?s abstract): Among different forms of epilepsy, frontal lobe epilepsy (FLE) is one of the most poorly understood and difficult to treat surgically. The general aim of this proposal is to provide detailed characterization of FLE in human patients with a multidisciplinary approach. The investigators postulate that the poor surgical outcome in treating FLE is due to the presence of multiple generators of interictal and ictal activities. They propose to identify these multiple interictal spike generators with magnetoencephalography (MEG), using two inverse solution algorithms, rather than assuming that the generators can be represented by single foci as in most of the previous MEG studies. The interictal generators estimated with MEG will be compared to electrocorticography (ECoG) recordings to be obtained from the same subjects in preparation for surgery. The generator locations will be also compared with those from follow-up postoperative MEG measurements to determine the significance of residual interictal activity in understanding the surgical outcomes. The investigators will characterize the metabolic abnormalities in the neocortex of epilepsy patients using magnetic resonance spectroscopy (MRS) to measure N-acetylaspartate (NAA), choline (CHO), and creatine signals, initially with a voxel method and eventually with a 2D MRS imaging. They will correlate the degree of metabolic abnormality with the location of interictal generators and frequency of interictal activity at each location as determined with preoperative MEG to assess whether the MRS can be used to predict the locations of interictal generators, as it was the case in a preliminary study. The MRS results will be also compared with the interictal and ictal generators to be identified with the EcoG. Assuming that the interictal sites are close to the ictal site and often included in the resected tissue containing the ictal zone, they will characterize the neocortical tissue resected during the surgery, using both electrophysiological and molecular biological techniques, to see how the interictal and ictal sites of the tissue differ in their abilities to generate epileptiform activities intrinsically in slice preparations and how these sites are related to the underlying molecular signals of cell death, reactive synaptogenesis and sprouting. The resected ictal tissue is expected to show augmented voltage-gated calcium influx compared to interictal tissue when measured with intracellular recording and in vitro calcium imaging. Field and optical dye recordings will determine the excitatory connections in vitro. The investigators will measure the expression levels, regional distributions and layer specificities of markers of reactive astrocytes and synaptic plasticity in the resected tissue to relate to the electrophysiological properties of the interictal and ictal sites.
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