Neocortical pathological high-frequency oscillations are associated with frequency-dependent alterations in functional network topology

George M. Ibrahim, Ryan Anderson, Tomoyuki Akiyama, Ayako Ochi, Hiroshi Otsubo, Gabrielle Singh-Cadieux, Elizabeth Donner, James T. Rutka, O. Carter Snead, Sam M. Doesburg

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


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 highfrequency 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.

Original languageEnglish
Pages (from-to)2475-2483
Number of pages9
JournalJournal of neurophysiology
Issue number10
Publication statusPublished - Nov 15 2013
Externally publishedYes


  • Cross-frequency
  • Epilepsy
  • Functional connectivity
  • Graph theoretical analysis
  • Graph theory
  • Intracranial EEG
  • Network
  • Neural oscillations
  • Neural synchrony
  • Pathological high-frequency oscillations
  • Phase synchronization
  • Seizure

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology


Dive into the research topics of 'Neocortical pathological high-frequency oscillations are associated with frequency-dependent alterations in functional network topology'. Together they form a unique fingerprint.

Cite this