Derailment of Sleep Homeostatic Plasticity Affects the Most Plastic Brain Systems and Carries the Risk of Epilepsy

Although a critical link between non-rapid eye movement (NREM) sleep and epilepsy has long been suspected, the interconnecting mechanisms have remained obscure. However, recent advances in sleep research have provided some clues. Sleep homeostatic plasticity is now recognized as an engine of the synaptic economy and a feature of the brain's ability to adapt to changing demands. This allows epilepsy to be understood as a cost of brain plasticity. On the one hand, plasticity is a force for development, but on the other it opens the possibility of epileptic derailment. Here, we provide a summary of the phenomena that link sleep and epilepsy. The concept of "system epilepsy", or epilepsy as a network disease, is introduced as a general approach to understanding the major epilepsy syndromes, i.e., epilepsies building upon functional brain networks. We discuss how epileptogenesis results in certain major epilepsies following the derailment of NREM sleep homeostatic plasticity. Post-traumatic epilepsy is presented as a general model for this kind of epileptogenesis.