When PR for Junk Neuroscience Studies Is Passed Off as "Medical News"

The site MedicalXPress.com is a site that positions itself as a medical news site. The site seems to be one of those sites (such as ScienceDaily.com or Eurekalert.com) that mainly just uncritically publishes the latest university and college press releases, and positions its latest collection of these as either "science news" or "medical news." What's wrong with that? Well, for one thing,  university and college press releases these days are  notorious for their hype, exaggerations, misstatements and frequent untrue headlines, when they are announcing newly published research done at their institution.  So if you run a site that mostly publishes unedited the latest latest research press releases of universities and colleges, you are aiding and abetting the proliferation of false and misleading information. 

Another thing wrong with what goes on at MedicalXPress.com is that the site is guilty of frequently trying to pass off very low-quality neuroscience research as "medical news."  The type of junk rodent research that neuroscientists typically do has no relevance to human health, and it is often very misleading to be selling such shoddy work as medical news, particularly since the work did not involve any attempt to develop a medicine or treatment for humans. 

Let's look at an example of some of the news items that have appeared at the site, involving work utterly unworthy of the attention of people interested in keeping up with medical news. A recent article at the site had the untrue headline "Study shows that dendritic plasticity contributes to the integration of memories."  It was an article attempting to persuade us that microscopic structures in brains called dendritic spines have something to do with memory. There is no good evidence that this is true. 

By the third paragraph of the article, we got some baloney shoveling. Scientist Alcino Silva made grandiose boasts about a very low quality study he co-authored, stating, "A few years back, in a landmark study published in Nature in 2016, we demonstrated that memories formed a few hours apart are linked because they are stored in a common set of neurons in the hippocampus." He was referring to his very low-quality junk science study "A shared neural ensemble links distinct contextual memories encoded close in time," which you can read here.  It was a rodent study using way-too-small study group sizes such as only 4 or 7 or 8 mice. No study of this type should be taken seriously unless it uses at least 15 or 20 subjects per study group. The study also hinged upon the utterly unreliable technique of trying to judge recall in rodents by making subjective judgments of so-called "freezing behavior."  All neuroscience studies that use that utterly unreliable technique are examples of junk science, for reasons I explain here.  The fact that this study has been cited over 1000 times shows the dismally dysfunctional state of neuroscience, in which researchers routinely cite very low-quality junk science studies. 

We then have an equally grandiose and equally groundless boast by another neuroscientist. We read, " 'We showed that when mice form two memories close in time, we can see that many of the same somas, dendritic branches, and spines are involved in forming these two memories,' explained Megha Sehgal, the first author and a co-corresponding author of the paper." Nothing of the sort was done. Dendritic spines are constantly forming and disappearing throughout the brains of every mammal. On any day in the brain of any mammal, there are many millions of dendritic spines appearing; there are many millions of dendritic spines disappearing; there are many millions of dendritic spines enlarging; and there are many millions of dendritic spines shrinking. An observation of something happening to dendritic spines is never evidence that those dendritic spines had anything to do with the formation of a memory. 

Later, getting very excited about her grandiose but groundless claims, Seghal states this: "When we forced independent memories to be stored in the same neuronal somas or even the dendrites and found just this simple intervention in one brain region, the retrosplenial cortex, was enough to link these memories!" The claims are groundless. Scientists have no evidence that memories are stored in any place in a brain, and any claim by a scientist that he or she forced a memory to be in some particular place is a bogus boast. 

The groundless boasts being made are based on research reported in the very low-quality paper here, a paper entitled "Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time." It's the usual type of very low-quality work we see from rodent memory researchers.  The paper uses way-too-small study group sizes such as only 4 mice per group or only 9 mice group or only 12 mice per group. No rodent research paper of this type using fewer than 20 subjects per study group should be taken seriously, unless it mentions that did a sample size calculation showing that fewer than 20 subjects was sufficient to achieve a good statistical power such as 80% (which this paper does not).  Again, we have a paper that hinges upon attempts to measure rodent recall by using the utterly unreliable technique of trying to judge  "freezing behavior." All neuroscience studies that use that utterly unreliable technique are examples of junk science, for reasons I explain here.  

Among the very many reasons why attempting to judge "freezing behavior" is a marker of junk neuroscience is the fact that there is no standard approach as to how such judgments occur, in regard to the interval of time used. So a researcher can try to judge a mouse's immobility for three minutes, and if he gets a claimed "freezing percentage" he likes, he can use that; but if the percentage is not what he likes, he can use only the first two minutes; and if that percentage is not what he likes, he can use only the first minute; and if that percentage is not what he likes, he can use only the first 30 seconds. That is a "see whatever you want to see" kind of deal, rather than trustworthy measurement. To help show that is not going on, a researcher must always list the time interval used for each and every one of his "freezing behavior" graphs, to show that at least the same time interval was used each time. In the case of the the very low quality paper I am discussing here, the paper "Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time," we see many "freezing behavior" graphs, none of which mention the time interval corresponding to the graph.  This is science at its clumsiest. Were these claimed degrees of freezing behavior occurring over 30 seconds, 60 seconds, 90 seconds, 120 seconds, or 180 seconds? We are not told, and we cannot tell whether the time interval is different for each graph. So we cannot even tell whether there is a match between the technique used and experimental conventions of neuroscientist rodent researchers. 

