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Showing posts with label synapse theory of memory. Show all posts
Showing posts with label synapse theory of memory. Show all posts

Monday, December 10, 2018

The Bandwidth of Memorization Defies Brain Memory Dogmas

The main theory of a brain storage of memories is that people acquire new memories through a strengthening of synapses. There are many reasons for doubting this claim. One is that information is generally stored through a writing process, not a strengthening process. It seems that there has never been a verified case of any information being stored through a process of strengthening.

If it were true that memories were stored by a strengthening of synapses, this would be a slow process. The only way in which a synapse can be strengthened is if proteins are added to it. We know that the synthesis of new proteins is a rather slow effect, requiring minutes of time. In addition, there would have to be some very complicated encoding going on if a memory was to be stored in synapses. The reality of newly-learned knowledge and new experience would somehow have to be encoded or translated into some brain state that would store this information. When we add up the time needed for this protein synthesis and the time needed for this encoding, we find that the theory of memory storage in brain synapses predicts that the acquisition of new memories should be a very slow affair, which can occur at only a tiny bandwidth, a speed which is like a mere trickle. But experiments show that we can actually acquire new memories at a speed more than 1000 times greater than such a tiny trickle.

One such experiment is the experiment described in the scientific paper “Visual long-term memory has a massive storage capacity for object details.” The experimenters showed some subjects 2500 images over the course of five and a half hours, and the subjects viewed each image for only three seconds. Then the subjects were tested in the following way described by the paper:

Afterward, they were shown pairs of images and indicated which of the two they had seen. The previously viewed item could be paired with either an object from a novel category, an object of the same basic-level category, or the same object in a different state or pose. Performance in each of these conditions was remarkably high  (92%, 88%, and 87%, respectively), suggesting that participants successfully maintained detailed representations of thousands of images.

In this experiment, pairs like those shown below were used. A subject might be presented for 3 seconds with one of the two images in the pair, and then hours later be shown both images in the pair, and be asked which of the two was the one he saw.



Although the authors probably did not intend for their experiment to be any such thing, their experiment is a great experiment to disprove the prevailing dogma about memory storage in the brain. Let us imagine that memories were being stored in the brain by a process of synapse strengthening. Each time a memory was stored, it would involve the synthesis of new proteins (requiring minutes), and also the additional time (presumably requiring additional minutes) for an encoding effect in which knowledge or experienced was translated into neural states. If the brain stored memories in such a way, it could not possibly keep up with remembering images that appeared for only three seconds each in a long series. It would be a state of affairs like that depicted in what many regard as the funniest scene that appeared in the “I Love Lucy” TV series, the scene in which Lucy and her friend Ethel were working on a confection assembly line. In that scene Lucy and Ethel were supposed to wrap chocolates that were moving along a conveyor belt. But while the chocolates moved slowly at first, the conveyor belt kept speeding up faster and faster, totally exceeding Lucy and Ethel's ability to wrap the chocolates (with ensuing hilarious results).


The experiment described above in effect creates a kind of fast moving conveyor belt in which images fly by at a speed so fast that it should totally defeat a person's ability to memorize accurately – if our memories were actually being created through the slow process imagined by scientists, in which each memory requires a protein synthesis requiring minutes, and an additional time (probably additional minutes) needed for encoding. But nonetheless the subjects did extraordinarily well in this test.

There is only one conclusion we can draw from such an experiment. It is that the bandwidth of human memory acquisition is vastly greatly than anything that can be accounted for by neural theories of memory storage. We do not remember at the speed of synapse strengthening, which is a snail's speed similar to the speed of arm muscle strengthening. We instead are able to form new memories in a manner that is basically instantaneous. The authors of the scientific paper state that their results “pose a challenge to neural models of memory storage and retrieval.” That is an understatement, for we could say that their results are shockingly inconsistent with prevailing dogmas about how memories are stored.

There are some people who are able to acquire new memories at an astonishing rate. The autistic savant Kim Peek was able to recall everything he had read in the more than 7000 books he had read. Here we had a case in which memorization occurred at the speed of reading. Stephen Wiltshire is an autistic savant who has produced incredibly detailed and accurate artistic works depicting cities that he has seen only from a brief helicopter ride or boat ride. Of Wiltshire, savant expert Darold Treffert says, "His extraordinary memory is illustrated in a documentary film clip, when, after a 12-minute helicopter ride over London, he completes, in 3 hours, an impeccably accurate sketch that encompasses 4 square miles, 12 major landmarks and 200 other buildings all drawn to scale and perspective." Again, we have a case in which memories seem to be formed at an incredibly fast rate. Savant Daniel Tammet (who one time publicly recited accurately the value of pi to 22,514 digits) was able to learn the Icelandic language in only 7 days. Derek Paravicini is a blind and brain-damaged autistic savant who has the incredible ability to replay any piece of music he has heard for the first time. In 2007 the Guardian reported the following:

Derek is 27, blind, has severe learning difficulties, cannot dress or feed himself - but play him a song once, and he will not only memorize it instantly, but be able to reproduce it exactly on the piano. One part of his brain is wrecked; another has a capacity most of us can only dream of.

Other savants such as Leslie Lemke and Ellen Boudreaux have the same extraordinary ability to replay perfectly a song heard for the first time. 

Cases such as these are inconsistent with prevailing theories of memory. Are we to believe that such people (typically with substantial brain damage) can somehow synthesize proteins in their brains ten times or thirty times faster than the average human, so that their synapses can get bulked up ten times or thirty times faster? That's hardly credible. But if memories are not actually stored in brains, but stored in or added to a human psychic or spiritual facility, something like a soul, then there would be no reason why the brain-damaged might not have astonishing powers of memorization.

Some people can form memories 1000 times faster than should be possible under prevailing theories of brain memory storage, which involve postulating protein synthesis and encoding operations that should take minutes. This thousand-fold shortfall in only one of three thousand-fold shortfalls of the prevailing theory of brain memory storage. The two other shortfalls are: (1) humans can remember things for 50 years or more, which is 1000 times longer than the synaptic theory of memory storage can account for (synapses having average protein lifetimes of only a few weeks); (2) humans can recall things 1000 times faster than should be possible if you stored something in some exact location of the brain. If you stored a memory in your brain (an organ with no numbering system or coordinate system), it would be like throwing a needle onto a mountain-sized heap of needles, in the sense that finding that exact needle at some later point should take a very long time.

