Dynamics underlying interictal to ictal transition in temporal lobe epilepsy: insights from a neural mass model

Abstract

We propose an approach that combines a neural mass model and clinical intracranial electroencephalographic (iEEG) recordings to explore the potential pathophysiological mechanisms (at the neuronal population level) of ictogenesis. Thirty iEEG recordings from 10 temporal lobe epilepsy (TLE) patients around seizure onset were investigated. Physiologically meaningful parameters [average excitatory (A ), slow (B), and fast (G) inhibitory synaptic gain] were identified during interictal to ictal transition. Four ratios (A /G, A /B, A /(B + G), and B/G) were derived from these parameters, and their evolution over time was analyzed. The excitation/inhibition ratio increased around seizure onset and decreased before seizure offset, indicating the impairment and re-emergence of excitation/inhibition balance around seizure onset and before seizure offset, respectively. Moreover, the slow inhibition may have an earlier effect on excitation/inhibition imbalance. We confirm the decrease in excitation/inhibition ratio upon seizure termination in human temporal lobe epilepsy, as revealed by optogenetic approaches both in vivo in animal models and in vitro. The increase in excitation/inhibition ratio around seizure occurrence could be an indicator to detect seizures.

Seizure evolution can be characterized as path through synaptic gain space of a neural mass model

“…During Sz however, they diffuse mostly to regions in the synaptic gain parameter space where the excitatory/inhibitory synaptic gain ratios increase (see the arrows in Figure c). It is consistent with previous work from our group (Fan et al., ; Hocepied, Legros, Van Bogaert, Grenez, & Nonclercq, ), showing that the excitation/inhibition ratios increase around seizure onset and decrease before/around seizure offset.…”

“…To achieve a fine temporal resolution, the recordings were processed within a sliding window and three physiologically meaningful parameters, i.e., the average excitatory (A), as well as the slow and fast inhibitory synaptic gains (B and G), were identified within each window to reproduce those recordings. We have shown previously the global trend of temporal evolution of excitation/inhibition synaptic gain ratios during interictal to ictal transition (Fan et al., ). In this paper, we analyzed the distribution of synaptic gains in the parameter space and their temporal evolution.…”

“…The same database was used as in our previous study (Fan et al., ), which includes thirty depth‐EEG recordings recorded from ten patients diagnosed with TLE (Table ). The seizure onset, offset and seizure onset patterns (SOP) were determined by an expert epileptologist.…”

“…(a) Illustration of the neural mass model (+/− represents excitatory/inhibitory); (b) Detailed schematic representation of the model ( EPSP / IPSP denotes excitatory/inhibitory postsynaptic potential), cited from (Fan et al., ) and adapted from (Wendling et al., ) [Colour figure can be viewed at wileyonlinelibrary.com]…”

“…The relative power within seven specific frequency bands (i.e., 0.5–1.5, 1.5–2.5, 2.5–4.5, 4.5–8.5, 8.5–16.5, 16.5–32.5 and 32.5–65 Hz) were computed as spectral features. See (Fan et al., ) for more details about the parameter identification procedure.…”