Showing posts with label microscopic analysis of brain tissue. Show all posts
Showing posts with label microscopic analysis of brain tissue. Show all posts

Thursday, January 16, 2025

Microscopes Will Never Find the Slightest Trace of Learned Information in a Human Brain

A recent story at the LiveScience.com site has the title "Could we ever retrieve memories from a dead person's brain?" The story has many  inaccurate claims, and fails to tell us the most important facts that are relevant to the question being considered. The subtitle of the article makes this claim: "Neuroscientists have identified the physical locations where memories are stored in the brain."  No, they have not done any such thing, and the article fails to present any good evidence that any such thing was done. 

We have this claim about a method to retrieve a memory from a brain:

"With today's technology, retrieving memories might go something like this. First, identify the set of brain cells, or neurons, that encoded a specific memory in the brain and understand how they are connected. Then, activate those neurons to create an approximate neural network, a machine learning algorithm that mimics the way the brain works."

This does not make any sense as an idea about how one would go about trying to start to read a memory from a brain. The first step in such a process would be to use microscopes to look for any speck of a trace of learned information in a brain. No one has ever succeeded in doing any such thing. Microscopic examination of brain tissue has never revealed a single word anyone ever learned. Microscopic examination of brain tissue has never revealed a single letter or character of anything anyone previously learned, and has never revealed a single pixel (an image dot) of anything anyone ever previously saw. Neural networks are a misnamed type of computer technology that do not actually mimic the brain and its physical shortfalls. 

We have quotes by a neuroscientist (Don Arnold) doing some vague hand-waving and speaking as if he knew things he does not actually know. We read,  "Memories are encoded by groups of neurons, Arnold said." That's the kind of vacuous, vague hand-waving that someone may use when he lacks any actual knowledge of how a brain could store memories.  When people make big important-sounding claims that are not well-supported by evidence, they typically speak in a kind of vague, hand-waving way.  For example, when asked where there existed the weapons of mass destruction that the US claimed were in Iraq before invading it in 2003, US defense secretary Donald Rumsfeld said this:

"We know where they are. They're in the area around Tikrit and Baghdad and east, west, south and north somewhat."

Such weapons of mass destruction were never found in Iraq in 2003 or in the next twenty years. 

Reminding me of the Rumsfeld statement, the LiveScience article claims that long-term memories are formed in the hippocampus, a claim not backed up any robust evidence. The main research paper on the hippocampus and memory is the paper "Memory Outcome after Selective Amygdalohippocampectomy: A Study in 140 Patients with Temporal Lobe Epilepsy." That paper gives memory scores for 140 patients who almost all had the hippocampus removed to stop seizures.  Using the term "en bloc" which means "in its entirety" and the term "resected" which means "cut out," the paper states, "The hippocampus and the parahippocampal gyrus were usually resected en bloc."  The "Memory Outcome after Selective Amygdalohippocampectomy" paper does not use the word "amnesia" to describe the results. That paper gives memory scores that merely show only a modest decline in memory performance.  The paper states, "Nonverbal memory performance is slightly impaired preoperatively in both groups, with no apparent worsening attributable to surgery."  In fact, Table 3 of the paper informs us that a lack of any significant change in memory performance after removal of the hippocampus was far more common than a decline in memory performance, and that a substantial number of the patients improved their memory performance after their hippocampus was removed. 

The LiveScience article tells us, "Other parts of the brain store different aspects of a memory, like emotions and other sensory details, according to the Cleveland Clinic." We are referred to a page on some web site of the Cleveland Clinic that has no named author, and is the kind of article that you might get if you asked ChatGPT about how memory works. That Cleveland Clinic page does not actually make the claim that the LiveScience article attributes to it. The Cleveland Clinic does not claim that different aspects of a memory are stored in different places, but merely claims that other parts of a brain "participate in memory processes."

The LiveScience article then makes a false claim, repeating a groundless achievement legend. It states this:

"Neuroscientists have identified engrams in the hippocampuses of mouse brains. For instance, in a 2012 study published in the journal Nature, researchers found the specific brain cells associated with a memory of an experience that induced fear." 

