NIH's Million-Dollar "Epigenetic Memory" Bet Fails

In 2021 there was a press release from the National Institute of Health entitled "NIH supports 106 grants featuring high-risk, high-reward research."  The research discussed were projects with a high risk of failure, but which might yield a high reward if they succeed.  We read the following: "Supported research this year includes understanding how long-term memory might be encoded in the shape of folded DNA in our neurons, mining data from unconventional sources to reveal social determinants of suicide, establishing new paradigms to address the functional consequences of health disparities in drug development, and looking at the impact of high school and collegiate athlete injuries on long-term health." 

The first project mentioned (apparently NIH Project # 1DP2MH129985-01 discussed on this page) is relevant to the question of whether scientists currently have any credible theory of the storage of long-term human memories.  For many decades scientists have been telling us that long-term memories are stored in synapses.  There has never been any robust evidence or any credible detailed theory backing up such an idea.  Everything we know about synapses suggests that they are totally unsuitable for the task of storing memories that can last for 50 years. For example, the proteins in synapses have average lifetimes of only a few weeks or less. Synapses have a high degree of structural dependency on dendritic spines, which are short-lived things that do not last for years.  No one has ever proven that a synapse lasts for years, and we have good reason for believing they do not last for years. 

What was interesting about this NIH Project # 1DP2MH129985-01 is that it is a kind of "heresy" project that was totally contrary to the "orthodoxy" that our neuroscientists have been spouting for decades about memory.  The project had the wildly speculative title "The epigenetic encoding of learning and memory," which is a research project title as speculative as "Extraterrestrial UFO mother-ships near Jupiter."  The idea that human memories are encoded in the genome or the epigenome is an idea totally contrary to what neuroscientists have been telling us for decades, that memories are stored in synapses.  The genome and the epigenome are found in the center of cells, in chromosomes of a cell nucleus. A synapse is a unit vastly tinier than a cell, outside of a cell or or on the outer edge of a cell.  In the visual below depicting a neuron (one of the cells in the brain), the brown circle at the center is the location of the genome and the epigenome, and synapses (too small to show) would be located around the orange parts on the edges:

We see from the project page that the NIH has granted $1,434,188 of public funds for this recent project. The project page presents no detailed research project plan. We merely get a vague project description that left the researchers free to play around pretty much in any way they want.  That description often resorts to speculation stated as if it were fact. Here is the description (I'll put in boldface the very speculative parts that are not at all statements of fact):

"The nervous system requires tight control of transcription for processes such as learning and memory formation. The field of epigenetics seeks to understand how changes to gene transcription occur in response to environmental cues and external signals such as those that our brains experience during learning. This proposal lies at the intersection of neuroscience and epigenetics, with a particular focus on chromatin biology. Chromatin is the complex of DNA and the histone proteins that wrap up DNA into complex structures, recruit key transcriptional regulators, and in doing so, control gene expression. In recent years, it has become clear that disruptions to chromatin regulation lead to a range of neurological and mental health disorders such as post- traumatic stress disorder (PTSD). However, we have a limited understanding of how chromatin functions in the brain or how its disruption can lead to disease. We will apply the tools and techniques of the epigenetics field to the study of neuronal function. In doing so, we hope to elucidate the molecular mechanisms that allow our brains to perform incredibly complex tasks and how disruption of these mechanisms can lead to neuronal dysfunction. We propose overcome long-standing hurdles in the field using a combination of novel techniques to reveal how the epigenetic landscape encodes the transcriptional changes that underlie memory formation. Specifically, we seek to uncover the transcriptional signature of memory formation and memory maintenance within single neurons in an in vivo context. We then will examine the epigenetic underpinnings of this transcriptional signature and manipulate specific components of the chromatin environment to define their contribution to learning and memory maintenance. First, in order to elucidate the gene program associated with learning, we will use single-nucleus RNA-sequencing in combination with mouse models that label the specific neurons activated during learning. This will allow us to examine the transcriptional programs activated in neurons that form a memory engram compared to their neighboring cells at various times after learning. Next, we will employ a quantitative biochemical approach uniquely available to our group as part of the Epigenetics Institute to characterize the chromatin landscape changes the occur during memory formation, memory maintenance, and reversal learning. Finally, we will modify the chromatin landscape by manipulating specific histone proteins in combination with numerous sequencing approaches to elucidate how chromatin controls learning and the transcriptional program. Employing this novel combination of techniques will allow us to uncover the mechanisms through which the epigenome encodes information within neurons to modify behavior both in the context of normal learning and in the context of maladaptive responses that lead to disorders such as PTSD. If successful, these methods will 1) identify the transcriptional signature that encodes a memory in neurons, 2) map how this signature is encoded by specific epigenetic regulatory mechanisms, and 3) define how the chromatin landscape affects memory formation and contributes to mental health disorders."

What we have here (in the boldface parts) are statements of an unfounded and wildly speculative theory: the contrarian idea that memories are stored in chromatin (consisting of DNA and proteins surrounding it) and an  associated epigenome (consisting of kind of chemical marks next to parts of DNA) . Such statements are made in a matter-of-fact manner, as if such a "yet-to-reach-first-base" theory was fact.  The not-yet-popular theory being suggested is one very different from what neuroscientists have been claiming for decades.  For decades, neuroscientists have been telling us that memory formation occurs through "synapse strengthening," not through "transcriptional changes."  We see no mention of the word "synapses" or "synaptic" in the quotation above. 

The boldface above states an idea that makes no sense. "Transcriptional signatures" are transitory fleeting fluctuating biomarkers of the rates at which particular genes are being expressed. Conversely, for a long-term memory to be encoded in a brain there would need to be some all-but-miraculous effect that caused learned information or sensory experience to be permanently stored as brain states or synapse states, rather like letters being written into clay.  Referring to "the transcriptional signature that encodes a memory in neurons" is rather like saying the words from your lips are a tape  recorder that permanently store what you are saying. But since "transcriptional signatures" bear no resemblance to sensory experience, it's far worse, and would be more like making the double-goofy claim that your heart rate fluctuations are a tape recorder that record all the words you speak. 

