Wednesday 27 Jul 2016: Dynamics seminar: Partial Seizures: Thoughts on Propagation Mechanisms and Biomarkers
Wim van Drongelen - University of Chicago
Epilepsy is a serious neurological disorder that affects ~1% of the population. About 1⁄3 of patients does not respond to medication and in spite of development of new anticonvulsants, this fraction of intractable patients has remained constant over the past decades. The lack of success in treatment provides a rationale for the investigation of the mechanisms involved in epileptic activity, and motivates the search for biomarkers that can assist the clinician in localizing the seizure onset zone.
Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate. We examined the effect of such a saturation in the Wilson–Cowan formalism by adapting the nonlinear activation function; we substituted the commonly applied sigmoid for a Gaussian function. We discuss experimental recordings during a seizure that support this substitution. Next we perform a bifurcation analysis on the Wilson–Cowan model with a Gaussian activation function. The main effect is an additional stable equilibrium with high excitatory and low inhibitory activity. Analysis of coupled local networks then shows that such high activity can stay localized or spread. Specifically, in a spatial continuum we show a wavefront with inhibition leading followed by excitatory activity. We relate our model simulations to observations of spreading activity during seizures (Meijer et al., 2015).
High gamma (HG, 80-150Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, where multiunit spiking correlates with seizure activity. However, the effects of the seizure’s spatiotemporal dynamics on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multi-scale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts (PDSs) and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays (MEAs) recorded during human seizures (n=8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the seizure’s core region. Third, we used volume conduction based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales (Eissa et al., 2016).