No, there does any exist any robust evidence for engrams (neural storage places of memories) in any animal.  The paper the LiveScience article links to is the 2012 paper “Optogenetic stimulation of a hippocampal engram activates fear memory recall.” That is a very low-quality paper guilty of several bad examples of Questionable Research Practices. We see in Figure 3 of that paper that inadequate sample sizes were used. The number of animals listed in that figure (during different parts of the experiments) are 12, 12, 12, 5, and 6, for an average of 9.4. That is not anything like what would be needed for a moderately convincing result, which would be a minimum of 15 or 20 animals for each study group, and probably more. The experiment relied crucially on judgments of fear produced by manual assessments of freezing behavior, which were not corroborated by any other technique such as heart-rate measurement. All mouse research papers relying on "freezing behavior" judgments are junk-science papers, for reasons I discuss in my post here, "All Papers Relying on Rodent 'Freezing Behavior' Estimations Are Junk Science."  The 2012 study does not describe in detail any effective blinding protocol, which is another bad defect.  The study involved stimulating certain cells in the brains of mice, with something called optogenetic stimulation. The authors have assumed that when mice freeze after stimulation, that this is a sign that they are recalling some fear memory stored in the part of the brain being stimulated. What the authors neglect to tell us is that stimulation of quite a few regions of a rodent brain will produce freezing behavior. So there is actually no reason for assuming that a fear memory was being recalled when the stimulation occurs. 

There does not exist any observational or experimental support for the existence of engrams (memory storage places) in any animal. Some papers have claimed to have produced such evidence, but their claims do not stand up to critical scrutiny. Papers claiming to produce such evidence are generally guilty of multiple types of Questionable Research Practices such as way-too-small study group sizes, lack of a blinding protocol, and the use of one or more unreliable techniques for judging memory performance. 

The LiveScience article then gives us this bit of excuse-making for why no one has ever read a memory from a brain: "The retrieval of a dead person’s memories is further complicated because the discrete parts of a memory are dispersed throughout the brain; for instance sensory details that can also be stored in the parietal lobe and sensory cortex." This is an appeal to the theory that a single memory is stored not in one tiny part of the brain but in multiple scattered parts of the brain. There is no evidence for such a theory, and the theory makes things worse for the person claiming that the brain stores memories, for reasons I discuss in my post "Why the 'A Memory Is Stored Throughout the Brain' Idea Makes Things Much Worse."  If a single memory were to be stored in multiple locations in the brain, then finding all of those locations and assembling them instantly (in a brain without any addresses or indexes or sorting) would be something even more impossible to explain than imagining that the memory existed in a single spot that was instantly found. 

Giving us its second example of claiming a cited source said something that it did not actually say, the LiveScience article states, "Neurons within a given engram are connected through synapses, the spaces between neurons where electrochemical signals travel, according to the National Library of Medicine."  The page that it links to does not ever use the word "engram," and does not refer to either memory or learning. The LiveScience article claims that according to the neuroscientist Arnold, "there is evidence that memories move to different locations as they are consolidated in the brain." There is no robust evidence of any such thing. Neuroscientists have no credible evidence of memories being stored in any part of the brain of any organism, and they do not have any decent evidence of a memory moving around from one part of the brain to another. 

Arnold is quoted as saying, "You get this sort of cascade of neurons that encode these different things, and each one of them is connected in this engram." That is hand-waving. Scientists lack any robust evidence of any such thing as an engram or an encoding of learned information or experiences in the brain. No scientist has a credible detailed theory of how such encoding could occur.  An ocean of difficulties arises when you start to consider the endless problems that would arise when trying to translate human learned knowledge and experiences into brain states through any imaginable system of encoding. Part of the problem is the extreme variety of things that people can learn and experience (concepts, facts, theories, visual  experiences, auditory experiences, smell experiences, taste experiences, pain experiences, touch experiences, and emotional reactions), meaning there could be no simple encoding scheme (something as simple as the genetic code) that could handle even a tenth of all the types of memories people can form. 