We should be extremely suspicious and skeptical whenever scientists suddenly start giving some new answer to a fundamental question,  an answer completely different from the answer they have been dogmatically declaring for years. For example, if scientists were to suddenly start telling us that galaxies are not held together by gravity (as they've been telling us for decades), but by, say, “dark energy pulsations,” we should be extremely skeptical that the new explanation is correct. In this case, there are very good reasons why the speculations in boldface above cannot be right.

Chromatin is a term meaning DNA and surrounding histone protein molecules. Histone molecules are not suitable for storing very long-term memories because they are too short-lived. 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 histone molecules are not a stable platform for storing very long-term memories that can last for 50 years. But what about DNA? The DNA molecule is stable. But there are several reasons why your DNA molecules cannot be storing your memories. The first reason is that your DNA molecules are already used for another purpose – the storing of genetic information used in making proteins. DNA molecules are like a book that already has its pages printed, not a book with empty pages that you can fill. The second reason is that DNA molecules use a bare bones “amino acid” language quite unsuitable for writing all the different types of human memories. The idea that somewhere your DNA has memory of your childhood summer vacations (expressed in an amino-acid language) is laughable.

The third reason is that the DNA of humans has been exhaustively analyzed by various multi-year projects such as the Human Genome Project and the ENCODE project, as well as various companies that specialize in personal analysis of the DNA of individual humans. Despite all of this huge investigation and analysis, no one has found any trace whatsoever of any type of real human memory (long-term or short-term) being stored in DNA. If you do a Google search for “can DNA store memories,” you will see various articles (most of them loosely-worded, speculative and exaggerating) that discuss various genetic effects (such as gene expression) that are not the same as an actual storage of a human memory. Such articles are typically written by people using the word “memories” in a very loose sense, not actually referring to memories in the precise sense of a recollection.

The fourth reason is that there is no known bodily mechanism by which lots of new learned information can be quickly written to the storage area inside a DNA molecule. The fifth reason is that the DNA we see in brain neurons is basically identical to the DNA we see in other parts of the body (such as the DNA from foot cells). If memories were stored in DNA, the DNA in brain neurons would be much different from that of the DNA in other body parts.  We can read DNA (including an epigenome) from dead bodies, and no one has ever found a memory in a dead body. 

It takes about 1 minute for a cell to read only the small part of the DNA needed to make a single protein (and DNA has recipes for thousands of proteins). If your memories were stored in DNA, it would take you hours to remember things that you can actually recall instantly. Thinking that DNA can store your memories is like thinking that your refrigerator can print out your resume. 

The epigenome consists of chemical "marks" on particular parts of DNA that can act to turn off or turn on particular genes. We already know the function of such chemicals (a function different from memory), and no one has any credible theory of how such chemicals could possibly fulfill such a function and also do the infinitely more complex task of storing a memory (which would be something like a functional broom that also lets you fly around like a witch).  Reading and writing such chemical "marks" is a very slow affair, meaning the epigenome can't be the explanation for realities such as the instant recall of a memory or the instant formation of a new permanent memory. 

But couldn't very-long term memories just be stored in some unknown part of a neuron? No, because the proteins that make up neurons have short lifetimes. A scientist explains the timescales:

"Protein half-lives in the cell range from about 2 minutes to about 20 hours, and half-lives of proteins typically are in the 2- to 4-hour time range. Okay, you say, that's fine for proteins, but what about 'stable' things like the plasma membrane and the cytoskeleton? Neuronal membrane phospholipids turn over with half-lives in the minutes-to-hours range as well. The vast majority of actin microfilaments in dendritic spines of hippocampal pyramidal neurons turn over with astonishing rapidity—the average turnover time for an actin microfilament in a dendritic spine is 44 seconds...As a first approximation, the entirety of the functional components of your whole CNS [central nervous system] have been broken down and resynthesized over a 2-month time span. This should scare you. Your apparent stability as an individual is a perceptual illusion."

There is no credible theory of how human learned memories could be stored and retrieved by brains. The low-level facts we have learned about the brain reveal it to be an organ with enormous signal noise, unreliable synaptic transmission, billions of synaptic-gap signal slowers, and very high molecular turnover, an organ bearing no resemblance to a system for permanently storing and instantly retrieving memories with high information accuracy.  The fact that the NIH  bet $1,434,188 on some new theory of neural memory completely different from the memory storage doctrine neuroscientists have been teaching for decades is something that should lead us to suspect cognitive neuroscientists are in disarray, and very much lacking in credibility in their statements about brains and memory.  Similarly, you should have little confidence in some  astronomer if he told you (after twenty years of telling you that star shine is caused by nuclear fusion) that now he has a totally different theory of what causes starlight.

