title: Dynamic modulation of epileptic high frequency oscillations by the phase of slower cortical rhythms.
abstract: Pathological high frequency oscillations (pHFOs) have been proposed to be robust markers of epileptic cortex. Oscillatory activity below this frequency range has been shown to be modulated by phase of lower frequency oscillations. Here, we tested the hypothesis that dynamic cross-frequency interactions involving pHFOs are concentrated within the epileptogenic cortex. Intracranial electroencephalographic recordings from 17 children with medically-intractable epilepsy secondary to focal cortical dysplasia were obtained. A time-resolved analysis was performed to determine topographic concentrations and dynamic changes in cross-frequency amplitude-to-phase coupling (CFC). CFC between pHFOs and the phase of theta and alpha rhythms was found to be significantly elevated in the seizure-onset zone compared to non-epileptic regions (p<0.01). Data simulations showed that elevated CFC could not be attributed to the presence of sharp transients or other signal properties. The phase of low frequency oscillations at which pHFO amplitudes were maximal was inconsistent at seizure initiation, yet consistently at the trough of the low frequency rhythm at seizure termination. Amplitudes of pHFOs were most significantly modulated by the phase of alpha-band oscillations (p<0.01). These results suggest that increased CFC between pHFO amplitude and alpha phase may constitute a marker of epileptogenic brain areas and may be relevant for understanding seizure dynamics.
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: george.m.ibrahim@gmail.com.
authors.forename: George M
authors.initials: GM
authors.lastname: Ibrahim
authors.affiliation: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Simeon M
authors.initials: SM
authors.lastname: Wong
authors.affiliation: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Singh-Cadieux
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ochi
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otsubo
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Tohru
authors.initials: T
authors.lastname: Okanishi
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Taufik A
authors.initials: TA
authors.lastname: Valiante
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Donner
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sam M
authors.initials: SM
authors.lastname: Doesburg
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D058407:Electroencephalography Phase Synchronization; D004827:Epilepsy / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications; D017711:Nonlinear Dynamics; D012815:Signal Processing, Computer-Assisted
keywords: Cross-frequency coupling; Epilepsy; HFOs; High frequency oscillations; Intracranial EEG; Networks; Seizure