Getting to know Roshan Cools

Roshan Cools is a Professor of Cognitive Neuropsychiatry and PI at the Donders Institute for Brain, Cognition and Behaviour.

This post is also available in Dutch.

Following a PhD with Trevor Robbins in Cambridge University, Roshan Cools 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.

This interview is in English only. For the full video, visit: OHBM Blog

Can you describe your research?

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, 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.

What is your biggest achievement?

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 so often—not just if you have ADHD, but also our healthy adult brain fails to exert control all the time. And one reason for that, I believe, is that exerting control all the time is a bad thing. What our brain does is basically decides whether it’s good or bad to exert control and then makes a decision. If you wanted to regulate all kinds of computational trade-offs, including the trade-off between paper, working hard, exerting mental effort, mental control, willpower, or letting go—and that is exactly what the large ascending neuromodulatory systems like dopamine, but also noradrenaline, are important for and that is something that we’re starting to show, to demonstrate in the lab. And we do that with a combination of techniques: pharmacology, but also fMRI and chemical PET, where we measure these neural modulators directly in the brain—so dopamine PET in particular.

I guess there’s a few things that we’ve shown that I could say I would be 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 it acts. A lot of people are studying 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 neuromodulators just depends on where in the brain it acts. In the prefrontal cortex, for example, dopamine has a very different effect from the striatum—compared to 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.

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.

How to use that knowledge?

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 and 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.

By: Roselyne Chauvin & Christienne Gonzales Damatac

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