How does the human brain keep track of the order of events in a sequence?

Research suggests that 'time cells' – neurons in the hippocampus thought to represent temporal information – could be the glue that sticks our memories together in the right sequence so that we can properly recall the correct order in which things happened.

Evidence for these kinds of sequence-tracking time cells has previously been found in rats, where specific neuron assemblies are thought to support the recollection of events and the planning of action sequences.

But for a long time, less was known about how episodic memory is encoded in the human brain.

To investigate, a team of researchers led by neuroscientist Leila Reddy from the Brain and Cognition Research Center (CerCo) in France monitored electrical activity in the brains of 15 epilepsy patients, using microelectrodes implanted in the hippocampus.

"Creating episodic memories requires linking together distinct events of an experience with temporal fidelity," the researchers explained in their study, published in 2021.

"Given the importance of the hippocampus in sequence order learning and temporal order judgments, we tested whether human hippocampal neurons represented temporal information while participants learned the order of a sequence of items."

The experiments were conducted during medical tests that used the electrodes to localize the source of their seizures in the brain.

As a result, the research didn't require any invasive or risky implantations that the patients wouldn't already be undergoing for the purposes of prospective epilepsy treatment.

In the experiments, the participants were presented with a sequence of images in a pre-determined order and were asked to memorize the sequence.

During the sessions, the electrodes recorded specific neurons in the hippocampus firing in response to the experiment, both during specific moments as images were displayed, during gaps when no images were shown, and at pauses where participants were asked to predict what image would be shown next from a sequence already displayed.

According to the researchers, the neurons involved are evidence of time cells: "neurons whose activity is modulated by temporal context within a well-defined time window".

The researchers said some of these neurons were actively engaged in memorizing or recalling the sequence of images in the experiments, but some were also active when no visual stimulus was present, suggesting they were encoding the flow of time even when nothing in particular was happening.

"Time cells were observed to fire at successive moments in these blank periods," the researchers explained in their paper.

"Temporal modulation during these gap periods could not have been driven by external events; rather they appear to represent an evolving temporal signal as a result of changes in the patients' experience during this time of waiting."

According to the researchers, time cells in the human brain are "multi-dimensional", capable of encoding information in relation to time but also responding to different kinds of sensory information or stimuli.

It's possible, the team thinks, that the multi-dimensional behavior of these time neurons might be what records the 'what', 'where', and 'when' of experiences, stitching elements together to make up coherent memories from a jumble of inputs.

"The phenomenon of subjective 'mental time travel' is a cornerstone of episodic memory," the researchers said.

"Central to our experience of reliving the past is our ability to vividly recall specific events that occurred at a specific place and in a specific temporal order… Our results provide further evidence that human hippocampal neurons represent the flow of time in an experience."

The findings are reported in The Journal of Neuroscience.

An earlier version of this article was published in July 2021.