The most likely cause of the migraine aura, Leão’s cortical spreading depression (CSD), consists of a brief neuronal depolarisation followed by a long-lasting wave of neuronal depression that often spreads postero-anteriorly in the occipital cortex and can reach the parietal and/or temporal lobes [4, 5]. Indirect evidence for CSD occurrence in migraine patients stems from functional neuroimaging [6–8] and electrophysiological [9] studies. Although in animal models CSD is able to activate peripheral and central trigeminovascular neurons that underlie the migraine headache [10, 11], knowledge is lacking on the possible relation of CSD to interictal neural alterations that may predispose to migraine attacks.