Q&A

Highlights from a discussion with Dr. K.C. Brennan, a specialist in migraines and headaches at the University of Utah.

NIHNiH: What is your method for treating migraines?

Brennan: Migraine is a disorder involving networks throughout the brain, so treatment needs to take the entire person into account in order to be effective.

Many areas of the nervous system are overstimulated during a migraine. This heightened sensitivity affects how we experience light, sound, and even smell—making these sensations uncomfortable or even painful. The digestive system is also affected, leading to nausea or vomiting. Although these symptoms can be overwhelming, each is an opportunity for targeted care.

There are ways to ease light sensitivity without medication. It's possible to manage both the digestive issues and the muscle tension that can trigger migraines using therapy methods such as physical therapy or yoga.

Migraine pain also disrupts emotional pathways in the brain. If you’re hurting frequently, it can take a toll on your mood, contributing to anxiety or depression. To truly help someone recover, it's important to address these emotional circuits as well.

I prefer to use the word “healing” rather than “curing.” Although a cure for migraine doesn’t exist yet, healing means reducing the impact of the condition so it no longer overshadows your life. It’s about regaining control, even if some symptoms remain.

NIHNiH: Why do some migraine sufferers experience aura?

Brennan: Around one in three people with migraines report experiencing aura symptoms. These often appear as visual effects like flashing lights or as physical sensations such as tingling moving through the body, most often just before a headache begins. Science has identified a cause for this phenomenon, known as spreading depolarization.

The nervous system is a complex network of pathways sending signals at incredible speeds—much like lights blinking rapidly across a circuit board. During normal operation, electrical activity is controlled and highly patterned.

Spreading depolarization is different—more like an electrical storm than a signal. It’s a massive, slow-moving wave that forces nerve cells and surrounding structures to fire intensely, using up energy reserves and leaving areas of the brain temporarily inactive in its path. Imagine a ripple of lights turning on and off as it spreads across a surface, leaving darkness behind.

At the leading edge of this wave, intense activity may trigger visual disturbances like shimmering lights. Once the wave passes, people may experience sensory loss in the affected areas.

NIHNiH: What new insights has your research provided into migraine aura?

Brennan: A long-standing mystery has been why such powerful waves of activity arise suddenly in brains that appear otherwise healthy.

Our attention has turned to glutamate, the brain’s main chemical signal for exciting neurons. This molecule plays a key role not only in migraines but in other neurological conditions like epilepsy and pain syndromes.

Using a novel tool—a special fluorescent marker for glutamate—we can observe this chemical in the brains of mice. The marker is introduced through genetic means, and it glows when glutamate is released, offering a glimpse into brain activity in real time.

What we observed was revealing: moments before a spreading depolarization wave begins, small bursts of glutamate begin to pop up—like tiny sparkles here and there. These build up in number and intensity, eventually merging into a single region that kicks off the migraine wave.

These initial bursts appear to predict where and when the wave will start. This is the first real clue we’ve had about how these waves might begin. Our next step is to uncover what leads to these glutamate bursts. If we can understand that, we may be able to develop new ways to keep migraines from starting at all.