Dynamics of seizure termination in a non-human primate kindling model of mesial temporal lobe epilepsy

Epilepsy is characterized by recurrent, unprovoked seizures which involve transient neuronal hyperexcitability or hypersynchrony. Focal seizures with impaired awareness (FIAS) are commonly related to mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis and potentially status epilepticus. How seizures terminate spontaneously remains an unanswered question fundamental to epileptology. To study seizure termination, we induced FIAS in a nonhuman primate (NHP) model with electrical kindling. Kindling stimulation was delivered to the basolateral amygdala once weekly for 30 weeks. Chronic linear microelectrode arrays were implanted in NHP mesial temporal lobe targets: the hippocampus, amygdala and entorhinal cortex. Daily electrophysiologic recordings were obtained from all targets before, during and after stimulation to monitor changes to local field potential activity. We detect prominent changes in electrophysiologic dynamics before after-discharge (AD; subclinical, electrographic seizures which begin after a stimulus) self-termination. Specifically, at seizure termination the power of the extra-focal theta rhythm increased, and the theta phase was shown to couple with the gamma rhythm within the seizure focus. The electrical current threshold for eliciting an after-discharge decreased from >700µA to 15µA. The refractory period, which prevents the induction of seizure events at threshold, was initially 3 minutes in duration. At 30 weeks after FIAS induction the refractory period increased to over 5 minutes in duration. Understanding the electrophysiologic dynamics that reflect endogenous seizure termination mechanisms may be a valuable consideration for refining intervention strategies for treatment of epilepsy. Clinical Relevance- Our findings provide further electrophysiologic description of the endogenous mechanisms behind seizure termination in a healthy brain. This work specifically highlights the importance of considering targets outside the epileptogenic zone for therapeutic intervention.