Study Identifies Individual Human Brain Memory Trace Cells that Recall Spatial Position of Objects


Screenshot of spatial memory task.
Left: Screenshot of spatial memory task. Middle: MRI scan showing the placement of recording electrodes (black circles) in a patient’s brain. [Salman Qasim/Columbia Engineering]

An important part of human memory is the ability to recall specific moments and events out of a vast array of experiences that may occur in any given setting. Studies headed by neuroengineers at Columbia University’s department of biomedical engineering have now found the first evidence that individual neurons in the human brain, known as “memory-trace cells,” target specific memories when we are tasked with recalling them. For example, the team noted, if you are asked to recommend a tourist itinerary for a city that you have visited many times, your brain can selectively recall and distinguish specific memories from different trips, so that you can provide an answer.

“Our study demonstrates that neurons in the human brain track the experiences we are wilfully recalling, and can change their activity patterns to differentiate between memories,” commented Salman E. Qasim, a PhD student in the lab of biomedical engineering professor Joshua Jacobs, PhD, and lead author of the study, which is published in Nature Neuroscience. “They’re just like the pins on your Google map that mark the locations you remember for important events. 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.” Research lead Jacobs, Qasim, and colleagues described their studies and results in a report titled, “Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex.”

Studies have shown that declarative memory—the kind of memory that allows you to consciously recall, say, your home address or your mother’s name—depends on healthy medial temporal lobe (MTL) structures in the brain, including the hippocampus and entorhinal cortex (EC). These regions are also important for spatial cognition, something that was demonstrated by the Nobel-Prize-winning discovery of “place cells” and “grid cells” in these regions of the brain. These neurons are activated to represent specific locations in the environment during navigation (akin to a GPS).

However, to date, 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. “Although lesion studies have demonstrated that many declarative memory processes depend on intact MTL structures, such as the hippocampus and entorhinal cortex, how neuronal activity in these regions enables the targeting of a particular memory for retrieval among related experiences is not clear,” the authors wrote.

To investigate this in more detail, the Columbia University-led team took advantage of a rare opportunity to measure the activity of individual neurons in the human brain. They were able to invasively record the activity of 299 neurons in the brains of 19 neurosurgical patients at hospitals including the Columbia University Irving Medical Center. The patients demonstrated drug-resistant epilepsy, and already had recording electrodes implanted in their brains for their clinical treatment.

The researchers designed experiments as virtual reality computer tasks, which the bedridden patients carried out using laptops and handheld controllers to move through a virtual environment. The 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 again, and mark the location of one specific object on each trial.

Video of example trials of spatial memory task showing memory encoding and retrieval.

The team measured the activity of the individual neurons as the patients moved through the environment and marked their memory targets first, when the objects were present, and again when the objects had been removed and the participants had to recall where each object had originally be placed. “The task consisted of separate encoding and retrieval trials, which followed the same general structure except that objects were visible on the track during encoding trials, and absent during retrieval trials,” the authors wrote. “We examined how the activity of individual neurons represented the spatial location of participants in the task by computing the firing rate of each neuron as a function of the position of the participant along the track during retrieval trials.”

Initially, the researchers identified purely spatially tuned neurons, similar to place cells, which 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,” said Qasim. But the researchers also noticed that other neurons were activated only in locations relevant to the memory the patient was recalling on that trial. These individual neurons, or “memory-trace cells,” were active only when patients were instructed to target a different, specific memory for recall, and matched the new target’s remembered location. Individual memory-trace cells in effect appeared spatially tuned to the location where subjects remembered encountering specific objects. Significantly, the team could actually decode the specific memory a patient was targeting, based on the activity of these neurons.

“… this analysis revealed two groups of neurons with distinct firing patterns. We found neurons with firing rates that varied as a function of only participant location, similar to conventional place cells,” the scientists commented. “The key distinction between memory-trace cells and these other cell types is that memory-trace cells do not significantly activate when objects, the putative goal, are visible in the environment. As such, memory-trace cell activity is probably more specifically related to memory retrieval processes, rather than goal coding in general.… Our observations suggest that memory-trace cell activity represents object locations that a person is trying to remember.”

Conceptual illustration of neurons that “map” memories in the human brain. [Salman Qasim/Columbia Engineering]

Jacobs suggested the findings could help scientists better understand some neurodegenerative disorders. “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. 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.”

Jacobs and Qasim plan next to look for evidence that these neurons represent memories in nonspatial 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 stated.