Because no reliable technique was used to measure fear or recall, we should disbelieve the claim made in the MedicalXPress article that "Silva, Sehgal and their colleagues found that, following their experimental intervention, mice became scared of a box that was previously unimportant to them, simply because the memory of this box was stored in the same dendrites that stored memories of a box in which they experienced an electric shock."  Such researchers could  have used a reliable technique for measuring fear in mice (heart rate measurement), a technique very reliable because heart rate very dramatically spikes when mice are afraid. Like typical rodent memory researchers, the authors chose the unreliable technique of trying to judge "freezing behavior" rather than the reliable method of looking for heart rate spikes in mice. 

We have the usual lame-as-lame-can-be confession in this paper that the authors failed to do a sample size calculation, as good experimental scientists should do. We read, "No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications." It is a great scandal that neuroscientists routinely use way-too-small group sizes, creating papers without any decent statistical power, papers mostly reporting only false alarms. Trying to excuse yourself by pointing out that other researchers are using the same way-too-small study group sizes is as lame and laughable as saying, "I don't pay my taxes, but lots of my friends also don't pay their taxes." 

The junk science paper "Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time" is another joke of a neuroscience research paper in which the study group sizes are smaller than the number of authors, which should make us laugh hard and say: "What was the rule here: only one mouse per researcher?"

You can do a Google image search for "Effect size versus sample size" to get an idea about the relation between the two, and another thing called statistical power. Some of the visuals you will see may be hard to understand. The visual below describes the situation in an easy to understand way. 

The smaller the effect size, the larger the study group size needed to show something in a convincing manner (such as a statistical power of 80%).  Most effect sizes in neuroscience are small.  That means in the great majority of cases a study group of 25 or more is needed. No experimental neuroscience should be taken seriously if it uses a smallest study group size smaller than 15 subjects. It is conceivable that a neuroscience experimental study using 15 or 20 subjects might provide modest evidence for something, but only in the very unlikely case of a high effect size. For the much more likely case of an effect size that is only medium or low, then at least about 35 subjects per study group are needed. 

As a general rule, we should be dismissing as junk science any experimental neuroscience study that fails to either use at least 15 subjects per study group or fails to do a sample size calculation to determine whether the number of subjects was adequate to achieve a good statistical power such as 80%. If the smallest study group size is between 15 and 30, we should only regard the paper as being possibly modest evidence for something if the authors did a sample size calculation to show that with the effect size of the type they are dealing with, the study group size they used was adequate to achieve a good statistical power. 

Strangely in this paper with 17 listed authors we have a reference to "The investigator who collected and analyzed the data including behavior, imaging and staining." So there were 17 people listed as paper authors, but only one person "who collected and analyzed the data"? Who was that person? Was it a PhD, or merely a graduate student? Was it someone who had any experience in doing this kind of extremely tricky easy-to-get-wrong work, involving lots of high-tech equipment easy to misuse, and lots of "freezing behavior" estimations so easy to get wrong? Or was it some graduate student fumbling around while doing such work for the first time? We'll never now, because this "investigator who collected and analyzed the data including behavior, imaging and staining" has not been named. The failure of papers such as this to list the specific people who observed things and when they observed the things is another huge reason for distrusting such papers. And why were 17 people listed as authors, when there was only a single "investigator who collected and analyzed the data"?  Elsewhere a scientist tells us, "Anytime you critique a paper in my field, you might think you’re critiquing the senior scientists on the paper, but they usually have a graduate student or a postdoc who wrote the thing." 

What goes on nowadays in science literature is that scientists massively list themselves as authors of papers they did not write, involving research they had no substantial involvement in.  Then scientists make their accomplishments sound ten times greater than they are, by making claims such as "I am the author of 100 scientific papers," when they were merely the co-author of such papers, with the papers typically having a dozen or more listed authors. 

We should distrust or not believe the claim in the paper that "The investigator who collected and analyzed the data including behavior, imaging and staining was blinded to the mouse genotypes and treatment conditions." Blinding is an important feature of well-designed experiments, as it helps to reduce the chance of "see whatever you want to see" kind of bias. Effective blinding requires a well-designed blinding protocol that takes at least a long paragraph to state. Whenever you read a mere one-sentence assertion that some blinding occurred, without any detailed discussion of an effective blinding protocol, the claim that blinding occurred should not be trusted. An effective blinding protocol in a neuroscience experiment typically requires multiple people involved in collecting and analyzing data. For example, one person might perform some intervention (such as injecting something) into one group of mice (not a group of control mice); some other person not knowing which mice got the shot might perform some performance test on both the mice that got the shot and the control mice; and some third person not knowing which mice got the shot might analyze the performance data. But when you have a single "investigator who collected and analyzed the data," there's no way for that person to be blind about which rodents are in the control group -- unless some very complicated and ingenious scheme was followed to assure effective blinding. If there had been so clever a scheme, we may assume that whoever wrote up the paper would want to tell us about such ingenuity. Since no details about a blinding protocol have been given, other than the bare claim that blinding occurred, we should distrust or disbelieve the claim that this single investigator "was blinded to the mouse genotypes and treatment conditions." 

