The rhythmic electric fields generated by the brain during deep sleep and other periods of intensely coordinated neural activity could amplify and synchronize actions along the same neural networks that initially created those fields, according to a new study. The finding indicates that the brain's electric fields are not just passive by-products of neural activity—they might provide feedback that regulates how the brain functions, especially during deep, or slow-wave, sleep. Although similar ideas have been considered for decades, this is the first direct evidence that the electric fields generated by the cerebral cortex change the behavior of the neurons that engender them.

"I think this is a very exciting new discovery," says Ole Paulsen, a neuroscientist at the University of Cambridge who was not involved in the recent study. "We knew that weak electric fields can impact brain activity, but what no one had really tested before was whether electric fields produced by the brain itself can influence its own activity."

The brain is an intricate network of individual nerve cells, or neurons, that use electrical and chemical signals to communicate with one another. Every time an electrical impulse, or action potential, races down the branch of a neuron, a tiny electric field surrounds that cell. "A few neurons are like individuals talking to each other and having small conversations," explains David McCormick, a neurobiologist at Yale University and co-author of the study published online July 15 in Neuron. "But when they all fire in unison, it's like the roar of a crowd at a sports game." That "roar" is the summation of all the tiny electric fields created by organized neural activity in the brain—it's what scientists record using electroencephalography (EEG), when they place a net of electrodes on a person's scalp.

"The question going into the study," McCormick says, "was whether electric fields generated by synchronous activity in the brain were passive consequences of that neural activity or somehow actively involved in regulating that activity." Investigating this question in the brain of a living animal would be ideal, but raises both ethical dilemmas and experimental difficulties because researchers need to do more than just record electrical activity in the brain—they need to manipulate it.

Instead, McCormick and colleagues created an experimental model that mimicked what might happen in the intact brain of a living animal. First, the researchers suspended a slice of brain tissue from the visual cortex of a ferret in artificial cerebrospinal fluid. The living cortical tissue behaved as though the ferret brain were in slow-wave (non–rapid eye movement), sleep, during which the brain produces sluggish but highly synchronous waves of electrical activity. The team's next step was to find out what would happen to the neural activity in the brain slice when it was subjected to a weak electric field.

They surrounded the cortical sample with an electric field that approximated the size and polarity of the fields produced by an intact ferret brain during slow-wave sleep to create an exaggerated version of the exact feedback loop they were investigating. Essentially, they enveloped the brain slice in an echo of itself.

When the team applied this electric field echo, they found it amplified and synchronized the neural activity in the brain slice. The field didn't create disorder—it increased harmony. The "roar" of the brain slice became louder and more regular. "It’s kind of like if you were cheering at a football game and someone played over the speaker the sound of the crowd cheering and you started responding to that, too, cheering along with both the real crowd and the speaker playback," McCormick explains. "It's a kind of reinforcing feedback."

Not only did the researchers show that this positive feedback facilitated the synchronous slow waves of electrical activity in the slice of ferret brain, they also showed that an electric field of the same strength, but opposite polarity, disrupted its synchronous neural activity. In other words, they showed that they could break the amplifying feedback loop with negative feedback. "Adding a positive feedback loop on top of what the slice produces itself increased synchronization," Paulsen explains, "but the clever bit was to demonstrate that negative feedback reduces synchronization. To me, it's the negative feedback experiment that is important here, and that really demonstrates that the endogenous [internally generated] fields are contributing to the synchronization."

The new study faces a couple methodological imperfections: First, the simple and uniform electric field created by electrodes in the laboratory does not perfectly mimic the complexity of electric fields generated by a living brain. Second, the experimental model relied on an incredibly thin slice of neural tissue—hardly the same as an intact brain. Paulsen says these flaws are unlikely to change the general conclusions of the study, however, because the underlying mechanisms of electrical activity remain consistent enough between the lab model and a living organism.

Because the brain produces especially large electric fields during highly synchronized neural activity, like that of slow-wave sleep, the researchers suspect the feedback loop they discovered could coordinate such phases of deep sleep—which are thought to bolster memory consolidation. "During slow-wave sleep, all your neurons march in order. The whole cortex takes part in this activity and the electric field feedback might help keep the neurons synchronized," McCormick says. "I think this is really going to change how people view the brain's electric fields."

Right now, though, researchers can only speculate as to the exact role of this feedback loop in everyday brain function, says Joseph Francis, a physiologist at the State University of New York Downstate Medical Center who has studied similar feedback in the hippocampus of a rat. "Originally, when I was doing my thesis work, what I wanted to know was whether one part of the brain could interact with another without physical contact," Francis explains. "What this new study shows is that it's possible for electric fields to have an influence on the neural activity itself without direct contact. But now we need to determine how much it has to do with normal functioning."