UC Irvine

Epilepsy is one of the most common neurological disorders, with over five million people being diagnosed every year. Roughly one third of patients with epilepsy have poorly controlled seizures, despite treatment with one or more medications. In such cases, surgical resection of the seizure-generating tissue is an alternative and effective treatment. Post-surgical seizure freedom depends on the accurate localization of the epileptogenic zone (EZ), but there are currently no clinically validated biomarkers of this region. High frequency oscillations (HFOs), which are oscillatory events in the EEG, have been shown to have potential as a prognostic biomarker of surgical outcome in patients with epilepsy. However, some confounding factors limit their efficacy at the individual patient level. For example, within a single subject, electrodes of different sizes are often used, but there is currently no way to account for this difference when measuring HFO properties. Another barrier is the presence of physiological HFOs (events generated as a part of healthy brain function) which confound estimates of rate of occurrence of pathological HFOs. Therefore, we aimed to address these limitations.

First, we developed and validated a novel method to dynamically change the size of an electrode after implantation in the human brain and determined the impact of electrode size on intracranial EEG (iEEG) characteristics. We then used this method to compare morphological features of HFOs across three electrode sizes. We found that the rate and amplitude of HFOs decreased significantly as electrode size increased. These results suggest that HFO rates from electrodes of different surface areas cannot be compared directly when used as a tool for surgical planning. Second, we detected physiological HFOs in the scalp EEG of 15 healthy infants using a combination of automated and visual methods and characterized their features across different sleep stages and anatomical regions. We found that rapid eye movement (REM) stage of sleep exhibited the highest density of HFOs compared to other stages. The results of this study will serve as baseline values of physiological HFOs to improve the identification of pathological HFOs associated with epilepsy. Together, these methods contribute to the use of HFOs as an efficient clinical biomarker for achieving improved post-surgery freedom in patients with epilepsy.