We have no discussion of some of the chief facts relevant to the topic discussed. Some of these facts are below:

(1) Human brain tissue has already been exhaustively studied at very high microscopic resolutions. My post "They Stored and Studied Thousands of Brains, But Still Failed to Show Brains Store Memories" discusses how places such as the Lieber Institute have microscopically studied thousands of brains, most of which were preserved very soon after death. The same post describes how Denmark's University of Odense has stored more than 9000 brains, microscopically examining a large fraction of them. Very much healthy brain tissue just-extracted from living patients has been microscopically examined, because normal brain tissue is often extracted from epilepsy patients when operations are done to prevent intractable seizures resistant to medicine. 
(2) Despite all of that microscopic examination, no one has ever found the slightest trace of any learned information by microscopically examining a brain. Microscopic examination of brain tissue has never revealed a single letter or character of anything anyone learned, and has never revealed a single pixel of anything anyone ever saw. It isn't just that no one ever found anything like "The US has 50 states" by microscopically examining brain tissue; it's that no ever found a U or an S from microscopically examining brain tissue. 
(3) The discovery of a bit of learned information from microscopically examining brain tissue is something that would be many times easier to do than the "recreation of a full memory" imagined by the LiveScience article, but neither of these things has occurred. 
(4) Modern microscopic techniques are powerful enough to discover traces of learned information in the brain if they existed, but no such discovery has occurred. 
(5) Nothing in the brain looks like any type of mechanism for storing learned information or storing memories.  Nothing in the brain looks like any type of apparatus for writing learned  information. 
(6) Nothing in the brain looks like any type of mechanism for reading a stored memory. We can imagine how some organism's brain might physically look like something capable of reading information from a particular spot, by means of something like a moving cursor or moving reading component. The brain has no such thing, and the brain has no moving anatomical parts. 
(7) The places claimed to be sites of brain memory storage (synapses) are unstable places of high molecular turnover, where all the proteins last for only a few weeks or less. There is no credible theory of how places so unstable could be storage places for memories that can reliably last for 60 years. 
(8) There is nothing in the brain that looks like learned information stored according to some systematic format that humans understand or do not understand. Even when scientists cannot figure out a code used to store information, they often can detect hallmarks of encoded information. For example, long before Europeans were able to decipher how hieroglyphics worked, they were able to see a repetition of symbolic tokens that persuaded them that some type of coding system was being used. Nothing like that can be seen in the brain. We see zero signs that synapses or dendritic spines are any such things as encoded information. 
(9) Many humans can remember with perfect accuracy very long bodies of text, but synapses in the brain do not reliably transmit information. An individual chemical synapse transmits an action potential with a reliability of only 50% or less, as little as 10%. A recall of long bodies of text would require a traversal of very many chemical synapses. A 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."

Below is a diagram from the paper "Materials Advances Through Aberration-Corrected Electron Microscopy." We see that since the time the genetic code was discovered about 1953, microscopes have grown very many times more powerful. The A on the left stands for an angstrom, a tenth of a nanometer (that is, a ten-billionth of a meter). 


Currently the most powerful microscopes can see things about 1 angstrom in width, which is a tenth of a nanometer. How does this compare to the sizes of the smallest units in brains? Those sizes are below:

Width of a neuron body (soma): about 100 microns (micrometers), which is about 1,000,000 angstroms.

Width of a synapse: about 500 nanometers, about 5000 angstroms.  When you search for "width of a synapse," you will commonly get a figure of 20 to 40 nanometers, but that is the width of the synaptic cleft, the gap between two synapses or between a synapse and a dendrite. The full head is much wider, as you can see from the page here.

Width of a dendritic spine: about 50 to 500 nanometers, about 500 to 5000 angstroms.

Length of a dendritic spine: the site here says, "the thin spine neck, which connects the spine to the main dendritic branch, has lengths between 0.04 and 1 μm [microns] and has 'door knob'-shaped head structures with diameters that between 0.5 and 2 μm [microns]." That length dimension is between 400 and 10,000 angstroms; and that head diameter is between 500 and 20,000 angstroms. 

