This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The primary objective of the proposed research is to advance the understanding of the neurophysiologic mechanisms of action of three neurostimulation modalities for the treatment of epilepsy: vagus nerve stimulation, deep brain stimulation, and epileptic focus stimulation, by determining the effects of direct and remote electrical stimulation on electrographic activity and regional cerebral metabolism.
The specific aims / hypotheses are: 1) desynchronizing effects of neurostimulation will be associated with a decreased occurrence of interictal epileptiform discharges, 2) neurostimulation therapies will alter EEG frequency content within regions and its correlation between regions, particularly at the most epileptogenic cortical regions, 3) neurostimulation will change abnormal cerebral metabolic rates near epileptic foci as measured by quantitative fluorodeoxyglucose PET with co-registered computed tomography (FDG-PET/CT) imaging, 4) neurostimulation-related changes in regional cerebral metabolic rates, interictal epileptiform discharge occurrence, and EEG frequency spectral measures will be correlated. We will prospectively and longitudinally employ quantitative EEG and FDG-PET/CT techniques to study the mechanisms of action of neurostimulation therapies for epilepsy. A greater understanding of the mechanism of action of neurostimulation techniques is likely to result in an increased efficacy of this evolving mode of treatment for patients with refractory epilepsy, which remains an important problem despite the many recently approved anticonvulsants and advances in resective surgery. Fuerthermore, in carrying out this mentored research project and the training components of this proposal, I hope to gain the skills and experience that will lead to a productive and independent career as a researcher in clinical neurophysiology and epilepsy.
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