Seizure localization for epilepsy surgery using high frequency electrophysiological markers

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PROJECT SUMMARY/ABSTRACT In the most severe cases of epilepsy, where seizures persist despite multiple trials of anti-seizure medications, patients may benefit from surgical removal of seizure-generating brain tissue. Prior to surgery, electrodes are often implanted directly into or onto the patient’s brain and are used to continuously record electrical brain activity over days. This is done to capture seizure activity and determine its point of origin, i.e. the seizure onset zone. If the seizure onset zone is identified, clinicians then use this information, in combination with the results of brain imaging and other testing, to guide removal of the corresponding brain tissue. While epilepsy surgery may lead to seizure freedom, 70-90% of surgery patients remain on anti-seizure medications and roughly 50% of patients continue to have seizures. The long-term goal of this work is to improve the outcomes of patients undergoing epilepsy surgery by developing more accurate methods to localize seizure-generating tissue. High frequency oscillations (HFOs) have garnered considerable excitement for their potential to identify and localize epileptogenic brain tissue. HFOs are short bursts of high-frequency electrical activity that occur in the brains of patients with epilepsy. They occur more frequently in the epileptogenic zone (EZ, the hypothetical area that must be excised to attain post-operative seizure freedom), and surgically removing HFO-generating brain tissue increases the likelihood of seizure freedom. While ongoing clinical trials are attempting to assess their prospective value for epilepsy surgery planning, there are multiple barriers to their widespread use. While group-level results are robust, HFO analysis is not yet predictive for single subjects. Recordings lack the sensitivity to reliably measure HFOs in every patient, and the occurrence of non-epileptic HFOs confounds the results. Therefore, HFOs are poised to revolutionize epilepsy surgery, but there is a critical need to optimize their measurement and maximize single-subject accuracy. The overall objective of this proposal is to improve EZ localization accuracy through systematic determination of the optimal HFO measurement methodology, coupled with novel, robust methods for HFO analysis. The rationale is that developing these novel methods with improved measurement techniques will increase the accuracy and robustness of HFOs as a biomarker of the seizure onset zone, thus improving the surgical management of epilepsy. To attain our objective, we will pursue three specific aims: (1) Demonstrate that electrode size is a crucial factor in HFO measurement. (2) Develop an automated method for patient-specific localization of the EZ based on HFOs. (3) Evaluate the effects of electrode size and HFO analysis method on EZ localization. The proposed research is significant because it will provide specific recommendations for the measurement and analysis of HFOs, enabling accurate, detailed localization of epileptogenic brain tissue. The expected outcome of this work is that it will guide surgeons in choosing which brain regions to remove and will increase the pool of potential surgical candidates. Overall, this will have a positive impact by leading to a greater chance of seizure freedom and improved quality of life for patients with the most severe cases of epilepsy.