Focal seizures are organized by feedback between neural activity and ion concentration changes

Abstract

Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. We show that the disturbance of K+ and Cl− homeostasis by the fast discharge of inhibitory interneurons is sufficient to initiate seizures, which are maintained by positive feedback between ion concentration changes and neuronal activity. Gradual Na+ accumulation increases the rate of the Na+/K+-pump, creating negative feedback which slows down and terminates ictal discharges and contributes to the postictal state. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.