Scientists monitor brains replaying memories in real time

Brain abstract illustration (stock image).

In a study of epilepsy patients, researchers at the National Institutes of Health monitored the electrical activity of thousands of individual brain cells, called neurons, as patients took memory tests. They found that the firing patterns of the cells that occurred when patients learned a word pair were replayed fractions of a second before they successfully remembered the pair. The study was part of an NIH Clinical Center trial for patients with drug-resistant epilepsy whose seizures cannot be controlled with drugs.

"Memory plays a crucial role in our lives. Just as musical notes are recorded as grooves on a record, it appears that our brains store memories in neural firing patterns that can be replayed over and over again," said Kareem Zaghloul, M.D., Ph.D., a neurosurgeon-researcher at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and senior author of the study published in Science.

Dr. Zaghloul's team has been recording electrical currents of drug-resistant epilepsy patients temporarily living with surgically implanted electrodes designed to monitor brain activity in the hopes of identifying the source of a patient's seizures. This period also provides an opportunity to study neural activity during memory. In this study, his team examined the activity used to store memories of our past experiences, which scientists call episodic memories.

In 1957, the case of an epilepsy patient H.M. provided a breakthrough in memory research. H.M could not remember new experiences after part of his brain was surgically removed to stop his seizures. Since then, research has pointed to the idea that episodic memories are stored, or encoded, as neural activity patterns that our brains replay when triggered by such things as the whiff of a familiar scent or the riff of a catchy tune. But exactly how this happens was unknown.

Over the past two decades, rodent studies have suggested that the brain may store memories in unique neuronal firing sequences. After joining Dr. Zaghloul's lab, Alex P. Vaz, B.S., an M.D., Ph.D. student at Duke University, Durham, North Carolina, and the leader of this study decided to test this idea in humans.

"We thought that if we looked carefully at the data we had been collecting from patients we might be able to find a link between memory and neuronal firing patterns in humans that is similar to that seen in rodents," said Vaz, a bioengineer who specializes in deciphering the meaning of electrical signals generated by the body.

To do this they analyzed the firing patterns of individual neurons located in the anterior temporal lobe, a brain language center. Currents were recorded as patients sat in front of a screen and were asked to learn word pairs such as "cake" and "fox." The researchers discovered that unique firing patterns of individual neurons were associated with learning each new word pattern. Later, when a patient was shown one of the words, such as "cake," a very similar firing pattern was replayed just milliseconds before the patient correctly recalled the paired word "fox."

"These results suggest that our brains may use distinct sequences of neural spiking activity to store memories and then replay them when we remember a past experience," said Dr. Zaghloul.

Last year, his team showed that electrical waves, called ripples, may emerge in the brain just split seconds before we remember something correctly. In this study, the team discovered a link between the ripples recorded in the anterior temporal lobe and the spiking patterns seen during learning and memory. They also showed that ripples recorded in another area called the medial temporal lobe slightly preceded the replay of firing patterns seen in the anterior temporal lobe during learning.

"Our results support the idea that memories involve coordinated replay of neuronal firing patterns throughout the brain," said Dr. Zaghloul. "Studying how we form and retrieve memories may not only help us understand ourselves but also how neuronal circuits break down in memory disorders."

This study was supported by the NINDS Intramural Research Program and NIH training grants (NS113400, GM007171).

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Materials provided by NIH/National Institute of Neurological Disorders and Stroke. Note: Content may be edited for style and length.

Specific neurons that map memories now identified in the human brain

An important aspect of human memory is our ability to conjure specific moments from the vast array of experiences that have occurred in any given setting. For example, if asked to recommend a tourist itinerary for a city you have visited many times, your brain somehow enables you to selectively recall and distinguish specific memories from your different trips to provide an answer.

Studies have shown that declarative memory -- the kind of memory you can consciously recall like your home address or your mother's name -- relies on healthy medial temporal lobe structures in the brain, including the hippocampus and entorhinal cortex (EC). These regions are also important for spatial cognition, demonstrated? by the Nobel-Prize-winning discovery of "place cells" and "grid cells" in these regions -- neurons that activate to represent specific locations in the environment during navigation (akin to a GPS). However, it has not been clear if or how this "spatial map" in the brain relates to a person's memory of events at those locations, and how neuronal activity in these regions enables us to target a particular memory for retrieval among related experiences.

A team led by neuroengineers at Columbia Engineering has found the first evidence that individual neurons in the human brain target specific memories during recall. They studied recordings in neurosurgical patients who had electrodes implanted in their brains and examined how the patients' brain signals corresponded to their behavior while performing a virtual-reality (VR) object-location memory task. The researchers identified "memory-trace cells" whose activity was spatially tuned to the location where subjects remembered encountering specific objects. The study is published today in Nature Neuroscience.

"We found these memory-trace neurons primarily in the entorhinal cortex (EC), which is one of the first regions of the brain affected by the onset of Alzheimer 's disease," says Joshua Jacobs, associate professor of biomedical engineering, who directed the study. "Because the activity of these neurons is closely related to what a person is trying to remember, it is possible that their activity is disrupted by diseases like Alzheimer's, leading to memory deficits. Our findings should open up new lines of investigation into how neural activity in the entorhinal cortex and medial temporal lobe helps us target past events for recall, and more generally how space and memory overlap in the brain."

The team was able to measure the activity of single neurons by taking advantage of a rare opportunity: invasively recording from the brains of 19 neurosurgical patients at several hospitals, including the Columbia University Irving Medical Center. The patients had drug-resistant epilepsy and so had already had recording electrodes implanted in their brains for their clinical treatment. The researchers designed experiments as engaging and immersive VR computer games and the bedridden patients used laptops and handheld controllers to move through virtual environments. In performing the task, subjects first navigated through the environment to learn the locations of four unique objects. Then the researchers removed the objects and asked patients to move through the environment and mark the location of one specific object on each trial.

The team measured the activity of neurons as the patients moved through the environment and marked their memory targets. Initially, they identified purely spatially tuned neurons similar to "place cells" that always activated when patients moved through specific locations, regardless of the subjects' memory target. "These neurons seemed only to care about the person's spatial location, like a pure GPS," says Salman E. Qasim, Jacobs' PhD student and lead author of the study.

But the researchers also noticed that other neurons only activated in locations relevant to the memory the patient was recalling on that trial -- whenever patients were instructed to target a different memory for recall, these neurons changed their activity to match the new target's remembered location. What especially excited Jacobs and Qasim is that they could actually decode the specific memory a patient was targeting based on the activity of these neurons.

"Our study demonstrates that neurons in the human brain track the experiences we are willfully recalling, and can change their activity patterns to differentiate between memories. They're just like the pins on your Google map that mark the locations you remember for important events," Qasim says. "This discovery might provide a potential mechanism for our ability to selectively call upon different experiences from the past and highlights how these memories may influence our brain's spatial map."

Jacobs and Qasim plan next to look for evidence that these neurons represent memories in non-spatial contexts to better characterize their role in memory function. "We know now that neurons care about where our memories occur and now we want to see if these neurons care about other features of those memories, like when they occurred, what occurred, and so on," Qasim notes.

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Materials provided by Columbia University School of Engineering and Applied Science. Original written by Holly Evarts.