The insinuations in the junk science papers mentioned above (that dendritic spines help store memories) makes no sense. Dendritic spines no more resemble a place of written information than the twigs on trees. And dendritic spines are too unstable to explain memories that can last for decades.  

 The 2015 paper "Impermanence of dendritic spines in live adult CA1 hippocampus" states the following, describing a 100% turnover of dendritic spines within six weeks:

"Mathematical modeling revealed that the data best matched kinetic models with a single population of spines of mean lifetime ~1–2 weeks. This implies ~100% turnover in ~2–3 times this interval, a near full erasure of the synaptic connectivity pattern."

The paper here states, "It has been shown that in the hippocampus in vivo, within a month the rate of spine turnover approaches 100% (Attardo et al., 2015; Pfeiffer et al., 2018)." The 2020 paper here states, "Only a tiny fraction of new spines (0.04% of total spines) survive the first few weeks in synaptic circuits and are stably maintained later in life."  The author here is telling us that only 1 in 2500 dendritic spines survive more than a few weeks.  Given such an assertion, we should be very skeptical about the author's insinuation that some very tiny fraction of such spines "are stably maintained." No one has ever observed a dendritic spine lasting for years, and the observations that have been made of dendritic spines give us every reason to assume that dendritic spines do not ever last for more than a few years. Conversely, human knowledge and human motor skills can last for 50 years or more, way too long a time to be explained by changes in dendritic spines or synapses, both of which change too much and too frequently to be a stable storage place for human memories. 

The failure of neuroscientists to listen to what dendritic spines are telling us is epitomized by a 2015 review article on dendritic spines, which states, "It is also known that thick spines may persist for a months [sic], while thin spines are very transient, which indicate that perhaps thick spines are more responsible for development and maintenance of long-term memory."  It is as if the writers had forgotten the fact that humans can remember very well  memories that last for 50 years, a length of time a hundred times longer than "months." 

A 2019 paper documents a 16-day examination of synapses, finding "the dataset contained n = 320 stable synapses, n = 163 eliminated synapses and n = 134 formed synapses."  That's about a 33% disappearance rate over a course of 16 days. The same paper refers to another paper that "reported rates of [dendritic] spine eliminations in the order of 40% over an observation period of 4 days." A paper studying the lifetimes of dendritic spines in the cortex states, "Under our experimental conditions, most spines that appear survive for at most a few days. Spines that appear and persist are rare."

The 2023 paper here gives the graph below showing the decay rate of the volume of dendritic spines. It is obvious from the graph that they do not last for years, and mostly do not even last for six months. 

Page 278 of the same paper says, "Two-photon imaging in the Gan and Svoboda labs revealed that spines can be stable over extended periods of time in vivo but also display genesis (generation) and elimination (pruning) at a frequency of 1–4% per week." Something vanishing at a rate of 2% per week will be gone within a year. Discussing the motor cortex, the paper here says, "We found that 3.5% ± 1.2% of spines were eliminated and 4.3% ± 1.3% were formed in motor cortex over 2 weeks (Figures 3J, 3K, and 3O; 224 spines, 2 animals)." An elimination rate of 3.5% over two weeks would result in 90% elimination over a length of one year. 

The 2022 paper "Stability and dynamics of dendritic spines in macaque prefrontal cortex" studied  how long  dendritic spines last in a type of monkey. It says, "We found that newly formed spines were more susceptible to elimination, with only 40% persisting over a period of months." The same study found that "the percentage of elimination for pre-existing spines over 7 days was only 6% on average," which is a rate that would cause complete disappearance of pre-existing dendritic spines within a year. Dealing with a type of monkey, the 2015 paper "In Vivo Two-Photon Imaging of Dendritic Spines in Marmoset Neocortex" tells us that "The loss or gain rate at the 1 d  [one day] interval observed in this study was similar to those in previous studies of layer 5 neurons of the somatosensory cortex of transgenic mice (12% in 3 d [ 3 days] for both loss and gain; Kim

and Nabekura, 2011) and layer 2/3 neurons of ferret V1 by the virus vector method (4% in 1 d [ 1 day] for both loss and gain; Yu et al., 2011)."  The reported loss of dendritic spines is a rate that would cause 100% loss within a year. 

Most synapses are attached to dendritic spines, so all of these findings about the instability and short lifetimes of dendritic spines are also findings about the instability and short lifetimes of synapses. Both synapses and dendritic spines are way, way too unstable to be a credible storage place for human memories that can last for 50+ years. There is no place in the brain that can be reasonably postulated as a storage place allowing memories to persist for 50 years. 