The imaginary conversation below illustrates some of the many ways in which prevailing dogma about brain memory storage fails. It's the kind of conversation that might occur if memories were formed according to the "brain storage of memory" dogmas that currently prevail among neuroscientists. 

Costello: Alright, guy, I'm now going to teach you an important geographical fact: which city is the capital city of Spain.
Abbott: Go ahead, I'm all ears.
Costello: Okay, here it is. The capital city of Spain is Madrid.
Abbott: Okay, I'll try to remember that.
Costello: So what is the capital city of Spain?
Abbott: I haven't formed the memory of that yet. It takes time. I'm still synthesizing the proteins I need to strength my synapses, so I can remember that.
Costello: So try hard. Remember, Madrid is the capital city of Spain.
Abbott: I'm working on forming the memory.
Costello: So do you remember by now what the capital city of Spain is?
Abbott: Don't ask me too soon. It takes minutes to synthesize those proteins.

After five additional minutes like this, the conversation continues.

Costello: Okay, so it's been five minutes since I first told you what the capital city of Spain is. You should have had enough time to have formed your memory of this fact.
Abbott: I'm sure by now I have formed that memory, because there has been enough time for protein synthesis in my synapses.
Costello: So what is the capital city of Spain?
Abbott: I can't recall.
Costello: But you formed the memory by now. Why can't you recall it?
Abbott: The problem is that I don't know exactly where in my brain the memory was stored. So I can't just instantly recall the memory. The memory is like a tiny needle in a haystack. There's no way I can find that quickly.
Costello: Can't you just search through all the memories in your brain, looking for this one?
Abbott: I could try, but it would take hours or days to search through all those memories.
Costello: Sheesh, this is driving me crazy. How about this? I can teach you that Madrid is the capital city of Spain, and when you form the memory, you can tell me the exact tiny spot where your memory was formed. So maybe you'll tell me, “Okay I stored that memory at brain neuron number 273,835,235.” Then I'll just say to you something like, “Please look in your brain at neuron number 273,835,235, and retrieve the memory you stored of what is the capital city of Spain.”
Abbott: That's a brilliant idea!
Costello: Thanks.
Abbott: On second thought, it will never work.
Costello: Why not?
Abbott: Neurons aren't numbered, and the brain has no coordinate system. It's like some vast city in which none of the streets are named, and none of the houses have house numbers. So if I put a memory in one little “house” in the huge brain city, I'll never be able to tell you the exact address of that house.
Costello: So how the hell am I supposed to teach you anything?
Abbott: Beats me. And if I ever learn anything new, I'm sure I won't remember it for more than a few weeks. That's because there's a big problem with those proteins that I will synthesize to store those new memories. They have average lifetimes of only a few weeks.

As long as they cling to “brain storage of memory” dogmas, our neuroscientists will never be able to overcome difficulties such as those mentioned in this conversation.

Saturday, October 27, 2018

Fake News Academia-Style

One of the big problems in the culture of modern science is that web sites very often give us hype-filled stories that do not accurately state the findings of new scientific research. The problem is not at all limited to popular web sites. A large part of the problem is university press offices, which nowadays are shameless in exaggerating the importance of research done at their university. The authors of such press releases know the more some scientific research done at their institution is hyped, the more glory and attendees will flow to their university.

A scientific paper reached the following conclusions, indicating a huge hype and exaggeration crisis both among the authors of scientific papers and the media that reports on such papers:

Thirty-four percent of academic studies and 48% of media articles used language that reviewers considered too strong for their strength of causal inference....Fifty-eight percent of media articles were found to have inaccurately reported the question, results, intervention, or population of the academic study.

At this link you can find analysis of recent misleading press releases on health research, many of them issued by major organizations such as universities and hospitals. Here are some of the article titles from the past several months, each corresponding to a faulty scientific press release:


  • Claim that milk protein alleviates chemotherapy side effects based on study of just 12 people
  • University PR misleads with claim that preliminary blood test detects early pancreatic cancer
  • Supposed ‘breakthrough’ for detecting gut disorders tested in only 12 healthy people
  • Announcement oversells blood test for predicting treatment outcomes in prostate cancer
  • No, an asthma drug tested in mice does not bring 'new hope' to Alzheimer's patients, at least not yet
  • University touts new device to protect women from HIV, buries fact it was only tested in rabbits
  • Daily ibuprofen can prevent Alzheimer’s disease’ and other unproven claims by Canadian neuroscientist


But in none of these cases do we have a press release as faulty as a particular press release issued by Johns Hopkins University, a press release that very much misled the reader about an important scientific study. The study was one led by Richard Huganir to look for long-lived proteins in synapses. There is a reason why such a study was of considerable philosophical interest.

The most popular scientific doctrine concerning how memory is stored is the doctrine that memory is stored by a process of the strengthening of synapses of brains. But what we know about the lifetimes of proteins in synapses contradicts this doctrine. Humans can remember old memories for as long as 50 years. But as far as we know, the proteins in synapses have average lifetimes no longer than a few weeks. How could memories be stored in synapses that have their parts being constantly replaced? That would be like storing an essay written on leaves on a table, when the wind is frequently blowing away the leaves, and replacing them with other falling leaves -- not something suitable for long-term information storage.

The Huganir study was one specifically looking for long-lived proteins in synapses. If lots of long-lived proteins could be found in synapses, with lifetimes of many years, then it might be that the main theory of a brain storage of memories (the synapse memory doctrine) is not so unbelievable as it once seemed. But if few or no brain proteins were found with very long lifetimes, it would bolster the case that brains are not up to the job of storing human memories that can last for 50 years.

Now, judging from the press release about this study that was released by Johns Hopkins University, you would think that the study was a great success. The press release was entitled “In Mice, Long-Lasting Brain Proteins Offer Clues to How Memories Last a Lifetime.” Talking about two proteins in the body that last for years (crystallin in eyes and collagen in connective tissue), the press release states the following, ending with a quote from Richard Huganir, the leader of the study:

His team also knew of long-lasting proteins such as crystallin, which makes up the lens of the eye, and collagen, found in connective tissue. Proteins within nuclear pores, the transport tunnels in and out of a cell’s nucleus, and histones, a kind of “spool” that DNA winds around, also are very stable. “So, we reasoned, there must be proteins in those synapses that are long-lasting, too, and we believe we have found a lot of them.”

