Migraine consequence of critical tipping point in neural network

4 September 2013

One critical tipping point in a network of neurons in the brain initiates a migraine attack claim three NWO Spinoza laureates, Michel Ferrari, Marten Scheffer and Albert van den Berg, in Open Access journal PLoS One. If such a critical tipping point at the start of a migraine attack proves to be true, it will be possible to predict an attack and to treat it before the patient even experiences the symptoms.

A migraine attack probably starts with a wave of extreme depolarisation –discharge –of nerve cells, after which these remain exhausted for a period of at least 30 minutes. This depolarisation starts at one point in the brain and subsequently spreads further as an unstoppable wave through the cerebral cortex and areas deeper in the brain. The wave causes visual and other neurological phenomena and probably also activates the 'headache system' in the brain as a result of which the severe headache characteristic for migraine develops. Up until now, however, it was scarcely known how this wave starts.

In their article the researchers show that the wave can develop because known factors such as genetic disposition and hormonal fluctuations can result in the sensitivity of neurones temporarily increasing until a point is reached at which the slightest change –such as an impulse of light– can elicit a tipping to depolarisation. Mathematical biologist Marten Scheffer: 'The tipping point is comparable to leaning over backwards on a chair: if you are already leaning back you appear to be reasonably stable and nothing is wrong. However, the slightest disruption to that state can result in you suddenly falling over backwards. The less far you lean back, the easier it is for you to recover.'

Once neurones have reached their maximum state of sensitivity, a nearby neurone's activity can elicit the tipping. Neurones can therefore easily ‘set each other off’ allowing the wave to spread further. In mathematical models the team shows that known processes in the brain can indeed influence each other in the manner predicted.


Recovery time

'Now the big question is whether we can measure how close the brain comes to such a critical tipping point based on the time a neuron needs to return to a normal state after a stimulus. To use the chair analogy again: if you do not lean back very far then you can quickly recover if somebody pushes you. But the further you lean back the more time you need to recover your balance. It is a universal fact that complex systems which come close to a tipping point recover more slowly from minor disruptions and that provides starting points,' says Scheffer.

The researchers expect that the recovery time of nerve cells can be used to predict how far a patient is from an attack. The faster the brain returns to normal after small impulses (such as light flashes) the further away it is from the attack. Measuring the recovery time makes it possible to administer medication far more effectively. At present, migraine patients often take preventative medicines daily, despite the heavy side effects, to prevent such an incidental attack. In addition, this knowledge provides the opportunity to more accurately study the development of migraine. In this project from the three Spinoza laureates a study is currently underway into changes in the brain's recovery time in migraine patients.

Special collaboration

The collaboration between Michel Ferrari, Marten Scheffer and Albert van den Berg arose when they first met each other upon receiving the NWO Spinoza Prize in 2009. The NWO Spinoza Prize is the highest Dutch award in science. Behind the scenes at the prize awarding ceremony they came up with the idea of combining the knowledge from their three different disciplines to investigate migraine.

Michel Ferrari (Leiden University) is a neurologist who has specialised in research into migraines, mathematical biologist Marten Scheffer (Wageningen University) investigates critical tipping points in complex systems and nanotechnologist Albert van den Berg (University of Twente) works amongst other things on the accurate measurement of processes in the body using 'labs-on-a-chip’.


About NWO

With a budget of 625 million euros per year, the Netherlands Organisation for Scientific Research (NWO) is one of the biggest funding bodies for scientific research in the Netherlands. NWO promotes quality and innovation in science by selecting and funding the best research. It manages research institutes of national and international importance, contributes to strategic programming of scientific research in the Netherlands and brings science and society closer together. Research proposals are reviewed and selected by researchers of international repute. More than 5000 scientists can carry out research thanks to funding from NWO.


Further information

Source: NWO