Currently as the main story on MedicalXPress.com is a story groundlessly claiming that researchers found that groups of neurons encode different types of pain. It's another promotion of a junk science paper, because the study group sizes are so small, consisting of study groups such as 6 mice, 5 mice and 4 mice. Neuroscientists these days are guilty of very often making misleading uses of the terms "encode" and "representation," by claiming to have found "encoding" or "representation" when no robust evidence of any such thing was found. 

Folly of the "Train Them Then Dissect Them" Neuroscientists

"Train Them Then Dissect Them" is a phrase we can use to describe a particular type of animal experiment often done by neuroscientists. The experiment will work like this:

(1) Some animals (typically mice) will be trained to learn something. For example, they may be trained with the Morris Water Maze test to be able to go to a submerged platform within a water-filled tank after they are placed in such a tank. Or they may be trained over several days to keep their balance on a rotating rod, using something called a rotarod. 

(2) The animals will then be killed, and their bodies dissected, with the brain cut up into slices that can be microscopically examined. 

(3) The experimenters will look for some tiny area in the brain where they can claim to see some difference between the brains of the trained animals and a control group of animals who were not trained.  All kinds of things may be checked for.

(4) The paper will make some announcement that some tiny difference was found between the trained animals and the animals in the control group.  The reported difference might be any of 1000 different things, such as the size of dendritic spines in some tiny spot or the number of dendritic spines in some other part, or the length of synapses in some spot, or the thickness of synapses in some other part. The paper will claim that evidence has been found of "learned-induced remodeling" of the brain or "learning-induced modification of the brain." Neuroscientists will boast that they found evidence of a brain storage of memories. 

There are several reasons why these type of experiments are typically very bad examples of junk science. One reason is that you can always find hundreds of tiny little differences in two randomly chosen animals of the same species, when microscopically examining their dissected brains. So merely by showing that there is some brain difference, you do nothing at all to show that such a difference arose from the training or learning that occurred in the mice.  The same difference might have existed before the learning or training occurred. 

An example of a very poor-quality paper following this "train them then dissect them" technique is the paper "Learning-induced remodeling of inhibitory synapses in the motor cortex." Glaring defects in the paper include these:

(1) The authors failed to use adequate sample sizes, with study group sizes such as only 7 mice or only 4 mice. 

(2) The paper makes no mention of using any kind of blinding protocol, something essential for a paper of this type to be taken seriously. Neither the word "blind" nor the word "blinding" appear in the paper. The tiny differences reported in structures can easily be explained as being caused by biased ratings or biased size estimations being made  by non-blinded analysts who knew which mice were trained and which mice were not trained, and who had a motivation to estimate in a particular way, so that statistical significance could be reported. The very tiny blurry barely-visible not-very-distinct hard-to-measure things being judged for size are just the type of things where bias of  motivated and non-blinded analysts could be a big factor.  

(3) There was no pre-registration of the study committing the authors to make a small number of checks for a difference of only one specific type in only one or a few exact spots. The authors were apparently free to keep checking in a hundred different ways, until some tiny difference was found somewhere. 

(5) When the trained mice were compared to untrained mice, the control group of untrained mice was way too small, consisting of only 4 mice (Figure 2B).  15 subjects per study group (including 15 controls) is the minimum for any study like this to be taken seriously, with the required subjects probably being greater.  No mention is made of a sample size calculation, which would have revealed how inadequate the study group sizes were. 

(6) We have graphs supposedly showing some tiny difference found somewhere, but from a quick peek at the graphs you won't even notice any difference. 

Even if the paper had shown a difference much larger, it would not prove anything, because anyone microscopically examining two randomly selected brains of an animal will always be able to find little differences here and there. It is never clear or probable that such differences occurred because one set of mice got training that the others did not. No good evidence of brain-stored memories is ever produced by such studies. The people who do such junk science experiments are needlessly killing mice. 

Without a blinding protocol, it's a big joke

I can give a description of how an experiment of this type could be done so that it would meet at least some of the requirements of robust research. 

(1) There would be adequate study group sizes, such as maybe 30 mice in the group to be trained, and 30 mice in the control group. 

(2) The study would be pre-registered, so that there would be a commitment to gathering data and analyzing data in a specific, limited way. For example, the specification of the pre-registration document might state that exactly 25 microscope-readable slices would be taken from the same region of each mouse, such as the hippocampus or the motor cortex, and that the study would only analyze one parameter, such as the quantity of dendritic spines.   

(3) Each slice would be put in an envelope that had a subject number, and an indication of whether the mouse had been trained or not. 

(4) A simple computer programs would be written that would have two functions: (a) the ability to generate a 7-digit random number and the ability to store in a text file a supplied subject number, a "trained" indicator of either Y or N,  and that generated 7-digit number; (b) the ability to retrieve that subject number and its "trained" indicator when supplied the 7-digit random number. This is an elementary programming task.

