For many individuals with epilepsy, anti-seizure medications help control their seizures. However, about one-third of epilepsy patients do not respond to medication, and surgery may be needed to remove or disconnect the brain tissue responsible for generating seizures. Dysfunctional brain tissue causes seizure activity, and the brain typically adapts by shifting normal functions away from the affected area. The challenge for epileptologists is identifying the exact seizure onset zones (SOZ) so that they can safely remove the brain regions causing seizures without affecting vital neurological functions necessary for the patient's daily life. Traditional epilepsy surgery involves implanting electrode arrays directly into the brain using depth electrode probes or placing them on the surface with subdural grids and strips to identify where the seizures begin. However, the quality of the recordings from these electrodes is often limited because the electrodes that sample the brain's activity may be spaced too far apart. Now, researchers in the field of epilepsy have applied a common principle to brain recordings, potentially making epilepsy surgeries more effective for improving patient outcomes.

In an effort to improve the precision of determining which tissue should be removed during epilepsy surgery, researchers at UC San Francisco (San Francisco, CA, USA) utilized intracranial electroencephalogram (EEG) recordings, which measure the brain's electrical activity. They recreated electrode arrays of varying densities to identify the SOZ more effectively. The researchers then created seizure activity heatmap videos based on the EEG recordings and projected these heatmaps onto reconstructed brain images. By studying the heatmap videos, they were able to explore how different electrode densities influenced epileptologists’ ability to identify SOZs. The findings, published in the open-access journal eBioMedicine, revealed that higher-density intracranial EEG recordings improved the accuracy and agreement among epileptologists regarding the location of SOZs, compared to lower-density recordings.

The study involved placing high-density electrode grids onto the brains of patients with drug-resistant epilepsy. After implantation, the patients were observed in the hospital for several days to allow seizures to occur, enabling researchers to pinpoint the locations where they originated. The team asked trained epileptologists to locate the SOZ for these patients using both high-density array recordings (with 4 to 5 mm inter-electrode spacing) and lower-density recordings (with 8 to 10 mm spacing), both derived from the same seizure data. Seizure activity data was visualized as heatmap videos overlaid on reconstructed brain scans, with electrode locations hidden. Using a randomized crossover design, six epileptologists viewed the video visualizations under both higher and lower-density conditions, utilizing a custom computer program to outline the SOZ on the brain.

The results showed that higher-density depth and subdural intracranial EEG recordings led to greater agreement among the epileptologists and helped them identify a larger extent of the SOZ compared to lower-density recordings. The researchers noted that high-density electrode arrays could also allow for more precise mapping of brain function regions, which is typically done by physicians using electrical stimulation. While not assessed in this study, the researchers suggested that additional electrode details might help surgeons more accurately define surgical margins, ensuring the removal of abnormal tissue while preserving healthy tissue. The team emphasized that further studies with more patients are necessary to determine if higher electrode densities lead to better surgical outcomes. Nevertheless, the findings clearly suggest that increasing electrode density on implanted hardware provides clearer insights into the location and full extent of SOZs.

“One of the worst feelings we get is when a patient who underwent surgery begins having seizures again. It suggests some of the bad, seizure-generating tissue is still present,” said senior study author Jon Kleen, MD, PhD, an epilepsy specialist and UCSF assistant professor of neurology in the Weill Institute for Neurosciences. “We’re hopeful this may enable better appraisals of pathophysiological tissue margins and move the needle in the effectiveness epilepsy surgery.”

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