Clinical Applications of High-Frequency Oscillations (HFOs)

February 2, 2026 updated by: Children's Hospital Medical Center, Cincinnati

Localizing Functional Brain Cortices and Epileptogenic Zones With High Frequency Brain Signals

The objective of this study is to utilize high-frequency brain signals (HFBS) to localize functional brain areas and characterize HFBS in epilepsy, migraine, and other brain disorders. Our goal is to create the world's first high-frequency MEG/EEG/ECoG/SEEG database for the developing brain. HFBS include high-gamma activation/oscillations, high-frequency oscillations (HFOs), ripples, fast ripples, spikelets, fast spikelets, and very high-frequency oscillations (VHFOs). While terminologies and frequency bands may vary among reports, both HFOs and high-gamma waves are crucial for understanding brain function and developing potential treatments for neurological disorders.

We have been developing an intelligent software platform to analyze signals from low to very high-frequency ranges across multiple frequency bands. To achieve these goals, we have developed several innovative techniques and software packages:

Accumulated spectrogram
Accumulated source imaging
Frequency-encoded source imaging
Multi-frequency analysis at source levels
Artificial intelligence detection of HFOs
Neural network analysis (Graph Theory)
Other techniques (e.g., Independent Component Analysis, virtual sensors) These methods enable researchers to better understand the characteristics and significance of HFOs and high-gamma brain waves, contributing to advancements in the diagnosis and treatment of neurological disorders.

Study Overview

Status

Withdrawn

Conditions

Detailed Description

The purpose of this study is to go beyond conventional analyses of brain signals in narrow frequency bands (typically 1-30 Hz) by measuring brain signals from infraslow to very fast frequencies (0.01 - 2800 Hz). Specifically, we propose to study physiological high-frequency oscillations (HFOs) in sensorimotor, auditory, visual, and language-evoked magnetic fields, and to investigate pathological HFOs in epilepsy, migraines, and other disorders. This is clinically important for several reasons.

For instance, there are 400,000 to 600,000 patients with refractory epilepsy in the United States. As these patients' seizures cannot be controlled by medication, epilepsy surgery is a potential cure. Accurate identification of ictogenic zones (the brain areas that cause seizures) is essential for favorable surgical outcomes. Unfortunately, the existing method, electrocorticography (ECoG), requires placing electrodes on the brain surface to capture spikes (typically, 14-70 Hz), which is both risky and costly. Our study aims to use magnetoencephalography (MEG) and electroencephalography (EEG) to identify ictogenic zones non-invasively. To achieve this goal, we propose detecting high-frequency (70-2500 Hz) and low-frequency (< 14 Hz) brain signals using advanced signal processing methods. Our central hypothesis is that high-frequency brain signals will lead to significantly improved rates of seizure freedom compared to spikes. This hypothesis is based on recent reports that high-frequency brain signals are localized to ictogenic zones.

Leveraging our unique resources and expertise, we plan to address four specific aims:

Quantify the Spatial Concordance: We will quantify the spatial concordance between MEG and ECoG signals in both low and high-frequency ranges. We hypothesize that ictogenic zones determined by invasive ECoG can be non-invasively detected and localized by high-frequency MEG signals.
Quantify the Occurrence Concordance: We will quantify the occurrence concordance between EEG and ECoG signals in both low and high-frequency ranges. We hypothesize that epileptic high-frequency signals from the ictogenic zones determined by invasive ECoG can also be non-invasively detected by EEG, although the localization of EEG may be significantly inferior to that of MEG.
Improve Epilepsy Surgery Outcomes: We will determine whether epilepsy surgery based on multi-frequency signals (low-frequency brain signals, spikes, and high-frequency brain signals), instead of spikes alone, leads to better seizure outcomes. We hypothesize that epilepsy surgery guided by high-frequency brain signals detected with MEG/EEG will significantly improve surgical outcomes.
Enhance Pre-surgical Planning: We will determine whether multi-frequency analyses provide more information than single-frequency analysis for estimating epileptogenic zones for pre-surgical ECoG electrode implantation. We hypothesize that covering all brain areas generating low to high-frequency epileptic activity is a prerequisite to localize multiple ictogenic zones for favorable post-surgical outcomes.

To yield definitive results, we propose a multi-center study to determine if high-frequency brain signals are new biomarkers for significantly improving epilepsy surgery outcomes. According to our pilot data, localization of epileptogenic zones with MEG high-frequency signals can increase post-operative seizure freedom by approximately 30-40%. The proposed study should result in millions of intractable epilepsy patients being seizure-free. Additionally, this study lays the foundation for using low and high-frequency brain signals as new biomarkers for the diagnosis and treatment of various other disorders (e.g., migraine, autism).

Furthermore, we will incorporate Optically Pumped Magnetometers MEG (OPM-MEG) to enhance the detection of high-frequency brain signals. OPM-MEG offers higher sensitivity and spatial resolution compared to conventional MEG, making it an invaluable tool for our research objectives.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Ohio
  - Cincinnati, Ohio, United States, 45229
    - MEG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

The study will obtain MEG/EEG data from healthy subjects, recruiting only individuals without underlying health conditions. Additionally, this study will utilize clinical MEG/EEG data from patients, which are acquired as part of standard clinical care for clinical purposes. Since women, girls, and minorities are included in the population to whom recruiting materials are directed, we anticipate that subject selection will be equitable.

Description

Inclusion Criteria:

Healthy and cooperative.
Ages: from 1 day to 69 years (male or female).
Normal hearing and vision.
Normal hand movement.
No history of neurological or psychiatric diseases.
No family history of genetic neurological or psychiatric diseases.
No metal implants such as pacemakers, neuro-stimulators, cochlear implants, etc.

Exclusion Criteria:

Taking any medications for depression, neurologic, or psychiatric conditions.
Not feeling well, having epilepsy, or other brain disorders.
Recent concussion or head injury.
Presence of metal in the body, such as dental braces, which could cause "magnetic noise". A simple, quick "magnetic noise screening" can be conducted at the MEG Center to determine eligibility.
Presence of electrical or metal implants such as pacemakers, neuro-stimulators, or orthopedic pins or plates. The research nurse will discuss all exclusions in further detail before the magnetic resonance imaging (MRI) scan.
Inability to pass the pre-experimental screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Other
Time Perspectives: Prospective

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Pediatric Patients and Healthy Children Healthy children without dental works. Pediatric patients with epilepsy and migraine (headache).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
epileptic foci Time Frame: one year	Accuracy of localization of epileptic foci	one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

University of Cincinnati

Investigators

Study Director: Jing Xiang, Ph.D M.D., Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2000

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

June 14, 2007

First Submitted That Met QC Criteria

January 24, 2008

First Posted (Estimated)

January 25, 2008

Study Record Updates

Last Update Posted (Actual)

February 4, 2026

Last Update Submitted That Met QC Criteria

February 2, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

IRB 2012-0866; 2018-8108
2008-1439 (Other Identifier: CCHMC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.