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NIH/National Institute of Neurological Disorders and Stroke| March 7, 2022

Researchers have identified two types of cells in our brains that are involved in organizing discrete memories based on when they occurred. This finding improves our understanding of how the human brain forms memories and could have implications in memory disorders such as Alzheimer’s disease. The study was supported by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and published in Nature Neuroscience.

“This work is transformative in how the researchers studied the way the human brain thinks,” said Jim Gnadt, Ph.D., program director at the National Institute of Neurological Disorders and Stroke and the NIH BRAIN Initiative. “It brings to human neuroscience an approach used previously in non-human primates and rodents by recording directly from neurons that are generating thoughts.”

This study, led by Ueli Rutishauser, Ph.D., professor of neurosurgery, neurology and biomedical sciences at Cedars-Sinai Medical Center in Los Angeles, started with a deceptively simple question: how does our brain form and organize memories? We live our awake lives as one continuous experience, but it is believed based on human behavior studies, that we store these life events as individual, distinct moments. What marks the beginning and end of a memory? This theory is referred to as “event segmentation,” and we know relatively little about how the process works in the human brain.

To study this, Rutishauser and his colleagues worked with 20 patients who were undergoing intracranial recording of brain activity to guide surgery for treatment of their drug-resistant epilepsy. They looked at how the patients’ brain activity was affected when shown film clips containing different types of “cognitive boundaries” — transitions thought to trigger changes in how a memory is stored and that mark the beginning and end of memory “files” in the brain.

The first type, referred to as a “soft boundary,” is a video containing a scene that then cuts to another scene that continues the same story. For example, a baseball game showing a pitch is thrown and, when the batter hits the ball, the camera cuts to a shot of the fielder making a play. In contrast, a “hard boundary” is a cut to a completely different story — imagine if the batted ball were immediately followed by a cut to a commercial.

Jie Zheng, Ph.D., postdoctoral fellow at Children’s Hospital Boston and first author of the study, explained the key difference between the two boundaries.

“Is this a new scene within the same story, or are we watching a completely different story? How much the narrative changes from one clip to the next determines the type of cognitive boundary,” said Zheng.

The researchers recorded the brain activity of participants as they watched the videos, and they noticed two distinct groups of cells that responded to different types of boundaries by increasing their activity. One group, called “boundary cells” became more active in response to either a soft or hard boundary. A second group, referred to as “event cells” responded only to hard boundaries. This led to the theory that the creation of a new memory occurs when there is a peak in the activity of both boundary and event cells, which is something that only occurs following a hard boundary.

One analogy to how memories might be stored and accessed in the brain is how photos are stored on your phone or computer. Often, photos are automatically grouped into events based on when and where they were taken and then later displayed to you as a key photo from that event. When you tap or click on that photo, you can drill down into that specific event.

“A boundary response can be thought of like creating a new photo event,” said Dr. Rutishauser. “As you build the memory, it’s like new photos are being added to that event. When a hard boundary occurs, that event is closed and a new one begins. Soft boundaries can be thought of to represent new images created within a single event.”

The researchers next looked at memory retrieval and how this process relates to the firing of boundary and event cells. They theorized that the brain uses boundary peaks as markers for “skimming” over past memories, much in the way the key photos are used to identify events. When the brain finds a firing pattern that looks familiar, it “opens” that event.

Two different memory tests designed to study this theory were used. In the first, the participants were shown a series of still images and were asked whether they were from a scene in the film clips they just watched. Study participants were more likely to remember images that occurred soon after a hard or soft boundary, which is when a new “photo” or “event” would have been created.

The second test involved showing pairs of images taken from film clips that they had just watched. The participants were then asked which of the two images had appeared first. It turned out that they had a much harder time choosing the correct image if the two occurred on different sides of a hard boundary, possibly because they had been placed in different “events.”

These findings provide a look into how the human brain creates, stores, and accesses memories. Because event segmentation is a process that can be affected in people living with memory disorders, these insights could be applied to the development of new therapies.

In the future, Dr. Rutishauser and his team plan to look at two possible avenues to develop therapies related to these findings. First, neurons that use the chemical dopamine, which are most-known for their role in reward mechanisms, may be activated by boundary and event cells, suggesting a possible target to help strengthen the formation of memories.

Second, one of the brain’s normal internal rhythms, known as the theta rhythm, has been connected to learning and memory. If event cells fired in time with that rhythm, the participants had an easier time remembering the order of the images that they were shown. Because deep brain stimulation can affect theta rhythms, this could be another avenue for treating patients with certain memory disorders.

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