Cross-Scale Effects of Feedforward Inhibition during Human Neocortical Seizure Activity


Network dynamics are typically defined by activity at either the network scale or neuronal scale; however, under certain circumstances, a small number of neurons within the network may impose widespread effects. In order to unravel the relationship between neuronal functioning and large network dynamics, we analyzed eight multi-scale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multi-unit spike activity organizes into a sub-mm-sized wavefront, and this activity correlates significantly with low frequency rhythms across a 10-cm-sized cortical network. Notably, this correlation effect is specific to the ictal wavefront and is not present interictally or from action potential activity outside the wavefront territory.


We subsequently modeled these interactions as a multi-scale, nonlinear system and demonstrated a dual role for feedforward inhibition in seizures. While inhibition at the wavefront fails and allows for seizure propagation, feedforward inhibition of the surrounding cm-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination exist. Using our model to study multi-scale mechanisms in ongoing seizure activity, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process while the macroscopic, cm-sized, network responds with oscillatory seizure activity.

Wednesday 5 April 2017, 16:30 - 17:30 h

Building Carré - room CR 3.178