The project I refer to above  (NIH Project # 1DP2MH129985-01 discussed on this page) has now completed. From the standpoint of reaching its stated goals, the project was a failure. The project had a title of "The epigenetic encoding of learning and memory," but it did nothing to show any such thing. The project's official page lists a project end date of August 31, 2024. On this official project page there is an Outcomes section where a project manner might boast about successful outcomes produced. That section of the page is empty, as shown below:

On the same official project page, there is a Publications section that lists 11 publications that resulted from this project. There is a triple-listing for one of the papers, so actually only nine papers are listed.  None of them do anything to establish the "epigenetic encoding of learning and memory" mentioned in the project title.  The nine papers are these:

• "Autism spectrum disorder risk genes have convergent effects on transcription and neuronal firing patterns in primary neurons" (link). This is some laboratory study failing to mention memory or learning. 
• "Histone variants: expanding the epigenetic potential of neurons one amino acid at a time." The paper is behind a paywall. The abstract says nothing relevant, other than the bare claim that histone variants have a role in memory. 
• "Control of striatal circuit development by the chromatin regulator Zswim6" (link). This paper makes no mention of memory or learning. 
• "Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory" (link). The study provided no good evidence to back up its claim that H2BE has any relation to memory. To test the claim, the study produced "H2BE knockout" mice, whose performance was compared to normal test mice. The first test used was a "novel object recognition" test that is not an effective way of judging animal memory when a blinding protocol is not followed, and the result reported was an unimpressive "p < .05" (widely regarded as a marginal result easy to obtain by chance). In the test scientists attempted to judge how much time a mouse spends exploring a type of object it has already been exposed to, using manual scoring -- we are told, "Time spent interacting with each object was manually analyzed." Such a test is not a reliable way of judging memory in rodents whenever there is a failure to follow a blinding protocol, and no mention is made that a blinding protocol was followed. The unreliability of "novel object recognition" types of tests is discussed in my post here. The second and third tests used (Figures 6I and 6J) were tests requiring a judgment of "freezing behavior," and such tests are utterly unreliable in judging whether an animal recalled, for reasons discussed at length here.  These second and third tests as presented in this paper look fishy, as there is no real difference between the "H2BE knockout" mice and the control mice in a "freezing behavior" claimed test of memory taken after an interval of 24 hours or 48 hours (Figures 6I and 6J), with the authors having to retry the test at a 14-day or 15-day interval before they could get something they claimed as a positive result. That has a "keep testing until you can claim  the desired result" smell to it.  The paper has no robust evidence that the "H2BE knockout" produced a harm in the memory of the tested mice, and its reported results at the 24 hour interval and the 48 hour interval suggest that the knockout did not harm the memory of the mice. 
• "A nociceptive amygdala-striatal pathway for chronic pain aversion" (link). No mention is made of learning or memory in this paper. 
• "Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder" (link). The authors first discuss 11 humans who had variations in something called DOT1L The paper claims that 2 of these 11 had "intellectual disability" without giving us any specifics. This does not constitute any evidence of a relation between this DOT1L and memory. The paper also claims that DOT1L modification in zebrafish had some effect on their cognitive performance. But the claim has no clear reference to memory, and the claim is not demonstrated, because the number of zebrafish tested is way too small, being only 3 zebrafish. There is then a claim that DOT1L modifications have some effect on mice. But no clear claim is made of an effect on memory performance. 
• "Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling" (link). The research discussed does not involve learning or memory. 
• "SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry" (link). The research discussed does not involve learning or memory. 
• "Identification of a transcriptional signature found in multiple models of ASD and related disorders" (link). The research discussed does not involve learning or memory. It merely makes a passing reference to memory, claiming (without providing any specifics) that a "histone code" plays a role in memory. 

So that is the entire set of papers that resulted from the $1,434,188 spent on NIH Project # 1DP2MH129985-0. The project had the wildly speculative title "The epigenetic encoding of learning and memory," but the project did nothing to establish that any such thing exists. The project did nothing to establish any of the claims made in the project description quoted above. Does this mean that the synaptic theory of memory is redeemed? Certainly not. The evidence for the synaptic theory of memory is just as bad as the evidence for the theory that memory is stored in the chromosome or its DNA or chromatin or the epigenome. There is no theory of a brain storage of memory that is well-supported by evidence. All such theories fail to hold up to scrutiny. 

A search on Google Scholar for recent papers on the topic of "epigenetic memory" fails to find much of anything claiming that epigenetics can explain human episodic or conceptual memory.  The search gives some papers that are mainly using the term "epigenetic memory" to talk about something involving plants or muscles.  The project discussed above seems to have caused no news headlines claiming an epigenetic encoding of memory. A search on Google scholar for "epigenetic encoding of memory" produces only two results, neither of which is a scientific paper published in the past ten years. A search on Google scholar for "epigenetic encoding of learning" produces no results.  

Newspaper Accounts of Memory Marvels (Part 4)

 The credibility of claims that memory recollections come from brains is inversely proportional to the speed and capacity and reliability at which things can be recalled. There are numerous signal slowing factors in the brain, such as the relatively slow speed of dendrites, and the cumulative effect of synaptic delays in which signals have to travel over relatively slow chemical synapses (by far the most common type of synapse in the brain). As explained in my post here, such physical factors should cause brain signals to move at a typical speed very many times slower than the often cited figure of 100 meters per second: a sluggish "snail's pace" speed of only about a centimeter per second (about half an inch per second).  Ordinary everyday evidence of very fast thinking and instant recall is therefore evidence against claims that memory recall occurs because of brain activity, particularly because the brain is totally lacking in the things humans add to constructed objects to allow fast recall (things such as sorting and addressing and indexes). Chemical synapses in the brain do not even reliably transmit signals. Scientific papers say that each time a signal is transmitted across a chemical synapse, it is transmitted with a reliability of 50% or less.  (A paper states, "Several recent studies have documented the unreliability of central nervous system synapses: typically, a postsynaptic response is produced less than half of the time when a presynaptic nerve impulse arrives at a synapse." Another scientific paper says, "In the cortex, individual synapses seem to be extremely unreliable: the probability of transmitter release in response to a single action potential can be as low as 0.1 or lower.")  The more evidence we have of very fast and very accurate and very capacious recall (what a computer expert might call high-speed high-throughput retrieval), the stronger is the evidence against the claim that memory recall occurs from brain activity. 

