Memory Consolidation in Epilepsy Enhanced During Sleep With Deep Brain Stimulation

This article was originally published by Neurology Live^®. It has been lightly edited.

Itzhak Fried, MD, PhD

In a recent study published in Nature Neuroscience¹, findings revealed that targeted deep-brain stimulation during a critical time in the sleep cycle was associated with improvements in memory consolidation among patients with epilepsy. These findings provide evidence to support how the brain consolidates memory during sleep and offer new clues for how deep-brain stimulation during sleep could help patients with memory disorders like Alzheimer disease.²

Among 18 patients with epilepsy assessed across 2 nights and mornings, each one performed better on the memory tests given following a night of sleep and the use of electrical stimulation in their brain compared with a night of undisturbed sleep. Notably, the key electrophysiological markers displayed the flow of information between the hippocampus and throughout the cortex, which provided evidence to support memory consolidation.

“This provides the first major evidence down to the level of single neurons that there is indeed this mechanism of interaction between the memory hub and the entire cortex,” said coauthor Itzhak Fried, MD, PhD, director of epilepsy surgery at University of California, Los Angeles (UCLA) Health in a statement.¹ “It has both scientific value in terms of understanding how memory works in humans and using that knowledge to really boost memory.”

Led by author Maya Geva-Sagiv, PhD, postdoctoral research fellow, University of California, Davis, and colleagues, memory consolidation during sleep was investigated via electrodes in patients with epilepsy recruited from UCLA Health. Electrodes were implanted in the patients to help with identifying the source of their seizures during their hospital stays, which typically lasted around the span of 10 days. Researchers developed a real-time closed-loop system to deliver electrical stimulation to the participants. As noted in a statement from Fried, the system “listened” to the brain’s electrical signals, and when once patients fell into deep sleep, it gave gentle electrical pulses telling the rapidly firing neurons to “play” in synchronization.¹

Prior to bedtime, participants were shown photo pairings of 25 animals and celebrities. Immediately after, they were tested on their ability to recall which celebrity was paired with which animal, and then asked again in the morning following a night of undisturbed sleep. On the second night, participants were shown 25 new animals and celebrity pairings before bedtime. They were then given targeted electrical stimulation overnight and were once again tested on their ability to recall the pairings in the morning.

“We found we basically enhanced this highway by which information flows to more permanent storage places in the brain,” said Fried in a statement.¹ “In our new study, we showed we can enhance memory in general. Our next challenge is whether we have the ability to modulate specific memories.”

Published in the New England Journal of Medicine in 2012, Fried also coauthored a study that showed that electrical stimulation of the entorhinal region enhanced memory of spatial information when applied during learning.³ In the study, Fried and colleagues implanted intracranial depth electrodes in 7 patients to identify seizure-onset zones for subsequent epilepsy surgery. The patients completed a spatial learning task during where they learned destinations in virtual environments and during half the learning trials, focal electrical stimulation was given.

Fried’s work since the published study has continued to investigate how deep brain stimulation could potentially improve memory into the critical stage of sleep. Recently, he received a $7 million NIH grant to study whether artificial intelligence can help pinpoint and strengthen specific memories in the brain.⁴

References
1. Deep-brain stimulation during sleep strengthens memory. News Release. University of California, Los Angeles (UCLA), Health Sciences. Published June 1, 2023. Accessed September 6, 2023. https://www.uclahealth.org/news/deep-brain-stimulation-during-sleep-strengthens-memory
2. Geva-Sagiv M, Mankin E, Eliashiv D, et al. Deep brain stimulation during sleep enhances human brain synchrony and memory. Nat Neurosci. 2023;26(6):930-931. doi:10.1038/s41593-023-01342-3
3. Suthana N, Haneef Z, Stern J, et al. Memory enhancement and deep-brain stimulation of the entorhinal area. N Engl J Med. 2012;366(6):502-510. doi:10.1056/NEJMoa1107212
4. Finding a way to halt memory loss. News Release. UCLA Health. Published Janauary31, 2023. Accessed September 7, 2023. https://www.uclahealth.org/news/finding-way-halt-memory-loss