title: Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex.
abstract: High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (n = 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales.
authors.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637; Departments of Pediatrics, The University of Chicago, Chicago, Illinois 60637.
authors.forename: Tahra L
authors.initials: TL
authors.lastname: Eissa
authors.affiliation: Departments of Pediatrics, The University of Chicago, Chicago, Illinois 60637; Department Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
authors.forename: Andrew K
authors.identifier: 0000-0002-9610-9259
authors.initials: AK
authors.lastname: Tryba
authors.affiliation: Departments of Pediatrics, The University of Chicago , Chicago, Illinois 60637.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Marcuccilli
authors.affiliation: Department Physiology, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors.forename: Faiza
authors.initials: F
authors.lastname: Ben-Mabrouk
authors.affiliation: Department of Neurological Surgery, Columbia University , New York, New York 10032.
authors.forename: Elliot H
authors.identifier: 0000-0003-4323-4643
authors.initials: EH
authors.lastname: Smith
authors.affiliation: Department Neurosurgery, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Lew
authors.affiliation: Department of Neurosurgery, Mount Sinai Hospital , New York, New York 10029.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Goodman
authors.affiliation: Department of Neurological Surgery, Columbia University , New York, New York 10032.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Departments of Pediatrics, The University of Chicago, Chicago, Illinois 60637; Department Surgery, The University of Chicago, Chicago, Illinois 60637.
authors.forename: David M
authors.initials: DM
authors.lastname: Frim
authors.affiliation: The Computation Institute, The University of Chicago , Chicago, Illinois 60637.
authors.forename: Lorenzo L
authors.identifier: 0000-0002-8015-4653
authors.initials: LL
authors.lastname: Pesce
authors.affiliation: Departments of Pediatrics, The University of Chicago , Chicago, Illinois 60637.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kohrman
authors.affiliation: Department of Neurological Surgery, Columbia University, New York, New York 10032; Department of Neurology, Columbia University, New York, New York 10032.
authors.forename: Ronald G
authors.identifier: 0000-0002-8592-7539
authors.initials: RG
authors.lastname: Emerson
authors.affiliation: Department of Neurology, Columbia University , New York, New York 10032.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schevon
authors.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637; Departments of Pediatrics, The University of Chicago, Chicago, Illinois 60637; The Computation Institute, The University of Chicago, Chicago, Illinois 60637; Committee on Computational Neuroscience, The University of Chicago, Chicago, Illinois 60637.
authors.forename: Wim
authors.initials: W
authors.lastname: van Drongelen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000069279:Drug Resistant Epilepsy / Q000473:pathology* / Q000601:surgery; D004558:Electric Stimulation; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D065818:Gamma Rhythm / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D019579:Neocortex / Q000503:physiopathology*; D018408:Patch-Clamp Techniques
keywords: HFOs; epilepsy; human; modeling; neocortex; seizure