Clinical Applications of High-Frequency Oscillations

Study Overview
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Brief Summary
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The objective of this study is to use high-frequency brain signals (HFBS) to localize functional brain areas and to characterize HFBS epilepsy, migraine and other brain disorders. We hope to build the world's first high-frequency MEG/MEG/ECoG/SEEG database for the developing brain. HFBS include high-gamma activation/oscillations, high-frequency oscillations (HFOs), ripples, fast ripples, and very high frequency oscillations (VHFOs) in the brain. To reach the goals, we have developed several new MEG/EEG methods: (1) accumulated spectrogram; (2) accumulated source imaging; (3)frequency encoded source imaging; (4) multi-frequency analysis; (5)artificial intelligence detection of HFOs; (6) Neural network analysis (Graph Theory); and (7) others (e.g. ICA, virtual sensors).

Detailed Description
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I. PURPOSE OF STUDY The purpose of this study is to go beyond the conventional analyses of brain signals in a narrow frequency band (typically 1-30 Hz) by measuring brain signals from infraslow to very fast (0.01 - 2800 Hz). Specifically, we propose to study physiological HFOs in sensorimotor, auditory, visual and language evoked magnetic fields and to investigate pathological HFOs in epilepsy, migraine and other disorders. This is clinical very important for many reasons. For example, There are 400,000 to 600,000 patients with refractory epilepsy in the United States. Since those patients' seizures cannot be controlled by any drugs, epilepsy surgery is one potential cure. Accurate identification of ictogenic zones, the brain areas cause seizures, is essential to ensure a favorable surgical outcome. Unfortunately, the existing method, electrocorticography (ECoG), needs to place electrodes upon the brain surface to capture spikes (typically, 14-70 Hz), which is very risky and costly. The present study is to use magnetoencephalography (MEG) and electroencephalography (EEG) to identification of ictogenic zones noninvasively. To reach the goal, we proposed to detect high frequency (70-2,500 Hz) and low frequency (< 14 Hz) brain signals with advanced signal processing methods. Our central hypothesis is that high frequency brain signals will lead to significantly improved rates of seizure freedom as compared with spikes. This hypothesis is based on recent reports that high frequency brain signals are localized to ictogenic zones. Building on our unique resources and skills, we plan to address four aims. First, 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. Second, 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 been non-invasively detected by EEG, although the localization of EEG may be significantly inferior to that of MEG. Third, 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 a better seizure outcome. We hypothesize that epilepsy surgery guided by high frequency brain signals detected with MEG/EEG will significantly improve surgical outcomes. Fourth, 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 the 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 improve epilepsy surgery outcomes. According to our pilot data that localization of epileptogenic zones with MEG high frequency signals can increase about 30-40% post-operative seizure freedom, the proposed study should result in millions of intractable epilepsy patients being seizure free. This study also lays a foundation for using low and high frequency brain signals as new biomarkers for diagnosis and treatment of many other disorders (e.g. migraine, autism).

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

Conditions
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Healthy, Epilepsy, Migraine, Headache, Pain, Autism, Cerebral Palsy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy and cooperative Ages: from 1 day to 69 years (male or female) Normal hearing and vision Normal hand movement No history for neurological or psychiatric disease No family history for genetic neurological or psychiatric diseases. No metal implants such as pacemaker, neuron-stimulator, cochlear device, etc. Exclusion Criteria: If you are taking any medications for depression, neurologic, or psychiatric condition If you do not feel well, have epilepsy or other brain disorders If you have had a recent concussion or head injury If you have any metal, such as dental braces, in your body that would cause magnetic noise, you may not be able to be in this study. If you would like, we can do a simple, quick magnetic noise screening in the MEG Center, which can tell us whether you can be in the study. If you have any electrical or metal implants such as pacemakers, neuro-stimulators, or orthopedic pins or plates. The research nurse will discuss all exclusions with you in further detail before the magnetic resonance imaging (MRI) scan. If you could not pass the pre-experimental screening

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric Patients and Healthy Children<br>Healthy children without dental works. Pediatric patients with epilepsy and migraine (headache). | |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetoencephalography(MEG), Electroencephalography (EEG), Intracranial recordings (iEEG/ECoG/SEEG), Functional Mapping, Epilepsy, Migraine, High frequency oscillations (HFOs), ripples, fast ripples, high-gamma, very high frequency oscillations (VHFOs), ultra fast oscillations, spikelet, fast spikelet