An Up-Close View of Seizures

For the first time, scientists have recorded activity from hundreds of single cells in the human brain during a seizure. The research, published this week in Nature Neuroscience, is part of a growing movement to employ new technologies to study brain processes at the single-cell level, which until recently has been impossible to do in living humans.

In an epileptic seizure, the normally orderly activity of neurons goes haywire. The abnormal amounts of electricity that get discharged can be temporarily disabling. Scientists typically monitor human seizures using electroencephalogram (EEG), which measures electrical activity across millions of neurons at a time, an approach that has revealed much about the overall patterns of activity in seizures. But researchers hope that by studying single cells, they’ll learn how seizures spread.

The study, part of a longstanding collaboration between researchers at Brown University and Massachusetts General Hospital, examined four patients who were already undergoing a procedure to study the origins of their seizures. All of them had uncontrolled focal epilepsy, in which the seizures originate in a specific part of the brain.

In addition to fitting the patients with normal EEG electrodes, surgeons implanted a four-millimeter-square microelectrode array at the suspected origin of the seizures. The implant allowed them to record the activity of hundreds of individual neurons over the course of several days, during which patients experienced multiple seizures.

While scientists have previously recorded activity from the brains of epilepsy patients about to have surgery, this is the first study to examine the behavior of many individual cells during a seizure.

The researchers found that neighboring cells behaved very differently leading up to a seizure, some becoming excited, others dampened. “There’s really a complex interplay among different neurons leading up to seizure,” says co-lead author Sydney Cash, a neurologist at Massachusetts General Hospital, and this heterogeneity was surprising. In contrast, cells were more synchronous as they quieted down at the end of the seizures.

Brian Litt, associate professor of neurology and bioengineering at University of Pennsylvania, says that the study adds a critical piece of information as scientists try to understand seizures more completely. But he adds that the ideal approach would be to spread the fine detail of these microarrays over larger regions of the brain. He compares analyzing just a few cells to trying to see a riot by observing only a few people in a location—the heterogeneity of the cells could mean that patterns only come to view at a larger scale. Several groups are currently investigating technologies that could bridge multiple scales.

A similar microarray technique has been used as part of an experimental neural prosthesis called BrainGate to help paralyzed patients control computer systems and robotic limbs. The epilepsy study shows that these recording devices can also prove useful in studying brain disease. Cash hopes that as the team continues to study neurons during seizures, they can use data about cellular activity to actually predict seizures before they occur. While the device is currently used only for research, Cash’s team and others are working to make implants smaller and easier to use, with wireless transmitting of data, which could make them a tool for clinical monitoring as well.