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A new way to understand the intricate rhythm of the brain

Today, researchers long hours doing intricate experiments in the lab, listening to music or podcasts throughout the day. But in the early years of neuroscience, hearing was a key part of the process. To find out what the neurons cared about, the almost instantaneous signals emitted by the researchers, called “nails,” would return to sound. The louder the sound, the more often the neurons struck — and the louder it fired.

“You can hear how much pop comes out of the speaker, and if it’s very loud or really silent,” says Joshua Jacobs, an associate professor of biomedical engineering at Columbia University. “And that’s a very intuitive way to see how active a cell is.”

Neuroscientists are no longer dependent on sound; they can accurately record nails using embedded electrodes and computer software. To describe the rate of fire of a neuron, a neuroscientist will select a time window — he says, 100 milliseconds — and see how many times it fires. Through shooting rates, scientists have found a lot that we know how the brain works. Examination in a deep region of the brain called the hippocampus, for example, found spot cells, cells that become active when the animal is in a particular place. This 1971 discovery won the 2014 Nobel Prize for neuroscientist John O’Keefe.

Shooting rates are a useful simplification; they show the general level of activity of a cell, although they sacrifice detailed information about the timing of the points. But the individual sequences of lines are so intricate and so changeable that it can be difficult to guess what they mean. So focusing on shooting rates tends to fall into pragmatics, says Peter Latham, a professor in the Gatsby Computational Neuroscience Unit at University College London. “We never have enough data,” Latham says. “Every trial is completely different.”

But this does not mean that it is useless to study the time of the points. Although it is difficult to interpret the nails of the neuron, it is possible to find meaning in these patterns if you know what you are looking for.

That’s what O’Keefe did in 1993, more than two decades after he discovered place cells. Compared to the local oscillations when these cells fired (general patterns of wave-like activity in a region of the brain), he found a phenomenon. “Phase Precession.” When the mouse is in a certain location, that neuron will fire at the same time as the other most active neurons in the environment. But as the rat continues to move, this neuron will shoot a little before or shortly after peak resident activity. When the neuron is synchronizing with its neighbors over time, it shows the precession of the phase. Eventually, as the brain activity in the background follows a repetitive upward and downward pattern, it will be synchronized with it again before the cycle begins again.

Since O’Keefe’s discovery, phase precession has been studied in rats. But no one knew for sure what would happen to humans until May, when Jacobsen’s team published it in the magazine Cell du the first evidence of this in the human hippocampus. “The good news is that things are falling between different species and different experimental conditions,” says Mayank Mehta, a leading UCLA precession phase researcher who was not involved in the study.

The Columbia University team made the discovery through a decade of recordings in the brains of epileptic patients who monitored neural activity while patients navigated the computer in a virtual environment. Epilepsy patients are often hired to research neuroscience, as the treatment may involve deep electrodes in the brain placed in surgery, which gives scientists a unique opportunity to hear individual shots of neurons in real time.


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