OHBM2019 Keynotes: Roshan Cools

by Christienne Gonzales Damatac & Roselyne Chauvin

Roshan Cools is a Professor of Cognitive Neuropsychiatry and PI at the Donders Institute of Brain, Cognition and Behaviour. Following a PhD with Trevor Robbins in Cambridge University she completed a postdoc with Mark D’Esposito, before returning to Cambridge and eventually moving back to the Netherlands to start her own lab. Her work has resulted in multiple prestigious awards, including recognition from the James McDonnell foundations and the Royal Netherlands academy of Arts & Science.

Here, we found out about her work on the effects of dopamine and serotonin on the brain and cognition and how she pushes for open science practices in her lab.

Professor Roshan Cools

Roselyne Chauvin (RCh):You’re studying the chemistry of the adaptive mind,motivation and cognitive control. The aim of this interview is to help people see if they would need an adaptive mind to attend your lecture.

I would like to start with the basics. Imagine you met a random person on the street. How would you describe your research?

Roshan Cools (RCo): Well, first, thanks for giving me this opportunity.

What I would say? Well, I would say something like: Imagine you had to listen to me give a lecture or interview, or listen to this interview for the next half hour, but you forgot to turn off your phone and it's constantly beeping and there’s Facebook messages and there’s tweets and Mattermost messages, or whatever. The willpower that you need to continue to listen to this interview, or to my lecture—the cognitive control that you need—that's what we study and we are really good at that. It’s associated with a part of the brain that’s really well developed, but we fail to exert control, to exert willpower all the time. Why is that? What limits human cognition? That's really the overarching question of our research program.


RCh: Indeed, it’s really applied to society then. So what do you consider to be your greatest achievement?

RCo: Maybe I can just follow up on what I was just saying about what our overarching question is, which is about what makes us fail to pay attention so often. One reason for that, I believe, is that exerting control all the time is a bad thing. Our brain basically decides whether it’s good or bad to exert control and then makes a decision. We examine this by looking at the large ascending neuromodulatory systems like dopamine, but also noradrenaline, that are critical for these types of abilities. We do that in the lab using a combination of techniques: pharmacology, but also fMRI and chemical PET, where we measure these neuromodulators directly in the brain—so dopamine PET in particular.

I guess there's a few things that I could say I am proud of. What we do is we look at the effects of drugs that change these neural modulators like dopamine and serotonin—so dopaminergic drugs—and what we’ve found is that these effects are extremely variable. And the whole program so far has been focused on trying to elucidate the factors that determine whether you will benefit or not from these drugs, the so-called cognitive-enhancing drugs. And what we find is that the effects of these drugs depend on the baseline state of the system. If you have low levels of dopamine, you get better, but if you have high levels of dopamine, you get worse. The effects of these dopaminergic drugs, which are often used as smart pills—like Ritalin, for example, for ADHD, but also in academia actually, in schools—their effects depend very much on their baseline state and baseline levels of dopamine.

The other thing we found is that the effects depend on where in the brain these chemicals act. Many people study the neurophysiological signature of the cells that produce dopamine or noradrenaline with electrophysiology, for example, but what we find is that the effects of these neurons depends on where in the brain it acts. In the prefrontal cortex, for example, dopamine has a very different effect than in the striatum. If we want to understand what a drug that acts on the system does to human cognition, we have to take into account a number of factors.

Bit of a long answer to your question.


RCh: It’s perfect! I guess then you are working in the lab toward understanding if those baseline measures can have an interaction with the drugs depending on the area in the brain?

RCo: Yes, exactly. Just concretely, we’re asking very large groups of subjects to come to the lab. We measure their baseline level of dopamine with PET and then we ask them to undergo an MRI scan once, after intake of a placebo pill, and once after intake of, for example, the dopaminergic drug. The most commonly used drug is methylphenidate, also known as Ritalin, so we use that in the lab also. We assess whether the effect of, in this particular case, Ritalin depends on how much dopamine you have in your brain measured with PET, and we see that that is the case.

RCh: It’s really interesting because, indeed, it can be applied to society quite easily. How do you imagine the translation of your research?

RCo:  I think the first larger implication of the work is a pretty fundamental one. It’s a better understanding of the mechanisms—neurochemical mechanisms—of motivational cognitive control, and then ultimately also a better understanding of how we might maximally exploit mental capital, our human mental capital. And that has, possibly in the longer run, some implications for education. I guess that would be the first domain: How do we promote cognitive control? How do we promote creativity? This balance between focus and flexibility is very important.