(5) The program would be used to generate random numbers that would be written on envelopes.  Each envelope containing a slice of brain tissue and a subject number would be replaced with an envelope containing one of the random numbers generated by the program.

(6) You would now have a set of envelopes marked only with random 7-digit numbers that a human could not recognize. Such a set of envelopes could be shuffled, and given to microscope analysts. Such analysts would thereby be completely blind to whether the tissue slices belonged to mice that had been trained or mice that had not been trained. There would be no chance of some bias effect in which an analyst tended to analyze trained mice differently. The microscope-using analysts would look for differences in tissue, using only the limited hypothesis to be tested that was stated in the pre-registration document.  So, for example, if that document said that only the thickness of synapses would be analyzed, then only that one thing would be analyzed. 

(7) After the microscopic analysis had been completed, and an analysis report form put in each of the envelopes, the computer program could be used to retrieve the original subject numbers and training status corresponding to each envelope. So, for example, someone holding an envelope with a random number of 4477353 might type in that number to the computer program, and get a reply of "Subject #21, Trained" or "Subject #35, Not Trained," with the answer retrieved from the text file previously made by the program.  The answer could be written on each envelope. 

(8) Then the data could be tallied up to see whether there was any difference between the characteristics of the trained mice and the untrained mice.

(9) Since the experiment would strictly adhere to the protocol of the original pre-registration design document, there would be no chance that the final analysis would include fewer or more brain slices than specified in that document. 

That would be a decent design for an experiment of this type. No design like this is followed by the vast majority of these "train them then dissect them" experiments. Typically such experiments make no use of blinding at all. Any difference in the reported characteristics can be explained by either pure chance variation or bias of the microscopic data analyst, motivated to report some difference. 

A paper such as "Learning-induced remodeling of inhibitory synapses in the motor cortex" tries to suggest that learning of a motor skill is stored as changes in dendritic spines. There is a reason why such a hypothesis makes no sense. Dendritic spines are very unstable things. 

 The 2015 paper "Impermanence of dendritic spines in live adult CA1 hippocampus" states the following, describing a 100% turnover of dendritic spines within six weeks:

"Mathematical modeling revealed that the data best matched kinetic models with a single population of spines of mean lifetime ~1–2 weeks. This implies ~100% turnover in ~2–3 times this interval, a near full erasure of the synaptic connectivity pattern."

The paper here states, "It has been shown that in the hippocampus in vivo, within a month the rate of spine turnover approaches 100% (Attardo et al., 2015; Pfeiffer et al., 2018)." The 2020 paper here states, "Only a tiny fraction of new spines (0.04% of total spines) survive the first few weeks in synaptic circuits and are stably maintained later in life."  The author here is telling us that only 1 in 2500 dendritic spines survive more than a few weeks.  Given such an assertion, we should be very skeptical about the author's insinuation that some very tiny fraction of such spines "are stably maintained." No one has ever observed a dendritic spine lasting for years, and the observations that have been made of dendritic spines give us every reason to assume that dendritic spines do not ever last for more than a few years. Conversely, human knowledge and human motor skills can last for 50 years or more, way too long a time to be explained by changes in dendritic spines or synapses, both of which change too much and too frequently to be a stable storage place for human memories. 

The failure of neuroscientists to listen to what dendritic spines are telling us is epitomized by a 2015 review article on dendritic spines, which states, "It is also known that thick spines may persist for a months [sic], while thin spines are very transient, which indicate that perhaps thick spines are more responsible for development and maintenance of long-term memory."  It is as if the writers had forgotten the fact that humans can remember very well  memories that last for 50 years, a length of time a hundred times longer than "months." 

A 2019 paper documents a 16-day examination of synapses, finding "the dataset contained n = 320 stable synapses, n = 163 eliminated synapses and n = 134 formed synapses."  That's about a 33% disappearance rate over a course of 16 days. The same paper refers to another paper that "reported rates of [dendritic] spine eliminations in the order of 40% over an observation period of 4 days." A paper studying the lifetimes of dendritic spines in the cortex states, "Under our experimental conditions, most spines that appear survive for at most a few days. Spines that appear and persist are rare."

The 2023 paper here gives the graph below showing the decay rate of the volume of dendritic spines. It is obvious from the graph that they do not last for years, and mostly do not even last for six months. 

Page 278 of the same paper says, "Two-photon imaging in the Gan and Svoboda labs revealed that spines can be stable over extended periods of time in vivo but also display genesis (generation) and elimination (pruning) at a frequency of 1–4% per week." Something vanishing at a rate of 2% per week will be gone within a year. Discussing the motor cortex, the paper here says, "We found that 3.5% ± 1.2% of spines were eliminated and 4.3% ± 1.3% were formed in motor cortex over 2 weeks (Figures 3J, 3K, and 3O; 224 spines, 2 animals)." An elimination rate of 3.5% over two weeks would result in 90% elimination over a length of one year. 

