Mechanisms of migraine aura revealed by functional MRI in human visual cortex

Abstract

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept͞onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ؎ 1.1 mm͞min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.

A Continuum Neuronal Model for the Instigation and Propagation of Cortical Spreading Depression

“…To examine the effects of volume fraction and background ion concentration, we studied the cases: f = 0.15, 0.25, and 1, corresponding to increasing extracellular volume relative to the intracellular volume. In addition, we also change the background ion [9] and the remaining 11 equilibrium parameter values are close to those given in [9] and are obtained using the revised pump equation (6). Table 2, which are used for previous computations.…”

“…Leão [13], these waves are characterized by their slow speeds (1-10 mm/min) and their appearance in the cortices of a variety of brain structures in many different animals [1]. While there are many interesting phenomenological aspects of CSD waves, their connection with migraine with aura in humans makes it a particularly important neurophysiological phenomenon from the clinical point of view [6].…”

The role of BOLD-fMRI in elucidating migraine pathophysiology

“…These findings suggest that vasodilatation may be associated with the early phase of migraine attack and that brainstem nuclei could be considered as part of a neuronal network activated during a migraine attack. In the same years, Hadjikhani and colleagues [20] have shown that in MwA attacks BOLD signal increase originates in the extrastriate cortex (area V3A), is time locked and consistent with visual progression of a typical migraine aura. Further studies have supported that abnormal cortical excitability, likely due to a lower activation threshold of visual cortical and extra-striate areas [21][22][23][24], may represent an important pathophysiological mechanism in migraine aura.…”

Migraine and Cardiovascular Disease

“…An alternative theory proposes that spreading depression of cortical activity (cortical spreading depression -CSD) is the first neurological event happening in migraine 23 . CSD would explain the migraine aura and would cause further activation of trigeminovascular afferents ultimately associated with inflammation at the level of the extra-cephalic blood vessels 24 .…”

“…According to this view, the pain is understood as a combination of altered perception (due to peripheral or central sensitization) of stimuli, as well as the activation of a feed-forward neurovascular dilator mechanism in the first division of the trigeminal nerve 22 . The brainstem activation would induce a pro-noniceptive state and also lead to deficits in the autonomic vascular control 20 .An alternative theory proposes that spreading depression of cortical activity (cortical spreading depression -CSD) is the first neurological event happening in migraine 23 . CSD would explain the migraine aura and would cause further activation of trigeminovascular afferents ultimately associated with inflammation at the level of the extra-cephalic blood vessels 24 .…”