Migraine is a periodic disorder in which a patient experiences changes in the morphological and functional brain, leading to the abnormal processing of repeated external stimuli in the inter-ictal phase, known as the habituation deficit. This is a significant feature clinically of migraine in both two types with aura or without aura and plays an essential role in studying pathophysiological differences between these two groups. Several studies indicated that the reason for migraine aura is cortical spreading depression (CSD) but did not clarify its impact on migraine without aura and lack of habituation. In this study, 22 migraine patients (MWA, N = 13), (MWoA, N = 9), and healthy controls (HC, N = 19) were the participants. Participants were exposed to the steady state of visual evoked potentials also known as (SSVEP), which are the signals for a natural response to the visual motivation at four Hz or six Hz for 2 s followed by the inter-stimulus interval that varies between 1 and 1.5 s. The order of the temporal frequencies was randomized, and each temporal frequency was shown 100 times. We recorded from 128 customized electrode locations using high-density electroencephalography (HD-EEG) and measured amplitude and habituation for the N1–P1 and P1–N2 from the first to the sixth blocks of 100 sweep features in patients and healthy controls. Using the entropy, a decrease in amplitude and SSVEP N1-P1 habituation between the first and the sixth block appeared in both MWA and MWoA (p = 0.0001, Slope = −0.4643), (p = 0.065, Slope = 0.1483), respectively, compared to HC. For SSVEP P1–N2 between the first and sixth block, it is varied in both MWA (p = 0.0029, Slope = −0.3597) and MWoA (p = 0.027, Slope = 0.2010) compared to HC. Therefore, migraine patients appear amplitude decrease and habituation deficit but with different rates between MWA, and MWoA compared to HCs. Our findings suggest this disparity between MWoA and MWA in the lack of habituation and amplitude decrease in the inter-ictal phase has a close relationship with CSD. In light of the fact that CSD manifests during the inter-ictal phase of migraine with aura, which is when migraine seizures are most likely to occur, multiple researchers have lately reached this conclusion. This investigation led us to the conclusion that CSD during the inter-ictal phase and migraine without aura are associated. In other words, even if previous research has not demonstrated it, CSD is the main contributor to both types of migraine (those with and without aura).