The visual below (from the page here) shows an electron microscope image of a synapse. The width of the synaptic head is more than 500 nanometers (nm). We see nothing that looks like any kind of storage of human learned information. The neurotransmitters inside the spherical vesicles are short-lived chemicals that don't even last a week. 

synapse photograph

Below we see a closeup electron microscope photograph of some dendritic spines which are 500 nanometers (5000 angstrom) wide, from the scientific paper here "Ultrastructural comparison of dendritic spine morphology preserved with cryo and chemical fixation," by Tamada et. al.  We see nothing that looks anything like stored learned information or stored memory information. Do a Google search for "diagram of dendritic spine head" and you will get diagrams that look like nothing that could be any system for storing information long-term. The diagrams will show that such dendritic spine heads are just bags of short-lived  proteins and chemicals. A few of these diagrams may show actin filaments looking a bit like a structure, but searching for "lifetime of actin filaments" you will be told that such filaments have lifetimes of only minutes. 

dendritic spine closeup

The only thing in the brain smaller than the structures shown above are protein molecules. But we know a reason why protein molecules cannot be a storage place for memories that can last for 50 years. The reason is that the average lifetime of a brain protein molecule is 1000 times shorter than the longest length that people can remember things.  Proteins in the brain have an average lifetime of two weeks or shorter. 

A scientific paper states this:

"Experience-dependent behavioral memories can last a lifetime, whereas even a long-lived protein or mRNA molecule has a half-life of around 24 hrs. Thus, the constituent molecules that subserve the maintenance of a memory will have completely turned over, i.e. have been broken down and resynthesized, over the course of about 1 week."

Research on the lifetime of synapse proteins is found in the June 2018 paper “Local and global influences on protein turnover in neurons and glia.” The paper starts out by noting that one earlier 2010 study found that the average half-life of brain proteins was about 9 days, and that a 2013 study found that the average half-life of brain proteins was about 5 days. The study then notes in Figure 3 that the average half-life of a synapse protein is only about 5 days, and that all of the main types of brain proteins (such as nucleus, mitochondrion, etc.) have half-lives of 15 days or less.  The 2018 study here precisely measured the lifetimes of more than 3000 brain proteins from all over the brain, and found not a single one with a lifetime of more than 75 days (figure 2 shows the average protein lifetime was only 11 days). 

The paper here states, "Experiments indicate in absence of activity average life times ranging from minutes for immature synapses to two months for mature ones with large weights."

Clearly the resolution of the most powerful microscopes is powerful enough to read memories stored in neurons or synapses or dendritic spines, if such memories existed. And more than 10,000 brains have been microscopically studied in recent years. The failure to microscopically read any  memories from human brain tissue is a major reason for thinking that brains do not store human memories. 

If memories were stored in the brain, roughly about the year 1960 humans would have been able to read learned information stored in brains, when the resolution of microscopes reached about 10 angstroms. If memories were stored in the brain, we would have discovered irrefutable evidence of such a thing about 60 years ago. The total failure to find a single speck of learned information in the brain by microscopic examination is one of the strongest reasons for disbelieving in a brain storage of memories. 

I predict with great confidence that microscopes will never find the slightest trace of learned information in the human brain, because memories are not stored in brains. But we may have in the future some occasional "false alarm" claims to have accomplished such a thing, claims that are not supported by robust evidence. Neuroscientists have often been guilty of both smoke-and-mirrors trickery and pareidolia, when someone claims to see something that isn't really there, typically because he is eagerly scanning large bodies of random, ambiguous data, eagerly hoping to find something that isn't really there. So we may see some pareidolia in which a neuroscientist claims to see a memory by microscopic examination. Such a thing will be like some fervent believer in animal ghosts in the clouds examining thousands of photos of clouds, and claiming that this one or that looks like the shape of an animal. 

evidence-ignoring neuroscientist

Note that in the LiveScience article there is not any mention of any scientist sounding hopeful about a possibility of discovering stored information in the brain. 

