"We need to learn more about what it is that is shaping our kids’ brains."
Tomáš Paus, MD, PhD
Tomáš Paus knew as a teenager that he wanted to study the human brain. “I’m someone who really wants to know how the brain generates behavior.”
Can you describe the path that brought you to the work that you are doing now?
Tomáš: When we were teenagers, things were very exciting. It’s an amazing period of life — the transition between being dependent and being an adult. Lots of stuff is happening with our brains and our bodies. It’s happening around us in school with our peers. Adolescence is an extremely dynamic period. Look, it was very exciting for me when I was doing my first science project as a teenager. It can set you on a particular path. We have all that energy and fearlessness of getting to do things that may to us now look crazy or not doable. But also it’s a period of risks. It’s a period, especially in girls, of mood disorders. It’s a period, especially in young men, when the risk of schizophrenia is going up. I want to understand what it is that makes those brains more vulnerable during that period.
I became interested in the human brain a long time ago. When I was a teenager I was reading Freud; my biology teacher saw my curiosity and he sent me to his friend who was a psychiatrist. I designed my very first study, studying vitamin C and attention, when I was seventeen. My participants were my fellow students in the grade below, sixteen-year-olds. And that’s really how I started studying the brain.
I went to medical school to learn more about the brain and the body, and continued with PhD studies on human physiology. When I was finishing my PhD — both my medical degree and PhD were done in Czechoslovakia — I wanted to continue this kind of work as a post-doctoral fellow. I came to Montreal Neurological Institute in the early 90s, when imaging was becoming the next big thing. I was fortunate to be in the middle of it — learning how to use those tools to see the brain. I had lots of good teachers in psychology and human behavior, but also in the physiology of the human brain — what happens when you are listening to the cells. I’m a brain person, not a psychologist. I really want to know how it works. How does the brain generate behavior?
‘We need to learn more about what it is that is shaping our kids’ brains.’
And what have you found? How do we answer these questions?
At the end of the day, it’s going to be about our genes and our environment. How these two things interact, the twenty thousand genes that we have in our brains and our bodies and the uncountable number of different environments that are influences — physical environments, social environments, nutrition — it’s incredibly complex.
One way to deal with that complexity is that you study it in the context of a large population, and you combine genetics, epidemiology and imaging into what I call population neuroscience. Why? It’s all about synthesizing large amounts of information into new and useful knowledge.
Over the past twenty years we have made incredible advances in genetics; there is so much information in that one drop of blood.
Epidemiology asks questions about how diseases progress on a large scale, hundreds of thousands of people. The limitation is the tools that we have available at the population scale. Typically we ask people to fill out surveys, or take very simple measurements — height, weight, maybe blood pressure.
That’s not satisfying to me. I want to understand what’s happening at the level of the organs, like the brain, like the liver. And that’s where imaging comes in. With magnetic resonance imaging (MRI), in sixty minutes, I get an amazing amount of information about the structure and function of the brain or any other organ that I can scan. And I can do that now in thousands, or tens of thousands of individuals.
So we bring those three disciplines together. Epidemiology gives us a big picture view of what’s happening out in the real world. Genetics reveals so much complexity based on that one blood sample. And then the brain imaging that I acquire with MRI lets us ask deeper, fundamental questions.
What is the goal of population neuroscience?
Tomáš: Our traits, our behavior, our brains vary; in the extremes, that variability becomes a vulnerability and we need help. So what shapes that vulnerability? In order to address this, you really need big numbers. Epidemiology was the first science of big numbers. And genetics, in a way, is a type of population science because we need big numbers to figure out all those tiny genetic variations. We take those two disciplines, epidemiology and genetics, and marry it with what we have learned over the past twenty years when imaging brains in ten or twenty or thirty people. Except now we do it in 300, 3,000, 30,000 people. We also get all the other information about their genes and their environment, and that’s population neuroscience.
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Why are you choosing to do this at CMI?
Tomáš: There are two very interesting features about the Child Mind Institute. One is that it reminds me of the Montreal Neurological Institute, founded in the 30s by an American neurosurgeon who decided that he needed to put a clinic and a research facility under one roof. That’s what the Child Mind Institute is about. The other thing is the interest in population studies, what Mike Milham has started with the Healthy Brain Network. Mike realizes there is incredible power in data and there in no single lab that in a short period of time can collect enough data to answer some of the big questions we’re asking.
I see the Child Mind Institute as a hub that reaches out to different spokes to the different populations and population studies where the data are collected in different contexts and they all come back here. That’s where we make our discoveries.
CMI: Why is big data and open science so important?
Tomáš: Big data are important in all scientific disciplines nowadays. Well, in the past I think physics was way ahead of us in life sciences. In life sciences we tend to be very restricted by the experimental approach. You do your experiments in your own lab. It was only when technology allowed us to collect large amounts of data and genetics that we realized the power is in numbers — big numbers. And of course big numbers are easier to come by if you pool across many labs, many institutions, and you can do that only if the data are of such quality that you can actually bring them all together. We need to test and verify some of the associations that we see in the brain, or in this gene or in this disorder. And the only way to verify that is to share all of this data and collaborate on a massive scale.
CMI: How is this going to help kids?
Tomáš: There are two answers to this question. First: We just don’t know enough. We need to learn more about what it is that is shaping our kids’ brains. What is good for them and what is not. There are no immediate pay-offs, but think about penicillin. A little thing dropped into Fleming’s petri dish and he noticed that the bacteria stopped growing around this. And it took twenty or thirty years before we had penicillin as a medication. We are collecting data that no one has ever seen before. That’s very important. We need new information so that we can derive new knowledge. Can I predict now what that knowledge is going to be good for? No. But knowledge is power.
Now, the second thing is what we can do when we’re studying a population — we can intervene and see the results of our intervention. Of course it’s easier to manipulate an experiment in the lab, but in fact, Healthy Brain Network is an ideal platform for this. We can also “manipulate” by, for example, preventive interventions. So if you start implementing into your population a systematic intervention of some sort, that’s a manipulation. The Child Mind vision and aspiration is really to take that step. To go beyond data sharing, beyond population base studies and to potentially also think about ways in which we can help those participants in our studies in a systematic way, that also gives us new knowledge about what’s going on in the brain.
For instance, we know that physical health is very good for brain health. So how do we improve physical health? Maybe we can design programs that will lead to a reduction of obesity. Everyone would agree that obesity is not a good thing. It’s not a good thing for cardiovascular health even in kids, and it also affects their brain health. So let’s design a smart way of helping kids to be more active, to eat the right way and to support each other — and then, at the same time, collect data. So now we are helping those kids who are engaged in our research and that’s a good thing. And we are learning. We are gaining new knowledge. That’s another element of population science — you’re embedding a helpful intervention into your science project. And because you can do it at a population level, it has potential immediate ramifications for public health.
I went to medical school. I wanted to be a doctor. I knew from the beginning I wanted to do research, but for the first six years it was a good feeling to be doing both. To be doing research but having a sense that you are helping an individual. Now, as a scientist, after many years, don’t ask me to treat you. But if I come up with something useful at the level of public health, then I feel that my physician’s duty is fulfilled in some way. And population neuroscience is one way to do that: getting the knowledge to assess whether different interventions are useful or not. Or to come up with new ones.