The problem is that this statement does not at all match what is in the actual scientific paper, which found no such thing. Quite to the contrary, the paper found the following:
  • Studying thousands of brain proteins, the study found that virtually all proteins in brains are very short-lived, with half-lives of less than a week.
  • Table 2 of the paper gives specific half-life estimates for the most long-lasting brain proteins, and in this table only 10 out of thousands of brain proteins had half-lives of 10 days or longer.
  • Of the proteins whose half-life is estimated in Table 2, only one of them has a half-life of longer than 30 days, that protein having a half-life of only 32 days.
  • A graph in the paper indicates that none of the synapse proteins had a half-life of more than 35 days.

Below is a graph from the Huganir paper. It shows that the study found that virtually all proteins in synapses are very short-lived.



Below is another graph from the same paper. It shows that the study found that virtually all proteins in synapses are very short-lived.




Judging from these graphs, none of the proteins found had a half-life of longer than 35 days, and only a few had a half-life of more than 14 days.

Given these results, it is extremely misleading for Huganir to be saying in the press release that he found “a lot” of “long-lasting” proteins in synapses. He found no such thing, and did not even find a single protein with an average lifetime of years.

So far from offering “clues to how memories last a lifetime,” as the misleading Johns Hopkins press release states, this study gives us all the more reason for thinking that memories would not even last a year if they were stored in our synapses as our neuroscientists maintain. An accurate title for the press release would have been “Study Indicates Synapses Cannot Store Memories for Longer Than a Month.”



synapses

The results in the Huganir paper are consistent with the results from this 2018 paper by German scientists that studied a similar topic. The paper starts out by noting that one earlier 2010 study found that the average half-life of brain proteins was about 9 days, and that a 2013 study found that the average half-life of brain proteins was about 5 days. The study then notes in Figure 3 that the average half-life of a synapse protein is only about 5 days, and that all of the main types of brain proteins (such as those in the nucleus, mitochondrion, etc.) have half-lives of less than 20 days. 
The 2018 study here precisely measured the lifetimes of more than 3000 brain proteins from all over the brain, and found not a single one with a lifetime of more than 75 days (figure 2 shows the average protein lifetime was only 11 days). 

In this paper by German scientists, tubulin proteins are the only type of brain proteins identified as having a half-life of longer than 14 days. Tubulin proteins are used in tube-shaped microtubules. But there's no chance that such microtubules could be a stable storage site for memory, because microtubules are known to be very short-lived. A scientific paper tells us how short-lived these microtubules are:

Neurons possess more stable microtubules compared to other cell types (Okabe and Hirokawa, 1988; Seitz-Tutter et al., 1988; Stepanova et al., 2003). These stable microtubules have half-lives of several hours and co-exist with dynamic microtubules with half-lives of several minutes.


The Johns Hopkins press release misleadingly suggested that there were some proteins in synapses that could account for memories that lasted for decades, something completely contrary to the actual data in the paper it was discussing, and also entirely contrary to the data in the other paper I have cited above. This reminds us of a type of bogus language use that has been going on among neuroscientists for decades.  For decades neuroscientists have been trying to suggest that an effect misleadingly called long-term potentiation might account for human memory. But the term long-term potentiation is a great misnomer. The effect is actually a short-term effect that almost always disappears within a few weeks, and has never been observed to last for years. Neuroscientists have known from the time of its discovery that so-called long-term potentiation is really a very short-lived effect. So why do they keep using this deceptive term “long-term potentiation”?

In this case of the Hopkins press release, personnel at a university are to blame for bad science reporting. That is very often how it is. An article entitled, “How Scientists Contribute to Bad Science Reporting” refers to a study that found that about one third of science press releases contain exaggerated causal claims. The article states the following:

But a recent study suggests that journalists aren't the weakest link. The source of misrepresentations and exaggerations in science news stories is often much closer to the scientists themselves: press releases put out by researchers' own institutions. Surveying hundreds of news stories and press releases about medical research, a group of scientists at Cardiff University found that most exaggerations and misrepresentations of science in print news "did not occur de novo in the media but was already present in the text of the press releases produced by academics and their establishments." …. When a press release had no exaggerations or misleading claims, relatively few—less than 20 percent—of the related news stories carried misleading claims. But when a press release did include an exaggerated or misleading claim, the majority of the associated news stories also featured exaggerations and misleading claims....More than a third of the press releases examined contained misleading statements or exaggerations, so the bad influence of academic institutions on science reporting is very likely substantial.

Who should we blame for all this exaggeration and misinformation coming from college and university press offices? You might want to blame it on lowly press office staff members, but remember that any careful scientist will review the press release describing any study he led.  

Saturday, September 1, 2018

Memory Engram Theorists Vacillate All Over the Map

In a February post entitled "Turmoil of the Baffled Engram Theorists," I discussed a Science News article that showed the theoretical disarray of engram theorists, scientists who speculate about a physical brain basis for human memories. Three scientific papers in recent years suggest that claims that human memories are stored in brains do not have a solid theoretical basis well-substantiated by experiments.

One paper was entitled “The mysteries of remote memory,” and was published in the Philosophical Transactions of the Royal Society B. Speaking of long-lasting memories, the authors told us that “our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce.” Using the term “engrams” to mean the hypothesis that there are cells in the brain that store memories, the authors state “what and where engrams are implicated in remote memory storage and how they change over time have received little experimental attention thus far.” The authors also frankly tell us that “From engrams to spines surprisingly little evidence exists in the literature on the grounds of remote information processing, maintenance and storage to account for the lifelong and persistent nature of the mnemonic signal.” This type of candor is a refreshing contrast from the click-bait hype about memory research that we get in the science news, where dubious studies using insufficient experimental groups are often trumpeted as scientific breakthroughs.

