Virtual Roller-coaster May Explain the Ups and Downs of Migraine

Erik Greb

July 28, 2021

The drops, loop-the-loops, and freefalls of a virtual roller-coaster ride are shedding new light on the migraine brain and may explain the mechanisms underlying common symptoms and increased activity in certain brain regions in migraine patients.

In a new study, the prevalence of dizziness was 65% among migraine patients who underwent a virtual roller-coaster ride, vs 30% among those without migraine. In addition, imaging showed greater neuronal activity after the simulation in those with migraine.

"Migraine patients reported more dizziness and motion sickness, as well as longer symptom duration and intensity, in a virtual roller-coaster ride," even though the videos and timing were identical for both groups, study investigator Arne May, MD, PhD, professor of neurology at the University of Hamburg, Hamburg, Germany, told Medscape Medical News.

"We found differences not just in behavioral results but also in specific activations of areas within the cerebellum and the frontal gyrus. Migraine patients process such visual input differently from controls and activate a specific brain network to do so," he added.

The findings were published online July 21 in Neurology.

The Brain's Response

Nausea, which is among the diagnostic criteria for migraine, is the main symptom of motion sickness. Vestibular symptoms such as dizziness are also components of migraine.

Previous research has examined how the brain processes visual and motion stimuli in migraine, but the reasons patients with migraine are susceptible to motion sickness and dizziness remain unclear.

The researchers used a simulated roller-coaster ride to study the clinical and brain responses to motion among participants with and participants without migraine. They enrolled 20 consecutive patients with migraine who presented to a tertiary headache clinic between January and March 2020 and enrolled 20 healthy participants from a university hospital and the community. The average age of the study population was 30 years, and more than 80% were women.

In response to a questionnaire, participants provided information about demographics and headache features, including onset, frequency, and intensity. They also provided information about their status within the migraine phase and about vestibular symptoms experienced in daily life.

While undergoing functional MRI (fMRI), all participants watched two short videos that provided a first-person perspective of a roller-coaster ride. During the videos, they wore ear buds that conveyed the sound of a car riding over the rails.

The first video included more horizontal perspectives, and the second had more vertical perspectives. Each video was shown three times in random order.

During fMRI, participants reported intensity of nausea and vestibular symptoms using an 11-point Likert scale. After the experiment, they responded to a questionnaire that evaluated intensity and duration of nausea, dizziness, and vertigo experienced during the videos.

Participants also were given the Simulator Sickness Questionnaire (SSQ), which assessed motion sickness. A 100-point visual analogue scale (VAS) was used to rate how realistic the roller-coaster experience had been.

There were no differences in sex or age between the migraine group and the healthy control group. Half of the patients with migraine reported aura. The mean number of migraine attacks within the previous month was 3.7. The mean Migraine Disability Assessment score was 21.5, which indicates severe disability.

Nausea, Dizziness Often Neglected

Baseline prevalence of vestibular symptoms was 75% in the migraine group and 5% in the control group (P < .0001). These symptoms included dizziness (60% and 5%, respectively; P < .0001) and postural symptoms (40% and 0%, respectively; P = .003).

At baseline, vestibular symptoms were more frequent (P = .001), more intense (P < .0001), and were associated with greater disability (P = .001) in patients with migraine compared with participants without migraine. The migraine patients were also more susceptible to motion sickness (P = .02) and had higher depression scores (P = .001).

During the roller-coaster simulation, dizziness was more prevalent among patients with migraine than among those without migraine (65% vs 30%; P = .03). Patients with migraine also reported more motion sickness (SSQ score, 47.3, vs 24.3; P = .004), longer symptom duration (1:19 min, vs 00:27 min; P = .03), and symptoms of greater intensity (VAS, 22.0, vs 9.9; P = .03).

Brain activity also differed between groups. Among patients with migraine, neuronal activity was greater in clusters within the right superior and left inferior occipital gyrus, the left pontine nuclei, and the left cerebellar lobules V and VI.

There was a moderately negative correlation of activation of the inferior occipital gyrus with migraine disability (r = -0.46, P = .04). Activation within the pontine nuclei correlated positively with motion sickness scores (r = 0.32, P = .04).

In addition, among patients with migraine, activity in the cerebellar lobule VIIb and in the left middle frontal gyrus was decreased in comparison with persons without migraine. Also among patients with migraine, there was enhanced connectivity between the pontine nuclei, cerebellar areas V and VI, and the interior and superior occipital gyrus and numerous cortical areas.

Clinicians often neglect to treat dizziness and nausea in patients with migraine, said May. However, these symptoms are part of migraine, even when attacks are not occurring.

"I have learned that if we can explain such symptoms, they are better accepted," said May. "We need more and better basic research because we need to understand before we treat."

Toward Faster, More Effective Treatment

Commenting on the study for Medscape Medical News, Erik Viirre, MD, PhD, professor in the Department of Neurosciences, the University of California, San Diego (UCSD), said, "We can be excited and celebrate that these researchers are using these news tools to investigate the operation of the migraine brain.

"That will combine with the new therapies and the genomics to give us a powerful approach to this particular condition," said Viirre, who was not involved with the research.

The findings provide significant detail about the interconnections between the various brain regions affected by migraine, he noted. These regions include not just the sensory centers but also areas involved in higher executive function and emotional responses.

By identifying these regions, the findings show "some of the underlying mechanisms of these clinically relevant features," said Viirre, who is also director of UCSD's Arthur C. Clarke Center for Human Imagination.

The investigators set up the motion simulation well and used sound fMRI methodology, he added. However, imaging studies of the brain's response to motion pose several challenges.

"The biggest challenge in any of these circumstances is that you can't put an actual fMRI scanner on a roller-coaster," said Viirre. "The actual acceleration and gravitational sensations delivered by a roller-coaster and gravity, of course, do not occur when you're lying still in an MRI scanner."

Nevertheless, the pseudo-acceleration produced by a visual stimulus is a reasonable proxy, he said.

The findings also suggest that researchers in the future could examine whether any new therapeutic interventions for migraine modulate the brain functions differently for individuals with migraine than for those without migraine, he noted.

"That's going to lead us to a faster, more effective, more reliable suite of migraine therapies," said Viirre.

The study also reminds clinicians to take a broader approach to patients with migraine, and it underscores the value of strategies such as self-calming techniques, which can reduce the number and intensity of headaches, he said.

"Literally demonstrating these functional differences in the migraine brain is a hugely important message of advocacy for people with migraine," Viirre concluded.

The study was funded by the German Research Foundation. May and Viirre have reported no relevant financial relationships.

Neurology. Published online July 21, 2021. Abstract

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