Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Martinez-Trujillo, Julio

2nd Supervisor

Suller Marti, Ana

Co-Supervisor

Abstract

More than 15 million patients with epilepsy suffer from drug-resistant epilepsy (DRE). In these cases, a successful surgical outcome entails the removal of the seizure onset zone (SOZ), the brain region(s) responsible for seizure initiation. In this regard, finding robust biomarkers of epileptogenicity will help clinicians to accurately localize the SOZ. In focal epilepsies, interictal epileptiform discharges (IEDs) are paroxysmal events observed in both epileptogenic and non-epileptogenic zones.

To identify the SOZ, extraoperative cortical stimulation (CS) is used during phase II of the presurgical investigation. We evaluated the impact of CS on IEDs to find biomarkers of epileptogenicity to accurately find SOZ.

In this study, intracranial signals were recorded from thirty DRE patients (seizure-free post-surgery) implanted with depth electrodes (stereo-electroencephalography) for presurgical evaluation. Bipolar and high frequency (50 Hz) CS was performed with a pulse width of 300 µs and current spanning 1–6 mA. Following preprocessing, IEDs were automatically detected pre- and post-stimulation, and their normalized absolute changes were compared between SOZ and non-SOZ.

Our findings reveal a significant increase in IED numbers following CS over SOZ compared to non-SOZ stimulation (Mann-Whitney U test, p< 0.001). Furthermore, this increase extended beyond the stimulated site, indicating a broader effect of stimulation on the SOZ. These results feature the potential of tracking post-stimulation changes in IEDs’ characteristics as a quantitative method for SOZ identification, enhancing localizing the SOZ with greater precision.

Summary for Lay Audience

Millions of people worldwide suffer from epilepsy, and some have a severe form that does not respond well to medication. When surgery becomes an option, clinicians need to find the exact spot in the brain where seizures start to remove them.

In our study, we looked at how stimulating certain parts of the brain helps clinicians find this spot. We studied thirty patients who did not become seizure-free with medication. We used a special type of brain stimulation and applied mild electric pulses to specific brain regions. Then, we looked at the electrical activity in different areas before and after the pulses.

We found that after stimulating the spot where seizures start, there was a clear increase in abnormal brain activity. This increase was not just in the stimulated area but spread out, showing that stimulation could help clinicians find the right spot to be resected more accurately.

By understanding these changes, clinicians can improve their ability to treat epilepsy with surgery, giving patients better chances for a seizure-free life.

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