Abstract
Pharmacoresistant epilepsy is a common neurological disorder in which increased neuronal intrinsic excitability and synaptic excitation lead to pathologically synchronous behavior in the brain. In the majority of experimental and theoretical epilepsy models, epilepsy is associated with reduced inhibition in the pathological neural circuits, yet effects of intrinsic excitability are usually not explicitly analyzed. Here we present a novel neural mass model that includes intrinsic excitability in the form of spike-frequency adaptation in the excitatory population. We validated our model using local field potential (LFP) data recorded from human hippocampal/subicular slices. We found that synaptic conductances and slow adaptation in the excitatory population both play essential roles for generating seizures and pre-ictal oscillations. Using bifurcation analysis, we found that transitions towards seizure and back to the resting state take place via Andronov–Hopf bifurcations. These simulations therefore suggest that single neuron adaptation as well as synaptic inhibition are responsible for orchestrating seizure dynamics and transition towards the epileptic state.
Footnotes
The authors declare no competing financial interests.
This work was supported by the Swartz Foundation, FRM FDT20140930942, ANR-10-LABX-0087 IEC, and ANR-10-IDEX-0001-02 PSL grants. B.G. was supported by funding from the RF (Russian Federation) Program 5-100 to the National Research University Higher School of Economics. C.C.K. was supported by the Australian Research Council (ARC) Discovery Early Career Researcher Award DE140101375.
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