“Knowing where we are, where we have been, and where we are going is critical to many behaviors,” note scientists of a new study that demonstrates for the first time that neurons in the human brain use a time coding mechanism called “phase precession” to record sequential information—a mechanism previously seen only in other animals.

The investigators show phase precession plays a significant role in the human brain in coding sequences of concrete objects and locations, as seen in animals, as well as abstract progression towards specific goals.

These findings that may unlock key understandings on human cognition, are reported in the Cell paper, “Phase precession in the human hippocampus and entorhinal cortex” by Joshua Jacobs, PhD, associate professor of biomedical engineering at Columbia Engineering, in collaboration with Itzhak Fried, MD, PhD, professor of neurosurgery at the David Geffen School of Medicine at UCLA, director of the epilepsy surgery program at the University of California, Los Angeles (UCLA) Health and co-author on the study.

Current understanding on how the brain encodes information is based on conventional approaches that measure how many times individual neurons fire during particular behaviors (rate coding). A recent hypothesis proposes that neurons signal information by changing the timing when they activate.

Phase precession is one such timing code for sequential information, previously observed in rodents as they navigate through spaces but never seen in humans before now. In phase precession, neurons code information by spiking or firing faster than local oscillations of neuronal activity.

“We were convinced that phase precession held a lot of promise as a widespread neural code that could be used for learning and cognition,” says Salman E. Qasim, lead author of the study who received his PhD from Columbia Engineering in 2021. “There’s no reason the human brain wouldn’t take advantage of this mechanism to encode any kind of sequence, spatial or otherwise.”

The study included 13 participants diagnosed with drug-resistant epilepsy. These patients had surgically implanted micro-electrodes as part of their medical treatment. The researchers analyzed direct brain recordings while the participants performed a virtual-reality spatial navigation task where they had to find and return to six specific buildings. The patients used laptops and handheld controllers to move through virtual environments to complete the spatial navigation task designed by the research team.

The researchers use an internal clock in the form of low-frequency (2–10 Hz) brain oscillations to measure how the relative timing of neuronal action potentials correlates with sequential spatial locations. They were especially excited to find that this temporal code extended beyond representing spatial location to episodic progress toward specific non-spatial goals.

The researchers were struck by how often neurons seemed to fire in concert with slow brain waves and identified phase precession in the hippocampus as subjects moved through different locations, similar to earlier studies in rodents.

“This study demonstrates the unique insights at the level of single brain cells that we may gain in special clinical settings of brain surgery for patients with epilepsy and other disorders,” says Fried. “Here, a simple task performed by patients unveils a fundamental brain code for human negotiation of their environment.”

Qasim next probed whether phase precession tracked more complex cognitive sequences, such as the more abstract progress a person had made towards specific goals, e.g. locations of specific buildings. The researchers measure the temporal relationship between sparse, inconsistent brain-waves and neural spiking without any reference to spatial position, toward this end and were surprised to find evidence for phase precession in the frontal cortex, where it has never been observed before, as subjects sought specific goals.

Jacobs says, “We hope to further explore whether phase precession is a universal code throughout the human brain, and for different kinds of behaviors. Then we can begin to better understand how this neuronal coding mechanism can be used for brain-machine interfaces, and be manipulated by therapeutic brain stimulation.”

Through demonstrating the prevalence of phase precession in multiple brain regions, with respect to multiple aspects of a task, the team hopes to open new avenues of research to decoding brain activity that rely on temporal coding. Furthermore, it is a clear possibility that phase precession might be important for ordering events in our memory. Rodent researchers have primarily observed phase precession in brain circuits disrupted by Alzheimer’s disease. The discovery of phase precession in humans may provide new clues into neuronal biomarkers of memory.

“It is hard to study the neural representations of complex cognitive functions, like goal-seeking, in many animal models. By demonstrating that phase precession in humans might represent particular goal states, this study supports the idea that temporal codes like phase precession could be critical to understanding human cognition,” says Sameer Sheth, MD, PhD, a leading neurosurgeon and neuroscientist at the Baylor College of Medicine who is not affiliated with the study.

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