothly. But when you have to solve difficult tasks, when you have to do social activities, memory… Any of these things you call in the special commander, you call in the prefrontal cortex that then uses extra energy and extra computation to be able to make you solve that. 

It’s like a ring, and this is the famous Catalan work of Fuster who is living in  L.A. He was forced, of course, to move to America. But he has basically pioneered this study, and he has shown that there is this action-perception cycle, and he’s shown that in monkeys, he’s shown that theoretically for many things. But I think we’ve found the first kind of indication that there is, in the words of Tolkien, “one ring to rule them all”. And that ring is something that goes through the prefrontal cortex and allows us to interact with the world. So, there are different parts of the brain and they are not active all the time. That’s why we do stupid things.

What would your advice be for someone that wants to go on this type of research that is now studying a degree? 

Morten: These people that are in our labs are all neuroscientists of some sort although, you know, we have medical doctors as well and we have psychologists, but I think they all are interested in how it is that you can quantify what is happening in the brain. So obviously, you need to learn, you have to know some animatics in order to be able to run these models. But most people can learn how to use these models. And then of course, once they get interested in it, they start to adapt them and make sure they get better and better like we’ve done. What do you think, Gustavo?  

Gustavo We are by definition basically multidisciplinary, so all of our students are coming from totally different backgrounds. That’s important: from psychology, biology, physicists, mathematicians, computer science… really we have the whole spectrum. I mean, the way to go, probably just to answer directly your question, is, after this very general background you really have to specialize, and the best way for you to specialize is going to the right master. 

There are many offers in Europe and many offers in Barcelona: the master in Neuroscience in the UB, which is interuniversitary. We have our own master at the UPF and I think that is the entrance. You get then really acquainted with neuroscience, you’re training by doing the master thesis in a very concrete group. There are very good groups in Barcelona and in all the universities working on neurosciences, experimental or theoretical neuroscience. And the Ph.D, I think is the normal way. Now it is easier. I mean, when we started it was much more difficult because neurosciences were not so well-defined and the field was dominated by biology in a medical sense but right now, they really went round, dominated by more technical people, extremely interdisciplinary and the way to get into neuroscience much better defined.

Morten: “[Referring to research] In Spain the funding is really absolutely suboptimal. But the good news is that we are in Europe, and we have access to European money.”

Where do you think research stands now? Because, for example, now in Spain there’s always this critique that there’s not enough money invested in research. What do you think is the situation for research nowadays? 

Gustavo Well, it’s very different in Oxford. In Spain the funding is really absolutely suboptimal. But the good news is that we are in Europe, and we have access to European money. In fact, I mean, in my case, in my group in Barcelona, I don’t remember the exact number, but I would say that 90% of my funding is European-funded. So they are very good sources of funding, like the ERC European Research Council, which is very, very good and gives a lot of money. Obviously, we would be even happier if there was much more money than we have now.

Morten The other thing I would say is that it’s a very international field. So, you know, you have students coming from Barcelona, coming to Oxford and the other way around. And I think the really important thing is to remember excellence. And there are not many labs around the world that are as excellent as Gustavo’s. So even with the lack of funding within Spain, he’s managed to run a world-class lab. 

Going back to your study. How did this idea come through your mind? How did this project start? You had worked together, so how did this come together?

Morten I think there was some cava involvement. 

Gustavo: More than a bottle. 

Morten I think coffee and cava are what fuels our ideas. Well, I think we were fascinated with… Both of us have been great admirers of working with this work. And we are both obsessed with the hierarchy in the brain. What are the musical directors of the brain and how does it work? Why is it that this brain of ours can work on so little energy and still do amazing things? Fuster showed this and so we wanted to test this. This hypothesis of the “ring to rule them all”. 

Morten I was just going to say, we also, of course, were very excited by Tolkien who, as you know, was based in Oxford and I think had some wonderful ideas. And so another thing that again, the testing through the interdisciplinary nature of our work, we are always fascinated by other ideas. It’s not just about physics and mathematics. We are interested in literature. So we did another research a while ago when we talked about an amazing book, which is about the slowness of things because, of course, the brain is both very fast but also very slow. And so we get ideas from anywhere and we can get it. 

It’s clear that you work well together and do some fantastic study. Now, you were talking about the necessity of different funds other than from the European Union. But what is the role of the different universities in this kind of study, for example, in Europe? How come you get together, on a superior level than just being friends?