This week I was reminded of the ability of the human mind to retain memories for 50 years, contrary to what we would expect from the high molecular turnover in brains.  I had a recollection which proved the ability of the mind to recall very old memories that have not been recalled in half a century. For some reason I recalled a book I had read about 50 years ago, and never since: the science fiction book "Galaxies Like Grains of Sand" by Brian Aldiss. I remembered some lines from the book. I wrote them down on paper like this:

"The mirror of the past lies shattered. The fragments you hold in your hand."

After I wrote this recollection of something I had not read, thought of or heard quoted in fifty years, I borrowed the book on www.archive.org.  I see that the lines were these (almost exactly as I remembered them)

"The long mirror of the past is shattered...Only a few fragments are left, and these you hold in your hand." 

For a person like me, the mirror of the past is not shattered, but remains well preserved after 60 years, contrary to what we would expect if memories were stored in brains with such high molecular turnover and such constant remodeling of synapses and dendritic spines. 

Below is a quote on the same topic from an earlier post discussing why brains cannot be the storage place of very old memories:

"I know for a fact that memories can persist for 50 years, without rehearsal. Recently I was trying to recall all kinds of details from my childhood, and recalled the names of persons I hadn't thought about for decades, as well as a Christmas incident I hadn't thought of for 50 years (I confirmed my recollection by asking my older brother about it). ...Upon looking through a list of old children shows from the 1960's, I saw the title “Lippy the Lion and Hardy Har Har,” which ran from 1962 to 1963 (and was not syndicated in repeats, to the best of my knowledge). I then immediately sung part of the melody of the very catchy theme song, which I hadn't heard in 53 years. I then looked up a clip on a youtube.com, and verified that my recall was exactly correct. I also recently recalled 'The Patty Duke Show' from the 1960's, a show I haven't seen in 50 years, and recalled that in the opening title sequence we saw Patty walking down some stairs. I looked up the title sequence on www.youtube.com, and verified that my 50-year-old memory was correct. This proves that a 53-year-old memory can be instantly recalled."

The prediction I make here is just one of several predictions in my 2019 post "Contrarian Predictions Regarding Biology, the Brain and Technology."  So far my predictions in that post are holding up very well. 

Saturday, November 18, 2023

They Stored and Studied Thousands of Brains, But Still Failed to Show Brains Store Memories

The failure of scientists to find any memories by the microscopic examination of brain tissue is one of the strongest reasons for rejecting claims that the human brain stores memories. There is encoded genetic information in the nucleus of most cells, information which is pretty much the same in every cell, and is not memory information. That information was discovered around 1953. Since 1953 our technology has grown enormously. But there is still not a single case of anyone ever reading a memory from any brain (human or animal) outside of his own body. Scientists have never been able to read a memory by scanning with a microscope a living person's brain, or scanning some brain tissue. Do not be fooled by press accounts that sometimes grossly exaggerate scientific experiments, and give us headlines such as “Scientists invent mind-reading device.” Such experiments (typically trying to read neural correlates of visual perception) do not actually involve thought reading, and do not at all involve a reading of stored information in the brain.

When reminded of the non-existence of claims to have read memory information from human tissue by microscopic methods, someone might respond like this: 

"Well, the problem is that scientists don't have time to study a brain after someone dies, because the body is buried or cremated. If scientists were able to spend lots of time studying the brains of people who had just died, they would probably be able to find memories in the brains of dead people."

But this claim is not correct. There actually exists an institute of scientists devoted to studying the brains of dead people. And they have had over 4000 brains to study, mostly cases of brains that were donated very soon after someone died, and quickly preserved. 

The institute is called the Lieber Institute, and its web site is here. The site says that the  Lieber Institute has 48,000 square feet of laboratory space at Johns Hopkins University.  The Lieber Institute claims to have a repository of about 4000 brains.  On another page of the institute, we are told, "Each brain is donated by a bereaved family just hours after the loss of their loved one." A Washington Post article  describes  a guy working for that institute who has the job of calling the families of people who just died (often from suicide), asking them for the brain of the dead person to be donated. We are told such requests must occur very quickly. The article says this guy "has a small window of time in which to get that consent — just one to three hours." The Post story says, "Researchers try to obtain brains within 24 to 36 hours." We are told the brains are "flash frozen."

