May 3rd 2021

Mapping Memory-Making Neural Substrates in the Human Brain


The human brain is a marvel of evolutionary engineering. Beyond the basic functions needed for survival, our brains have incredible capacity for creativity, compassion and connection. But how do we keep track of it all?

The recent discovery of so-called “time cells” may help to explain the human ability to recognize short-term intervals, reliably assess longer time frames and remember specific events. Here, we’ll dive into the basics of biological bookkeeping, map the memory-making process and explore the impact of new neural substrates on the subjective experience of time.

Tackling Temporal Mechanics

How do we tell time? It seems like an easy question. Take a quick look outside to see if it’s night or day, listen to your body for cues around time-sensitive biological needs such as sleeping and eating, or glance at your watch for some second-by-second specifics. The problem? While we’ve developed an agreed-upon definition around seconds, minutes, hours, months and years based on natural processes, we’ve refined them using artificial constructs in an effort to mimic the fundamental framework of time. However, as research from NTNU notes, our internal neural networks use their own temporal techniques to help track everyday processes and provide experience-based signals for time-sensitive events using a combination of sequence and suggestion.

Small-scale sequential timekeeping stems mostly from the hippocampus. Cells in this brain structure can precisely track time spans of up to 10 seconds. According to Scientific American, damage to the hippocampus impairs this function. Rats with damaged hippocampi performed no better than chance when detecting small time differences, though they were still able to discern the difference between longer time periods.

Memory and experience, meanwhile, aren’t so easily explained. Consider the familiar act of driving to work. Take the same route enough and you don’t need to consciously think about it. Instead, you’ve created a mental memory map of where you’re headed, where to turn and approximately how long it should take to arrive. But what happens if you’re not paying attention because your morning started badly? Perhaps a fight with your spouse or looming work deadlines has you thinking about other things and you miss the turnoff for your best route, then the second, then the third. Even without conscious recognition that you’re on the wrong road, your brain will eventually notice the drive is taking too long — and you’ll take notice.

When the NTNU researchers tried to map this suggestive temporal pattern, they ran into problems. Using the work of May-Britt and Edvard Moser on “grid cells” — specialized spatial mapping cells that live in the medial entorhinal cortex (MEC) — PhD candidate Albert Tsao went looking for similar structures in the nearby lateral entorhinal cortext (LEC). The problem? No pattern was apparent. Instead, the data collected seemed random and disjointed.

That was until Tsao realized that, unlike grid cells, these temporal counterparts were changing with time. Rather than a single cell offering insight into what happens — and when — the human brain uses a distributed neural network to create timescales for memories and experiences.

Thanks for the Memories

Arrow or circle? Unending river or tangled web? Is the human perception of time fixed or flexible? The answer is simple: yes.

The explanation of this apparent paradox is, unsurprisingly, not so simple.

Let’s start with Time’s Arrow: the straight and steady march of time from event to event at a fixed pace. Humans have a broad sense of this implacable motion as we watch the sun rise and set, the seasons turn and world around us change. The bulk of our memories exist as points on this line — not always accurate but generally sequential and typically remembered in bits and pieces. A particular song or smell may trigger a specific recollection of time and place, while memories surrounding it are fuzzy and indistinct.

But some of our memories are more serpentine. These shot-for-shot remakes provide an episodic experience we can revisit again and again, seemingly circumventing temporal common sense. According to recent research from the University of Texas Southwestern Medical Center in Dallas, these episodes are governed by “time cells” that provide more movie-like memories tied to specific moments or events. Unlike more hardwired biological clocks, these cells aren’t timekeepers — instead, they’re affected by factors such as mood and stress to create memories that are full of vivid detail and powerful feeling but largely disconnected from ticking clocks and passing seconds.

It makes sense — commonplace, repetitive actions such as driving to work or getting a coffee aren’t usually fraught with stress or full of joy. As a result, they become the memory markers on your timeline; close enough to the initial event, you can probably recall how full the coffee shop was or approximately how long you waited. Try again in a few weeks and these similar, low-stress memories begin to blend together.

Meanwhile, meaningful events — whether joyful, sad or terrifying — create a different kind of memory. Consider a childhood spent sledding down slick, snow-covered hills on favorite toboggans. Altogether, these memories are one of fuzzy and familiar comfort — except for the time you lost control and hit a tree. This memory is specific and sequential: You remember the chill of the air on your face, the sled accelerating out of your control and sudden fear as the massive trunk loomed. You can play it over and over in your mind at will and recall a level of detail that far outpaces other typical trips down the hill. This is one function of time cells: providing detailed recollections of significant events in chronological order. But accuracy isn’t guaranteed. Go back in person, and you’ll probably discover that tree isn’t quite so big as your memory makes it out to be — but these emotional episodes help to anchor our brains in place and time.

Let’s Do the Time Warp Again

These time cells also help to explain our perception of time — why it appears to speed up in some cases and slow down in others. As neuroscientist Gyorgy Buzsaki makes clear in an article in The New York Times, “Strictly speaking, there is no such thing as ‘time cells’ in the brain. There is no neural clock. What happens in the brain is neurons change in response to other neurons.” Instead, what Buzsaki calls a “neural substrate” is effectively a framework that helps to assess the perceptual passage of time.

To assess the impact of this substrate at scale, the team from Southwest Medical had 27 patients being monitored prior to epilepsy surgery play memory games that involved remembering words after being asked to memorize a set list. Collected data found that during the first two to five seconds of the recall period, specific neuron cells activated to track the progression of the allotted 30-second recall time. According to study lead Dr. Bradley Lega, these cells only fired in response to time-related demands. “There’s no internal metronome, or clock,” he says. Instead, the cells are “firing to support what you’re doing.” They’re assisted by another nearby group of cells — known as ramping neurons — that help human brains adjust to the temporal demands in the moment, then wind down when they’re not needed. In other words, our brains effectively create time based on perceptual demand.

As the Times piece points out, this human ability to warp time as required helps to explain some strange phenomena surrounding the 2020 pandemic. Under pressure to process massive amounts of new information in early crisis stages, time was steadily tracked and days seemed to fly. However, as context and clarity improve, the drive for precise timekeeping gave way to perceptive pallor, in turn creating a subjective reality that feels like the same day delivered ad nauseam.

Future Imperfect

The human brain is a remarkably resilient timekeeper. While accuracy isn’t our strong suit — memories may be jumbled and time stretched or compressed — newly discovered neural substrates help to explain our ability to detect temporal disconnects, create episodic memories and activate chronological cell clusters on-demand.