The Critical Role of Self-Inhibition in Epileptic Seizures Based on Dynamic Analysis of the Corticothalamic Model

Studies have shown that inhibitory interneurons include inhibitory interneurons on fast time scales (I1) and inhibitory interneurons on slow time scales (I2), both of which can modulate epileptic activities. Based on this, we improve the corticothalamic model by introducing self-inhibition of I1 and I2 to explore the onset and transitions of epileptic activities from the dynamic perspective. First, we investigate the case that the excitatory loop between the excitatory pyramidal neurons (PY) and the thalamic relay neurons (TC) induces epileptic activities in the absence of self-inhibition. The emergence of multistability drives the system to produce a variety of epileptic activities, such as m-spike-wave discharges, tonic and clonic oscillations. Subsequently, we introduce self-inhibition of inhibitory interneurons and find that the advancement or disappearance of the Hopf bifurcation leads to a reduction in the area of epileptic discharges. Finally, we explore epileptic activities induced by the self-inhibition of I1 and the excitability of TC on I1. The strong self-inhibition can effectively modulate seizures, but excessive exchange of information between TC and I1 induces absence seizures. In addition, the paper focuses on revealing the loop mechanisms and related bifurcation characteristics in various situations. Besides Hopf and fold limit cycle bifurcations, period-doubling and homoclinic bifurcations are also key factors leading to the state transitions. These may provide some theoretical guidance for the generation and evolution of seizures.