Gaining a thorough understanding of the mechanisms that initiate and inhibit body movements can lead to new treatments for diseases that disrupt them, such as Parkinson’s disease and Tourette syndrome. Marcus Missal, whose work has been published in a special issue of Philosophical Transactions of the Royal Society B, explains.
While Parkinson’s and Tourette’s seem categorically different, they have one thing in common: a disruption in the delicate balance of motor stimulation and inhibition. Parkinson’s is characterised by a reduction of spontaneous movements (over-inhibition), Tourette’s by irrepressible tics, grimaces and/or verbal obscenities (under-inhibition). ‘The body should be able to control these movements but can’t’, says Marcus Missal, a researcher at the UCL Institute of Neuroscience. ‘I work on the motor control of eye movement, that is, how it’s triggered and inhibited. Inhibition is an often neglected yet essential aspect and it’s no less important than the triggering of movement. Indeed, to initiate a movement at the right moment, you have to be able to inhibit it at all other times as well as inhibit movements that could interfere with it. When I teach a class, for example, I have to explain the subject matter to my students and at the same time inhibit everything other movement that might cross my mind, whether it’s tap-dancing or belting out an aria.’ Thus triggering and inhibiting movement are closely linked and demand an equal amount of energy.
Eye movement: a closer look
To better understand this mechanism, Prof. Missal has focused for several years on eye movements controlled by only six muscles in each eye. Thus it can be used as a relatively simple model from which to extrapolate and apply findings to more complex systems. ‘Eye movements have to be precise: if they’re not under control, vision is blurry, and if they don’t occur at all, visual perception is impossible.’ Prof. Missal studies the specific role neurons play in these movements, using electrophysiological techniques to record their electrical activity. ‘This is how we can analyse precisely the inhibition and activation of eye movement.’
Anticipation and inhibition
Prof. Missal’s experiments have revealed a common inhibition mechanism for different types of eye movement. It’s a mechanism controlled by a superior cognitive system that can anticipate and predict. ‘It’s not just inhibiting a movement at a specific moment, the system anticipates when the inhibition will be necessary, in the same way we anticipate braking as a function of distance and time when a traffic light turns red.’
When anticipation is lacking
After conducting his fundamental research, Prof. Missal and his colleagues tried to gain a better understanding of a mechanism common in many psychiatric diseases: impulsiveness. ‘It’s a character trait defined by a tendency to act without premeditation and without anticipation of possibly harmful consequences. The most extreme example is someone with Tourette’s syndrome, which will lead to insanity if the person can’t control it. Our fundamental research helped us understand where to intervene from a neuronal perspective so that anticipation and thus inhibition can occur normally. In collaboration with my colleague Pierre Pouget of the Brain and Spine Institute in Paris (at the Pitié Salpêtrière Hospital), we identified a molecule that could re-establish the delicate balance between premotor activation and inhibition. It’s currently being tried in animals, human trials are being prepared and a patent is pending.’
A contribution and international publication
Although movement inhibition is a relatively new research subject, researchers are lining up with new projects. ‘Researchers working on inhibition and related aspects have pooled their knowledge in a special issue of the journal Philosophical Transactions of the Royal Society B under the title “Movement suppression: brain mechanisms for stopping and stillness”. It’s a comprehensive approach to this mechanism in the animal kingdom. Many types of research are being pooled: mathematical models, clinical studies, human behavioural studies and electrophysiological studies like mine. Such collaboration is indispensable to advancing new prospects.’
Elise Dubuisson
A glance at Marcus Missal's bio
1989 Bachelor’s Degree in Zoology, Faculty of Sciences, UCL
1992 Master’s Degree in Biology, Faculty of Sciences, UCL
1993 Medal of the Belgian Royal Academy of Medicine, ‘Concours ordinaire régulier de la 1ère Section’
1994 PhD in Sciences, Faculty of Medicine, UCL
1998-2000 Long-term Fellowship, Human Frontier Science Program, Smith-Kettlewell Eye Research Institute, San Francisco, CA
2000-2001 Fellow of the Smith-Kettlewell Eye Research Institute, San Francisco, CA
2002-2007 FNRS Research Associate, Associate Professor, UCL
2007 Thesis, Higher Education Teacher Training Certificate (AES), Faculty of Medicine, UCL
2007-2012 FNRS Senior Research Associate, Permanent Associate Professor
2010-2011 Visiting Fellow, Gonville and Caius College, University of Cambridge, UK
Since 2012 Professor, UCL