Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine

Headache disorders are quite common. In the 2016 Global Burden of Disease Study, migraine was the second highest cause of disability overall and the most common disease causing disability in young adults (15-49 years). When there are frequent or severe migraine attacks, pharmacological agents are used to reduce the frequency of migraine attacks. Standard migraine prophylactic treatments show either low efficacy or undesirable side effects, and most of them are licensed for other diseases and not for migraine. Additionally, some migraine patients are hesitant to choose pharmacological treatment. Compliance with these treatments is also quite low in the medication-using group. Recently used calcitonin gene-related peptide (CGRP) monoclonal antibody treatments are quite expensive treatments. Therefore, there remains a need for an effective, tolerable and affordable prophylactic treatment for migraine.

Migraine is complex, involving several circuits of both the central and peripheral nervous system and has a still unclear pathophysiology. Trigeminovascular activation is the key event of migraine pain, mostly related to the peripheral nervous system, but the central nervous system also plays a role in the formation and perception of migraine. The cerebral cortex of migraineurs is hypersensitive (overexcitable) to external stimuli, possibly due to altered functional connectivity in subcortical structures, including the thalamus. This resulting "thalamo-cortical dysrhythmia" and changes in excitability can be controlled with non-invasive neuromodulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS).

Non-invasive neuromodulation is applied to various forms of primary headaches and is recommended as an easily applicable method for both episodic and chronic migraine. So far, only single pulse transcranial magnetic stimulation (sTMS), vagus nerve stimulation (VNS), and supraorbital neurostimulation have been approved by the FDA for the treatment of migraine. Transcranial direct current stimulation (tDCS; direct current stimulation) is an electrical stimulation method used for non-invasive brain stimulation, where a weak electrical current of approximately 2 milliamps is applied through two scalp electrodes with a portable battery-powered system. tDCS is an electrical stimulation technique in which low-amplitude direct current is applied to the skull via surface electrodes, thereby modulating neural brain activity. The applied current changes the transmembrane neuronal potential and thus affects the level of excitability. Depending on the polarity of the active electrodes, tDCS can increase or decrease cortical excitability. tDCS has been shown to trigger changes in neuropsychological and motor activity in the brain. Protocols with variable session numbers (1-20 days) applied to different targeted brain regions provide promising results in pain syndromes by regulating pain-related pathways in various ways. Stimulation of the motor cortex with tDCS has already been shown to relieve pain in patients with traumatic spinal cord injury and other chronic pain syndromes, including fibromyalgia. Migraine patients are often hypersensitive to pain. A treatment that targets areas of the brain involved in the experience of pain may also help reduce pain in migraine patients. According to the results of systematic review and meta-analysis of studies conducted so far; tDCS has been evaluated as an effective, reliable method that can improve migraine symptoms by activating the motor cortex or activating/inhibiting the visual cortex. Additionally, tDCS treatment repeated for days over a period of 4 weeks or longer is effective in reducing migraine pain severity and attack duration. The benefit of tDCS may persist for at least 4 weeks after completion of the last tDCS session. Both anodal and cathodal stimulation have been evaluated as effective for reducing migraine pain severity. The study protocol present here aims to test a unique protocol with simultaneous anodal stimulation to the motor area and cathodal stimulation to the visual cortex. In the meta-analyses conducted so far; In future clinical studies using tDCS in migraine, the importance of simultaneously measuring neuronal activity using EEG or fMRI(Functional magnetic resonance imaging)( is also emphasized in order to better understand the underlying mechanisms of action. Electrophysiological techniques, such as quantitative electroencephalography (qEEG), provide important information about brain functioning at rest and during sensory stimulation. A large amount of data has demonstrated the presence of some excitability changes in the occipital cortex during the interictal period of migraine patients.While some studies have demonstrated hyperexcitability, only a few studies have been able to document a decrease in occipital excitability. This increase in occipital excitability has recently been recognized as an inhibition phenomenon, and a new term "hyperresponsiveness" in migraine has come into use in the last decade. This hyperexcitability has been demonstrated in many neurophysiological and neuroimaging studies as loss of habituation to recurrent stimuli. Clearly, spectral analysis of different frequency bands of qEEG helps us understand the intrinsic activity of the migraineur brain. Differences in peak latency, amplitude, and synchronization of EEG frequency bands in response to sensory stimulation have been reported in migraine patients compared with healthy subjects. In this study, it is planned to make comparative evaluations in the following months with EEG recordings to be taken before and after simultaneous motor cortex and visual cortex stimulation. In this way, the relationship between anodal and cathodal transcranial direct current stimulation and different frequency bands in the occipital region will be determined by comparing the active treatment and sham groups.

Review studies and recent studies from our country have shown that tDCS treatment is an effective and safe prophylactic treatment in migraine patients with allodynia in both short and long-term follow-ups. In order to obtain better clinical evidence in this field, as emphasized in the Cochrane analysis conducted in 2018; Randomized controlled studies with larger samples and clinically meaningful long-term results are needed. In these studies, it is planned to test the clinical effect of a protocol combination, which has been shown to be particularly effective, in prophylaxis in migraine patients in a large sample group, while also evaluating its neurophysiological responses in active and sham groups.