Morte Sort of a personal conviction. What do you say, Gustavo? I mean, you have a very rich network around the world, and I think it’s really because people we meet, we get similar ideas. We have fun together. I have a formula for the people in my lab. I called it KFC, you know, this Kentucky Fried Chicken, but this is not what we do in my lab. No, we go for what I call Kindness, Fun, and Curiosity. And those are the kind of things that I also look for in my collaborators. And I think Gustavo is a great example of that. If anything, you not only say he is KFC himself, but he also makes me more KFC. 

Gustavo I think that, especially in science, all the collaborations need to be driven bottom up and not up down. So it’s not that the University of Oxford and UPF want to collaborate. It’s that we want to collaborate, and the people in our labs and so on. And we are driving the cooperation. So I don’t believe especially in science on top-down organization. We believe that happens in the brain because we researched about that, but not at the academic level. So we are running the show, and not the deans.

You work well together, you “KFC” together, but have you had to overcome any complications? Analyzing 1000 people  has to be some sort of challenge. Do you have a bigger group of people researching? How do you manage everything, even in the sense that you live quite far away? 

Morten We had, of course, a problem with something called a pandemic. But in fact, having it was even better for us because it meant that we didn’t have to be bosses, that we could just be postdocs working together. And so we could sit and work every day. Even though I, in the beginning, had very bad Covid and I could only work for a number of hours, Gustavo still got me up every morning and we worked through these kinds of problems. That was fantastic. But in terms of the group, Gustavo runs a large group and, of course, one of the things we do is try to provide the best possibilities for them to do their work and help them as much as we can. But certainly in our case, we both believe very strongly in doing our work. We don’t like to tell people you need to do this and that and this, you know, we do all the work ourselves. We, of course, are involved in their things as well, but that’s how we operate. That doesn’t mean everybody operates like that, that’s what we’ve chosen to do. 

Gustavo It’s also, and I least I like to think it’s important, that when we were young students, we got into the field that we wanted to stay in researching because we were really absolutely in love with our examples, with our professors that were both professors and working with us, students. 

During the last few years, it has been changing a lot worldwide. Because of the social pressure of professors to look for money, to supervise people, to do things that we don’t know how to do. I am a disaster in administration because I don’t like it. And I think it’s also part of our job and it’s the reason why our groups, which are very large, work, because they see our enthusiasm. And even if it’s not my main job in life, to give an example, they still see that.  It’s not that I actively try to give an example to anybody, but, if they see that we are enthusiastic and we work like  students, then they will also work and they cooperate as well. 

Morten I like to compare my role to a doula. Do you know what a doula is? Back in the 1960s you had midwives, but you also had these crazy hippie midwives that basically helped you bring a baby into life, but also, you know, do all these other things related to birth giving and children. And I think that’s my role. I’m a midwife. I’m helping my students become scientists, but I’m doing it like Gustavo says, by example. Some of my colleagues like to have long meetings where they tell people what to do and they come back and they give them results, and then they go forth; not our style. 

Do you have any projects now planned for the future?

Morten I mean, we work every day and we have many things but it’s also important to remember that the definition of a clown is a jongleur, but with one ball, too many. So, of course, we have the projects that we do together, the ones where we have students involved, and then we are helping students do their work. That’s also why we don’t like to do too much administration, because then we become clouds. Then we have too many goals.

Gustavo I mean, in that direction, there are many ideas and many projects, which is a good place to start, we always say. I am coming originally from physics and I was doing my Ph.D. in quantum physics, a very different field. I fell down with the nostalgia that all the good times of physics were at the beginning of the 20th century, and now, in neurophysics I am feeling that I am in that good time. To me, it’s really like that, because there are a lot of things to do. That’s it. It’s well known that it’s like a cool idea for hope. I mean, I’m sure we will continue developing our theoretical ideas: thermodynamics, turbulence, the brain and many things… 

Graphical scheme about Morten & Gustavo theory, that explains the heriarchy among functionalities inside our brains and its capacity to solve complex issues

One of the objectives of our magazine is to bring research and university knowledge to the general public. How would you explain this study, your findings, neuroscience… to, for example, a grandma or a 10-year-old kid?

Morten It’s a good question. We always try to do that. I usually use my mother as an example. If I can’t explain it to my mother, what I’m doing it’s probably not worth. So I think that in this particular study, we were, as I said, interested in who are the conductors in the brain. And when you do difficult tasks, are they still the same people that are on the show all the time, or is it like musical chairs? So when you have a really difficult problem, do you call in the experts?

And somehow, the general way to interpret this is: yes, in fact, this is what happens. The prefrontal cortex, which is what is most developed in humans, comes in. What it does is basically like special commando soldiers coming in, consuming a lot of energy, but helping you solve problems efficiently. And that’s really, I think, the exciting thing about the studies and what is even more exciting is that it’s very well backed up with data from other animals. Monkeys do this as well, but they don’t do it as well as humans do. 

