[tt] For the Brain, Remembering Is Like Reliving

[Eugen Leitl]

http://www.nytimes.com/2008/09/05/science/05brain.html?_r=1&ref=science&oref=slogin

September 5, 2008

For the Brain, Remembering Is Like Reliving

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
same neurons that fired most furiously when the recalled event had been
experienced. Researchers had long theorized as much but until now had only
indirect evidence.

Experts said the study had all but closed the case: For the brain,
remembering is a lot like doing (at least in the short term, as 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 previous 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 short film clips they had just seen.

This ability to richly reconstitute past experience often quickly
deteriorates in people with Alzheimer’s 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 American and Israeli 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 television shows like “Seinfeld” and others depicting animals or
landmarks like the Eiffel Tower. The researchers recorded the firing activity
of about 100 neurons per person; the recorded neurons were concentrated in
and around the hippocampus, a sliver of tissue deep in the brain known to be
critical to forming memories.

In each person, the researchers identified single cells that became highly
active during some videos and quiet during others. More than half the
recorded cells hummed with activity in response to at least one film clip;
many of them also responded weakly to others.

After briefly distracting the patients, the researchers then asked them to
think about the clips for a minute and to report “what comes to mind.” The
patients remembered almost all of the clips. And 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, which signaled 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.

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

In studies of rodents, including a paper that will also appear Friday in the
journal Science, neuroscientists have shown that special cells in the
hippocampus are sensitive to location, activating when the animal passes a
certain spot in a maze. The firing pattern of these cells forms the animals’
spatial memory and can predict which way the animal will turn, even if it
makes a wrong move.

Some scientists argue that as humans evolved, these same cells adapted to
register a longer list of elements — including possibly sounds, smells, time
of day and chronology — when an experience occurred in relation to others.

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.

Though it did not address this longer-term process, the new study suggests
that at least some of the neurons that fire when a distant memory comes to
mind are those that were most active back when it happened, however long ago
that was.

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