It is therefore very important to collect and study all cases of exceptional human memory performance. The more such cases we find, and the more dramatic such cases are, the stronger is the case against the claim that memory is a neural phenomenon. Or to put it another way, the credibility of claims that memory is a brain phenomenon is inversely proportional to the speed and reliability of the best cases of human mental performance.  The more cases that can be found of humans that seem to recall too quickly for a noisy address-free brain to do ever do, or humans that seem to recall too well for a noisy, index-free, signal-mangling brain to ever do,  the stronger is the case that memory is not a neural phenomenon but instead a spiritual or psychic or metaphysical phenomenon.  In part 1  and part 2 and part 3 of this series, I gave many newspaper clips giving examples of such exceptional human memory performance. Let us now look at some more of such newspaper clips. 

The 1906 account below is one that is rather hard-to-believe, as it is a claim that a man memorized the entire Bible.

You can read the claim on the newspaper page here:

https://chroniclingamerica.loc.gov/lccn/sn84026843/1906-08-24/ed-1/seq-5/

It is well known that quite a few Muslim scholars memorized the entire Quran, a work of 6236 verses. In the newspaper story here, we read of a 90-day scripture memorization contest; and we have the claim that the winner memorized the entire New Testament (a work of 7,957 verses) and also a good deal of the Old Testament: 

"On the day of the award it was found that among the older competitors the winner was Miss Leste May Williams, a young woman 16 years of age. With these ninety days, during which she had an attack of measles, she committed to memory and recited to the committee 12,236 verses of Scripture, covering the entire New Testament ...and including liberal selections from Genesis, Psalms, Ecclesiastes and other parts of the Old Testament."

The length of memorization claimed above (roughly 10,000 verses) is in the same league as the claim made in a scientific paper that between age 59 and age 67 a person memorized all 10,565 lines of Milton's Paradise Lost, recalling the entire work over a three-day period. But the total number of verses in the Bible is about 31,102.  So a person memorizing the entire Bible would seem to display an unprecedented human ability of memorization, in terms of the total length. 

The 1923 news story here in the Washington Times claimed that  H. H. Halley had memorized the entire New Testament. The 1926 newspaper account here claims that H. H. Halley of Chicago, USA memorized the entire Bible. The same paper (the Indianapolis Times) had made the same claim in the 1925 newspaper account here. 

In the 1888 newspaper article here, we read of a Rev. Nathan Smith here, and it claimed that he had memorized the entire Bible. We are told he can name the verse, chapter and book of any Bible quotation. 

The newspaper page here has in its "Lived Under All Presidents" article a claim that an old woman named Elizabeth Freeman "memorized nearly the entire Bible."

The newspaper account below appeared in 1925.

"Germans believe that a member of the staff of the Prussian State library has the finest memory in the world. He has specialized in weather reports and from memory he can describe the weather of any day from 1881 up to the present time. His wonderful memory recently was tested by the Berlin Meteorological society and he came through with flying colors. Colonel Charratle of England once memorized the entire Issue of a newspaper on a wager; a stoker memorized Haydn’s  'Dictionary of Dates,' and Lord Randolph Churchill, also of England, was able to repeat a page of print after a single reading."

You can read the account on the page below:

https://chroniclingamerica.loc.gov/lccn/sn83032307/1925-08-27/ed-1/seq-5/

The account above refers to a perfect recall of weather reports over a period of 44 years (1881 to 1925), involving about 16,000 days. If we assume that each weather report would require on average a number of words equal to a single verse, the claim above is roughly equivalent to a claim that a man memorized  a body of material about as long as 16,000 verses.

Below are some accounts of extraordinary memory powers held long ago, from the newspaper account here:

The newspaper account claims that Thomas Cranmer memorized an entire translation of the Bible, and that Lord Granville memorized the entire New Testament. We also have a claim that a Corsican could repeat in order 36,000 names, and could also repeat the names in reverse order. 

In the newspaper account below, from the page here, we have a claim that a man memorized a catalog of more than 1,100 pages, and that he demonstrated his memorization of the catalog:

In the 1963 newspaper account here, we read of a man who every week would memorize the entire Saturday Evening Post, a magazine that at that time would have very many pages in each edition, with a page typically consisting of three of four columns of small print adding up to more than 700 words per page.

In the newspaper account here, we read of an opera singer with an astonishing memory: 

"Julia Rosewald, the prima donna with the Abbott opera company, has, perhaps, the most astonishing memory on the lyric stage. Her repertoire consists of sixty-eight operas, in nine of which she sings double roles. Besides this marvelous selection she adds ten oratorios, and what is more wonderful still, she memorizes the entire work and will instantly detect the slightest error in harmony or instrumentation. The rapidity with which she studies is almost incredible. On one occasion, to save the company, she studied an entirely new role in twenty-four consecutive hours, and without rest appeared in the part without an error. This is vouched for by the conductor, Tomasi, and the entire company."

Derek Paravicini was born 25 weeks early, with severe brain damage, but he has reliably demonstrated countless times the ability to very accurately play back on a keyboard any song that is played to him, note for note, even if he has never heard the song before. In the newspaper account below, which can be read here, the claim is made that such an ability was demonstrated repeatedly by an entire orchestra, which could play from memory some newly written march it had only heard once.. We read this:

"Practically all Latin Americans possess, in marked degree, what is known as ‘musical memory'....This ability to memorize has been exemplified on many occasions in San Antonio, Tex., when the visiting Mexican band has been asked to ‘stand by’ while the latest march from the United States is being played by the American band. With all standing at attention, the Mexican bandsmen have waited until the finish of the first strain and then came the marvelous test; the playing of this number in harmony by the entire group. Audiences have been astounded at this exhibition and some in the audience have expressed the thought that ‘there was some trick in it.’ That is absolutely true, for there is a trick, but it has taken thousands of years to produce it, and it is in the form of this musical memory . .. Leaders of the great orchestras in Latin America, with but little effort, are able to memorize the entire scores of dozens of operas.”