The 2022 paper "Stability and dynamics of dendritic spines in macaque prefrontal cortex" studied  how long  dendritic spines last in a type of monkey. It says, "We found that newly formed spines were more susceptible to elimination, with only 40% persisting over a period of months." The same study found that "the percentage of elimination for pre-existing spines over 7 days was only 6% on average," which is a rate that would cause complete disappearance of pre-existing dendritic spines within a year. Dealing with a type of monkey, the 2015 paper "In Vivo Two-Photon Imaging of Dendritic Spines in Marmoset Neocortex" tells us that "The loss or gain rate at the 1 d  [one day] interval observed in this study was similar to those in previous studies of layer 5 neurons of the somatosensory cortex of transgenic mice (12% in 3 d [ 3 days] for both loss and gain; Kim

and Nabekura, 2011) and layer 2/3 neurons of ferret V1 by the virus vector method (4% in 1 d [ 1 day] for both loss and gain; Yu et al., 2011)."  The reported loss of dendritic spines is a rate that would cause 100% loss within a year. 

Most synapses are attached to dendritic spines, so all of these findings about the instability and short lifetimes of dendritic spines are also findings about the instability and short lifetimes of synapses. Both synapses and dendritic spines are way, way too unstable to be a credible storage place for human memories that can last for decades. There is no place in the brain that can be reasonably postulated as a storage place allowing memories to persist for decades. 

Imaging of Dendritic Spines Hint That Brains Are Too Unstable to Store Memories for Decades

Scientists have very fancy equipment for examining brains at very high resolution. But no microscopic examination of a brain has ever proven or even supported the claim that brains store memories.  The most common claim about a brain storage of memories is that memories are stored in synapses. But the paper here confesses, "Very few studies report long-lasting structural changes of synapses induced by behavioral training."

There are two types of ways to examine brain tissue: in vivo or in vitro. An in vitro examination means looking at some tissue that has been removed from an organism, or some tissue in a dead organism. An in vivo examination means examining tissue in a living organism.  When examining human tissue, there are rather severe constrains on what can be seen in vivo. But there are no constraints on in vitro examinations of newly deceased humans, whenever such humans have donated their bodies to medical science.  The brains of quite a few such humans have been minutely examined with the most sophisticated equipment. No one has ever found evidence of a memory stored in a brain. No one has ever read a memory from a dead person. 

There are a number of ways to do in vivo examinations of the brains of living organisms.  One technique is called time-lapse two-photon laser microcopy.  Such technology is not good enough to clearly inspect individual synapses, which are very small. But such microscopy is good enough to show what are called dendritic spines. 

A dendritic spine is a tiny protrusion from one of the dendrites of a neuron. The diagram below shows a neuron in the top half of the diagram. Some dendritic spines are shown in the bottom half of the visual. The bottom half of the visual is a closeup of the red-circled part in the top of the diagram. 

An individual neuron in the brain may have about a thousand such dendritic spines. The total number of dendritic spines in the brain has been estimated at 100 trillion, which is about a thousand times greater than the number of neurons in the brain.  The total number of synapses in the brain has also been estimated at 100 trillion. A large fraction of synapses are connected to dendritic spines. So by studying how long dendritic spines last, we can tell a good deal about how long synapses last. 

It has been hoped that some relation could be drawn between learning and the formation of new dendritic spines.  But scientists try to insinuate a connection between LTP and learning, and a paper says that "Sorra and Harris measuring three-dimensional reconstructed spines from serial section EM pictures, could not find any significant effect of LTP on morphological properties of spines."

No doubt the first scientists who examined dendritic spines were hoping to see some nice regularity and order, perhaps something that might be some kind of coding system by which dendritic spines might store information.  But dendritic spines show no such regularity. Unlike positions in a DNA molecule (which must be one of only four nucleotide base pair types), dendritic spines can be any of many sizes, shapes or lengths. A length of dendrite and its spines (like the length shown in the bottom half of the visual above) seem to bear no resemblance to encoded information.  The vast majority of new dendritic spines do not last longer than a few months.  

Some unconvincing science papers have attempted to suggest a link between learning and dendritic spines.  Here's what goes on in a typical paper of this type:

(1) Some rodent will be given some learning, such as fear conditioning. 

(2) Various dendritic spines will be examined.

(3) Some newly formed dendritic spines will be declared to be "experience dependent," because they appeared while the learning took place. 

It is easy to explain why such papers use an illegitimate methodology. There are very many billions of dendritic spines in the brain, and they come and go rapidly and randomly. So anyone with a good enough microscope could find some stretch of dendritic spines that increased during learning, just as you could find some stretch of dendritic spines that decreased during learning. There is never any good basis for claiming that some stretch of dendritic spines increased because of some particular type of learning.  Similarly, looking around outside I could find some row of leaves that grew bigger when I was studying something, but there would be zero reason for thinking that such an increase was caused by my learning. 

