In addition to suffering seizures, many people with epilepsy also experience bursts of abnormal brain activity called interictal epileptiform discharges (IEDs). These can happen thousands of times a day and interfere with attention, memory, language, and sleep. New data from a study led by scientists at University of California, San Francisco (UCSF) shows that these brain blips are not random events as once thought. The data shows that they unfold in a predictable pattern that can be detected before they occur, suggesting it may be possible to prevent them. 

Details of their work are published in Nature Neuroscience in a paper titled “Laminar organization of cellular microcircuits modulating human interictal epileptiform discharges.” In it, the scientists explain that they used a high-resolution technology recently adapted for humans that records individual neuron activity to track more than 1000 neurons in four patients undergoing surgery for epilepsy. The so-called Neuropixel probes provide “a view into new ways we might address a debilitating aspect of epilepsy that we haven’t been able to tackle,” said Jon Kleen, MD, PhD, an associate professor of neurology at UCSF and co-senior author of the study. 

Preventing brain blips would be a boon for patients’ quality of life because over time, the effects of these mental disruptions can be significant and may account for some of the cognitive impairment experienced by about half of people with epilepsy. 

Neuropixels probes, which are thin devices lined with hundreds of sensors, are designed to record activity throughout the human cortex. This means that unlike current sensors which are limited to brain signals on the surface of the brain, Neuropixels can provide a three-dimensional view of brain activity. For the study, the scientists implanted the probes seven millimeters deep into the part of the brain where patients’ seizures originate—this is the tissue that surgeons typically remove to reduce epilepsy symptoms. 

Inserting the probes here made it possible to observe what happened in the neurons before, during, and after each IED. While seizures appear as a burst of neurons firing in synchrony, when IEDs occur, they unfold sequentially. Specifically, one set of neurons was active about a second before the IED started followed by another set that generated the sharp electrical spike at its peak, and then a third set became active as the IED faded. “We could see individual neurons that were just microns apart from each other playing different roles in the process,” said Alex Silva, the study’s first author and a medical student and doctoral candidate in the UCSF-UC Berkeley Joint PhD program in bioengineering. “It was really striking.”

Previous studies have demonstrated that most neurons involved in IEDs are used in normal cognitive processing. According to this study, nearly 80% of the neurons involved in IEDs were also involved in language and perception. Current implantable devices for epilepsy may be able to help. They include closed loop neurostimulators that can detect abnormal brain activity and deliver electrical pulses that interrupt it. So in the case of IEDs, devices that monitor single neurons could use the activity of the first set of neurons announcing the arrival of the abnormal pattern as a warning signal. “That would be a major step forward, changing treatment from reactively responding to abnormal brain bursts to proactively preventing them in the first place,” Kleen said.

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