Functional MRI of migraine

Summary

Migraine is a disabling neurological condition manifesting with attacks of headache, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea, and vomiting. Exposure to sensory stimuli, such as odours, visual stimuli, and sounds, commonly triggers migraine attacks, and hypersensitivities to sensory stimuli are prominent during migraine attacks, but can persist with less magnitude between attacks. Functional MRI (fMRI) has been used to investigate the mechanisms that lead to migraine sensory hypersensitivities by measuring brain responses to visual, olfactory, and painful cutaneous stimulation, and functional connectivity analyses have investigated the functional organisation of specific brain regions and networks responsible for sensory processing. These studies have consistently shown atypical brain responses to sensory stimuli, absence of the normal habituating response between attacks, and atypical functional connectivity of sensory processing regions. Identification of the mechanisms that lead to migraine sensory hypersensitivities and that trigger migraine attacks in response to sensory stimuli might help to better understand neural dysfunction in migraine and provide new targets for migraine prevention, and could provide fMRI biomarkers that indicate early responses to preventive therapy.

Introduction

Migraine is a disabling and common neurological disorder with a 1-year prevalence of 12% in the general population.¹ A migraine attack comprises moderate-to-severe intensity headache, with a combination of nausea, vomiting, and hypersensitivities to visual, auditory, olfactory, and somatosensory stimuli.2, 3 Visual, olfactory, and auditory stimuli are also common triggers of migraine attacks.4, 5, 6 About a third of patients with migraine have aura associated with at least some of their migraine attacks.⁷ Although many different neurological symptoms can occur during a migraine aura, visual symptoms are the most common.⁸ Between migraine attacks, migraineurs often have persistent but less prominent migraine symptoms, including hypersensitivity to visual, auditory, olfactory, and somatosensory stimuli.³

Because migraine is mainly a disorder of brain function, brain functional MRI (fMRI) studies are useful to study the underlying mechanisms of migraine. Although the aura and headache associated with migraine have been attributed to abnormal vasoconstriction and vasodilation of intracranial arteries, the symptoms are now known to be mostly due to brain dysfunction.⁹ Minor and transient changes in the calibre of extracranial and intracranial arteries might occur during a migraine attack, but such changes are not always a component of migraine.¹⁰ fMRI is also useful to study sensory hypersensitivities in migraine. The sensory hypersensitivities that trigger and are present both during and between migraine attacks are specific to migraine and are not noted to the same extent in other headache or pain disorders. A description of the mechanisms underlying these features of migraine should lead to an improved understanding of pathophysiology and possibly to mechanistic distinction of migraine from other headache and pain disorders. Furthermore, fMRI localisation of atypical stimulus-induced activations and atypical functional connectivity in migraineurs might identify targets for preventive therapies in migraine. Normalisation of these atypical imaging findings might serve as biomarkers of an early response to preventive therapies in migraine. In the past few years there has been a substantial increase in the number of published migraine fMRI studies, which have helped to identify the location and clinical significance of migraine-associated brain dysfunction.

Many studies examined stimulus-induced brain activation; most have used noxious thermal stimulation of the skin, trigemino-nociceptive activation by intranasal ammonia, olfactory stimuli, or visual stimuli. Other studies have used analyses of functional connectivity to investigate the organisation of specific brain regions and functional networks implicated in migraine pathophysiology. Most fMRI studies of migraine have focused on the migraineur between migraine attacks, in the so-called interictal phase, whereas only a few have been done during the migraine attack (ie, in the so-called ictal phase). fMRI studies of migraine have enhanced our understanding of hypersensitivities in migraine, including identification of brain regions and networks that contribute to atypical processing of sensory stimuli. This kind of processing is a key feature of migraine that leads to increased sensitivity to painful and non-painful touch, and visual and olfactory stimuli, and enables typically non-noxious environmental stimuli, such as flashing lights and odours, to trigger migraine attacks. In this Review we summarise the findings of fMRI studies that investigated migraine hypersensitivities, describe how these have helped to clarify understanding of the anatomy and biology of migraine, discuss the limitations of these studies, and propose avenues for future research using fMRI to study migraine.