high da: stable prefrontal cortex dopamine: cognitive stability low da: distractible functional and neurochemical reciprocity low da: inflexible striatum dopamine: cognitive flexibility high da: flexible A balancing act with dopamine Human beings are extremely capable of adapting to their constantly aim to provide more insight into this proc- changing environment. But often we need to ignore those changes, ess, with the ultimate aim of understanding stay as we are, and continue acting as normal. So how do we know the neurobiological basis of neuropsychiat- when it’s appropriate to change our behaviour and how do we balance ric disorders such as ADHD and Parkinson’s fl exibility and stability? Roshan Cools is working on the hypothesis disease. One characteristic of these disorders that this is mediated by the brain substance dopamine, which regu- is a neurochemical imbalance, leading to in- lates the dynamic interaction between two regions of the brain. flexibility, impulsivity and/or compulsivity. We hope that our approach will eventually lead to individualized treatment strategies that target the complex cognitive deficits ‘Things developed so quickly’, Cools associated with these conditions. ’ observes, referring to her position as Prin- cipal Investigator at the Donders Institute, Two interacting regions where she started only two years ago, ‘We appear to need both cognitive flexibility soon after which she obtained a NWO and stability. If we’re too flexible, we tend Vidi grant. ‘There are fourteen people in to be distracted and our behaviour becomes my group if I include my affiliated and unstable and, if we’re too stable, we become Master’s students,’ she says. Thanks to a inflexible. A pure form of reciprocity would flourishing research programme, initial imply that we need only a single mechanism results are already coming in. that can be adjusted dynamically, depending on the task at hand. However, we often need With a command of English language that to be both flexible and stable at the same reflects the time she’s spent in the Anglo- time. That is, while we should be flexible Saxon world – Cools was a PhD student in response to relevant changes, we should at St. John’s College in Cambridge (UK) remain stable when there are irrelevant with Trevor W Robbins and a postdoc in changes. To resolve this apparent paradox, Berkeley California with Mark D’Esposito it’s plausible to postulate two separate – and a pace that reflects her quick mind, mechanisms that work together. We think she explains the main hypothesis of her the prefrontal cortex – commonly associated research project: ‘It’s not only the abnor- with complex cognitive requirements – and mal mind that has difficulty adapting. the striatum, a deep brain subcortical struc- Prolonged or severe periods of stress and ture traditionally associated only with move- fatigue also make the usually healthy mind ment control, work together. Dopamine inflexible or unfocused. In our research we balances this interaction. 2 Donders Institute for Brain, Cognition and Behaviour Roshan Cools Baseline levels sensitive brain areas in rats. Roshan, York University) for a multidisciplinary ‘The assumption that two separate mecha- trained as a psychologist, advocates new project on serotonin and dopamine. One nisms are involved in the balancing act is behavioural studies with rodents, if only third of the $1 million plus grant will not enough to account for the paradox- to reduce the hassle involved with using go to research at the Donders Institute. ical effects of dopaminergic drugs,’ Cools human subjects. ‘Imagine one of my PhD Serotonin is a brain substance that, like explains. ‘How can drugs that enhance students is doing an fMRI study on the dopamine, has long been seen as cru- dopamine improve cognitive flexibility in effect of dopamine on a simple reward cial to processes that control behaviour, some individuals (e.g. those with Parkin- and punishment learning task,’ she says. including decision making and reinforce- son’s) while improving cognitive stability Her subjects have to come in four times: ment learning. However, compared to in others (e.g. those with ADHD)? And as for a trial with a dopamine enhancer, one dopamine, there’s much less known well as influencing the brain region that with a dopamine blocker, one with both about the mechanisms through which the dopaminergic drug innervates, its ef- drugs to control for placebo effects, and serotonin affects behaviour. Cools and her fects will also depend on the baseline lev- one control study with no drugs at all. ‘It colleagues will address this issue by using els of dopamine in that region. The drug takes 18 months to organize this and it’s existing understanding of dopamine and will remedy brain functioning in regions very expensive.’ a constellation of methods that have shed with low baseline levels of dopamine, much light on the role of dopamine, in- while detrimentally overdosing function Roshan is about to return to Berkeley tegrating functional magnetic resonance in brain regions in which the baseline – not to accept the job they offered her imaging, psychopharmacology and neur- levels of dopamine are already optimal.’ (she intends to stay at Donders), but to onal recordings in monkeys and humans spend a month on ‘contemplative’ writing – all guided by computational theory. Move or freeze? alongside old colleagues and to enjoy the − Iris Roggema An intriguing question is how do we know American can-do attitude. It’s pretty ad- when it’s appropriate to change? What dictive she admits and, suddenly putting kinds of clues are considered relevant? on a Californian accent, she says: Oh, we To understand this issue in the normal just love what you’re doing. It’s so incred- brain a lot of work is needed on patients ibly fantastic, we love you!’ with neurochemical disorders, hopefully leading to a model for cognitive flexibility. Explorative steps with serotonin List of publications: ‘We also shouldn’t ignore all the rodent This year, one of the highly prestigious www.ru.nl/neuroimaging/staff/cognitive_control/ work that’s been done,’ Cools says with Human Frontiers Science Program (HFSP) roshan_cools/ a smile, referring to the fact that she is grants was awarded to Roshan Cools, in the daughter of Professor Lex Cools, the collaboration with Kae Nakamura (Kansai neuropharmacologist from Nijmegen Medical University, School of Medicine, who did so much work on dopamine- Osaka Japan) and Nathaniel Daw (New Newsletter 15 October 2009 3 Exploring Brain Computer Interfacing Finding true motivation lies in bridging the gap between scientifi c that picks up a specific brain signal and trans- specialisations, university and society, says Peter Desain, the director of lates it into a computer signal, be it a cursor, a BrainGain – a special project set up to investigate potential applications mouse or a spelling programme. of neuroscientifi c research fi ndings. He’s just been celebrating the sub- mission of a new patent application. Deciphering the neural code might Patent on Noise be considered the holy grail of cognitive neuroscience, but this ultimate ‘The best ideas arise when applying technology goal is not yet within reach. Many interesting detours have been identi- from one field of knowledge to another, says fi ed en route, so why wait to explore them or perhaps even exploit them? Desain states. ‘For example, broadband mobile phone signals are labelled with an individual random bit pattern that makes it possible to identify your personal call from the blurred, Bridge builder mixed signal of all the phones in an area.’ It’s At the Donders Institute at Radboud University exactly this idea that Desain and his colleague Nijmegen it’s Professor Peter Desain – head of the Farquhar apply in a newly patented BCI system. Artificial Intelligence department – who plays a key role in developing tools for inferring the state of ‘We watermark the stimuli with a characteris- cognitive processes directly from measurements of tic, possibly subliminal, noise, which you can brain activity. Trained as both a technical mathema- then trace back to a brain signal in the subject. tician and a psychologist, and now working as a fun- So, if we present two stimuli, for example a damental researcher and inventor, he really enjoying sound on the left side and one on the right side, bringing people together; he’s the incarnation of a we can distinguish the one that the subject is bridge builder. paying attention to. With visual stimulation it works even better. And selective attention is BrainGain – a consortium of 23 research groups often an easier and more natural task than the and companies both large and small led by Desain classic BCI task of imaged movement. Systems – translates insights from neuroscience into applica- like this are still quite cumbersome and hard to tions that benefit both healthy users and people train, both for the user and the machine’. suffering from autism, ADHD and ALS. The latter are progressively locked in their mind due to loss of Another idea Desain’s team is currently testing muscle control. The communication by eye blinks is a sort of mental juke-box. When you recall they use is movingly portrayed in the film The a song, it generates a specific brain signal. Diving Bell and the Butterfly. But Brain Computer Imagine your favourite Christmas carol and Interfacing (BCI) offers hope for a more efficient your computer directly links this to a specific communication. BCI is a general term for any device action. It’s relatively easy to recall songs and the 4 Donders Institute for Brain, Cognition and Behaviour Peter Desain system can be tailored to your personal ‘There’s also a link to our neurocognition preferences. Though it is still quite hard research as ALS patients could benefit to detect these reliably by computer, the from RE-phrase as well.