EXPERIMENTAL-COMPUTATIONAL ANALYSIS OF VIGILANCE DYNAMICS FOR APPLICATIONS IN SLEEP AND EPILEPSY

Epilepsy is a neurological disorder characterized by recurrent seizures. Sleep problems can cooccur with epilepsy, and adversely affect seizure diagnosis and treatment. In fact, the relationship between sleep and seizures in individuals with epilepsy is a complex one. Seizures disturb sleep and sleep deprivation aggravates seizures. Antiepileptic drugs may also impair sleep quality at the cost of controlling seizures. In general, particular vigilance states may inhibit or facilitate seizure generation, and changes in vigilance state can affect the predictability of seizures. A clear understanding of sleep-seizure interactions will therefore benefit epilepsy care providers and improve quality of life in patients. Notable progress in neuroscience research—and particularly sleep and epilepsy—has been achieved through experimentation on animals. Experimental models of epilepsy provide us with the opportunity to explore or even manipulate the sleep-seizure relationship in order to decipher different aspects of their interactions. Important in this process is the development of techniques for modeling and tracking sleep dynamics using electrophysiological measurements. In this dissertation experimental and computational approaches are proposed for modeling vigilance dynamics and their utility demonstrated in nonepileptic control mice. The general framework of hidden Markov models is used to automatically model and track sleep state and dynamics from electrophysiological as well as novel motion measurements. In addition, a closed-loop sensory stimulation technique is proposed that, in conjunction with this model, provides the means to concurrently track and modulate 3 vigilance dynamics in animals. The feasibility of the proposed techniques for modeling and altering sleep are demonstrated for experimental applications related to epilepsy. Finally, preliminary data from a mouse model of temporal lobe epilepsy are employed to suggest applications of these techniques and directions for future research. The methodologies developed here have clear implications the design of intelligent neuromodulation strategies for clinical epilepsy therapy