New research provides detailed look at how epileptic seizures are sustained

Credit: CC by A DigitalRalph

New research from the University of Chicago Medicine provides a more detailed look at how epileptic seizures are sustained and how, in turn, physicians might learn to stop them.

Published Monday in the Proceedings of the National Academy of Sciences (PNAS), the paper examines brain activity during seizures and reveals how a small network of several neurons can impose widespread effects on the large network dynamics of millions of neurons. The researchers obtained the data by analyzing eight multiscale recordings of spontaneous seizures from four epilepsy patients. They monitored the patients while the seizures took place.

Wim van Drongelen, a pediatrics professor who was one of the study's authors, said the team measured seizure activity in greater detail by going beyond the common method known as electroencephalography (EEG).

This primary method of analyzing brain activity is like "listening to a church choir via a stethoscope on the church wall," van Drongelen said, explaining scientists record the electrical potentials generated during neuronal activity in the cerebral cortex by using devices attached to the scalp.

"That's been the common approach of how seizures in patients with epilepsy are evaluated," he said.

But to examine seizure activity at a more detailed level, van Drongelen and his coauthors used electrocorticography, or ECoG, which collects data directly from the brain's cortical surface. Using the church choir analogy, van Drongelen said the ECoG is like listening to the choir from inside the church.

Then the team dove deeper still. Using a more detailed method to study the seizures, they placed arrays of microelectrodes inside the brain's cortex. If aimed correctly, these microelectrode arrays called MEAS can pick up activity inside the core of the seizure. Subsequently, that shows how the activity of relatively few neurons relate to the ECoG signals across a much larger surrounding cortical area.

"Our result was a big surprise to us," said van Drongelen. "The seizure core is a tiny area with huge effects across larger cortical areas. And this finding may have important consequences for evaluation prior to surgery and treatment of patients with epilepsy."

In addition, the combined analysis and modeling of the clinical data set revealed a dual role for the neural inhibition function that normally constrains cortical activation. During the seizure this constraint fails inside its small core, but the same inhibitory function plays an important role in the larger area of the cortex that is affected by the seizure core. In other words, the function that inhibits seizures fails in a small area of the activity but is important in the larger area. It contributes to the typical seizure oscillations seen in the ECoG as well as the EEG and, more importantly, it creates a distinct path for the seizure to stop.

Van Drongelen, who is also technical director and research director of UChicago Medicine's Pediatric Epilepsy Center, said a better understanding of how seizures are sustained may lead to a more rational approach to therapy. That could benefit a large group of patients who cannot be treated with current medication.

The paper is titled "Cross-scale effects of neural interactions during human neocortical seizure activity" and is available for viewing on the PNAS website.