Contrary
to claims sometimes made, scientists have no solid evidence for any
such thing as a memory trace (also called an engram), a physical
change in a particular part of the brain that corresponds to the storage of a memory. How memory works is a great mystery. There are some
scientists that have claimed to have learned or discovered something
about memory traces or engrams, but such claims are not well founded.
An engram is a hypothetical group of cells that might store a
memory.
In
2013 we had an example of a very dubious scientific paper claiming to
have found something relevant to this issue. Two scientists (Xu Liu and
Steve Ramirez) claimed to have created a false memory in a mouse. Their
paper was entitled “Inception of a false memory by
optogenetic manipulation of a hippocampal memory engram.” Their
claim was picked up by countless mainstream news sources, which failed
to apply critical scrutiny to the very dubious claim.
The
experiment was done using some mice that were genetically engineered
to be light sensitive. An optical device was connected to
part of their brains. Mice were put into a box and given an
electric shock. This, the scientists claimed, created a memory in
part of the brains of the mice.
Then
later, when the mice were in a different room, light was transmitted
over the optical device, into the brains of the mice. This, the
scientists claimed, activated the memory that had been stored in the
brain of the mice – supposedly because the mice “froze.” I may
note that the use of the term “froze” and “freezing” in the
study is kind of loaded terminology, a kind of non-objective
“assuming what you are trying to prove” terminology. The correct
objective way to describe a mouse that is not moving is to say the
mouse was temporarily not moving. “Froze” is a loaded term
specifically designed to get someone to think that a mouse stopped
moving because of fear, but you can't tell how a mouse is feeling or
what it is recalling merely by the fact that it stops moving.
We
are told that this was an “implanted memory,” because the
original memory was created not in the second box but the first box.
This term is inaccurate. If an experiment like this were ever done in
a convincing manner, the most it would demonstrate is an electronic
activation of a memory. It is also inaccurate to describe the result
as an inception or implant of a false memory (as their scientists did
in their scientific paper). If I have a memory of being punched on
Fifth Avenue, and then I recall or relive that memory while on
Lexington Avenue, that is not a false memory. It is a true memory of
something that happened in a different place.
A
more serious objection to the research is that is did not provide
convincing evidence of a memory activation or any type of unusual
memory effect at all in the mice being studied. There are three
reasons why I make this claim.
The
first reason is that the number of mice tested was very small. When
you read the paper, you will find the number of mice used was only
about 6. That's way too small a sample size to be drawing any
reliable conclusions. With a sample size that small, the results
could easily have been due to coincidence. An experimenter wishing to
show some particular effect could just keep trying until some round
of experiments showed the desired effect. That would be hard to do
with a large sample size, but easy to do with a very small sample
size such as only 6 or 8 mice.
The
second reason is that the conclusion about whether the memory was
being remembered was presumably based on an observer judging whether
a mouse froze, or stopped moving. The authors did not explain how it
was determined that particular mice had “frozen,” and we can only
assume that such a determination was reached from a subjective human
judgment. Given the start-stop, helter-skelter way in which mice
move, any judgment about whether a mouse froze is going to be a
subjective judgment. So there is too much of a possibility of
observational bias here, one in which an observer subjectively
reports the effect he is hoping to find. Similarly, you might
subjectively report that your goldfish in a goldfish bowl tends to
move towards you when you are looking into the bowl, but that would
probably tell us more about your desire to see something than about
the goldfish.
The
third reason is that the freezing effect could have been produced not
by a recall of memories, but by the very fact that the energy was
being transmitted into the brain of the mice. Imagine you are running
along, and suddenly a scientist switches on some weird thing that
causes some energy to pour into your brain. This all by itself might
cause you to stop, even if it didn't cause you to recall some memory
that caused you to stop. What could have been going on in the mice
was just a kind of pausing effect caused by a novel stimulus rather
than a recalled fear effect.
