The New York Times – September 5, 2008

Brain Cells Observed Summoning a Memory
By BENEDICT CAREY

Scientists have for the first time recorded individual brain cells in the act of summoning a spontaneous memory, revealing not only where a remembered experience is registered but also, in part, how the brain is able to recreate it.

The recordings, taken from the brains of epilepsy patients being prepared for surgery, demonstrate that these spontaneous memories reside in some of the very same neurons that fired most furiously when the recalled event was first experienced. Researchers had long theorized as much but until now had only indirect evidence.

The new study, experts said, has all but closed the case: For the brain, remembering is a lot like doing (at least in the short term; the research says nothing about more distant memories).

The experiment, being reported Friday in the journal Science, is likely to open a new avenue in the investigation of Alzheimer’s disease and other forms of dementia, some experts said, as well as help explain how some memories seemingly come out of nowhere. The researchers were even able to identify specific memories in subjects a second or two before the people themselves reported having them.

“This is what I would call a foundational finding,” said Michael J. Kahana, a professor of psychology at the University of Pennsylvania, who was not involved in the research. “I cannot think of any recent study that’s comparable. It’s a really central piece of the memory puzzle, and an important step in helping us fill in the detail of what exactly is happening when the brain performs this mental time travel” of summoning past experiences.

The new study moved beyond most earlier memory research in that it focused not on recognition or recollection of specific symbols but on free recall — whatever popped into people’s heads when, in this case, they were asked to remember a series of short film clips they had just seen.

This ability to richly reconstitute past experience often deteriorates quickly in people with Alzheimer’s disease and other forms of dementia, and it is fundamental to so-called episodic memory: the catalog of vignettes that together form our remembered past.

In the study, a team of Israeli and American researchers threaded tiny electrodes into the brains of 13 people with severe epilepsy. The electrode implants are standard procedure in such cases, allowing doctors to pinpoint the location of the mini-storms of brain activity that cause epileptic seizures.

The patients watched a series of 5- to 10-second film clips, some from popular TV shows like “Seinfeld,” others depicting animals or landmarks, like the Eiffel Tower. The researchers recorded the firing activity of about 100 neurons per person during the viewing of repeated series of videos; the recorded neurons were concentrated in and around the hippocampus, a sliver of tissue deep in the brain that is known to be critical to forming new memories.

In each individual, the researchers identified single cells that became highly active during some videos and quiet during others. About half the recorded cells hummed with activity in response to at least one film clip, and responded weakly to another.

After distracting the patients for a few minutes, the researchers then asked the subjects to think about the clips for a minute and report “what comes to mind.” The patients remembered almost all of the clips. And, sure enough, when they recalled a specific one — say, a clip of Homer Simpson — the same cells that had been active during the Homer clip reignited. In fact, the cells became active a second or two before people were conscious of the memory — signaling to researchers the memory to come.

“It’s astounding to see this in a single trial; the phenomenon is strong, and we were listening in the right place,” said the senior author, Dr. Itzhak Fried, a professor of neurosurgery at the University of California, Los Angeles, and the University of Tel Aviv. His co-authors were Hagar Gelbard-Sagiv, Michal Harel and Rafael Malach of the Weizmann Institute of Science in Israel; and Roy Mukamel, of U.C.L.A.

”These patients were on a noisy ward, there was a whole lot happening all around them, but still you see this absolutely robust response in the individual neurons.”

The single neurons recorded firing most furiously during the film clips were not acting on their own, Dr. Fried added, in a phone interview; they were, like all such cells, part of a circuit responding to the videos, including perhaps a million other cells. .

Single-cell recordings cannot capture the entire array of circuitry involved in memory, which may be widely distributed beyond the hippocampus area, experts said. And as time passes, memories are consolidated, submerged, perhaps retooled, and often entirely reshaped when retrieved later. The new study, though it did not address this longer-term process, suggests that at least some of the neurons that fire when a distant memory pops to mind are those that were most active back when it happened, however long ago that was.

“The exciting thing about this,” Dr. Kahana said, “is that is gives us direct biological evidence of what before was almost entirely theoretical.”

---