One of the ideas about a brain storage of memory is that memories get stored in dendritic spines, little bumps on dendrites. But this study found that dendritic spines in the hippocampus last for only about 30 days. And this study found that dendritic spines in the cortex of mice brains have a half-life of only 120 days. So such dendritic spines don't last enough to store memories that last for years. The “Mysteries of remote memory” paper mentions a study that found that studied the persistence of dendritic spines, and found a “near full erasure of the synaptic connectivity pattern within 15 days post-learning.” The paper says “these incongruent findings point to the need for an alternative explanation to spine dynamics for remote memory stability.” In other words, we can't explain dendritic spines as some physical basis for long-term memory. Referring to the often stated speculations that memories start out in the hippocampus and are transferred to the cortex, the paper states unequivocal experimental evidence in support of it is lacking.” The paper then spends some time talking about the very speculative possibility that DNA methylation has something to do with long-term memory, an idea for which there is no evidence. 

The overall impression we get from reading such a paper is one of uncertainty and disarray, as if no clear idea was emerging from brain studies on the long-term storage of memory. We get such an impression even more strongly from two other papers on this topic published in recent years. One is the 2016 paper “What Is Memory? The Present State of the Engram.” Very oddly for a scientific paper, the paper consists of ten sections, each written by a different author or authors. We get conflicting theories as to how a brain might store memories, with little agreement between the sections.

The 2017 paper here is entitled, "On the research of time past: the hunt for the substrate of memory." It is a portrait of memory theorists in disarray, presenting no one theory about how memory might be stored in a brain, and instead suggesting seven or more possibilities, none of which is plausible. The paper is all over the map in its speculations, like someone shooting a gun in all different directions.



The paper tells us on its sixth page that “Engram-labeling studies have shown that certain populations of neurons encode specific memories in mice.” This is not correct. The studies in question are typically small-sample studies with very low statistical power, in which there is a high chance of false alarms. In a typical such study, an experimenter will zap some small portion of a mouse's brain, and claim that he has elicited a fear memory stored in that part, producing a freezing effect in the mouse. But such freezing effects (which require subjective judgments) mean little, since it is known that there are many parts of a mouse's brain that can be stimulated to produce a freezing effect in a mouse.

The paper tells us on page 9 that “synaptic weight changes can now be excluded as a means of information storage.” But for many years neuroscientists have been pushing the very dubious dogma that memories are stored by changes in synaptic weights. As discussed here, this idea never made any sense, for there has never been a proven case of any information that was ever stored as changes in the weights of something, and also synapses are too volatile to store memories that last for decades, for reasons discussed later in this post. 

The authors then proceed to discuss a wide variety of possibilities for how memory might be stored in a brain.  These include the following (the quotes below in italics are from the paper):

Theory 1: “The particularly longlived proteins associated with DNA (i.e., nucleoporins and histones).” This is not a good option because a scientific paper tells us that the half-life of histones in the brain is only about 223 days, meaning that every 223 days half of the histone molecules will be replaced. So histones are not suitable for storing memories lasting decades.

Theory 2: “Some have suggested that DNA (or the epigenetic modifications on it) is the most suitable candidate for memory, being the cellular storage mechanism for other (lifelong) information.” For why this speculation is untenable, see the section entitled “Why Very Long-Term Memories Cannot Be Stored in the Cell Nucleus” in this post. Human DNA molecules have been exhaustively analyzed by multi-year projects such as the Human Genome Project and the ENCODE project, and no evidence has been found of human memories stored in DNA. See the "Why Long-Term Memories Cannot Be Stored in the DNA Methylome" section of this post for why DNA methylation is also an unsuitable possibility for memory storage. If DNA molecules stored memories, we would find that the DNA molecules in the brain of a dead person would vary a lot, with one DNA molecule in the brain being very different from another. Instead, all DNA molecules in the brain are basically the same, and are the same as DNA molecules in other parts of the body. 

Theory 3: “The late Roger Tsien recently proposed the notion that perineuronal nets, the extracellular matrices around neurons and synapses, provide the architecture for information.” Wikipedia tells us that these perineuronal nets are “composed of chondroitin sulfate proteoglycans,” but this paper tells us that the half-life of such molecules is only 10 days, making them unsuitable for a storage of memories lasting a lifetime. The idea behind this perneuronal nets speculation is that memory may be stored in a pattern of holes, like punch cards. The idea is absurd. IBM punchcards worked back in the 1960's because they worked with a punchcard reader which shined light through the punch cards. The brain has nothing like a punchcard reader to read information if it had information stored in such a way, and such a system only works with flat two-dimensional surfaces, not three-dimensional surfaces like that in the brain. There are two research papers that claim to have a result suggesting that perineuronal nets may be important in memory, but both do nothing to establish such a claim, because they both used fewer than 10 animals in some of their study groups (for a moderately reliable research result, 15 is the minimum number of animals per study group).

Theory 4: “Structures composed of short-lived components could constitute a long-term memory if the configurations were preserved by normal homeostatic replenishment.” To the contrary, there is certainly no “normal” bodily mechanism that might allow “structures composed of short-lived components” to store memories for decades.

Theory 5: “Other theories involve information storage or processing in microtubules, the long polarized helices of tubulin subunits that compose the cellular skeleton.” There is no evidence for such theories, and there is a good reason for rejecting them: the fact that there is high molecular turnover in microtubules. This paper tells us, “Neurons possess more stable microtubules compared to other cell types...These stable microtubules have half-lives of several hours and co-exist with dynamic microtubules with half-lives of several minutes.” So microtubules in the brain last less than a week, and are not any place that memories lasting decades could be stored.

Theory 6: “The physical connectivity within neural ensembles is a plausible new candidate substrate for memory information storage, with many merits, including robustness to insult, bioenergetic efficiency, stability of information storage in a potentially binary format, and a high capacity for informational content.” This is a completely different idea from all the previous things discussed, and the paper does not discuss it truthfully. Far from being a "plausible" idea having “many merits,” the idea has no merits. No one has any plausible idea as to how mere “physical connectivity” could be storing the complex things human remember. The paper refers us to the previously mentioned “What Is Memory? The Present State of the Engram” paper, but the sketch of the idea given in that paper does not present the idea in a coherent manner. We see a diagram showing what looks like a necklace of green beads as a representation of how "physical connectivity" could supposedly store information.  That's not a way to store complex information like humans learn. If there is “stability of information storage” in the connections between neurons, it is not the type of stability that would allow memories to be stored for years, let alone decades. The proteins in synapses have an average half-life of less than a week, and synapses themselves have a lifetime of less than a year. The research of Stettler suggests that synaptic connections do not last longer than about three months. In a paper he stated the following, referring to remodeling which would break any "connectivity pattern":

Depending on whether the population of boutons is homogeneous or not, the amount of bouton turnover (7% per week) has different implications for the stability of the synaptic connection network. If all boutons have the same replacement probability per unit time, synaptic connectivity would become largely remodeled after about 14 weeks.

