Migraine May Be Explained by Hyperexcitability of Brain Networks

Barbara Boughton

September 24, 2010

September 24, 2010 (San Francisco, California) — A new study deepens the scientific understanding of the biological mechanisms in the brain that lead to migraine in those afflicted by the disorder.

This new understanding could pave the way for new drug therapies targeted to areas of the brain that are hyperexcitable in people with migraine or to areas that fail to control response to visual stimulation and other cues, said presenting study author Peter J. Goadsby, MD, PhD, a neurologist at the University of California–San Francisco (UCSF) and director of the UCSF headache center.

"The core finding of our study is that the brain is more active in migraineurs, and that's probably due to the fact that the modulatory systems in the brain are dysfunctional in those with migraine," he told Medscape Medical News.

Dr. Goadsby presented their results here at the American Neurological Association 135th Annual Meeting.

Networks of Activity

In previous studies, researchers have described several networks of coherent spontaneous brain activity that respond to activation of sensory, motor, and cognitive tasks using connectivity mapping — a technique that allows scientists to look at active regions of the brain as a matrix.

In the study, researchers used task-free functional magnetic resonance imaging (fMRI) to image the brains of 21 interictal migraineurs and 21 age- and sex-matched healthy controls. "The primary question we were asking is, ‘To what extent is the brain the pivotal organ in migraine?'" Dr. Goadsby said. "We wanted to use fMRI to look at brain networks that we hypothesized would be affected by migraine," he said.

Their results indicated that in the brains of migraineurs, there was increased activity in the somatosensory network, the visual network, the auditory network, and bilaterally in the somatotopic representations of the face.

This enhanced activity corresponds to the enhanced sensitivity of migraineurs to visual cues such as light, as well as the physical pain experienced by those with migraine, Dr. Goadsby said. The researchers also found that there was reduced network activity in the posterior part of the default mode network — a network that acts to dampen or control response to brain stimulation, he added.

Dr. Goadsby noted that there are translational implications to the study's findings — and might lead toward research aimed at understanding how preventive migraine medications might alter activity in the brain's networks.

As well as helping researchers test the medications that already exist for migraine, it could also lead to development of new targeted medicines aimed at altering the hyperexcitability seen in the brain networks of people with migraine.

Yet Dr. Goadsby noted that it is possible that changes in brain network activity could also be seen in people with other types of headache, other than migraine, as well as people with chronic pain.

"We do know that people with chronic pain experience changes in the brain, so the question on the table remains, ‘To what extent are the findings of our study specific to migraine?'" he said.

"They could also indicate changes that occur with other types of head pain, such as cluster headache, as well as migraine — or they might indicate a pain problem," he said.

Important Step Forward

"This study is an important step forward in our understanding of the mechanisms that underlie migraine," commented Charles Flippen, MD, associate professor of neurology at the University of California–Los Angeles.

"We've always wondered why people with migraine have this enhanced sensory sensitivity, and this gives us a firmer understanding of the neurobiological mechanisms underlying these symptoms," he said. "It underlines the basic concept that people with migraine have different brains than nonmigraineurs — that migraine is a neuronally based disorder, not primarily a vascular condition," he said.

Dr. Flippen has investigated agents, such as memantine (Namenda), that target glutamatergic neurotransmission in the brain. Memantine is a medication now primarily used in Alzheimer's disease, but results of uncontrolled trials indicate that it might be an effective preventive medication for migraine, Dr. Flippen said.

Since it modulates neuronal glutamate transmission, memantine may dampen the hyperexcitability seen in the brains of people with migraine, Dr. Flippen said.

Placebo-controlled trials of memantine are planned, and the UCSF study implies that other agents that target the brain's networks in migraine might have success as well, Dr. Flippen added.

The study was supported by the German Research Foundation. Dr. Goadsby and Dr. Flippen have disclosed no relevant financial relationships.

American Neurological Association (ANA) 135th Annual Meeting: Abstract M-46. Presented September 13, 2010.


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