Migraine Strikes as Neuronal Excitability Reaches a Tipping Point

Self-propagating waves of cerebral neuronal firing, known as spreading depolarisations, are believed to be at the roots of migraine attacks. We propose that the start of spreading depolarisations corresponds to a critical transition that occurs when dynamic brain networks approach a tipping point. We show that this hypothesis is consistent with current pathogenetic insights and observed dynamics. Our view implies that migraine strikes when modulating factors further raise the neuronal excitability in genetically predisposed subjects to a level where even minor perturbations can trigger spreading depolarisations. A corollary is that recently discovered generic early warning indicators for critical transitions may be used to predict the onset of migraine attacks even before patients are clinically aware. This opens up new avenues for dissecting the mechanisms for the onset of migraine attacks and for identifying novel prophylactic treatment targets for the prevention of attacks.