Does the migraine attack start in the cortex and is the cortex critical in the migraine process?

Migraine is a pure human neurovascular disorder with no reliable corresponding animal model. The cerebral cortex (CC) has long been discussed as a crucial element of its complex mechanism. The present review considers the state of the art of experimental evidence on the involvement of CC in migraine. An ample series of research data points to a role of CC in the migraine process, also at the beginning of the attack, especially in the form with aura. However, in spite of several CC, peculiarities emerged in experimental settings, the enigma on their significance (cause or consequence of the disease?) remains. All in all, we believe that pure clinical observations and reasoning, i.e., its exclusive human nature and the precipitating role of stress, are still the most persuasive cues supporting the CC involvement in migraine.