A very important recent scientific paper is the paper “Synaptic Tenacity or Lack Thereof: Spontaneous Remodeling of Synapses.” The paper used the term “synaptic tenacity” for the idea that synapses (brain connections) are relatively stable. Making a devastating case against such a claim, the paper stated the following:

The aim of this Opinion is to discuss challenges to the notion of synaptic tenacity that come from general biological considerations and experimental findings. Such findings collectively suggest that synaptic tenacity is inherently limited, since synapses do change spontaneously and to a fairly large extent....It is probably unrealistic to expect that synapses maintain their particular contents and, by extension, their functional properties with pinpoint precision. This expectation is further challenged by the fact that synapses are not rigid structures but rather are dynamic assemblies of molecules (and organelles) that continuously migrate into, out of, and between neighboring assemblies through lateral diffusion, active trafficking, endocytosis, and exocytosis....Closer examination reveals, however, that properties of individual synapses, such as spine volume, presynaptic bouton volume, synaptic vesicle number, active zone (AZ) molecule content, and PSD protein content fluctuate considerably over these timescales....Imaging studies in primary culture indicate that synaptic configurations erode significantly over timescales of a few days....The findings summarized above indicate that synaptic tenacity is inherently limited or, using the terminology of Rumpel, Loewenstein, and others, that synapses are intrinsically ‘volatile’....When it comes to cognitive functions, long-term memory is one area where the notion of synaptic volatility raises perhaps some of the most challenging questions. In light of findings discussed in this Opinion article, and possibly others, age-old notions concerning relationships between histories of ‘elementary brain-processes’, connection strengths, and memory traces might need to be revisited; put differently (to paraphrase James, modern science might need to improve on this explanation.

The evidence presented by this “Spontaneous Remodeling of Synapses” paper is devastating evidence against the predominant theory of the brain storage of memories (that memories are stored by changes in synapse strength), and also Theory 6 mentioned above, that memories are stored by some “connectivity pattern” created by synaptic connections. Neither theory can be true if synapses have the kind of volatility described in the paper.

In a 2010 book two neuroscientists state that they are “profoundly skeptical” about the main theory of a physical storage of memory, but suggest that they have nothing like a substitute theory to offer:

We take up the question that will have been pressing on the minds of many readers ever since it became clear that we are profoundly skeptical about the hypothesis that the physical basis of memory is some form of synaptic plasticity, the only hypothesis that has ever been seriously considered by the neuroscience community. The obvious question is: Well, if it’s not synaptic plasticity, what is it? Here, we refuse to be drawn. We do not think we know what the mechanism of an addressable read/write memory is, and we have no faith in our ability to conjecture a correct answer.

I submit that the reason for such hesitancy is that there is no theory of a physical storage of memory that can stand up to careful scrutiny, no theory that can explain both memories that can form instantly and the fact that we can instantly retrieve memories of things learned or experienced long ago. Deprived of any credible neural explanation, we should conclude that human episodic and conceptual memory must be a spiritual or psychic or soul phenomenon, not a neural phenomenon.

One of the many reasons for rejecting claims that memories are stored in brains discussed at this site is the essentially instantaneous speed at which humans are able to remember very rarely recalled pieces of information. You say to me, “Dizzy Dean,” and I may in less than two seconds start saying, “eccentric St. Louis Cardinals pitcher, in the 1930's,” even though I haven't thought or read about Dizzy Dean in decades. How could a brain achieve this effect through reading just the right little spot where the information was stored, which would be like instantly finding a needle in a mountain-sized haystack, given a million little spots in the brain where a memory might be stored?

One major reason why it seems hard to believe that the brain could achieve instant recall is that neurons are slow. Information is passed around in a brain at the slow speed of about 100 meters per second, which is only the tiniest fraction of the speed at which electrical signals move about in a computer. Based on this fact we should consider a brain absolutely incapable of performing memory recall as quickly as humans do.

It is often claimed that the brain “makes up” for its slow speed of nerve transmission by being “massively parallel.” The claim that the brain is massively parallel is false. In the computer world, a computer system is massively parallel if it consists of multiple CPUs or central processing units, each of which is running a computer program. We know of nothing in the brain that acts like a computer CPU, nor do we know of anything like a program that the brain runs to compute. It is false to claim that each neuron is like its own CPU. Neurons do not run any program like a computer CPU does. So we cannot at all overcome the problem of low signal transmission speeds in the brain by claiming that the brain is “massively parallel.” It is true that the brain consists of many neurons working together, but that does not make the brain massively parallel. My television set has many transistors working together, but my television set is not massively parallel; and my arms have many cells working together, but that does not make my arms massively parallel. The brain does does not consist of multiple programs running together on multiple processors, and we don't even know of a single program running anywhere in the brain.

Let us imagine some weird group of conspiracy theorists who maintain that secret information from the World War II era is stored in the leaves lying about in modern Germany. If the theorists were to maintain that such information is written on individual leaves, you could easily show the absurdity of the theory by pointing out that leaves don't last much longer than a year. If the theorists were to maintain instead that it was the arrangements of the leaves that stored the information, with one type of leaf pile representing one thing and another type of leaf pile representing something else, you could also show the error of the theory by pointing out that leaf piles are unstable and ever-changing, being blown around by the wind. Similarly, the protein turnover, synaptic volatility and synaptic remodeling discussed in the "synaptic remodeling" paper above are constraining effects as powerful as the short lifetimes of leaves and the instability and impermanence of leaf piles. Anyone claiming that memories persist in synapses for 50 years is advancing a claim as unbelievable as the 50-year "leaf storage" claims of such conspiracy theorists. 

Sunday, August 12, 2018

Two Reasons the Synapse Theory of Memory Storage Is Untenable

How is it that humans can remember things for decades? For decades neuroscientists have been offering an answer: that memories are stored when synapses are strengthened. But this idea has never made any sense. There are two gigantic reasons why it cannot be correct.

