Migraine Visual Aura and Cortical Spreading Depression—Linking Mathematical Models to Empirical Evidence

Abstract

This review describes the subjective experience of visual aura in migraine, outlines theoretical models of this phenomenon, and explores how these may be linked to neurochemical, electrophysiological, and psychophysical differences in sensory processing that have been reported in migraine with aura. Reaction–diffusion models have been used to model the hallucinations thought to arise from cortical spreading depolarisation and depression in migraine aura. One aim of this review is to make the underlying principles of these models accessible to a general readership. Cortical spreading depolarisation and depression in these models depends on the balance of the diffusion rate between excitation and inhibition and the occurrence of a large spike in activity to initiate spontaneous pattern formation. We review experimental evidence, including recordings of brain activity made during the aura and attack phase, self-reported triggers of migraine, and psychophysical studies of visual processing in migraine with aura, and how these might relate to mechanisms of excitability that make some people susceptible to aura. Increased cortical excitability, increased neural noise, and fluctuations in oscillatory activity across the migraine cycle are all factors that are likely to contribute to the occurrence of migraine aura. There remain many outstanding questions relating to the current limitations of both models and experimental evidence. Nevertheless, reaction–diffusion models, by providing an integrative theoretical framework, support the generation of testable experimental hypotheses to guide future research.

Dural Immune Cells, CGRP, and Migraine

“…One trigger associated with migraine with aura is cortical spreading depression (CSD) ( 12 ). CSD causes an increase in trigeminal ganglion (TG) firing following application in animal models ( 13 ).…”

Abnormally Increased Effective Connectivity of the Periaqueductal Gray in Migraine Without Aura Patients

“…Various noxious stimuli induce an inhibitory zone of neuroelectrical activity originating in the posterior cerebral cortex (occipital lobe), which extends to the adjacent cortex and is accompanied by an extended blood volume reduction 20. Various studies have previously illustrated structural and functional alterations of the occipital cortex in participants with migraine, which are generally thought to be associated with the aura phenomenon, especially visual aura 21. The occipital cortex has been shown to be a potential target of acupuncture treatment for migraine, and the feasibility of predicting the clinical efficacy of acupuncture treatment for MwoA using the spontaneous activity patterns of the middle occipital gyrus 22…”

Transcranial Electrical Stimulation in Migraine – How Does It Work and What Can We Learn from It?

“…It is unclear what might trigger attacks, and how to prevent their initiation, which is crucial for developing effective preventative treatments. Migraine attacks are associated with a phenomenon called "cortical spreading (depolarisation and) depression", which is a spreading wavefront of strong cortical activity (depolarisation), followed by a cortical "silent period" of reduced activity (depression; for a review, see [15]). Although the role of CSD in migraine is not universally accepted, and does not account for several important clinical features of migraine (e.g.…”