Some studies compare two different sets of subjects, one that was exposed to learning, and another that was not exposed to learning. The studies may report that the subjects exposed to learning had a greater growth of dendritic spines. This is not at all good evidence that dendritic spines have anything to do with learning. We would expect that if dozens of experiments compared sets of dendritic spines undergoing random fluctuations, that some of them would report (purely by chance) that in some of those sets there was a greater growth of dendritic spines. Similarly, if 100 experimenters tracked the pimples of young teenagers with acne both during the first three months of the school year and during summer vacation, some of the experimenters might report greater numbers of new pimples growing during the first three months of the school year, even though there is no causal connection between learning and the number of pimples a teenager may have on his or her skin. 

By examining the tiny protrusions that are dendritic spines, scientists can get some idea of how stable or unstable these dendritic spines are.  If such spines are very unstable, it is a great problem for any theory that memories are stored in synapses.  Unstable dendritic spines would suggest that synapses are unstable, and are unlikely to be a place where memories could be stored for decades.  Even without studying dendritic spines, we have the strongest reason for believing in the instability of synapses: the fact that proteins in synapses have average lifetimes of only a few weeks. 

Dendritic spines last no more than a few months 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 hippocampus have a turnover of about 40% each 4 days. This study found that dendritic spines in the cortex of mice brains have a half-life of only 120 days. The wikipedia article on dendritic spines says, "Spine number is very variable and spines come and go; in a matter of hours, 10-20% of spines can spontaneously appear or disappear on the pyramidal cells of the cerebral cortex." Referring to in vivo observations of dendritic spines in the mouse hippocampus, the paper here says the authors "measured a spine turnover of ~40% within 4 days."  The 2017 paper here ("Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex") found the following regarding dendritic spines in the cortex of rodents:

"About 80% of synapses were detectable for a day or longer; about 60% belonged to the stable pool imaged for at least 8 days. Even this stable pool was found to turn over, with only, 50% of spines surviving for 30 days or longer. Assuming stochastic behaviour, we estimate that the mean lifetime of the stable pool would be on the order of 120 days."

We have no good evidence that any dendritic spines survive for more than  a few years. There is an often-cited paper from the year 2000 with the title "Stably maintained dendritic spines are associated with lifelong memories." The title is misleading, like the title of so many scientific papers.  The paper actually found that "a tiny fraction of daily formed new spines (~0.2% of the total spines) could persist for 3–5 months." So the paper found that only 1 in 500 dendritic spines persist for as long as 5 months.  The paper resorts to some dubious math to try to hypothesize that some dendritic spines may last for years. 

More recent papers have made even more clear the high turnover rate of dendritic spines, and have made it seem less likely that any dendritic spines survive for more than a few years.  The 2015 paper 

"Impermanence of dendritic spines in live adult CA1 hippocampus" states the following, describing a 100% turnover of dendritic spines within six weeks:

"Mathematical modeling revealed that the data best matched kinetic models with a single population of spines of mean lifetime ~1–2 weeks. This implies ~100% turnover in ~2–3 times this interval, a near full erasure of the synaptic connectivity pattern."

The paper here states, "It has been shown that in the hippocampus in vivo, within a month the rate of spine turnover approaches 100% (Attardo et al., 2015; Pfeiffer et al., 2018)." The 2020 paper here states, "Only a tiny fraction of new spines (0.04% of total spines) survive the first few weeks in synaptic circuits and are stably maintained later in life."  The author here is telling us that only 1 in 2500 dendritic spines survive more than a few weeks.  Given such an assertion, we should be very skeptical about the author's insinuation that some very tiny fraction of such spines "are stably maintained." No one has ever observed a dendritic spine lasting for years, and the observations that have been made of dendritic spines give us every reason to assume that dendritic spines do not ever last for more than a few years. 

The same studies that show such short lifetimes for dendritic spines show that while they exist, dendritic spines very rarely maintain the same size and shape.  During their short lifetimes, dendritic spines tend to change very much in size and shape.  One paper says that even among a more stable subset of dendritic spines, "The majority of those (~80%) underwent a fluctuation in head size and neck length of more than 10% (~40% even of more than 30%) within 3 to 4 days."

One 2005 paper ("Development of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex") claims to have imaged some mouse dendritic spines in a way so that you could compare how badly some spines decayed after an interval of 18 months. The claim is extremely doubtful, because the paper fails to give any description of how so hard a thing to do was accomplished.  Given the lack of a decent description of how this feat was supposedly accomplished, we should regard the claim with high suspicion. What probably occurred is that some piece of dendrite was examined, and later 18 months later the scientists went looking for some other dendrite with a fairly similar appearance. But we can have no confidence that the exact same little stretch of dendrite was found. Because little stretches of dendrites with a few dendritic spines look so similar, it would be very easy for someone to do a "closest appearance" search, and find a little stretch of dendrite that was not the same little stretch of dendrite examined 18 months earlier. We can have no confidence that the two pairs of dendrites shown in Figure 4 of the paper are actually the same little stretch of dendrite in the same organism. From the author's way-too-scanty description of what was going on, we don't even know whether the images are photos from living mice (as opposed to slides of extracted tissue that were photographed 18 months apart).  We also don't know whether the authors went looking for some fairly stable dendritic spines, in a cherry-picking affair, extracting the most stable-looking dendritic spines from some larger pool where very little stability existed.  