In support of such a claim, you could cite the huge number of opera roles memorized by Placido Domingo, who knew 151 opera roles in several different languages. 

On the newspaper page here, we have the claim that the Belgian shcolar Joest Lips (also called Justus Lipsius) memorized the entire text of the Histories of Tacitus, a work of 50,000 words. The page also claims that he once challenged a man to stand over him with a dagger, and to stab him if he transposed a single word. 

When Neuroscientists Doing Shoddy Studies Make Grandiose Boasts

Misleading statements are extremely abundant in neuroscience literature. One incredibly common type of misstatement is when neuroscientists produce scientific papers that claim in their titles and abstracts to have shown things that their research never showed.  You should never forget that you simply cannot take for granted the truth of achievement claims made in the titles or abstracts of biology papers, which often do not correspond to any achievements made in the paper. Then there are the huge number of misstatements made in university and college press releases announcing new science research. Such press releases often make grand achievement claims not matching any claims made by the scientific papers the press releases are promoting. 

In such cases a neuroscientist may be able to semi-credibly claim that it was not him who was deceiving people. Neuroscience papers typically have many different authors. So if you are one of seven authors of a neuroscience paper with a title claiming to have shown something the study did not actually show, you might be able to make a claim such as: "It was not me who wrote the title." If you are a co-author of a paper that is incorrectly described by a university press release making groundless boasts, then maybe you can semi-credibly say something like, "Well, you know how those PR guys are -- they are always making crumbs sound like castles." I don't find such excuses to be very credible. If you are a researcher at a university, and a press release is being written to announce your research, you should be able to review that press release for accuracy, and to make sure it does not make boastful misstatements about your research. 

In the case of a personal narrative in which one individual scientist makes untrue claims that something was done by him or his team of scientists, we have a case in which such excuses for misstatements cannot be used. If scientist Joe Smith says, "My colleagues and I have shown..." and makes a claim that is untrue, then we have very clear evidence that scientist Joe Smith has not told us the truth. In such a case Joe Smith cannot excuse his misstatement by using some "joint authorship" excuse or some excuse in which misstatements are blamed on overenthusiastic "hype everything" public relations writers. 

In the article here, we have an example of a neuroscientist personal narrative with some accuracy shortfalls. The article entitled "While do some memories stick while others fade" is written by neuroscientist Sadegh Nabavi.  Referring to a recently published study that he co-authored (a very bad example of poorly-designed junk science), Nabavi makes some grand boasts of achievement that are untrue. 

Nahavi starts out by stating a half-truth. He states this: "Research shows that emotionally impactful events strengthen the neural connections in the brain that store our memories." It is true that emotions help us remember things better and longer, but there is no scientific basis for the claim that it is "neural connections in the brain that store our memories." No memories have ever been found in a brain by microscopic examination. 

Nahavi then begins boasting, telling us this:

"My colleagues and I conducted a study using mouse models, whose brain functions are remarkably similar to humans. Our findings offer new insights into what happens in the brain during memory formation and help explain why some things are remembered while others are not."

Mice have brain functions remarkably similar to humans? This is not a story line that a "brains make minds" persons should feel comfortable making, given the gigantic difference between the intellectual capabilities of mice and humans. The paper referred to offers no such insights, because of defects in it I will soon list. 

Nahavi then makes this claim:

"Scientists agree that memories are formed (and lost) by changes in the strength of these synapses—a process known as synaptic plasticity. Synaptic plasticity can be increased or decreased in two ways: by altering the number of synapses or by making existing synapses larger or smaller."

The claim about scientists agreeing on this topic is untrue. The claim that memory is stored by changes in synapse strength is an utterly untenable theory, for a large number of reasons I explain in my post here, entitled "10 Reasons Synapses Cannot Be a Storage Place for Human Memories." Quite a few scientists have recognized that claims of memory storage by synapse strengthening are untenable or dubious, or recognized that scientists lack any well-established or credible theory of memory creation. I quote some of these scientists in the appendix of this post.

Nahavi makes this misleading claim: "At the same time, we observed that the synapses active during the event were strengthened – either by forming more channels or by expanding existing ones." Mice have billions of synapses, most of which are continually active at any given time, because neurons throughout the brain are constantly firing at random intervals, (between about 1 and 200 times a second), and that causes activity in synapses. It is utterly beyond today's technology to simultaneously study all the active synapses in the brain of a rodent, or even a hundredth of them, to tell whether they are strengthening.  And it is utterly untrue that when something is learned, particular synapses act in some distinctive way different from average synapses, some "standout" way that would allow a neuroscientist to credibly say, "Oh, I see, those are the synapses that are storing the memory just learned." 

What happens in studies like this is that scientists will arbitrarily pick some tiny fraction of a rodent's synapses to study, some miniscule fraction like .000001 of the total synapses.  It is misleading to identify some tiny fraction of these synapses (chosen for study by neuroscientists) as "synapses active during the event," when 99.99% of the synapses that were active are not being studied.  Synapses throughout a brain are continually undergoing random changes that may be interpreted as strengthening or weakening. We know this because synapses are connected to dendritic spines that have short lifetimes, and also because synapses are built from proteins that have an average lifetime of only a few weeks or less. There is no way to convincingly correlate the strengthening of some little group of synapses with an experience event of an organism. What goes on in studies such as this is that some tiny group of synapses will be chosen for study, and neuroscientists will act as if they luckily happened to have chosen some group of synapses that are being affected by something a mouse recently experienced. Such an assumption is never warranted. 

What goes on is cases like this is like what might go on if someone had the theory that his memories are stored in flowers. Such a person might choose for study a few of the flowers in Central Park, and observe that the flowers were growing stronger as he got more memories by taking a school course. This would be nonsense, because flowers getting stronger is something happening continuously and massively, and there would be no sound basis for correlating the observed strengthening of a few flowers and your memory formation. Similarly, because in every brain there are always countless synapses strengthening and countless synapses weakening, you never validate some theory of synapse memory storage by showing that some synapses strengthened when something was learned. 