So we have a modern institute with 4000 brains frozen within about a day after death.  The Lieber Institute has been studying such brains for about a decade, mainly for the purpose for trying to find links between brain states and mental illness. The work of the Lieber Institute has involved a huge amount of studying brains frozen in the state they were put in within a day after death. You would think that if human brains stored memories, that by now such an institute would have been able to find abundant evidence of stored memories in brain.  But no such evidence has been found. Nowhere in the 10-year progress report of the Lieber Institute is there any mention of finding any memories in the brains of dead people. 

Could it be that one of the 100 or so publications on the institute's Publications page is one mentioning the finding of a memory stored in the brain? It seems not. Below is a list of all the papers on that page that use the word "memory":

  • "THE DOPAMINE D5 RECEPTOR IS INVOLVED IN WORKING MEMORY." This is a poorly designed Questionable Research Practices study involving only mice, one using a way-too-small study group size of only eight mice. 
  • "BRAIN CATECHOL-O-METHYLTRANSFERASE (COMT) INHIBITION BY TOLCAPONE COUNTERACTS RECOGNITION MEMORY DEFICITS IN NORMAL AND CHRONIC PHENCYCLIDINE-TREATED RATS AND IN COMT-VAL TRANSGENIC MICE." This study is another poorly designed Questionable Research Practices study involving only rodents, one using a way-too-small study group size of only six rats. 
  • "NEUROPROTECTIVE EFFECTS OF DOCOSAHEXAENOIC ACID ON HIPPOCAMPAL CELL DEATH AND LEARNING AND MEMORY IMPAIRMENTS IN A VALPROIC ACID-INDUCED RAT AUTISM MODEL." The paper is behind a paywall, and the abstract does not give any specifics to back up the claim in the title.
  • "STRONG COMPONENTS OF EPIGENETIC MEMORY IN CULTURED HUMAN FIBROBLASTS RELATED TO SITE OF ORIGIN AND DONOR AGE." The epigenetic "memory" referred to is not actual memory in the sense of being to recall anything. 
  • "DOPAMINE TRANSPORTER 3′ UTR VNTR MODULATES STRIATAL FUNCTION DURING WORKING MEMORY UPDATING ACROSS THE ADULT AGE SPAN." The study merely did some experiment claiming to show that working memory performance decreases with age, something already known (20-year-olds for example are better at remembering 5 just-mentioned 4-digit numbers than 80-year-olds). 

  • So based on The Publications page of the site, we should conclude that the Lieber Institute has not been able to find any evidence (through microscopic examination of thousands of brains) that memories are stored in brains. Its scientists have not read one single memory through microscopic examination. The Publications page of the site has no studies using the word "engram," a word sometimes when scientists claim to observe something in a brain they think may be a storage place for memory.  

    4000 human brains microscopically studied with state-of-the-art equipment, but no sign was found of any stored human memories. Not even a tiny fragment anywhere.  Not so much as a single bit of brain tissue storing a home address or a telephone number of the name of a historical figure. 

    The rationalizations given to explain failures of this type are amusing. It is sometimes claimed that the brain must use some "secret code" to store information, one that humans have not been able to crack. For comparison, the Bletchley Park analysts in England were able in the 1940's to crack the Enigma code used by the Nazis to transmit secret information. That was a code specifically designed to be impossible to decipher by anyone who did not know the secret code. The Bletchley Park analysts were able to crack the Enigma code using only the most primitive predecessors of modern computers.  Can we really imagine that today's scientists would fail to unravel a code used by the brain to store memories,  even though they have microscopes vastly better than those that unraveled the Genetic Code discovered around 1953, and even though they have computers a million times better than the Bletchley Park analysts had? 