The first reason has to do with how long humans can remember things. People in their sixties or seventies can reliably remember things that they saw 50 or more years ago, even if nothing happened to refresh those memories in the intervening years. I have a long file where I have noted many cases when I remember very clearly things I haven't thought about, seen or heard about in four or five decades, memories that no sensory experiences or thoughts ever refreshed. I have checked the accuracy of very many of these memories by using resources such as Google and Youtube.com (where all kinds of clips from the 1960's TV shows and commercials are preserved). A recent example was when I remembered a distinctive characteristic of the “Clutch Cargo” animated TV show (circa 1960) that I haven't watched or thought about in 50 years, merely after seeing a picture of Clutch Cargo's head. The characteristic I remembered was the incredibly poor animation, in which only the mouths moved. Using youtube.com, I confirmed that my 50-year old recollection was correct. A scientific study by Bahrick showed that “large portions of the originally acquired information remain accessible for over 50 years in spite of the fact the information is not used or rehearsed.”

Is this reality that people can remember things for 50 years compatible with the idea that memories are stored by a strengthening of synapses? Synapse strengthening occurs when proteins are added to a synapse, just as muscles are strengthened when additional proteins are added to a muscle. But we know that the proteins in synapses are very short-lived. The average lifetime of a synapse protein is less than a week. But humans can reliably remember things for 50 years, even information they haven't reviewed in decades. Remarkably, the length of time that people can reliably remember things is more than 1000 times longer than the average lifetime of a synapse protein.

The latest and greatest research on the lifetime of synapse proteins is the June 2018 paper “Local and global influences on protein turnover in neurons and glia.” The paper starts out by noting that one earlier 2010 study found that the average half-life of brain proteins was about 9 days, and that a 2013 study found that the average half-life of brain proteins was about 5 days. The study then notes in Figure 3 that the average half-life of a synapse protein is only about 5 days, and that all of the main types of brain proteins (such as nucleus, mitochondrion, etc.) have half-lives of less than 20 days.

Consequently, it is absurd to maintain that long-term memory results from synapse strengthening. If synapse strengthening were the mechanism of memory storage, we wouldn't be able to remember things for more than a few weeks. We can compare the synapse to the wet sand at the edge of a seashore, which is an area where words can be written for a few hours, but where long term storage of information is impossible.

It may be noted that scientists have absolutely not discovered any effect by which synapses undergo any type of strengthening lasting years. Every single type of synapse strengthening ever observed is always a short-term effect not lasting for years.

There is another equally gigantic reason why it is absurd to maintain that memories are stored through synapse strengthening. The reason is that it is, in general, wrong to try to explain information storage by appealing to a mere process of strengthening. Strengthening is not storage. We know of many ways in which information can be stored, and none of them are cases of strengthening.

Below are some examples:

  1. People can store information by writing using a paper and pen. This does not involve strengthening.
  2. People can store information by using a typewriter to type on paper. This does not involve strengthening.
  3. People can store information by drawing pictures or making paintings. This does not involve strengthening.
  4. People can store information by taking photographs, either by using digital cameras, or old-fashioned film cameras. In neither case is strengthening involved.
  5. People can store information by using tape recorders. This does not involve strengthening.
  6. People can store information by using computers. This does not involve strengthening.

So basically every case in which we are sure information is being stored does not involve strengthening. What sense, then, does it make to claim that memory could be stored in synapses through strengthening?

In all of the cases above, information is stored in the same way. Some unit capable of making a particular type of impression or mark (physically visible or perhaps merely magnetic) moves over or strikes a surface, and a series of impressions or marks are made on the surface. Such a thing is not at all a process of strengthening.

Consider a simple example. You have a friend named Mary, and you one day learn that Mary has a black cat. Now let us try to imagine this knowledge being stored as a strengthening of synapses. There is no way we can imagine such knowledge being stored by a strengthening of synapses. If you happened to have stored in your brain the knowledge that Mary has a black cat, it could conceivably be that a strengthening of synapses might allow you to more quickly remember that Mary has a black cat. But there is no way that the fact of Mary having a black cat could be stored in your brain through a strengthening of synapses.

Every protein molecule of a particular type has exactly the same chemical contents – for example, every rhodopsin molecule has the same chemical contents. Unlike nucleic acids, which can store strings of information of indefinite length, a protein molecule cannot store arbitrary lengths of information. So we cannot imagine that there is some particular tweak of protein molecules added to a synapse (when the synapse is strengthened) that would allow information to be stored such as the fact that Mary has a black cat.

In his Nautilus post “Here's Why Most Neuroscientists Are Wrong About the Brain,” C. R. Gallistel (a professor of psychology and cognitive neuroscience) points out the absurdity of thinking that mere changes in synapse strengths could store the complex information humans remember. Gallistel writes the following:

It does not make sense to say that something stores information but cannot store numbers. Neuroscientists have not come to terms with this truth. I have repeatedly asked roomfuls of my colleagues, first, whether they believe that the brain stores information by changing synaptic connections—they all say, yes—and then how the brain might store a number in an altered pattern of synaptic connections. They are stumped, or refuse to answer....When I asked how one could store numbers in synapses, several became angry or diverted the discussion with questions like, “What’s a number?”

What Gallistel describes sounds dysfunctional: a pretentious neuroscientist community that claims to understand how memory can be stored in a brain, but cannot give anything like a plausible answer to basic questions such as “How could a number be stored in a brain?” or “How could a series of words be stored in a brain?” or “How could a remembered image be stored in a brain?” Anyone who cannot suggest plausible detailed answers to such questions has no business claiming to understand how a brain could store a memory, and also has no business claiming that a brain does store episodic or conceptual memories.

Gallistel suggests a radically different idea, that a memory is stored in a brain as a series of binary numbers. There is no evidence that this is true, and we have strong reasons for thinking that it cannot be true. One reason is that there is no place in the brain suitable for storing binary numbers, partially because nothing in the brain is digital, and everything is organic. Another reason is there is no plausible physiology by which a brain could write or read binary numbers. Another reason is that we cannot account for how a brain could possibly be converting words and images into binary numbers. A computer does this through numerical conversion subroutines and by using a table called the ASCII code. Neither numerical conversion subroutines nor the ASCII code is available for use within the brain.

