Behaviour and the Brain: A Conversation with Roshan Cools

Hello, this is your host Jennifer Baker and welcome to the Human Brain Project podcast, where we talk to the scientists and researchers that have dedicated their lives to solving the mysteries of the human brain. We discover the humans behind the science and find out how tomorrow's discoveries will be shaped. Professor Roshan Kuhls is a professor of cognitive neuropsychiatry at Radburn University, Neymar. We'll be talking about cognitive control of human behavior and how dopamine could help with neuropsychiatric conditions. Thanks for joining us. Professor, let's start with setting the scene for our audience. Tell us what you're working on at the moment and what is your focus day to day. So thanks for having me. Yeah, much of what we do is driven by questions about neuropsychiatric disorders or kinds, particularly those characterized by failures of impulse control, cognitive control, so you can think about ADHD or addiction or depression, schizophrenia, Parkinson's disease. They're all characterized by cognitive deficits and impulse control failures. And so what we are interested in is to understand the mechanisms of these cognitive deficits across these different disorders and also their treatment mechanisms of their treatment. So we study effects of medication, also behavioral therapy and brain stimulation therapy and try and understand how they work. There's a major problem in psychiatry and neurology today and that's that there's huge variability in treat beneficacy, right? So the same treatment can have positive effects in some people and actually impair cognitive performance in other people and that poses a major problem and that's really what keeps us busy. And so those are if you identify the problem, what are the tools that you're using to make those investigations and examinations? How is that different from what was done in the past? We use lots of tools. So first of all, we're interested in cognition. So we try and measure cognition by using computerized tasks and then, you know, basically puzzles or games that we present to our patients and our subjects on a computer. And then we combine that with brain imaging. So we collect fMRI scans, but also we use PET imaging and this is a technique that allows us to measure brain chemicals like dopamine directly. And we also use other tools like brain stimulation and psychopharmacology. So we give people drugs to assess how they work in the brain. So I guess what's different is that we combine all of these in the same studies to get a handle on how these drugs work and what are the factors that predict whether someone will benefit or someone will be impaired by that drug. So it sounds like you're building up a really personally identifiable picture of a brain. Is this what we might think of as the forefront of individualized medicine or individualized treatment? Yeah, that's right. I mean that's kind of the ultimate aim to identify not just for which person, which drug works, but also at what moment. So one particular drug, think about retelling that's often used to treat ADHD. It might work well in one context, but not so well in another. So in the classroom, people might benefit from more focus, but then on the playground, all that focus can actually undermine social activity or creative activity. So we try and understand what those, what drug does helps which person in what context. That's right. And yeah, that's exactly what personalized medicine is all about. And so tell me a bit about how you ended up at this point working and researching this area. Was it an evolution of what you were doing before? Did you take a turn or a change at some point? Tell me a little bit about why this is what's fascinating for you now. I suppose as a kid, I always asked questions about why people think and behave and feel the way they do, which is what led me to study psychology. And then I, after my undergrad, I went to do a PhD with Trevor Robins in Cambridge. Trevor was a very inspiring supervisor. And what we did, we studied dopaminergic medication effects in Parkinson's disease. And together put forward an influential hypothesis, it's a dopamine overdose hypothesis to account for the contrasting effects of this dopaminergic medication on cognitive functions. So Parkinson patients suffer from mental inflexibility as well as motor rigidity for which they're often treated with drugs like Leverdopa, but the same drugs can also contribute to cognitive deficits. And some people actually develop severe psychiatric abnormalities like gambling, pathological gambling, they can develop addiction to their medication intake. So that's exactly the problem I was describing at the start of this interview. And so we put forward this overdose hypothesis, which states that medication doses that are necessary to remedy the severe lack of dopamine in some parts of the brain can actually detrimentally overdose dopamine levels in brain areas that are relatively intact. And so that was really quite influential for my own career. Also the connection with Trevor opened many doors for me, among others with Mark's esposito at Berkeley. So after my PhD, I went to Berkeley in the Bay area to work with Mark. And Mark was one of the pioneers of FRI. And so with Mark I pursued this principle of baseline dependency and established that contrasting effects of dopaminergic medication are seen not only in patients with Parkinson's disease, but also in healthy people, healthy students, basically. So healthy students, Berkeley students with low baseline levels of dopamine they benefited from a dopaminergic drug while students with high baseline levels of dopamine actually got worse. They perform more poorly after intake of dopaminergic drug. And we measured this using pet imaging. So we combined pharmacology with pet imaging that allowed us to directly measure how much dopamine people have in their brains. And so basically what we're doing now, you know, after my post office with Mark in Berkeley, I went to the Donors Institute in the Netherlands. And that's where I set up my current research group. And that's where we started to, when I started to apply these, these ideas to this neuropsychiatric disorders, ADHD depression, also gambling addiction, and started to collaborate with various other disciplines. But that's basically where it came from. It was a relatively straight line from from starting being interested in how people think to now building this prediction model of the dopaminergic drug effects on human cognition. Well, you mentioned collaboration. And so I'd like to move on to talking about the human brain project. I know you're not a hugely long-term member, but how have you found the experience? Yeah, so the human brain project