Light and Sound Sensitivity in Migraine Explained?
Medscape Medical News
March 19, 2015


Researchers have correlated light and sound sensitivity experienced by some patients with migraine who have heightened connectivity within primary sensory cortices, the pons and the anterior insula (AI).

The study results suggest patients with migraine, in this case without aura, have heightened regional connectivity between networks involved in processing upstream sensory information and those that represent the salience of such stimuli.

"We found a possible neuroanatomical explanation for why some migraineurs are sensitive to lights and sounds," said lead study author Amy R. Tso, MD, headache fellow, Department of Neurology, University of California at San Francisco.

The findings may provide a basis for developing novel imaging biomarkers for gauging the effect of therapeutics, said Dr Tso.

The study was published in the March 10 issue of Neurology.

Connectivity Hypothesis
A core feature of migraine is an alteration in sensory processing where different stimuli can become bothersome, said Dr Tso. "For some it might be lights and sounds, but for others it's smells or even light touch or motion."

Given this increased salience of sensory stimuli, Dr Tso and her colleagues hypothesized that migraineurs would have increased connectivity between the salience network thought to be involved in identifying homeostatically relevant internal and external stimuli, and primary visual and auditory networks, as well as with a region in the dorsal pons previously shown to activate ipsilaterally to pain during spontaneous and triggered migraine attacks.

To test this hypothesis, the research team studied 15 patients with migraine without aura aged 21 to 52 years who had light and sound sensitivity during their attacks and 15 age- and sex-matched healthy controls.

Using functional fMRI, researchers looked at areas of the brain responsible for processing vision and hearing using a region of interest-based correlation analysis.

This type of analysis is one of the most common ways to explore functional connectivity within the brain. It's based on the time series of a seed voxel, the authors explain. Connectivity is calculated as the correlation of time series for all other voxels in the brain.

On the basis of the hypothesis, seeds were placed in the left calcarine cortex, right Heschl gyrus, right dorsal pons, and right anterior insula, a major node in the salience network.

The task-free imaging was not done within 3 days before or after a migraine attack.

The study showed that the migraineurs had greater connectivity between primary visual and auditory cortices and the right dorsal AI (dAI), a region pivotally involved in coordinating responses to nociceptive and other salient internal and external stimuli.

"Surprised and Intrigued"
"We were somewhat surprised and intrigued" to find increased connectivity in areas overseeing both visual and auditory processes, said Dr Tso.

Heightened connectivity between the dAI and the visual and auditory cortices in migraineurs may set the stage for abnormally intensified response to sensory information, the authors speculate.

"Increased dAI-to-sensory cortex connectivity could provide a neuroanatomical framework for understanding why visual and auditory stimuli not noxious to controls can become unpleasant to migraineurs and evoke escape responses," they write.

The insula participates in a wide variety of functions and features known anatomic connectivity to nociceptive and visceral afferent streams, limbic structures, and prefrontal cortex. The AI contains two specialized nodes within a system representing homeostatic salience and mobilizes autonomic, cognitive, and motoric responses that address the identified salient stimulus.

The study also showed that the dorsal pons, a region active during migraine attacks, showed increased connectivity with the bilateral AI in migraineurs. And the right ventral AI showed increased connectivity with the left ventral AI in migraineurs. (The ventral AI activates during pain and may play a role in representing emotional salience across all stimulus domains, they note.)

As the heightened connectivity occurred outside a migraine attack, "it appears that this network change that we think underlies patients' sensitivity still persists between attacks when patients themselves wouldn't even feel like they are more sensitive to lights and sounds," commented Dr Tso.

During Attacks
Although it's "logistically challenging" to image patients while having a migraine attack because of their discomfort with lights and noise, "it would be interesting to see if the same connections we found have even more increased connectivity during an attack," she said.

This new study is among the first to look outside the pain system and examine the whole brain for clues to what triggers heightened sensitivities of migraine sufferers, said Dr Tso.

But while the study furthers the understanding of what may underlie the symptoms of migraine, it may be "a big step" to find a way to specifically target this area, she said.

As it stands, no therapies target this region. "Clinically, in general with migraine therapies, we only have medications that target the whole disorder," noted Dr Tso.

However, she said, the new information may further the development of an imaging biomarker. "We are suggesting that this could be a marker of migraine biology."

"If you identify an imaging marker, then you could use the presence or absence of that to track whether patients are responding to therapeutics."

Migraine is a disease with varied presentations, she said. "There is no single characteristic or symptom that every single person with migraine has."

While light and sound sensitivities are probably the most common of these symptoms, some patients with migraine are unable to withstand certain smells, while others are uncomfortable with or nauseated by movement, said Dr Tso. "Some patients want to lie still and even the slightest movements are uncomfortable for them."

Dr Tso is keen to find out whether the changes seen in this study are specific to migraine. She noted that other primarily headache disorders, for example cluster headaches, are also characterized by light sensitivity.

"An obvious next step is to find out if this is a marker for migraine particularly or if this is just a marker of this sensitivity, and whether it exists across all headaches that share the sensitivity."

Another interesting area to pursue is the relationship between migraine and anxiety disorders. Epidemiologic studies have shown that migraine is frequently comorbid with anxiety in general and also with post-traumatic stress disorders.

The same pattern of heightened connectivity observed in patients with migraine is also seen with anxiety disorder. "We thought that was interesting because clinically, migraine is more commonly seen with anxiety disorders than in the general population," said Dr Tso.

"It isn't clear whether this inter-insula connectivity is something that predisposes you to migraine and also to anxiety, or whether it's just a marker of having both conditions."

The study received no targeted funding. Dr Tso has disclosed no relevant financial relationships.

Neurology. 2015;84:1043-1050. Abstract