    It is much more logical and credible to believe that no such memories have been found by examining brains microscopically simply because brains do not store human memories. Nature never told us that brains store memories. It was merely overconfident scientists who told us that, scientists who never had any justification for such a claim. 

    It is also sometimes claimed that memories are stored electromagnetically in the brain, the way a computer stores its memories electromagnetically. Some people claim that you can't retrieve memories from dead brains because the memories are fragile electromagnetic things that are lost when you die, in something like the way you may lose something you were writing if someone suddenly turns off your computer. But if memories were stored in the brain electromagnetically, then why would neurologists often use electroshock therapy on people with depression, a "shock their brains with electricity" technique that would destroy all their memories if such memories were stored electromagnetically? And if memories were stored in the brain electromagnetically, would we not expect epileptic patients to lose all of their memories every time they had a major seizure, which is like an electrical storm in the brain? No such thing happens. Severe seizures often are not remembered by patients having them, but there is no effect of someone forgetting his school lessons because he had a major seizure. 

    When there is a hard-to-crack code what typically happens is that someone finds undeniable evidence that the code exists and was used, before anyone is able to crack the code. For centuries Egyptologists were unable to crack the code used in hieroglyphics, but they knew during those centuries that the walls of ancient Egyptian sites were using a code that had not yet been deciphered.  Such Egyptologists could see the repetition of symbolic tokens, alerting them that a code was being used.  In the case of the brain, not only can we find through microscopic examination no memories that can be read, but also we can find no indications that any code is being used in the brain other than the genetic code used to store genetic information, not memories. This is a very strong indication that brains do not store memories. 

    Elsewhere in the world is an even bigger collection of brains, one that also has failed to substantially support claims of a brain basis for memory storage. The Japan Times tells us this:

    " Countless shelves line the walls of a basement at Denmark's University of Odense, holding what is thought to be the world's largest collection of brains. There are 9,479 of the organs, all removed from the corpses of mental health patients over the course of four decades until the 1980s. Preserved in formalin in large white buckets labeled with numbers, the collection was the life's work of prominent Danish psychiatrist Erik Stromgren...The brains were collected after autopsies had been conducted on the bodies of people committed to psychiatric institutes across Denmark. Neither the deceased nor their families were ever asked permission."

    We hear not one word about any discovery that came from studying these brains. A web page of the University of Odense describes the collection of brains, but fails to mention any progress that has come from studying the brains.  There is no link to any papers that were produced using such brains. 

    There is another brain collection called the Human Brain Collection Core (HBCC). The collection is described here. The collection seems to consist of about 1000 brains, 700 from people who were diagnosed with mental illness. 300 of the brains are from normal people. We seem to have the same kind of method as used by the Lieber Institute. The families of people who recently died are asked to donate the brain of a family members, with a time pressure element of "we must act fast." 

    Related to this collection is a "Selected Publications" page, apparently listing the best results obtained from studying these brains. None of the 46 papers reports anything like a discovery of memories by analyzing brain tissue. None of the papers has a title referring to either memory or engrams. 

    Despite microscopically studying more than 14,000 brains (a large fraction of which were cryogenically preserved within a day after death), scientists are unable to read any memory from any of these brains, and are also unable to find any evidence of some neural code that could be used to translate learned information into brain states. The brains are saying "storing memories is not something brains do," but our scientists refuse to listen to what the brains are telling them.  

    Below is a diagram from the paper "Materials Advances Through Aberration-Corrected Electron Microscopy." We see that since the time the genetic code was discovered about 1953, microscopes have grown very many times more powerful. The A on the left stands for an angstrom, a tenth of a nanometer (that is, a ten-billionth of a meter). 


    Currently the most powerful microscopes can see things about 1 angstrom in width, which is a tenth of a nanometer. How does this compare to the sizes of the smallest units in brains? Those sizes are below:

    Width of a neuron body (soma): about 100 microns (micrometers), which is about 1,000,000 angstroms.