And I guess the second domain is [in] the clinic. Most concretely, we’re working on building a proxy model of dopamine synthesis capacity consisting of behavioural predictors mostly, but also physiological predictors, like spontaneous eyeblink rate, perhaps; and seeing how we can optimally combine all these predictors to provide a pragmatic and practical tool that can be used to predict how someone will respond to a dopaminergic drug. Because so far, there’s been a whole load of studies, including some of my own, suggesting that, for example, dopamine synthesis capacity is correlated with working memory capacity. And, indeed, we see that dopamine drug effects depend on working memory capacity. Of course, working memory capacity is much easier to measure in the lab or in the clinic than the PET scan to measure dopamine system capacity. So, if we can establish that these proxy measures of dopamine are equally good predictors of drug effects, then that gives a pragmatic handle on tailoring drug treatments to the individual. So, that’s the second promise, but I think we have to accept that this is not something that will be in use within the next five years or so.


RCh: Your research is multimodal, integrating PET and fMRI to study the effects of drugs. Is this what you’re going to present in your OHBM keynote lecture or do you have extra things that you want to talk about?

RCo: I think the general point that I will make is that the human brain faces a number of these computational trade-offs, like the trade-off between flexibility and stability, between labour and leisure and we need a way and ability to dynamically regulate this trade-off, depending on changes—the constantly changing tasks in the environment. And I’ll make the point that the ascending, the large ascending neuromodulators, like dopamine, are really perfectly suited to dynamically regulate these trade-offs. I’ll illustrate that by highlighting a number of general principles of chemical neuromodulation, like this baseline dependency principle. I might refer—I’m not sure yet—to the motivational opponency principle—that’s another observation which I won’t elaborate on now. But the general point is [that] I will talk about these multimodal projects that we’re doing, in which we combine PET, pharmacology, and fMRI to work towards a better prediction model of dopaminergic group effects.


RCh: OHBM is creating a number of different special interest groups to talk about trends in science, such as open science, or equality & diversity. Do those topics apply to your daily work life and what you promote in your lab?

RCo: Yes, we are certainly quite active in those areas. The diversity issue comes relatively naturally if we talk about gender diversity, at least. Simply by being me—I must admit that I’m not very active apart from just being me—and I’ve noticed that just by being me, I attract other women in science, so I think I fulfill a role there. We talk about it.

RCh: It’s important.

RCo: Yes.

For open science, reproducible science, yes. Like many other labs, we’ve also taken a number of steps, defined operating procedures. When new people arrive in the lab, we highlight those to them and those include that all studies we do are pre-registered now on the Open Science Framework.


RCh: Not everyone is doing that.

RCo: Yes, we’re trying to promote version-control. We have a lab Git account and we try to explicitly check each other’s code for analyses. It’s not the funnest thing for everyone, but for most projects now, I ask a lab member to rerun the analysis of another student because we want to make sure that the analysis is reproducible.

We promote the use of interactive notebooking, for example. I must admit that a lot of this was influenced very much by one of my postdocs, Bram Zandbelt, who is very active in this field; he had a great influence on us as a lab. He’s also teaching in our local Donders reproducibility course.


RCh:  What would you advise new researchers to do for their career?

RCo:   I think the most important thing for a scientist, but also for anyone, is to constantly ask yourself which things you can control and which you cannot control. And then accept the things that you can’t control, but act on the things that you can. Now for a new researcher, a new person entering the field, the things that they can control are selection of a mentor and I think that’s very important. By the way, I’m following the advice here from Jay McClelland. I just listened to his wonderful interview on the Brain Inspired Podcast by Paul Middlebrooks and I thought that was wonderful advice, and it was: Find the right mentor who you can bounce ideas off.

But the other point is that the key is to find a project—to define a project for yourself that you find is representative of a general, a larger question, but it’s still tractable. I think those two points are very important. But the starting point—the first one that I said—is to constantly ask yourself: What are the things that you can control? And what are the things that you can’t control? Because I noticed many people spend quite a lot of time and energy on things that are outside of their control. And that’s, you know, a missed opportunity in a sense.


RCh: Yes, for sure.

Well, thank you very much for your time and I’m really now looking forward to your lecture and learning more about cognitive control and [the] dopamine system.

RCo: Thanks, it was fun. I enjoyed it!