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

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. Migraine is characterized by recurrent attacks of moderate to severe headaches sometimes pre-ceded by visual, sensory, motor, or language dis-turbances. These so-called migraine aura symp-toms are caused by a chemical imbalance in the brain that lasts usually not longer than one hour, while the longer lasting headaches originate from neural activity in the brainstem. Both have been observed with non-invasive imaging. In this study, it is proposed how these events are linked together and that migraine pathophysiol-ogy should be considered as a dynamical network phenomenon. I