title: The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures.
abstract: The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area.
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Elliot H
authors.initials: EH
authors.lastname: Smith
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Jyun-you
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Davis
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Merricks
authors.affiliation: California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, California 91125, USA.
authors.forename: Spencer S
authors.initials: SS
authors.lastname: Kellis
authors.affiliation: Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Shennan A
authors.initials: SA
authors.lastname: Weiss
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Greger
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: House
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Goodman
authors.affiliation: Department of Neurology, Weill Cornell Medical College, New York, New York 10021, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Emerson
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bateman
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Trevelyan
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schevon
mesh_terms: D058256:Brain Waves / Q000502:physiology*; D003198:Computer Simulation; D004569:Electroencephalography; D065818:Gamma Rhythm; D006801:Humans; D008839:Microelectrodes; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology; D012640:Seizures / Q000503:physiopathology*