A significant proportion of patients with epilepsy are refractive to pharmaceutical treatments. Recurrent, untreated epileptic seizures are associated with risk of adverse neurological, cognitive, and psychological outcomes. Despite years of study, there are still significant barriers to the management of these disorders. In my proposal I advance the hypothesis that time-targeted perturbation of neural network oscillations by transcranial electric stimulation (TES) decreases the duration of seizures. I hypothesize further that spatially focused TES and chronically applied TES intervention can also permanently reduce seizure occurrence. Our specific aims are designed to perform in vivo studies in rodent models of two seizure types (absence seizures and complex partial seizures) to evaluate the effectiveness of TES in abrogating pathologic network activity, and to use high resolution recording techniques and optogenetical methods to assess the neural mechanisms involved. Our results may help to establish general principles of the diverse epilepsy pathophysiology and introduce novel therapeutic approaches. We will establish a focal TES stimulation protocol to selectively interfere with brain regions previously identified as key structures in the pathomechanism of epilepsy. The deliverables of these experiments will make a significant advancement in the understanding of the pathomechanisms of these disorders, and will offer a new alternative treatment option as a complimentary therapeutic approach to the state of the art pharmaceutical products. The methods used in this project are unique and advanced as the first attempt to perform 512 channel extracellular recordings in the behaving animal to investigate the evolution of epileptic seizures at the neuronal network and cellular levels and by achieving spatially selective TES. The combination of these methods are deployed for both understanding the mechanisms of seizure evolution, and termination of seizures.
Fields of science
- medical and health sciencesbasic medicineneurologyepilepsy
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicinephysiologypathophysiology
- natural sciencescomputer and information sciencesartificial intelligencecomputational intelligence
Call for proposal
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