What happens in your brain during a migraine attack?

The last few decades in particular have brought groundbreaking insights. We now know that migraine has an inherited component. A number of genetic factors are involved in causing migraine. But how do those genes cause a person to get this special type of headache disorder? What mechanisms are involved? Despite intensive research, scientists are still in the dark on a lot of things. To get clued into what happens in the brain during a migraine attack and discover what’s making waves in migraine research right now, read on!

Making waves in the brain

Recent publications have been taking a closer look at the events involved in migraine with aura. We now know for sure that certain nerve pathways that carry information to the meninges (membranes protecting the brain) are key players in causing migraine pain. Earlier researchers noticed that a wave of excitation spreads across the nerve cells in the cerebral cortex (the outer layer of tissue of the cerebrum of the brain) in the run-up to a migraine attack. Scientists call this wave “cortical spreading depression” or CSD. Think of the ripple that happens when you throw a pebble into a calm lake. The wave spreads out from the point of origin, eventually encompassing entire sections of the cerebral cortex.

Erregungswelle im Gehirn

The process was first described in 1944 by Aristides P. Leão, a scientist from Brazil. But it took decades of research until powerful enough testing and measuring tools were finally available. Only then could the existence of this phenomenon be confirmed.

Direct link with a migraine attack

As the waves spread, excited nerve cells all start (mis)firing at once. And they use up vast amounts of energy in the process, as you can imagine. This may be why nerve endings (synapses) are less active after such an event. The temporary reduction in activity slows down signal transmission. The brain is in a state of exhaustion for a while.

Direkter Zusammenhang mit der Migräneattacke

Blood flow to the brain is reduced too, a phenomenon that has long been known to trigger migraine attacks. Researchers now believe there is a direct link between the spreading wave event (CSD) and a migraine attack. The meningeal nerves are closely connected to the areas where CSD happens, and this connection is believed to drive the process.

Overactive nerve cells

These meningeal nerves are thought to be extra active in migraineurs. Moreover, the science is clear that the neurons in the cortex of migraineurs are exceptionally excitable and super-responsive to incoming sensory information. This characteristic, which scientists call "hyper-excitability" (over-excitability), has been observed in numerous studies. In some patients – the theory goes – this state leads very easily to the spreading wave described above (CSD) and sets the scene for a migraine attack.

Aura and attack

The temporal proximity between aura and migraine attack led scientists, almost 40 years ago, to propose a link between the aura and pain phases in migraine with aura. Extensive research since then has explored the links between the CSD wave, aura, and onset of pain. Today, aura development is thought to be part of the CSD wave in the run-up to a migraine attack. The optical illusions and distortions typical of a migraine aura happen when the CSD wave spreads across the visual center.

So what exactly happens during the CSD wave?

As the wave spreads in the cerebral cortex, brain tissue cells release massive quantities of neurotransmitters (chemical messengers). These include a number of substances that can influence the perception of pain. One hypothesis is that these so-called mediators move from the tissue toward the meninges in the affected regions. There, they trigger a sensation of pain at nearby nerve endings. The nerves respond by releasing pro-inflammatory substances into their environment. This causes so-called neurogenic inflammation (inflammation triggered by nerve tissue). Pain-causing agents are again released in this process, increasing the duration and perception of pain.

Was genau passiert während der Erregungswelle?

Another research finding provides insight into blood flow in the brain and the associated issue of oxygen supply, which is particularly important in nerve tissue. Especially in migraine with aura, blood flow to individual brain regions is impaired during the CSD wave. This leads to a reduced supply of oxygen. The resulting lack of oxygen can in itself cause a migraine attack. All these processes can worsen each other and lead to a classic vicious cycle.

Migraine: still a tough nut to crack for scientists

All the above is only part of the story. Research has uncovered many more processes believed to be involved in causing a migraine attack. The real trick for scientists will be to piece the various research outcomes together and arrive at a narrative that makes sense. Only then will we have the full story on what happens in the brain during a migraine attack, or be able to understand why migraine takes different forms (with and without aura, for instance). With migraine being such a diverse and complex disease, scientists truly have a mammoth task ahead. We promise to keep our readers up to speed on the latest research as the science evolves.