And so this cycle, this “ring to rule them all”, is a ring that is constantly changing. And of course, the next question could easily be: what happens when you have disease? What happens when you have problems with your impulse control? When you’re addicted? When you have memory problems? All of those things can change the state. And with the methods that we’ve looked at, we can now find out what it is that’s happening and perhaps long term, help fix this. You think your grandmother would understand that? 

Of course! Very well put. Did you find any discovery that you were not expecting to find? 

Morten What surprised us was the unity of this ring. So, you know, it’s the same regions, even though it’s very different to us, these experts, there are commonalities of the ones that are being brought in. We had thought that maybe some task there would be less recruitment of this prefrontal cortex, but it does point to a unity in how it is that this most advanced part of our brain is helping us essentially survive because that’s really what the brain is all about. But interestingly, it does more than that. It doesn’t just survive and thrive. And that, of course, sometimes and although we don’t really speculate about it, too much of this actually makes you less thriving. You start thinking too much about things. So there’s also a balance to be struck there. 

Gustavo I think we were not really expecting one ring to rule them all. I think that when we started with the methodology and the question was very clear, the methodology was also very clear. And our expectation was that there are many directors. Of course, a choir of musicians, but not really so much concentrated on one director. Basically around the region that, actually there are many regions of the ring, but that was relatively surprising and it seemed unexpected. And then we related these findings with the original ideas of Joaquín Fuster. And therefore we invited him to be part of the whole business and so on. But that came a posteriori, Joaquín was not there from the very beginning.

Gustavo: “Now, we can describe the orchestration of the brain… and the next question is how is this orchestration reconfigurated under different situations?”

So, what end up being the implications of these findings?

Morten In terms of being useful, I think now that we’ve identified what happens in the normal case, we can now state any kind of brain state and we can see how it’s affected. So personally I would love to know in cases like disorders, people that are bipolar. What is it that is happening with this prefrontal cortex? Is that part of the problem?

But if you know where the problem is, is there a way that we can rebalance that, what kind of interventions that we can use for that, whether they’re anthropological or whether they could use other things. So I think there’s a lot of potential for this. 

Gustavo Now, given our methodology, we can describe the orchestration of the brain, and the next question that we have nowadays is how is this orchestration reconfigurated under different situations? For example, disease, or even how we can restore the right reconfiguration if we had the disease. For example, with pharmacological or some very promising therapies. 

Morten And in other words, we can find out what it is that if you give people a drug, what makes them respond or not. And so we can find out both how the drug works, but also when it doesn’t work, what you could do instead. 

Gustavo Or even be predictive, which is the Holy Grail I mean, you are the press. I mean that there are some drug candidates for you. It would be nice to know a priori if you will respond to that particular drug. And we are finding some correlation. Of course it’s not a hundred percent certainty but at least we can tell you one that’s probable that you respond or not.

Morten And with time we like to think that they will get better.

What would you say the impact of this study has been?

Morten When you’ve published papers literally is just your mother who reads them. And, you know, depending on what happens, eventually people start reading them and they become excited by him. And at the moment, we’re still in the initial phase. We were delighted that people found it interesting enough to actually write about it in the newspapers. And most of our peers haven’t read it yet, but they will. And then hopefully they’ll think: “Wow, that’s a great idea”. 

Gustavo Yeah. The impact of the paper in general in science, you start to realize the impact of the paper after a couple of years.

Oh, okay. Interesting to see our play in all of this.  We were just wrapping up and we always end our interviews asking one personal question. What special memory do you have from your years in university or while studying?

Gustavo I have fabulous memories, I think it’s the best time. I always say that to my students. I mean, come on. I know that’s when you have a lot of lectures, I know that you are stressed and you care about examinations… Forget that. I mean, enjoy that. It’s the best time of your life because you are learning, you are enthusiastic, they are motivated, you are not obliged to come here and enjoy that. You’re discovering facts about nature, about, in our case, rings.

Morten Things nobody had seen before. And that, I think, is what keeps us in this game. But I think what is fabulous for us is also to have these students, to see their enthusiasm and to basically give our enthusiasm to them. 

Do you have any special memory of your university years, Morten?

Morten Yeah, I guess one of the best things was meeting Gustavo. And all after all these years, we’ve been able to continue working together. Yeah, absolutely. 

Entrevista realitzada per: Òscar Duran i Amàlia Cillero.