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September 5, 2008

BehindTheMedspeak: 'Tivo neurons' — This is your brain on 'The Simpsons'

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Long story short: "In many of the patients, one neuron responded every time they saw a particular video," wrote Emma Byrne in yesterday's Financial Times about a new study published online today in the journal Science.

To get you warmed up for the heavy stuff to come, here's Benedict Carey's September 4, 2008 New York Times front page story on the findings.

    For the Brain, Remembering Is Like Reliving

    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.”

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Here's the abstract of the original report by Fried et al, as published September 5, 2008 in the journal Science.

    Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall

    The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view television episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate of the subjective experience of spontaneous emergence of human recollection.

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The abstract of the Science paper (cited above) reporting findings in rodent brains follows.

    Internally Generated Cell Assembly Sequences in the Rat Hippocampus

    A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain's ability to self-generate sequential neuronal activity. We found that reliably and continually changing cell assemblies in the rat hippocampus appeared not only during spatial navigation but also in the absence of changing environmental or body-derived inputs. During the delay period of a memory task, each moment in time was characterized by the activity of a particular assembly of neurons. Identical initial conditions triggered a similar assembly sequence, whereas different conditions gave rise to different sequences, thereby predicting behavioral choices, including errors. Such sequences were not formed in control (nonmemory) tasks. We hypothesize that neuronal representations, evolved for encoding distance in spatial navigation, also support episodic recall and the planning of action sequences.

September 5, 2008 at 02:01 PM | Permalink


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Comments

There are a couple of important distinctions to be made here. Although this research points to the mechanism in which neurological activity REPLAYS an experience, this reportage avoids the problem of where or even if those "memories" are stored.

Other work performed by Fried's/UCLA/et. al labs show structural frequency responses. I would like to see some correlations established between physiological and functional with specific frequency modulations accounted for.

Perhaps not too soon in the future?

Posted by: FutureDani | Sep 6, 2008 11:52:21 AM

Hunh. I just read that, kind of, and the nearest I can make out is that our memories would be better if we all watched The Simpsons for a couple hours a day, and that a rat that has just watched an episode will probably find the cheese.

Posted by: Faultist | Sep 5, 2008 4:07:09 PM

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