Clinical Applications of High-Frequency Oscillations

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).

Inclusion Criteria:

- Healthy and cooperative

- Ages 6-18 (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