# Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

> **NIH NIH R01** · COOK CHILDREN'S MEDICAL CENTER · 2021 · $428,636

## Abstract

Project Summary
Crucial to the success of epilepsy surgery is the availability of a robust presurgical biomarker to identify the
epileptogenic zone (EZ). Complete resection of the EZ may lead to medication and seizure freedom. Since the
EZ cannot be measured directly, its location is estimated indirectly based on concordant data from a multitude
of noninvasive tests. Yet, the results of these tests are often insufficiently concordant or inconclusive.
Intracranial electroencephalography (iEEG) serves as the gold standard for the delineation of the seizure onset
zone (SOZ). However, the SOZ does not always predict the surgical outcome, and its delineation requires
many days of recordings to capture clinical seizures. High-frequency oscillations (HFOs), recorded with iEEG
are promising interictal biomarkers of the EZ. Yet, their clinical value for epilepsy surgery is still debated since
the HFO-generating area is often relatively large and its complete resection may overlap with eloquent areas.
This is often attributed to the presence of physiological HFOs in non-epileptogenic areas. In our recent iEEG
study, we showed that interictal HFOs are initiated by an onset generator and spread to other brain areas over
time. This generator constitutes a promising interictal biomarker of the EZ since its resection is associated with
good surgical outcome. Despite the copious literature on HFOs, the clinical value of HFOs for surgery has
been only investigated using iEEG, which presents serious limitations due to its invasiveness and its limited
spatial sampling. This application aims to noninvasively localize interictal HFOs with high-density
electroencephalography (HD-EEG) and magnetoencephalography (MEG) in children with medically refractory
epilepsy (MRE), distinguish pathological from physiological HFOs, and assess the noninvasive localization of
the HFO-onset generator with respect to the surgical resection and patients’ outcome. Our hypothesis is that
HD-EEG and MEG can distinguish pathological from physiological HFOs non-invasively and can localize the
HFO-onset generator whose removal leads to better surgical outcome than the removal of the area of
secondary spread. To test our hypothesis, we specifically aim to: (i) assess the ability of HD-EEG and MEG to
localize HFOs; (ii) differentiate physiological (nHFOs) from pathological (pHFOs) HFOs using unsupervised
machine learning; (iii) localize noninvasively the HFO-onset generator and compare it with the clinical gold
standard for resection tailoring, i.e. the iEEG-defined SOZ; and (iv) assess the predictive value of the HFO-
onset generator in terms of surgical outcome. To pursue these aims, we will record HD-EEG and MEG data
from 50 children (0-18 years old) with MRE and 50 typically developing (TD) children. This application
combines the use of cutting-edge pediatric neuroimaging instruments, 3D printing technology, and innovative
signal processing tools together with extensive neuroimaging experie...

## Key facts

- **NIH application ID:** 9944685
- **Project number:** 5R01NS104116-03
- **Recipient organization:** COOK CHILDREN'S MEDICAL CENTER
- **Principal Investigator:** Christos Papadelis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $428,636
- **Award type:** 5
- **Project period:** 2019-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944685

## Citation

> US National Institutes of Health, RePORTER application 9944685, Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients (5R01NS104116-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944685. Licensed CC0.

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