Migraine is a chronic, multifactorial and neurovascular disease manifested by recurrent attacks of headaches that promote disability and dysfunction of the autonomic nervous system [1]. The identification of preventive treatment that effectively controls this common neurovascular disorder has been very difficult since the pathophysiological mechanisms for migraine are still not entirely elucidated [2]. It is widely accepted that abnormal excitability of occipital cortex appears to play a pivotal role in migraine pathophysiology. Therefore, it has been proposed that excitability level of visual cortex neurons in migraine can drive appropriate therapeutic approaches [3].
Recently, non-invasive brain stimulation has been used to induce durable changes in cortical excitability and potentially correct the neural activity abnormalities found in migraine patients. However, as it is not clear whether the symptoms of migraine result on a hyper- [4] and [5] or a hypoexcitability of the visual cortex [6], [7] and [8] different stimulation paradigms have been applied depending on the author's hypothesis whether the migraine brain is hyper- or hypoexcitable. For instance, in order to decrease or prevent symptoms of the disease, some authors applied inhibitory stimulations over the visual cortex to correct an eventual cortical hyperexcitability [9] and [10]. In contrast, excitatory stimulation to increase a supposed abnormal hypoexcitability is also used [3] and [8]. Therefore, the lack of positive outcomes resulting from brain stimulation, as seen by Conforto et al. [11], could eventually be due to an incorrect baseline excitability assumption.
We performed a 2-step trial: on the first step we compared the interictal excitability of the visual cortex in migraine patients, with and without aura, on healthy subjects. On the second step, we modulated the impaired interictal excitability in migraineurs according to first-step findings and observed its clinical implications. To study cortical excitability, the phosphene threshold (PT), a representative of visual cortex excitability induced by transcranial magnetic stimulation (TMS), was analyzed. PT is defined as the lowest intensity of a TMS pulse required to evoke phosphenes [12]. Studies using TMS have found significantly lower PT and a much higher proportion to evoke phosphenes in migraineurs compared with healthy volunteers, which benefits the cortical hyperexcitability theory [4] and [13]. Other studies have achieved the opposite result [6] and [8] pointing out to decreased interictal cortical excitability in migraineurs. To modulate the abnormal interictal excitability in migraine patients, transcranial direct current stimulation (tDCS) was applied. TDCS results in motor cortical excitability changes in humans that occur during the application of direct current and remain stable for up to 1 h after stimulation. Anodal tDCS increases excitability, while cathodal tDCS decreases it [14], [15] and [16]. Some studies have demonstrated the effectiveness of using anodal [3] and cathodal tDCS [9] for migraine treatment