Abstract
Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD observed in animal cortex and aura symptoms mapped to the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value σ = 1 at the instability point. We predict that human cortex is only weakly susceptible to SD (σ<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. Moreover, we use retinal SD to give a proof of concept of the existence of this instability point and describe how cortical susceptibility to SD must be adjusted for migraine drug testing. Close to the instability point at σ = 1 the dynamical repertoire of cortical tissue is increased. As a consequence, the picture of an engulfing SD that became paradigmatic for migraine with aura needs to be modified in most cases towards a more spatially confined pattern that remains within the originating major gyrus or sulcus. Furthermore, we discuss the resulting implications on migraine pharmacology that is hitherto tested in the regime (σ>1), and potentially silent aura occurring below a second bifurcation point at σ = 0 on the susceptible scale.
Highlights
Migraine aura is a collection of transient neurological symptoms characterized by a gradual onset as the distinctive clinical feature
The perimetric data is taken from Lashley [1] and the corresponding spatio-temporal pattern in the primary visual cortex (V1) is obtained by reversed retinotopic mapping (Fig. 1 (b))
In a single migraine aura attack, migraineurs can experience diverse visual, as well as sensory, motor and language disturbances [44,45]. This variety clearly indicates that other areas beside early visual cortex can be affected, even cortical areas outside the occipital lobes, and it seemingly supports the idea that the process causing the aura can engulf all of posterior cortex on its course, like a cortical spreading depression (SD) wave observed in animal experiments
Summary
Migraine aura is a collection of transient neurological symptoms characterized by a gradual onset as the distinctive clinical feature. It may be classified into sensory and cognitive modalities. The remarkable slow velocity fits with the pace of spreading depression (SD), a profound but transient all-or-none type process characterized by redistribution of ions across cell membranes and nearly complete neuronal depolarization [10,11]. This suggests that both phenomena rely on the same propagation mechanism [12]. Evidence for further links between SD and migraine are complex and mostly indirect [13], and whether the migraine headache is initiated by SD remains an active debate
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