Targeting cortical activation by transcranial magnetic stimulation

Cortical spreading depression (CSD) is thought to be the underlying mechanism of the migraine aura. CSD is a slowly propagated wave of depolarisation followed by suppression of brain activity involving dramatic changes in neural and vascular function. Several studies showed that cortical stimulation can affect CSD-induced changes and act as a treatment option for migraine.

CSD can be induced mechanically, chemically, or electrically, and can be used as a lab model to study cortical excitation in migraine. Cortical activation or a single CSD wave can sensitise or desensitise third-order thalamic neurons, potentially through corticothalamic modulation. Cortical activation in migraine can be targeted by transcranial magnetic stimulation (TMS). This is a non-invasive form of brain stimulation in which a changing magnetic field is used to cause an electric current at a specific brain area through electromagnetic induction. Dr Anna Andreou (King’s College London, United Kingdom) and colleagues aimed to discover the effects of cortical stimulation and CSD in the thalamus and the hypothalamus, which are key brain nuclei involved in migraine pathophysiology, as well as discover effects of single-pulse TMS (sTMS) on CSD-induced changes [1].

sTMS can modulate cortical excitability and CSD, as was shown in a recent study in mice [2]. In this study, sTMS reduced spontaneous cortical neuronal firing in the occipital cortex and attenuated L-glutamate-evoked firing. sTMS distorts the velocity, spread, and depression phase of CSD. Active and chronic sTMS increases the threshold of CSD induction and the threshold of third-order thalamic neurons. Dr Andreou added that sTMS was shown to be an effective preventive migraine treatment.

sTMS is approved as a treatment for acute migraine in the USA and in the UK, but not in the rest of Europe. In a study with 201 migraine patients, early treatment of migraine with aura by sTMS resulted in increased freedom from pain at 2 hours compared with sham stimulation, which was sustained for 24 and 48 hours after treatment [3]. Results of an open-label study with 263 migraine patients suggested that sTMS may be an effective, well-tolerated treatment option for migraine prevention [4]. A very recently published open-label study suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat, high-frequency episodic migraine and chronic migraine [5]. After 3 months, 93/153 (60%) analysed patients were responders. The median reduction in monthly headache days for all patients at month 3 was 5 days, from 18 days at baseline to 13 days after sTMS.

These studies thus suggest that neuromodulation may be a promising nonpharmacological treatment approach for migraine.

1. Andreou A. Cortical Spreading Depression is the main clinical initiation wave for all migraine types. SYMP05-2, EAN 2022, 25‒28 April, Vienna, Austria.
2. Lloyd JO, et al. Neurotherapeutics. 2020;17(4):1973–87.
3. Lipton RB, et al. Lancet Neurol. 2010;9(4):373–80.
4. Starling AJ, et al. Cephalalgia. 2018;38(6):1038–48.
5. Lloyd JO, et al. J Headache Pain. 2022;23(1):63.

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Posted on 22 August, 2022