We should keep in mind that a typical neuroscientist studying the lifetimes of dendritic spines (a topic also called dendritic spine turnover or dendritic spine remodeling) is someone likely to be trying to show as much stability as he can find. This is because many  neuroscientists eagerly hope (very illogically) that dendritic spines might be something that can help explain the persistence of memory in humans. So when we see some visual showing some dendritic spines persisting over the course of four months, we are probably seeing something that is not common, something that was cherry-picked to show dendritic spines lasting for a relatively long time. Also, neuroscientists are probably overestimating by 50% or more whenever they estimate what fraction of dendritic spines are stable.

The 2022 paper "Stability and dynamics of dendritic spines in macaque

prefrontal cortex" studied  how long  dendritic spines last in a type of monkey. It says, "We found that newly formed spines were more susceptible to elimination, with only 40% persisting over a period of months."  The same study found that "the percentage of elimination for pre-existing spines over 7 days was only 6% on average," which is a rate that would cause complete disappearance of pre-existing dendritic spines within a year. Dealing with a type of monkey, the 2015 paper "In Vivo Two-Photon Imaging of Dendritic Spines in Marmoset Neocortex" tells us that "The loss or gain rate at the 1 d  [one day] interval observed in this study was similar to those in previous studies of layer 5 neurons of the somatosensory cortex of transgenic mice (12% in 3 d [3 days] for both loss and gain; Kim and Nabekura, 2011) and layer 2/3 neurons of ferret V1 by the virus vector method (4% in 1 d [1 day]  for both loss and gain; Yu et al., 2011)."  The reported loss of dendritic spines is a rate that would cause 100% loss within a year. 

Human memories can last a lifetime, but synapses and the dendritic spines they attach to are very unstable "shifting sands" types of things. "Unstable dendritic spines" implies "unstable synapses," which implies that scientists must be wrong when they claim that memories are stored in synapses.  Stable human memories can last for 50 years, so we cannot believe they are stored in things as unstable as synapses and dendritic spines. Studies on the lifetime of the proteins that make up synapses and dendritic spines tell us that such proteins last only a few weeks.  Synapses and dendritic spines are as unstable as fallen maple leaves.  The brain has no place that it could be storing memories that last for decades.

Postscript: The failure of neuroscientists to listen to what dendritic spines are telling us is epitomized by a 2015 review article on dendritic spines, which states, "It is also known that thick spines may persist for a months [sic], while thin spines are very transient, which indicate that perhaps thick spines are more responsible for development and maintenance of long-term memory."  It is as if the writers had forgotten the fact that humans can remember very well  memories that last for 50 years, a length of time a hundred times longer than "months." 

Electron microscope photos of dendritic spines show something that looks nothing like any organized structure capable of storing information. For example:

Dendritic spines seem to pop up out of dendrites as randomly as twigs pop up from the branches of trees. No one has been able to detect any kind of regularity in the appearance of dendritic spines that might be a  scheme for storing encoded information, just as no one has been able to find any such scheme in the twigs on trees. Just as there does not exist in nature any such thing as a twig reader that scans branches trying to extract encoded information from the twigs of branches, there does not exist anything in the brain that might be a dendritic spine reader. 

A 2019 paper documents a 16-day examination of synapses, finding "the dataset contained n = 320 stable synapses, n = 163 eliminated synapses and n = 134 formed synapses."  That's about a 33% disappearance rate over a course of 16 days. The same paper refers to another paper that "reported rates of [dendritic] spine eliminations in the order of 40% over an observation period of 4 days."  A paper studying the lifetimes of dendritic spines in the cortex states, "Under our experimental conditions, most spines that appear survive for at most a few days. Spines that appear and persist are rare." The rare persistence referred to was only a persistence of a few months. 

The 2023 paper here gives the graph below showing the decay rate of the volume of dendritic spines. It is obvious from the graph that they do not last for years, and mostly do not even last for six months. 

Page 278 of the same paper says, "Two-photon imaging in the Gan and Svoboda labs revealed that spines can be stable over extended periods of time in vivo but also display genesis (generation) and elimination (pruning) at a frequency of 1–4% per week." Something vanishing at a rate of 2% per week will be gone within a year. 

Post-postscript: The 2025 paper here states that  "the synaptic turnover rate is as high as 1% per day in the visual cortex." That is a rate of about 100% replacement every four months. If that is the typical rate at which synapses are replaced, synapses cannot be the storage place of memories lasting decades. Quoting an even higher rate of synaptic turnover, the paper here states, "A recent imaging study revealed that the synaptic turnover rate in hippocampal CA1 cells is very high, with an estimated lifetime of 1–2 weeks (Attardo et al., 2015)."