Sleep Microarchitecture, Epileptic Spikes, and Memory in Epilepsy: Implications for Developmental and Epileptic Encephalopathies.

Abstract

Summary: Healthy sleep is electrographically defined by oscillations that drive alternating up- and down-states that regulate neuronal excitability. Slow oscillations-the hallmark rhythm of deep nonrapid eye movement sleep, temporally organize faster, more focal rhythms, including thalamocortical sleep spindles and hippocampal sharp-wave ripples. These cascading rhythms have been implicated as a critical activity-dependent mechanism that binds coordinated neuronal activity to support systems-level consolidation of previous experience into long-term memory. Epilepsy is a disease characterized by sporadic pathologic neuronal activity, including interictal epileptiform discharges and seizures. Epileptic activity is frequently potentiated during sleep, but the interactions with specific graphoelements that comprise sleep microarchitecture are complex. Critically, the diverse ways in which epileptic activity interdigitates with sleep microstructure imply that epileptiform activity can distort and disrupt the same sleep rhythms that normally support memory consolidation. Cognitive comorbidities are common in epilepsy, and impairments in memory consolidation are increasingly recognized. In this review, we synthesize leading evidence on the complex interactions between sleep microarchitecture and interictal epileptiform discharges. We first summarize electrophysiologic data on how slow oscillations interact with spindles and interictal epileptiform discharges and then assemble these findings into a unifying framework for interictal epileptiform discharge-slow oscillation-spindle dynamics. Finally, we review evidence on how disruption of these sleep oscillations can contribute to cognitive dysfunction in epilepsy and highlight implications for developmental and epileptic encephalopathies.