The long-range objective of this research is to define the relationship between sleep and the electroencephalographic (EEG) manifestations of epilepsy in humans. Cellular neurophysiological studies suggest that synchronization of cortical and thalamic networks, which is enhanced during NREM sleep, contributes to activation of spike-wave discharges in experimental and human generalized epilepsy. Thalamocortical synchronization may also be important in activating focal epileptic cortex during NREM sleep. The proposed work will test the general hypothesis that deep NREM sleep, a highly synchronized state, activates interictal epileptiform discharges (spikes) and seizures in patients with partial epilepsy. EEG-polysomnography studies using scalp electrodes will be performed in 60 patients with focal epilepsy to test the specific hypotheses that (I) the number of spikes/minute is highest in deep NREM sleep and (2) the field of interictal epileptiform activity expressed at the cortical surface expands in deep NREM sleep, as manifested by surface EEG. A third specific hypothesis will determine the relationship between NREM sleep depth and the onset of seizure activity in 2O patients implanted with depth electrodes. In addition to visual analysis, EEG spectral analysis and other advanced signal processing techniques will be employed to provide objective and quantitative measures of the depth of NREM sleep. By providing better characterization of the relationship between sleep and epileptic activity, these studies are likely to increase our understanding of the relationship between the neurophysiology of sleep and that of epilepsy. Ultimately, such knowledge may lead to more targeted therapies for seizure disorders. The training aspects of this proposal are twofold. The first goal is to enhance the principal investigator's ability to apply quantitative signal processing techniques to the EEG of sleep in epilepsy patients. She will apply these techniques under the guidance of Dr. Michael Aldrich, Director of the University of Michigan Sleep Disorders Laboratory and Dr. William Williams, Professor of Electrical Engineering. Given the interdisciplinary nature of this work, additional support will be provided by consultants with expertise in the areas of electroencephalography, biostatistics, and cellular neurophysiology. The second goal is to expand the principal investigator's expertise in designing and carrying out comprehensive investigations in clinical research. To supplement the clinical research experienced gained through carrying out the experiments outlined in the Research Plan, the principal investigator will enroll in the On Job/On Campus Master of Science Program in Clinical Research Design and Statistical Analysis through the Department of Biostatistics in the School of Public Health at the University of Michigan. This program provides formal coursework in aspects of study design and data analysis, culminating in a Master of Science Degree.
| Malow, B A; Levy, K; Maturen, K et al. (2000) Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 55:1002-7 |
| Malow, A; Bowes, R J; Ross, D (2000) Relationship of temporal lobe seizures to sleep and arousal: a combined scalp-intracranial electrode study. Sleep 23:231-4 |
| Malow, B A; Selwa, L M; Ross, D et al. (1999) Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia 40:1587-92 |
| Malow, B A; Lin, X; Kushwaha, R et al. (1998) Interictal spiking increases with sleep depth in temporal lobe epilepsy. Epilepsia 39:1309-16 |
| Malow, B A; Bowes, R J; Lin, X (1997) Predictors of sleepiness in epilepsy patients. Sleep 20:1105-10 |
| Malow, B A; Kushwaha, R; Lin, X et al. (1997) Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy. Electroencephalogr Clin Neurophysiol 102:20-6 |