Nahavi then begins to make grandiose boasts. He claims to have found a memory in a mouse brain, and to have "activated" such neurons. He claims to have observed that there was synapse strengthening that had something to do with memory. He claims to have affected memory recall in a mouse by artificially strengthening synapses. 

"We strongly activated the neurons encoding the weak memory....In this case, the mice were able to recall the aversive memory even the following day. At the same time, we observed that the synapses active during the event were strengthened ...In our experiment, we artificially strengthened certain synapses, even though they weren’t directly linked to the trivial experience. The result? The mice could recall the 'trivial' event the next day. Even more interestingly, the synapses encoding the trivial experience also became stronger."

The claims are mostly false. The claim about "neurons encoding the weak memory" does not even agree with Navavi's earlier claim that synapses store memories. Neurons are not synapses.  Nahavi and his guys did not actually find any "neurons encoding the weak memory"; they did not actually find any good evidence that memory creation strengthens synapses; and they did not actually show that memory recall in a mouse can be changed by artificially strengthening certain synapses. The main reason none of these was done is that  Nahavi's paper is a very poorly-designed piece of junk science, guilty of very bad examples of Questionable Research Practices and an unreliable measurement technique (attempting to judge freezing behavior). 

Some of the defects of the paper are these:

(1) The study group sizes were way too small for any decent statistical power to be claimed. The study group sizes were way-too-small sizes such as only 4 mice or only 6 mice or only 9 mice, and never more than 11. As a general rule, no experimental neuroscience paper should be taken seriously unless it uses at least 15 or 20 subjects per study group; and usually a higher study group size is needed to produce a decent statistical power. 

The authors would have found out that the study group sizes they used were grossly inadequate if they had done a sample size calculation, like good experimental scientists; but they failed to do such a calculation. 

(2) No blinding protocol was used, and no study of this type should be taken seriously unless a rigorous and through blinding protocol was used. 

(3) The study was totally dependent upon a very unreliable method for judging whether mice recalled, the technique of trying to judge "freezing behavior." All studies using such a technique are junk science, for reasons explained at length in my post here. 

When this utterly unreliable technique is used, observers will look at mice, and attempt to judge whether they recalled a fearful stimulus, purely based on the percentage of time that is mouse is immobile, during some arbitrary time length (which can vary between 30 seconds and 180 seconds, based on the arbitrary whim of a researcher).  Such a technique does not reliably measure fear recall in mice. Mice afraid of something are just as likely or more likely to flee as to "freeze" or become immobile. So you cannot reliably tell whether a mouse is recalling something by trying to judge their immobility during some time span, and calling that "freezing behavior." Living a decade in an apartment where mice would appear an average of maybe 5 or 10 times a year, I never once saw a mouse "freeze in fear" when suddenly seeing a human who shrieked at the sight of the mouse. Instead, the behavior would inevitably be a fleeing behavior. 

There are reliable techniques for measuring fear recall in mice. You can measure heart rate, which has a very strong spike when mice are afraid. Or you can use a simple "fear stimulus avoidance" technique like the one shown below. With such a setup, if a mouse recalls a fearful stimulus, it will take the harder path to a food reward; it if does not recall, it will take the easier path. 

Why do neuroscientists continue to use the utterly unreliable method of trying to measure fear recall in rodents by trying to judge "freezing behavior"? Because such a technique is a "see whatever you want to see" type of thing allowing a neuroscientist to report whatever he wants to report. All papers using "freezing behavior" judgments are junk science, including Nahavi's paper. 

(4) We have in the paper claims such as "Mice showed significantly increased freezing response during optical stimulation." The optical stimulation was optogenetic brain-zapping. Mice were brain-zapped, and a claim made that this was producing memory recall of a fearful stimulus, because a mouse was inactive, interpreted as "freezing behavior." But zapping a mouse's brain can itself produce freezing behavior, even when no recall is involved. A science paper says that it is possible to induce freezing in rodents by stimulating a wide variety of regions. It says, "It is possible to induce freezing by activating a variety of brain areas and projections, including the hippocampus (Liu et al., 2012), lateral, basal and central amygdala (Ciocchi et al., 2010); Johansen et al., 2010; Gore et al., 2015a), periaqueductal gray (Tovote et al., 2016), motor and primary sensory cortices (Kass et al., 2013), prefrontal projections (Rajasethupathy et al., 2015) and retrosplenial cortex (Cowansage et al., 2014).”

So any experiment trying to judge recall during brain-zapping (as judged by "freezing behavior") is guilty of doing things in a doubly-unreliable way. Trying to judge recall by judging "freezing behavior" is unreliable by itself; and doing such a thing while zapping a mouse's brain (which can produce freezing behavior by itself) is doubly-unreliable. 

Nahavi's method here seems as silly as that of some scientist who claims that memories are stored in a human's cheek, and who tries to test this claim by giving someone an embarrassing memory and then slapping him hard five times on the cheek, with the scientist claiming that the person's resulting red cheek is caused by stimulation of the memory cells in the person's cheek, which caused a blush after the embarrassing memory was recalled. This would be nonsense. The red cheek could be explained as merely a response to the slapping, without assuming any memory recall. And if mice engage in more "freezing behavior" when brain-zapped, that's just more evidence that brain-zapping tends to cause non-movement or "freezing behavior," not evidence of memory recall.  

What these kind of "memory experiments" mainly tell us about is the rather bad memory of some neuroscientists. 

