Dmitrii Zendrikov (dmitrii@ini.uzh.ch), Alexander Paraskevov
Spontaneous focal synchronization of collective spiking followed by induced traveling waves can occur in the cortical sheet and in cultured planar neuronal networks. In the first case, it is focal epilepsy leading to a seizure and, in the second, it is synchronization that originates from one of a few steady nucleation sites resulting in a so-called population spike. Assuming functional similarity between the nucleation sites and non-lesional epileptic foci, the major unsolved issue in both cases is that whether activation of the focus occurs inside it (i.e., autonomously relative to the interaction with surrounding neuronal tissue) or from the outside. The "internal" scenario implies that the focus spatially contains some pacemakers. In turn, several experimental findings indicate a complex spatially non-local activation of epileptic focus [1-4]. In modeling studies, we address the issue in order to verify the validity of this conclusion.
We use generative mechanistic model of planar neuronal network exhibiting irregular spontaneous population spikes, which emerge from a few spontaneously-formed stationary nucleation sites. The model consists of leaky integrate-and-fire neurons connected by synapses with short-term plasticity, forming spatially-dependent "small-world" network topology, where synaptic connection probability decreases exponentially with the distance between neurons. Spiking activity in the network occurs due to some fraction of pacemaker neurons. Importantly, the spatial configuration of pacemaker neurons was artificially engineered in order to resolve the above-mentioned problem: all pacemakers were placed within a circular central spot so that their spatial density was equal to the average density of neurons. Leaving the global dynamic regime unaffected, this spatial configuration crucially helps to clarify the activation process, visualizing of which is hindered at spatially-uniform pacemaker distribution.
Extensive simulations [5] have shown that steady and spontaneous nucleation sites of population spikes (i) can emerge in spatial regions, which are far away from the spot with pacemakers and (ii) can be activated even without direct links from pacemakers. The results demonstrate the principle possibility of external, or remote, activation of a focal source of epileptic activity in the brain and favor the interpretation in above-mentioned experimental findings. The suggested deterministic model provides the means to study this network phenomenon systematically and reproducibly.
References
1. Schevon C.A., et al. Cortical abnormalities in epilepsy revealed by local EEG synchrony. NeuroImage. 2007, 35(1), 140-148.
2. Zaveri H.P., et al. Localization-related epilepsy exhibits significant connectivity away from the seizure-onset area. NeuroReport. 2009, 20(9), 891-895.
3. Bower M.R. et al. Spatiotemporal neuronal correlates of seizure generation in focal epilepsy. Epilepsia. 2012, 53(5), 807-816.
4. Paz J.T., Huguenard J.R. Microcircuits and their interactions in epilepsy: is the focus out of focus? Nat. Neurosci. 2015, 18(3), 351-359.
5. Paraskevov A., Zendrikov D. Capturing remote activation of epilepsy source? bioRxiv. 2018.
