title: Resilience of developing brain networks to interictal epileptiform discharges is associated with cognitive outcome.
abstract: The effects of interictal epileptiform discharges on neurocognitive development in children with medically-intractable epilepsy are poorly understood. Such discharges may have a deleterious effect on the brain's intrinsic connectivity networks, which reflect the organization of functional networks at rest, and in turn on neurocognitive development. Using a combined functional magnetic resonance imaging-magnetoencephalography approach, we examine the effects of interictal epileptiform discharges on intrinsic connectivity networks and neurocognitive outcome. Functional magnetic resonance imaging was used to determine the location of regions comprising various intrinsic connectivity networks in 26 children (7-17 years), and magnetoencephalography data were reconstructed from these locations. Inter-regional phase synchronization was then calculated across interictal epileptiform discharges and graph theoretical analysis was applied to measure event-related changes in network topology in the peri-discharge period. The magnitude of change in network topology (network resilience/vulnerability) to interictal epileptiform discharges was associated with neurocognitive outcomes and functional magnetic resonance imaging networks using dual regression. Three main findings are reported: (i) large-scale network changes precede and follow interictal epileptiform discharges; (ii) the resilience of network topologies to interictal discharges is associated with stronger resting-state network connectivity; and (iii) vulnerability to interictal discharges is associated with worse neurocognitive outcomes. By combining the spatial resolution of functional magnetic resonance imaging with the temporal resolution of magnetoencephalography, we describe the effects of interictal epileptiform discharges on neurophysiological synchrony in intrinsic connectivity networks and establish the impact of interictal disruption of functional networks on cognitive outcome in children with epilepsy. The association between interictal discharges, network changes and neurocognitive outcomes suggests that it is of clinical importance to suppress discharges to foster more typical brain network development in children with focal epilepsy.
authors.affiliation: 1 Division of Neurosurgery, Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada 2 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada georgem.ibrahim@utoronto.ca.
authors.forename: George M
authors.initials: GM
authors.lastname: Ibrahim
authors.affiliation: 3 Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cassel
authors.affiliation: 4 Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Morgan
authors.affiliation: 5 Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Smith
authors.affiliation: 6 Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otsubo
authors.affiliation: 6 Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ochi
authors.affiliation: 3 Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada 4 Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada 5 Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Margot
authors.initials: M
authors.lastname: Taylor
authors.affiliation: 1 Division of Neurosurgery, Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.affiliation: 2 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada 3 Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada 6 Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
authors.affiliation: 2 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada 3 Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada 4 Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada 5 Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Doesburg
mesh_terms: D000293:Adolescent; D000465:Algorithms; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002648:Child; D003071:Cognition / Q000502:physiology*; D004351:Drug Resistance; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D009415:Nerve Net / Q000254:growth & development* / Q000502:physiology*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012146:Rest / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D010100:Oxygen
keywords: IED; functional connectivity; graph theoretical analysis; resting-state functional MRI
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