We
have no idea what was going on in the minds of these mice. It is
not sound to assume that a mouse is “frozen in fear” merely
because it stops moving, or to assume that the mouse is remembering
something when it stops moving. We have no way of knowing what mouse
are remembering at any particular moments. We can also ask: why didn't the scientists try to use dissection to confirm their claim of a memory stored in some particular spot of the brain? The technique would be simple: train a mouse to fear some particular stimulus, then dissect some little part of the brain where you think the memory is stored, and see whether the mouse still fears the stimulus.
A
more recent paper by Ramirez and Liu was published in Nature, and was
entitled, “Activating positive memory engrams
suppresses depression-like behaviour.” But the paper shows the
same type of methodological problems of their earlier paper. Figure 2 of the paper says that in one group there were only 6 mice used, and elsewhere the paper states that a control group had only 3 mice. These sizes are way below the 15 animals per study group (control and non-control) recommended for a reliable experimental result. The authors
claim to have counted differences in the degree to which mice
“struggled” when presented with a maze – again something
involving a subjective interpretation in which a researcher might
tend to see whatever he wants to see. The authors' interpretation of
what is going on is speculative. The authors do not present any
solid evidence that they actually activated a memory by optogenetic
stimulation.
But
to its credit, Nature did publish an article entitled
“Brain-manipulation studies may produce spurious
links to behaviour,” pointing out that shooting light into one
part of a brain (the technique used by Ramirez and Liu) may cause
other parts of the brain to fire off, resulting in unpredictable
effects. “Manipulating brain circuits with light and drugs can
cause ripple effects that could muddy experimental results,” the
article cautions. That's another reason for doubting these mouse
memory studies based on optogenetic brain stimulation, since it
undermines the whole simplistic idea of “stimulate just this area
and activate just this memory.”
The
“mouse memory implant” research described above is inconsistent
with a body of memory research produced over a much larger period of
time: the memory research of
Karl
Spencer Lashley. Over many years, Lashley did extensive research in
which he tested how memory and learning is affected when you take out
various parts of an animal's brain. In one extensive set of
experiments, Lashley trained rats to run a maze. The rats then had
parts of their brains removed. Lashley found the rats were able to
run the maze just as well regardless of which part of the brain was
removed. Strongly indicating that particular memories are not localized in one particular part of the brain, this research
directly contradicts the “mouse memory implant” work that tried
to suggest that a memory was stored in one particular part of the
brain.
Lashley
tested using three types of mazes of varying difficulty. Astonishingly,
Lashley found that you could remove half of a rat's brain, and it had
very little effect on the rats ability to remember either of the two
simpler types of mazes.
Here
are some startling results listed by Lashley (and discussed here):
- Rats, trained to have a differential reaction to light, showed no reduction in accuracy of performance when the entire motor cortex of the brain, along with the frontal poles of the brain, was removed.
- Monkeys were trained to open various latch boxes. The entire motor areas of the monkeys' brains were removed. After 8 to 12 weeks of paralysis, during which they had no access to the latch boxes, the monkeys were then able to open the boxes “promptly” and “without random exploratory movements.”
- Rats were trained to solve mazes, and the rats then had incisions made separating different parts of their brains. This produced no effect in memory retention.
- Monkeys were trained to unlatch latch boxes. After having their prefrontal cortex removed, there was “perfect retention of the manipulative habits.”
- “A number of experiments with rats have shown that habits of visual discrimination survive the destruction of any part of the cerebral cortex except the primary visual projection area.”
After
discussing these and many other experiments he did for many years,
Lashley said this about the idea of an engram or memory trace: “It
is not possible to demonstrate the isolated localization of a memory
trace anywhere within the nervous system.”
