Epilepsy is best known for seizures, but many people with the condition also experience much more frequent and subtler disruptions. These brief bursts of abnormal brain activity, called interictal epileptiform discharges (IEDs), can happen thousands of times a day, interfering with attention, memory, language, and sleep.
Scientists at UC San Francisco have discovered that these "brain blips" are not random events, as had been believed. Rather, they unfold in a predictable pattern that can be detected a full second before they occur — raising new possibilities to ward them off altogether.
The researchers used a high-resolution technology recently adapted for humans that can record the activity of individual neurons. They tracked more than 1,000 neurons in four patients undergoing surgery for epilepsy.
"We've gotten 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, Lip-Bu Tan Endowed associate professor of Neurology. He is co-senior author of the study , which published April 30 in Nature Neuroscience.
Over time, the cumulative effect of these mental disruptions can be significant, and they may account for some of the cognitive impairment experienced by about half of people with epilepsy.
"Being able to prevent these brain blips would be revolutionary for patients' quality of life," he said.
Neuropixels see brain activity in 3D
To understand how IEDs form, the researchers used Neuropixels probes — hair-thin devices lined with hundreds of sensors that can record activity from individual neurons. While current sensors pick up brain signals only on the surface of the brain, Neuropixels can record throughout the human cortex, offering a three-dimensional view of brain activity.
The study's other co-senior author, Edward Chang , MD, chair of Neurological Surgery and the Margaret Liu Collins and Edward B. Collins Distinguished Professor, has been a pioneer in the use of these probes in humans.
For the study, Chang placed the Neuropixels seven millimeters deep into the part of the brain where the patient's seizures originated. This is the tissue that surgeons would remove to stem the person's epilepsy.
The technology gave the researchers a neuron-by-neuron view of what was happening before, during, and after each IED. Whereas seizures appear as a burst of neurons firing in synchrony, IEDs unfolded sequentially. One set of neurons was active for about a second before the IED started; then another set of neurons generated the sharp electrical spike at its peak; and finally, 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 medical student Alex Silva, the study's first author and a PhD candidate in the UCSF-UC Berkeley Joint PhD Program in Bioengineering. "It was really striking."
How brain blips derail cognition
Most of the neurons involved in IEDs are used in normal cognitive processing. Earlier, the team showed that patients can momentarily lose their train of thought during these events — struggling to recall a word or respond correctly.
This time, they found that nearly 80% of the neurons involved in IEDs were also involved in language and perception.
Toward earlier intervention
Today's implantable devices for epilepsy include "closed loop" neurostimulators, which detect abnormal brain activity and deliver electrical pulses to interrupt it.
The study suggests a path to stop the IED before it starts: The activity of the first set of neurons heralds the arrival of an IED, so a device that monitored single neurons could use that "warning signal" to prevent it.
"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.
Authors: Other authors include: Siddharth Marathe, Quinn R. Greicius, Duo Xu, Shailee Jain, Jason E. Chung, Xiaofang Yang, Ankit N. Khambhati, Matthew K. Leonard, Jonathan K. Kleen, all from UCSF.
Funding: This work was supported by the National Institutes of Health (grants R01-DC012379, K23NS110920, F30DC021872) and the Howard Hughes Medical Institute.
Disclosures: E.F.C. is cofounder of Echo Neurotechnologies, LLC. All other authors declare no competing interests.
About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health , which serves as UCSF's primary academic medical center, includes among the nation's top specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu or see our Fact Sheet .
