MODELING THE IMPACT OF LAMOTRIGINE ON INTERICTAL EPILEPTIC SPIKES

Epilepsy is a chronic neurological disorder resulting in recurrent abnormal brain activity such as interictal epileptic spike (IES). About two-thirds of epilepsy patients are treated with antiseizure medications (ASMs), one of the most commonly prescribed being Lamotrigine (LTG), for the treatment of both focal and generalized epilepsy. Here, we aimed to use a neuro-inspired microscale model of the hippocampus to study the impact of LTG on the IES of epileptic tissue. Experimental studies have shown that LTG primarily acts on voltage-gated Na⁺-channels, resulting in the blockage of excitatory neurotransmitter release and a reduction in sustained repetitive firing of action potentials.
In this study, we used a realistic biomathematical model of the hippocampus to model the impact of LTG on the local field potential (LFP). This was done by simulating a shift in the inactivation curve of the Na⁺-channel that was dependent on LTG dosage. We then analyzed the impact of LTG on neural spiking behavior from stereo-electroencephalographic (sEEG) recordings. The drug-induced variations observed in the IES detected in clinical recordings, in terms of spike amplitude and power, were compared to that of simulated LFPs. Thus, we were able to validate the simulated impact of LTG and consequently confirm the verity of our implementation. Such a neurophysiologically reliable model can offer a promising approach to improving ASM prescription, especially in the case of refractory epilepsy.