allowed me to to start working on this prediction model, which we combine from phlogener imaging with receptor mapping and machine learning. So I found this quite an impressive consortium of neuroscientists. I indeed entered quite recently. Slowly got used to, you know, working with so many different people and trying to find out who does what. But this this project did allow me to to get introduced to lots of really brilliant scientists with whom I was not connected until then. And so one of the people, Catherine Amundz, has built this impressive atlas with lots of information about where in the brain specific receptors are located. And so what we are doing now is combining our neuroimaging human brain imaging data with these atlas with these brain atlas that tell us exactly which brain region has how many receptors. And by combining this information, we think we can make much better predictions about which drug acts where and in whom to improve cognitive performance. So we hope by making connections. that did not yet exist, through these, through this big human brain projects, we can make a difference. And we're in the middle of this activity right now. Absolutely. And indeed, we do talk to Catherine in another episode on our podcast. So for the audience, stay tuned for that. Let me ask you about what the general public sort of understands about your work. I mean, a lot of people think they understand dopamine or they know what it means. We read it in newspapers and online. What do you wish people knew? What would be your message or what question do you get asked? So, a lot of people think that dopamine is that pleasure hormone. That's how dopamine is kind of known in the general public. And to some degree, that might be true, but dopamine is really much more. It doesn't just give you pleasure. In fact, it's debatable whether it gives you pleasure. Really what it gives us is motivation and not just motivation, also flexibility. So this is really what drove my interest, right? So dopamine is implicated so commonly in addiction, providing us with the drive to seek those drugs. And in that sense, it is also the basis for compulsive behaviors, right? Addiction can be seen as a form of composivity. At the same time, the same neuromodulator makes us flexible. You know, if you give dopamine to people with Parkinson's disease, they start to be able to behave more flexibly. So how can it be that the same neuromodulator makes us both kind of compulsive and inflexible as well as more flex? We don't know everything about dopamine. It is providing us with this reward signal that drives us to exert effort, but it does much more. And I think it would be great if we can share that nuance with the public. The other thing that I wish more people knew, you know, that brain science, the study of brain mechanisms of mental health, and these does not imply that people need to be reduced to things. It does not imply that psychiatry needs to be medicalized, right? To me, the ultimate challenge of brain science, particularly the brain science of mental health, is to arrive at a better understanding of experience, the subjective experience of people's inner world, and our control over that experience. So, so basically what I wish people would understand is that brain science does not imply that people are things or that experience need to be reduced to biological mechanisms if you want. That does make sense, but I'd like to come on to the issue of looking at the function of dopamine in wellness. We've talked about the pathologies there. You mentioned ADHD Parkinson's. Is there a way that in understanding better how the brain functions we can harness it to make us more effective? So, what the way that I think about these these neurochemicals, these large ascending neuromodulators, like dopamine, but this also applies to the other neuromodulators like neurodrenaline and serotonin, is that they help us adapt to the changing world. So, I was just talking about how dopamine can sometimes make us more flexible, and sometimes it can make us less flexible. And what I think that dopamine is all about is about kind of deciding when we should be flexible and when we should be flexible. So, if you want to read the current demands of our environment, it kind of reads whether we should be flexible or inflexible. It reads the current characteristics of the environment, and then promotes adaptive behavior. If our world is very changeable, very volatile, then or if at least we believe the world is very volatile, then we want to be flexible, we want to respond readily to changes in the world. And so, in that kind of context, dopamine will promote flexibility. If by contrast, the world is perceived as relatively stable, then the adaptive response is to boost focus and stability, co-project stability. So, what dopamine does is respond to current beliefs about the state of the world and then promote the appropriate environment specific, environment appropriate behavior. Now, of course, those beliefs are sometimes maladaptive. Sometimes we've developed beliefs as a result of childhood experiences or other more recent prior experiences, or maybe even genetically determined. And in those cases, dopamine will behave maladaptively if you want. So, I do think that if we want to optimize adaptive behavior, we need to work on those beliefs about the current environment, and this will then also have a sort of consequence for optimized neurochemical transmission. Well, tell us a little bit about your journey. You mentioned earlier that you were very curious asking questions when you were a child. Was there anyone in your family encouraged you down this path of research, or taking a choice in your university to career? I was certainly infected, I guess, by my dad. He was a passionate pharmacologist and neuroscientist who loved dopamine. But I was also influenced by my mom, who was a judge in high court. So, I remember many kind of vivid exchanges at the breakfast and dinner table about dopamine and hallucinations and reductionism, but also about free will and accountability. And I think those types of discussions really influenced me and drove me into this world very much so. Not necessarily so, both my brother and sisters did not end up in brain time, or law. But yeah, as the oldest, maybe I was more vulnerable. Well, also then, if we go back to say the point of beginning your career in work world, rather than sort of leaving university, is there any advice you give to yourself looking back other challenges that you needed to overcome? On the one hand, I'm tempted to advise her to combine the study of psychology with the study of AI and computational science, computer science, and maybe also the philosophy. On the other hand, I think that would have been