Another recent example of a neuroscientist making groundless boasts of having done grand things is to be found in the article here. A neuroscientist makes these boasts:

"We wanted to know if there are cells that organise the knowledge of our behaviour, rather than the outside world, and how they work. Specifically, what are the algorithms that underlie the activity of brain cells as we generalise from past experience? How do we rustle up that new pasta dish?

And we did find such cells. There are neurons that tell us 'where we are' in a sequence of behaviour (we haven’t named the cells)."

The neuroscientist is referring to his paper "A cellular basis for mapping behavioural structure," which is an example of a junk science study because of its use of way-too-small study group sizes, and its lack of any blinding protocol.  The study group sizes were merely sizes such as 7 mice, 9 mice and 13 mice, way too small for any decent statistical power. We have in the paper the typical confession that occurs when authors fail to do a sample size calculation. We read, "No statistical methods were used to pre-determine sample sizes but our sample sizes are similar to those reported in previous publications (for example, in ref. 12)."  This is like someone saying "I cheated on my income tax, but it's okay because my friends also cheat on their income taxes."  The use of way-too-small study group sizes is a deplorable epidemic in today's neuroscience research. You do nothing to show that your study group sizes were large enough by claiming that other researchers are also using similar study group sizes. 

Appendix: The statements below show that Nahavi was not correct when he claimed "scientists agree that memories are formed (and lost) by changes in the strength of these synapses—a process known as synaptic plasticity."  There is no such agreement, and in the statements below, scientists express skepticism about such a claim or the claim that scientists know how memories are created. 

