title: Neocortical pathological high-frequency oscillations are associated with frequency-dependent alterations in functional network topology.
abstract: Synchronization of neural oscillations is thought to integrate distributed neural populations into functional cell assemblies. Epilepsy is widely regarded as a disorder of neural synchrony. Knowledge is scant, however, regarding whether ictal changes in synchrony involving epileptogenic cortex are expressed similarly across various frequency ranges. Cortical regions involved in epileptic networks also exhibit pathological high-frequency oscillations (pHFOs, >80 Hz), which are increasingly utilized as biomarkers of epileptogenic tissue. It is uncertain how pHFO amplitudes are related to epileptic network connectivity. By calculating phase-locking values among intracranial electrodes implanted in children with intractable epilepsy, we constructed ictal connectivity networks and performed graph theoretical analysis to characterize their network properties at distinct frequency bands. Ictal data from 17 children were analyzed with a hierarchical mixed-effects model adjusting for patient-level covariates. Epileptogenic cortex was defined in two ways: 1) a hypothesis-driven method using the visually defined seizure-onset zone and 2) a data-agnostic method using the high-frequency amplitude of each electrode. Epileptogenic cortex exhibited a logarithmic decrease in interregional functional connectivity at high frequencies (>30 Hz) during seizure initiation and propagation but not at termination. At slower frequencies, conversely, epileptogenic cortex expressed a relative increase in functional connectivity. Our findings suggest that pHFOs reflect epileptogenic network interactions, yielding theoretical support for their utility in the presurgical evaluation of intractable epilepsy. The view that abnormal network synchronization plays a critical role in ictogenesis and seizure dynamics is supported by the observation that functional isolation of epileptogenic cortex at high frequencies is absent at seizure termination.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Hospital for Sick Children, Toronto, Ontario, Canada;
authors.forename: George M
authors.initials: GM
authors.lastname: Ibrahim
authors.forename: Ryan
authors.initials: R
authors.lastname: Anderson
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.forename: Ayako
authors.initials: A
authors.lastname: Ochi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otsubo
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Singh-Cadieux
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Donner
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
authors.forename: Sam M
authors.initials: SM
authors.lastname: Doesburg
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D058256:Brain Waves; D002648:Child; D003344:Cortical Synchronization; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*
keywords: cross-frequency; epilepsy; functional connectivity; graph theoretical analysis; graph theory; intracranial EEG; network; neural oscillations; neural synchrony; pathological high-frequency oscillations; phase synchronization; seizure