Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized.

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

Analyzing critical propagation in a reaction-diffusion-advection model using unstable slow waves.

The effect of advection on the propagation and in particular on the critical minimal speed of traveling waves in a reaction-diffusion model is studied. Previous theoretical studies estimated this effect on the velocity of stable fast waves and predicted the existence of a critical advection strength below which propagating waves are not supported anymore. In this paper, an analytical expression for the advection-velocity relation of the unstable slow wave is derived. In addition, the critical advection strength is calculated taking into account the unstable slow wave solution. We also analyze a two-variable reaction-diffusion-advection model numerically in a wide parameter range. Due to the new control parameter (advection) we can find stable wave propagation in the otherwise non-excitable parameter regime, if the advection strength exceeds a critical value. Comparing theoretical predictions to numerical results, we find that they are in good agreement. Theory provides an explanation for the observed behaviour.