• "Direct evidence that synaptic plasticity is the actual cellular mechanism for human learning and memory is lacking." -- 3 scientists, "Synaptic plasticity in human cortical circuits: cellular mechanisms of learning and memory in the human brain?" 
• "The fundamental problem is that we don't really know where or how thoughts are stored in the brain. We can't read thoughts if we don't understand the neuroscience behind them." -- Juan Alvaro Gallego, neuroscientist. 
• "The search for the neuroanatomical locus of semantic memory has simultaneously led us nowhere and everywhere. There is no compelling evidence that any one brain region plays a dedicated and privileged role in the representation or retrieval of all sorts of semantic knowledge."  -- Psychologist Sharon L. Thompson-Schill, "Neuroimaging studies of semantic memory: inferring 'how' from 'where' ".
• "How the brain stores and retrieves memories is an important unsolved problem in neuroscience." --Achint Kumar, "A Model For Hierarchical Memory Storage in Piriform Cortex." 
• "We are still far from identifying the 'double helix' of memory—if one even exists. We do not have a clear idea of how long-term, specific information may be stored in the brain, into separate engrams that can be reactivated when relevant."  -- Two scientists, "Understanding the physical basis of memory: Molecular mechanisms of the engram."
• "There is no chain of reasonable inferences by means of which our present, albeit highly imperfect, view of the functional organization of the brain can be reconciled with the possibility of its acquiring, storing and retrieving nervous information by encoding such information in molecules of nucleic acid or protein." -- Molecular geneticist G. S. Stent, quoted in the paper here. 
• "Up to this point, we still don’t understand how we maintain memories in our brains for up to our entire lifetimes.”  --neuroscientist Sakina Palida.
• "The available evidence makes it extremely unlikely that synapses are the site of long-term memory storage for representational content (i.e., memory for 'facts'’ about quantities like space, time, and number)." --Samuel J. Gershman,  "The molecular memory code and synaptic plasticity: A synthesis."
• "Synapses are signal conductors, not symbols. They do not stand for anything. They convey information bearing signals between neurons, but they do not themselves convey information forward in time, as does, for example, a gene or a register in computer memory. No specifiable fact about the animal’s experience can be read off from the synapses that have been altered by that experience.” -- Two scientists, "Locating the engram: Should we look for plastic synapses or information- storing molecules?
• " If I wanted to transfer my memories into a machine, I would need to know what my memories are made of. But nobody knows." -- neuroscientist Guillaume Thierry (link). 
• "While a lot of studies have focused on memory processes such as memory consolidation and retrieval, very little is known about memory storage" -- scientific paper (link).
• "While LTP is assumed to be the neural correlate of learning and memory, no conclusive evidence has been produced to substantiate that when an organism learns LTP occurs in that organism’s brain or brain correlate."  -- PhD thesis of a scientist, 2007 (link). 
• "Memory retrieval is even more mysterious than storage. When I ask if you know Alex Ritchie, the answer is immediately obvious to you, and there is no good theory to explain how memory retrieval can happen so quickly." -- Neuroscientist David Eagleman.
• "How could that encoded information be retrieved and transcribed from the enduring structure into the transient signals that carry that same information to the computational machinery that acts on the information?....In the voluminous contemporary literature on the neurobiology of memory, there is no discussion of these questions."  ---  Neuroscientists C. R. Gallistel and Adam Philip King, "Memory and the Computational Brain: Why Cognitive Science Will Transform Neuroscience,"  preface. 
• "The very first thing that any computer scientist would want to know about a computer is how it writes to memory and reads from memory....Yet we do not really know how this most foundational element of computation is implemented in the brain."  -- Noam Chomsky and Robert C. Berwick, "Why Only Us? Language and Evolution," page 50. 
• "When we are looking for a mechanism that implements a read/write memory in the nervous system, looking at synaptic strength and connectivity patterns might be misleading for many reasons...Tentative evidence for the (classical) cognitive scientists' reservations toward the synapse as the locus of memory in the brain has accumulated....Changes in synaptic strength are not directly related to storage of new information in memory....The rate of synaptic turnover in absence of learning is actually so high that the newly formed connections (which supposedly encode the new memory) will have vanished in due time. It is worth noticing that these findings actually are to be expected when considering that synapses are made of proteins which are generally known to have a short lifetime...Synapses have been found to be constantly turning over in all parts of cortex that have been examined using two-photon microscopy so far...The synapse is probably an ill fit when looking for a basic memory mechanism in the nervous system." -- Scientist Patrick C. Trettenbrein, "The Demise of the Synapse As the Locus of Memory: A Looming Paradigm Shift? (link).
• "Most neuroscientists believe that memories are encoded by changing the strength of synaptic connections between neurons....Nevertheless, the question of whether memories are stored locally at synapses remains a point of contention. Some cognitive neuroscientists have argued that for the brain to work as a computational device, it must have the equivalent of a read/write memory and the synapse is far too complex to serve this purpose (Gaallistel and King, 2009; Trettenbrein, 2016). While it is conceptually simple for computers to store synaptic weights digitally using their read/write capabilities during deep learning, for biological systems no realistic biological mechanism has yet been proposed, or in my opinion could be envisioned, that would decode symbolic information in a series of molecular switches (Gaallistel and King, 2009) and then transform this information into specific synaptic weights." -- Neuroscientist Wayne S. Sossin (link).
• "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."  -- Neuroscientists C. R. Gallistel and Adam Philip King, "Memory and the Computational Brain Why Cognitive Science Will Transform Neuroscience."  page Xvi (preface). 
• "Current theories of synaptic plasticity and network activity cannot explain learning, memory, and cognition."  -- Neuroscientist Hessameddin Akhlaghpourƚ (link). 
• "We don’t know how the brain stores anything, let alone words." -- Scientists David Poeppel and, William Idsardi, 2022 (link).
• "If we believe that memories are made of patterns of synaptic connections sculpted by experience, and if we know, behaviorally, that motor memories last a lifetime, then how can we explain the fact that individual synaptic spines are constantly turning over and that aggregate synaptic strengths are constantly fluctuating? How can the memories outlast their putative constitutive components?" --Neuroscientists Emilio Bizzi and Robert Ajemian (link).
• "After more than 70 years of research efforts by cognitive psychologists and neuroscientists, the question of where memory information is stored in the brain remains unresolved." -- Psychologist James Tee and engineering expert Desmond P. Taylor, "Where Is Memory Information Stored in the Brain?"
• "There is no such thing as encoding a perception...There is no such thing as a neural code...Nothing that one might find in the brain could possibly be a representation of the fact that one was told that Hastings was fought in 1066." -- M. R.  Bennett, Professor of Physiology at the University of Sydney (link).
• "No sense has been given to the idea of encoding or representing factual information in the neurons and synapses of the brain." -- M. R. Bennett, Professor of Physiology at the University of Sydney (link).
• ""Despite over a hundred years of research, the cellular/molecular mechanisms underlying learning and memory are still not completely understood. Many hypotheses have been proposed, but there is no consensus for any of these."  -- Two scientists in a 2024 paper (link). 
• "We have still not discovered the physical basis of memory, despite more than a century of efforts by many leading figures. Researchers searching for the physical basis of memory are looking for the wrong thing (the associative bond) in the wrong place (the synaptic junction), guided by an erroneous conception of what memory is and the role it plays in computation." --Neuroscientist C.R. Gallistel, "The Physical Basis of Memory," 2021.
• "To name but a few examples, the formation of memories and the basis of conscious  perception, crossing  the threshold  of  awareness, the  interplay  of  electrical  and  molecular-biochemical mechanisms of signal transduction at synapses, the role of glial cells in signal transduction and metabolism, the role of different brain states in the life-long reorganization of the synaptic structure or  the mechanism of how  cell  assemblies  generate a  concrete  cognitive  function are  all important processes that remain to be characterized." -- "The coming decade of digital brain research, a 2023 paper co-authored by more than 100 neuroscientists, one confessing scientists don't understand how a brain could store memories. 
• "The human brain isn’t really empty, of course. But it does not contain most of the things people think it does – not even simple things such as ‘memories’....We don’t create representations of visual stimuli, store them in a short-term memory buffer, and then transfer the representation into a long-term memory device. We don’t retrieve information or images or words from memory registers. Computers do all of these things, but organisms do not." -- Robert Epstein,  senior research psychologist, "The Empty Brain." 
• "Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy." -- Scientists claiming erroneously in 2024 that there have been recent advancements in identifying engram cells, but confessing there is no understanding of how they work (link).
• "Study of the genetics of human memory is in its infancy though many genes have been investigated for their association to memory in humans and non-human animals."  -- Scientists in 2022 (link).
• "The neurobiology of memory is still in its infancy." -- Scientist in 2020 (link). 
• "The investigation of the neuroanatomical bases of semantic memory is in its infancy." -- 3 scientists, 2007 (link). 
• "Currently, our knowledge pertaining to the neural construct of intelligence and memory is in its infancy." -- Scientists, 2011 (link). 
•  "Very little is known about the underlying mechanisms for visual recognition memory."  -- two scientists (link). 
• "Conclusive evidence that specific long-term memory formation relies on dendritic growth and structural synaptic changes has proven elusive. Connectionist models of memory based on this hypothesis are confronted with the so-called plasticity stability dilemma or catastrophic interference. Other fundamental limitations of these models are the feature binding problem, the speed of learning, the capacity of the memory, the localisation in time of an event and the problem of spatio-temporal pattern generation."  -- Two scientists in 2022 (link). 
• "The mechanisms governing successful episodic memory formation, consolidation and retrieval remain elusive,"  - Bogdan Draganski, cogntive neuroscientist (link). 
• " The mechanisms underlying the formation and management of the memory traces are still poorly understood." -- Three scientists in 2023 (link). 
• "The underlying electrophysiological processes underlying memory formation and retrieval in humans remains very poorly understood." --  A scientist in 2021 (link). 
• "As for the explicit types of memory, the biological underpinning of this very long-lasting memory storage is not yet understood." -- Neuroscientist Cristina M. Alberini in a year 2025 paper (link). "