Migraine generator network and spreading depression dynamics as neuromodulation targets in episodic migraine

TL;DR

This paper models the migraine generator network as a dynamic system involving neural and vascular components, exploring how it responds to cortical spreading depression and informing neuromodulation strategies.

Contribution

It introduces a simplified, explicit network model of migraine generation that links cortical perturbations to vascular and neural responses, aiding future mathematical modeling.

Findings

Migraine involves a complex neural-vascular network responsive to cortical spreading depression.

The model suggests the migraine generator can trigger spreading depression via vasomotor control failure.

Neuromodulation techniques are discussed in context of the proposed dynamic migraine model.

Abstract

Migraine is a common disabling headache disorder characterized by recurrent episodes sometimes preceded or accompanied by focal neurological symptoms called aura. The relation between two subtypes, migraine without aura (MWoA) and migraine with aura (MWA), is explored with the aim to identify targets for neuromodulation techniques. To this end, a dynamically regulated control system is schematically reduced to a network of the trigeminal nerve, which innervates the cranial circulation, an associated descending modulatory network of brainstem nuclei, and parasympathetic vasomotor efferents. This extends the idea of a migraine generator region in the brainstem to a larger network and is still simple and explicit enough to open up possibilities for mathematical modeling in the future. In this study, it is suggested that the migraine generator network (MGN) is driven and may therefore respond differently to different spatio-temporal noxious input in the migraine subtypes MWA and MWoA. The noxious input is caused by a cortical perturbation of homeostasis, known as spreading depression (SD). The MGN might even trigger SD in the first place by a failure in vasomotor control. As a consequence, migraine is considered as an inherently dynamical disease to which a linear course from upstream to downstream events would not do justice. Minimally invasive and noninvasive neuromodulation techniques are briefly reviewed and their rational is discussed in the context of the proposed mechanism.