Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.

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We present a simple rate-reduced neuron model that captures a wide range of complex, biologically plausible, and physiologically relevant spiking behavior. This includes spike-frequency adaptation, postinhibitory rebound, phasic spiking and accommodation, first-spike latency, and inhibition-induced spiking. Furthermore, the model can mimic different neuronal filter properties. It can be used to extend existing neural field models, adding more biological realism and yielding a richer dynamical structure. The model is based on a slight variation of the Rulkov map.

and all others not named here. The secretaries Linda and Mariëlle deserve a special mention for their assistance in booking flights, solving administrative issues, and arranging everything else. Furthermore, I want to thank my old friends from my hometown Kleve, who often provided a welcome distraction from work. I am particularly indebted to Joscha for designing the marvelous cover of this thesis, and to Marie for proofreading parts of the final manuscript. Of course, I am solely responsible for all remaining errors. I am honored that my my brother Jelle and my friend and colleague Wilbert have agreed to be my paranymphs. Thanks that you are willing to support me on the day of my promotion.Finally, a special thank you goes to my wonderful parents for their love and support throughout the years. Henk en Myriam, thanks for always giving me the freedom to follow my own path in life.