The long-range objective of this research is to define the relationship between sleep and the electroencephalographic (EEG) manifestations of epilepsy in humans so that targeted therapeutic interventions to treat sleep-related seizures may be developed. Cellular neurophysiological studies suggest that processes underlying the initiation and deepening of non-rapid eye movement (NREM) sleep, including progressive hyperpolarization in thalamocortical projection neurons, induce a state of relative neuronal synchronization associated with the facilitation of interictal and ictal activity. In partial epilepsy, interictal epileptiform discharges (IEDs) are more prevalent in delta NREM sleep and as sleep is deepening. The proposed experiments will test the hypotheses that generalized IEDs and sleep-related epileptic seizures are also activated by neurophysiological processes underlying the initiation and deepening of NREM sleep. Sleep depth will be measured by the quantity of delta activity in the EEG.
In Specific Aim 1, 120 subjects with partial or generalized epilepsy will undergo EEG-polysomnography in the General Clinical Research Center to characterize the relationship of IEDs to sleep state, sleep depth, and arousals from sleep.
In Specific Aim 2, the relationship of epileptic seizures to sleep state, sleep depth, and arousals from sleep will be defined in 120 additional subjects with sleep-related seizures undergoing monitoring with continuous EEG recordings as part of their epilepsy surgery evaluation. Multivariate analogs of logistic regression models will be applied to these data to determine the predictive value of sleep state, sleep depth, and arousals from sleep on IED and seizure occurrence. The training aspects of this career development proposal will (1) broaden the principal investigator's education in clinical research, specifically the statistical analysis of longitudinal data; (2) strengthen her expertise in the application of signal analysis techniques to the sleep EEG; (3) facilitate her development of a research team; and (4) enhance her clinical and teaching expertise in sleep neuroscience and epilepsy.
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