In short, the prevailing theory of memory storage advanced by neuroscientists is untenable. Why do they advance this theory? Because they have no better story to tell us. There is actually no theory of a brain storage of memories that can stand up to prolonged critical scrutiny. As discussed at length here, there is no part of the brain that is a plausible candidate for a place where 50-year-old memories could be stored. As discussed here, there is no part of the brain that acts like a write mechanism for stored memory or a read mechanism for stored memory.

What our neuroscientists should be doing is telling us, “We have no workable theory as to how a brain could store and instantly retrieve memories.” But rather than admit to such a lack of knowledge, our neuroscientists continue to profess the untenable synapse theory of memory.  For they want at all costs for us to stay away from a very plausible idea they abhor: that episodic and conceptual memory is a spiritual effect (a capability of the human soul) rather than a neural effect.

Many think that there is an exact match between the assertions of scientists and observations. But this is not correct. The diagram below shows something like the real situation. Claims such as the claim that memories are stored in synapses are part of the blue area, along with many dogmatic and overconfident pronouncements such as string theory, multiverse speculations and evolutionary psychology. The idea that memory is an aspect of the human soul rather than the brain is supported not only by many observations in the green area of the diagram (observations that a typical scientist would not dispute), but also by many observations in the red area (such as the massive evidence for psychic phenomena). See the posts at this site for a discussion of very many of these observations.


scientist overconfidence
Do not be fooled by the small number of scientific papers that claim to have found evidence for an engram or memory trace. As discussed here, I examined about 10 such papers, and found that almost all of them have the same defect: the number of animals tested was way below the standard of 15 animals per study group, meaning there is low statistical power and a very high chance of a false alarm.  Besides a reliance on subjective judgments of freezing, the papers all deal with small animals, and don't tell us anything about human memory. 

I can give a baseball analogy for the theory that episodic and conceptual memories are stored in the brain. We can compare such a theory to a batter at the plate.  If such a theory includes a plausible explanation of how human experiences and concepts could be stored as neural states, overcoming the extremely grave encoding problem discussed here, we can say the theory at least made contact with the pitched ball. If such a theory can credibly explain how memories could be written to the brain, we can say such a theory has reached first base. If such a theory can explain how a stored memory could last for 50 years, despite the very rapid protein turnover in brains and synapses, we can say such a theory has reached second base. If such a theory can explain how humans can so often instantly remember obscure things they learned or experienced decades ago, overcoming the seemingly insurmountable "finding the needle in a haystack" problem discussed here, we can say such a theory has reached third base. If such a theory were to be confirmed by someone actually extracting learned information from a dead brain, we can say such a theory reached home plate and scored a run.  But using this analogy it must be reported that the theory of conceptual and episodic memory storage in the brain never even reached first base and never even made contact with the ball. For none of these things has been accomplished. 

Postscript: The 2017 paper "On the research of time past: the hunt for the substrate of memory" was written by some leading neuroscientists. It states on page 9 that "synaptic weight changes can now be excluded as a means of information storage." The paper thereby disavows the main theory about memory storage that scientists have been pushing for the past few decades, the very theory I've rebutted in this post. The paper then suggests (in a pretty vacillating and tentative fashion) a variety of alternate possibilities regarding the storage of memory in the brain, none of which is suggested as the most plausible of the lot. See this post for why none of the alternate possibilities mentioned is a very credible idea. 

Monday, December 11, 2017

He's Off on a Wild Goose Chase to Help Save a Sinking Paradigm

The leading doctrine concerning how memory is stored is the doctrine that memory is stored by a process of the strengthening of synapses of brains. But what we know about the lifetimes of proteins in synapses contradicts this doctrine. Humans can remember old memories for as long as 50 years. But as far as we know, the proteins in synapses have lifetimes no longer than a few weeks. How could memories be stored in synapses that have their parts being constantly replaced? That would be like storing an essay written on leaves on a table, when the wind is frequently blowing away the leaves, and replacing them with other falling leaves -- not something suitable for long-term information storage. 

This paper finds that synaptic proteins turnover at a rate of about 17% per day. This paper says that a study of 90 synaptic proteins found an average lifetime of only about 12 days, with the most long-lived one lasting only 48 days. 

Such a fact is extremely troubling to those who think that long-term memory is stored in your brain. So what do you when there is a troubling fact that contradicts your theory of memory? You ask the government for lots of money to look for something that might help out your bad theory, even though that there is no evidence that the thing you are looking for exists.

That seems to be what is going on in the case of National Institute of Health Project # 1R01MH112152-01A1, described here. Some $610,745 has been granted to Richard L. Huganir of Johns Hopkins, so that he can look for “exceptionally long-lived proteins” in synapses. Given what we know about the extremely short lifetimes of synapse proteins, this seems to be like getting lots of money from the government to look for flying rats.

Below is an excerpt from the grant proposal:

Most of the individual proteins that are known to make up the synapse will turnover, being degraded and replaced within hours to a few days. Therefore the question remains as to what physical substrates underlie the persistence of long-lasting memories. One possibility is that exceptionally long-lived proteins (LLPs) reside in synapses and act as molecular anchors to maintain the synaptic strength or a network property that defines a given memory.

The grant proposal admits that there is no evidence that any such “exceptionally long-lived proteins” exist in synapses, for it says, “no studies to date have addressed whether such proteins exist at synapses and contribute to the establishment and maintenance of long-term memories.”

Given the known extremely short lifetimes of synaptic proteins, we should characterize this research project as a wild goose chase. It seems to be kind of a desperate shot-in-the dark to try to save the materialistic paradigm's claims about memory. No doubt our neuroscientists are troubled by the idea that because of synapse proteins with very short lifetimes, the brain is simply not up to the job of storing memories for years. That would seem to mean we could only explain human 50-year memories by supposing that our minds must involve something more than the brain, such as a soul or some mysterious immaterial consciousness infrastructure.

There is no reason to think that Huganir will find any synapse protein that can last for years.  Let's suppose you were to make the very surprising discovery that some protein in synapses lasts for years. We would still know that almost all the proteins in synapses are very short-lived. So the discovery of such a long-lived synapse protein would be futile. It would be like trying to explain the persistence of a much-used book supposedly lasting 50 years – a book made almost entirely of gossamer spider-web pages – by finding that every twentieth page is not made of flimsy short-lived gossamer but of paper. That doesn't do you much good in explaining how most of the book's information could persist for 50 years.

