Altered sleep homeostasis correlates with cognitive impairment in patients with focal epilepsy

Abstract

In animal studies, both seizures and interictal spikes induce synaptic potentiation. Recent evidence suggests that electroencephalogram slow wave activity during sleep reflects synaptic potentiation during wake, and that its homeostatic decrease during the night is associated with synaptic renormalization and its beneficial effects. Here we asked whether epileptic activity induces plastic changes that can be revealed by high-density electroencephalography recordings during sleep in 15 patients with focal epilepsy and 15 control subjects. Compared to controls, patients with epilepsy displayed increased slow wave activity power during non-rapid eye movement sleep over widespread, bilateral scalp regions. This global increase in slow wave activity power was positively correlated with the frequency of secondarily generalized seizures in the 3-5 days preceding the recordings. Individual patients also showed local increases in sleep slow wave activity power at scalp locations matching their seizure focus. This local increase in slow wave activity power was positively correlated with the frequency of interictal spikes during the last hour of wakefulness preceding sleep. By contrast, frequent interictal spikes during non-rapid eye movement sleep predicted a reduced homeostatic decrease in the slope of sleep slow waves during the night, which in turn predicted reduced daytime learning. Patients also showed an increase in sleep spindle power, which was negatively correlated with intelligence quotient. Altogether, these findings suggest that both seizures and interictal spikes may induce long-lasting changes in the human brain that can be sensitively detected by electroencephalographic markers of sleep homeostasis. Furthermore, abnormalities in sleep markers are correlated with cognitive impairment, suggesting that not only seizures, but also interictal spikes can have negative consequences.