rather and wise, given that one person cannot do it all. So, I think actually my younger self did a pretty good job at not setting the bar too high. Let's turn to the question of ethics. It's something that comes up quite a lot when we talk about studying the human brain, because people feel a little bit afraid. You mentioned earlier there saying that, you know, human experience cannot be reduced to a thing or we shouldn't view it in that way. I am not directly involved in developing neuro technology in the strictest sense of the word right now, although I might be in the future. So, there, I think it's an absolute, it's absolutely urgent to discuss the potential future consequences of the neurotech that we're developing, that are being developed in our field, I should say. There's many other ethical issues that we do face every day, including, you know, the privacy of the data that we acquire. So, we acquire data from the human brain, which is kind of the most, it's the the organ that makes us who we are. It's a very special data. It's very private data in some sense. We also acquire data from, for example, for people's smartphones, to track social activity, their emotions, and again, you know, the security of data is absolutely critical. So, we do interact with, with various centers here on campus, specialized in secure computing. So, we spend quite a bit of our time on that topic as a group. also as a center and an institute, as a donors institute, it's quite well organized. I was a member myself of the board of the Ratanau Institute, which is kind of a Dutch institute focused on promoting the public and political opinion of science, technology, innovation. And so in that context, we spent a lot of time talking about foresight, basically, what's gonna happen if we further develop these technologies and what needs to be, what scenarios need to be taken into account already during the development? - Well, this is one that comes up again again. I think with the question of ethics, we often see that it comes down to concerns particularly around technological developments and future tools that might be out there. So I think that's why we're actually looking at it because people are quite understandably a little bit concerned about knowing too much about the brain if that was put to use in their own hands. - Yeah, of course, of course. And we already see any impacts of digital technology and social media on people's behavior. In fact, that's very close to my interest, the effect of the enormous information overload also on what that does to people's sense of control. - Absolutely. Let's look at us like more optimistic view of the future. What would you define or how would you describe mental well-being? - So mental well-being I think is all about resilience, resilience to the many changes that we constantly face, maybe increasingly so today, right? So I was just referring to information overload as a result of all the technological advances that we see today. There's huge demands for our information processing capacity. So our ability to remain resilient in the face of this information overload and also major stressors ranging from the geopolitical to the climate change. I think that's what will determine them. That's how I think about mental health. And so to maintain resilience, well, this is one of the questions actually that we're working on right now is how do we compute whether changes in the environment are relevant, require us to act upon them or controllable in a sense versus which changes are irrelevant and should be ignored. So it's all about resolving fundamental dilemmas or trade-offs between flexibility and stability. Also between control and letting go of control. So I think resilience is about an ability to optimally trade off between cognitive flexibility and cognitive stability between exerting control and letting go of control between prioritizing speed versus prioritizing precision or accuracy. There's all kinds of computational dilemmas like these. And if we can arbitrate between these different computational cognitive strategies adaptively, that's when we maintain resilience, I believe. - Well, that's the way to look at it. I want to ask you then, looking to the future, what are the next steps for you personally in your career? Do you have a goal? What does success look like for you? - Well, I mean, it's very related to what I was just saying. So one of my goals is to unravel how we maintain resilience in the face of all these challenges and major stressors of today's society, including all this information overload. And to that end, what we need is to integrate, you know, across different disciplines, cognitive science, neuroscience, computer science, philosophy, technology, psychiatry, et cetera. And so then one of my kind of other aims associated with that same goal is to kind of inspire people around me. So that's kind of my students, so my researchers and my colleagues, so my children actually, to keep an open mind to alternative perspectives and to increase our bandwidth and versatility. - I think that's the best, yeah, that's probably the thing. I spent most of my energy on everyday working with my students and my children. Well, but laterally, what do you do for fun when you're not working or involved in childcare? It's the only thing you do to unwind, do you renege for pleasure, affection, or anything like that? - Yeah, well, I do cognitive neuroscience for fun. And also my children for fun, but it's true that I've always done this for fun because I've combined it with other stuff. When I was in college and I was race-flowing, you know, on a daily basis. And then in the next phase of my life, I was, you know, when I was a post-doc, I was kind of obsessed with wave surfing. But then, yeah, 10 years ago, I had my first son and then entered a whirlwind of modern family life, including a few bonus children and other kids, house renovations, dog, you know, family life, really. - Yeah. - And so, and I'll try and do some rowing and some surfing, wind surfing mostly. - I think I have a very rich life combined in science and family and occasionally have time for some friends. Another fun. - Sounds like you're getting the resilience and wellness balance quite by yourself. So hopefully that informs the work. - Not without effort, I have to admit. - Well, thank you very much for talking to us today. (upbeat music) - We hope you've enjoyed this episode of the Human Brain Project Podcast. If so, please subscribe and leave a five-star rating and most importantly, share with a friend. To learn more about the Human Brain Project, please visit humanbrainproject.eu and be sure to check out other episodes in this series packed with fascinating insight into how our minds work. Thanks for listening.