I may note an irony here. Human observers have got much evidence for astonishing things that cannot be explained by modern science: things such as extrasensory perception, apparition sightings, mysterious orbs with highly repeating stripe patterns, and near-death experiences. Such things challenge the dogmas of the materialistic  paradigm. If you were to ask for a half million dollars for a government grant to investigate further such things which have already been extensively observed, you would be turned down quickly, and you would be told: not one cent for such research. But if you seem to be in service of prevailing dogmas, you will have no problem getting a half million dollar grant to go on a quixotic quest looking for something that has never been observed, which is what Huganir has got. I guess the rule is: there's no government research money for anything that might challenge the materialistic paradigm, but plenty of government research money for any project that might help patch one of the many holes that have sprung up in such a paradigm, which are threatening to sink the paradigm. 


The government seems to have been very generous in giving lots of grants to Huganir, who we can assume is mainly involved with projects with a larger chance of success than this one.

Postscript: The latest and greatest research on the lifetime of synapse proteins is the June 2018 paper “Local and global influences on protein turnover in neurons and glia.” The paper starts out by noting that one earlier 2010 study found that the average half-life of brain proteins was about 9 days, and that a 2013 study found that the average half-life of brain proteins was about 5 days. The study then notes in Figure 3 that the average half-life of a synapse protein is only about 5 days, and that all of the main types of brain proteins (such as nucleus, mitochondrion, etc.) have half-lives of less than 15 days.

See this post to see Huganir's results. He got the result I predicted, basically the same result as the June 2018 discussed above. He found that virtually all synapse proteins are very short-lived, and the paper gives no clear evidence of any synapse proteins that last for years.  But the press release announcing the study announced the exact opposite of what the data found, in an outrageous case of the "press release doesn't match the scientific paper" phenomenon that is shockingly common in modern academia. 

Wednesday, November 1, 2017

Synaptic Density Studies Contradict Prevailing Memory Model

The leading doctrine concerning how memory is stored is the doctrine that memory is stored by a process of the strengthening of synapses of brains. But what we know about the lifetimes of proteins and synapses contradicts this doctrine. The proteins in synapses have lifetimes no longer than a few weeks (this paper finds that they have turnover at a rate of about 17% per day). The synapses themselves are short-lived compared to the 50-year time span that human memories can last.

The two main structural components that can increase in size or number when a synapse is strengthened are called boutons and dendritic spines. Stettler and his colleagues found that the boutons of synapses turn over at a rate of about 7% per week. Dendritic spines in synapses last no more than about a month in the hippocampus, and less than two years in the cortex. This study found that dendritic spines in the hippocampus last for only about 30 days. This study found that dendritic spines in the cortex of mice brains have a half-life of only 120 days. 

So what we know about the lifetime of synapse components contradicts the claim that human memories (lasting as long as 50 years) are stored in synapses. There is another neuroscience finding that contradicts such a dogma: the finding that there is no increase in synaptic density corresponding to an increase in human knowledge.

What should we expect from the idea that our memories are stored in synapses? We would expect that the density of synapses in the brain would increase as more memories accumulated. But that is not what we observe. In 1979 a scientific paper by Huffenlocher reached these conclusions:

  1. Synaptic density was constant throughout adult life (age 16 to 72 years), with a density of about 1100 million synapses per cubic millimeter.
  2. There was only a slight decrease in old age, with density decreasing to about 900 million synapses per cubic millimeter.
  3. Synaptic density increased during infancy, reaching a maximum at age 1--2 years which was about 50% above the adult mean.”

So according to the paper, the density of synapses sharply decreases as you grow up. The following image from a US government web site tells essentially the same story. The red line shows spine density, roughly the same as synapse density. We see this density declining after age 5. 


spine density growth

Here is a comparable graph from a National Academies Press online book. We see synaptic densities declining after age 5:

synapse density

 
Why are such findings inconsistent with the idea that memories are stored in synapses? If our memories are stored in synapses, synaptic densities should increase as memories accumulate. A 40-year old has many more memories than a 5-year old. But instead of synaptic densities increasing between age 5 and 16, we see synaptic densities falling sharply.

But what about that study of London cab drivers, the one that supposedly showed they had “bigger brains” after learning lots of location information? To become a London cab driver, you have to memorize a great deal of geographical information. A study followed London cab drivers for 4 years, taking MRI scans of their brains.

But the study did not find that such cab drivers have bigger brains, or brains more dense with synapses. The study has been misrepresented in some leading press organs. The National Geographic misreported the findings in a post entitled “The Bigger Brains of London Cab Drivers.” Scientific American also inaccurately told us, “Taxi Drivers' Brains Grow to Navigate London's Streets.” 

But when we actually look at a scientific paper stating the results, the paper says no such thing. The study found no notable difference outside of the hippocampus, a tiny region of the brain. Even in that area, the study says “the analysis revealed no difference in the overall volume of the hippocampi between taxi drivers and controls.” The study's unremarkable results are shown in the graph below. 


The anterior part of the left half of the hippocampus was about 25% smaller for taxi drivers (100 versus 80), but the posterior part of the right half of the hippocampus was slightly larger (about 77 versus 67). Overall, the hippocampus of the taxi drivers was about the same as for the controls who were not taxi drivers, as we can see from the graph above, in which the dark bars have about the same area as the lighter bars. So clearly the paper provides no support for the claim that these London cab drivers had bigger brains, or brains more dense with synapses.

In this case, the carelessness of our major science news media is remarkable. They've created a “London cab drivers have bigger brains” myth that is not accurate. 

The facts in this matter are completely at odds with the "synapses store memory" dogma that neuroscientists keep teaching (like theologians promulgating some tenet in their creed). The structural materials in synapses are way too short-lived for synapses to be a plausible place where 50-year-old memories could be stored. And instead of our synapses growing denser and denser as we accumulate memories, we have synapses much denser when we are very young with few memories than when we are adults with many times more memories.  Why do our neuroscientists keep advancing an unproven theory inconsistent with the facts?  Perhaps because otherwise they might have to concede that memory may well involve some spiritual component that cannot be explained through  neuroscience. 

See here for 10 posts explaining why current ideas about mind and memory are in need of radical revision.