Lashley's
research is completely inconsistent with the research claim of
Ramirez and Liu. Lashley's research provides compelling evidence
that particular memories are not stored in particular parts of a
brain. Conducted over more than 30 years with a huge number of
animals, Lashley's research was many times more extensive than the
scanty 6-mouse research of Ramirez and
Liu that got so much press coverage. Given a conflict between the
two lines of research, we should believe Lashley's research, which is
so much more voluminous. Contrary to the claims of some optogenetic
researchers using dubious methodology, there is no compelling
evidence that particular memories are stored in particular parts of
the brain, and no convincing evidence that specific memories can be
recreated by stimulating particular parts of the brain. There is no
good evidence for any such thing as a memory engram, a particular set
of cells that stores a particular memory. Lashley's many years of
research strongly indicates that such ideas are not valid, as does
the research of John Lorber (who, as described here, documented many cases of humans who
functioned very well, despite having most of their brains destroyed
through disease).
Postscript: In 2014 our credulous and exaggeration-prone news media reported that researchers Wiltgen and Tanaka had erased specific memories in a mouse. But the reports were based on a research paper that justified no such conclusions. The paper states in its Figure 2 that only 6 mice were used for a study group, and 6 mice for the control group. This is way below the standard of 15 animals per study group (control and non-control) needed for a reliable experimental result. The same problem is shown in Figure 3 and Figure 4 of the paper. The paper reported borderline results, bordering on statistical insignificance. It gave no clear evidence of having erased any memory in a mouse. The paper had some of the same methodological problems as discussed above, such as relying on judgments of a mouse's "freezing rate" that is very hard to objectively quantify.
Post-Postscript: The latest example of a memory experiment failing to actually prove anything (because of its too-small-sample size) is a study in Nature that has been hyped with headlines such as "Artificial memory created." The study has the inaccurate title, "Memory formation in the absence of experience." The study fails to prove any such thing occurred. When we look at the number of animals involved, we often find that the study fails to meet the minimum standard of 15 animals per study group. In Figure 1 we learn that two of the study groups consisted of only 8 mice. In Figure 2 we learn that two of the study groups consisted of only 10 mice. In Figure 3 we learn that one of the study groups consisted of only 7 mice. Moreover, the methodology used in the study is so convoluted that it fails to provide clear and convincing evidence for anything interesting. The only evidence of memory recall is that the mice supposedly avoided some area, something that might have occurred for any number of reasons other than a recall of some memory. A robust test of an artificial memory would test an actual acquired skill, such as the ability to navigate a maze in a certain time.
Postscript: In 2014 our credulous and exaggeration-prone news media reported that researchers Wiltgen and Tanaka had erased specific memories in a mouse. But the reports were based on a research paper that justified no such conclusions. The paper states in its Figure 2 that only 6 mice were used for a study group, and 6 mice for the control group. This is way below the standard of 15 animals per study group (control and non-control) needed for a reliable experimental result. The same problem is shown in Figure 3 and Figure 4 of the paper. The paper reported borderline results, bordering on statistical insignificance. It gave no clear evidence of having erased any memory in a mouse. The paper had some of the same methodological problems as discussed above, such as relying on judgments of a mouse's "freezing rate" that is very hard to objectively quantify.
Post-Postscript: The latest example of a memory experiment failing to actually prove anything (because of its too-small-sample size) is a study in Nature that has been hyped with headlines such as "Artificial memory created." The study has the inaccurate title, "Memory formation in the absence of experience." The study fails to prove any such thing occurred. When we look at the number of animals involved, we often find that the study fails to meet the minimum standard of 15 animals per study group. In Figure 1 we learn that two of the study groups consisted of only 8 mice. In Figure 2 we learn that two of the study groups consisted of only 10 mice. In Figure 3 we learn that one of the study groups consisted of only 7 mice. Moreover, the methodology used in the study is so convoluted that it fails to provide clear and convincing evidence for anything interesting. The only evidence of memory recall is that the mice supposedly avoided some area, something that might have occurred for any number of reasons other than a recall of some memory. A robust test of an artificial memory would test an actual acquired skill, such as the ability to navigate a maze in a certain time.
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