    Width of a synapse: about 500 nanometers, about 5000 angstroms.  When you search for "width of a synapse," you will commonly get a figure of 20 to 40 nanometers, but that is the width of the synaptic cleft, the gap between two synapses or between a synapse and a dendrite. The full head is much wider, as you can see from the page here.

    Width of a dendritic spine: about 50 to 500 nanometers, about 500 to 5000 angstroms.

    Length of a dendritic spine: the site here says, "the thin spine neck, which connects the spine to the main dendritic branch, has lengths between 0.04 and 1 μm [microns] and has 'door knob'-shaped head structures with diameters that between 0.5 and 2 μm [microns]." That length dimension is between 400 and 10,000 angstroms; and that head diameter is between 500 and 20,000 angstroms. 

    The visual below (from the page here) shows an electron microscope image of a synapse. The width of the synaptic head is more than 500 nanometers (nm). We see nothing that looks like any kind of storage of human learned information. The neurotransmitters inside the spherical vesicles are short-lived chemicals that don't even last a week. 

    synapse photograph

    Below we see a closeup electron microscope photograph of some dendritic spines which are 500 nanometers (5000 angstrom) wide, from the scientific paper here "Ultrastructural comparison of dendritic spine morphology preserved with cryo and chemical fixation," Tamada et. al.  We see nothing that looks anything like  stored learned information or stored memory information. 

    dendritic spine closeup

    Clearly the resolution of the most powerful microscopes is powerful enough to read memories stored in neurons or synapses, if such memories existed. And more than 10,000 brains have been microscopically studied in recent years. The failure to microscopically read any  memories from human brain tissue is a major reason for thinking that brains do not store human memories.  

    Besides failing to find specific memories and items of learned knowledge by microscopically examining brains (such as the information that the New York Yankees belong to the American League of US baseball), scientists can find no evidence of a mechanism for storing learned information in brains.  If such a mechanism existed, its fingerprints would be all over the place. Since humans can learn and remember so many different types of things (sights, sounds, feelings, facts, beliefs, opinions, numbers, smells, tastes, physical pains, physical pleasures, music, quotations, and so forth), any brain mechanism for storing all of these things would have a massive footprint in the brain and in the genome. No sign of any such thing can be found. The workhorses that get things done in the body are proteins, and humans have more than 20,000 types of proteins. No one has ever identified a protein that helps to write a memory of experiences or numbers or words to the brain or neural tissue, in any kind of way that helps explain how memories or knowledge could be stored in brains.  Of course, you can find studies maybe showing that protein XYZ was used when someone learned something, but that does nothing to show a mechanism of memory storage. 

    Saturday, November 11, 2023

    They Stored and Studied Thousands of Brains, But Still Failed to Show Mental Illness Comes From Sick Brains

    In 2019 the Washington Post had a long article entitled "Dissecting brains to find the biological answers to the mysteries of mental disorders."  We hear about a Lieber Institute of Brain Development that is engaged in the strange business of requesting brains from the relatives of those who very recently died, and then studying such brains.  But we read nothing substantial in the Post story about any progress made in understanding mental illness by studying brains.   We are told, "Since opening in 2011, the institute has amassed more than 3,000 of these post-mortem brains that they are studying to better understand the biological mechanisms behind such neuropsychiatric disorders as schizophrenia, major depression, substance abuse, bipolar disorder and post-traumatic stress disorder."  

    We are told of a guy working for that institute who has the job of calling the families of people who just died (often from suicide), asking them to donate the brain of the dead person. We are told such pleas must occur very quickly. The article says this guy "has a small window of time in which to get that consent — just one to three hours." We can only imagine how many families have been bothered in their worst hour of grief by such requests. Later the Post story makes it sound like some of the brains gathered are not that fresh, saying, "Researchers try to obtain brains within 24 to 36 hours." We are told the brains are "flash frozen." A 2019 annual report of the Lieber Institute tells us, "After consent, we obtain a detailed clinical history via interviews with the family." I can only imagine what a burden that would be on family members with a recently deceased relative. 

    A page of the Lieber Institute brags that it now has a collection of 4000 brains. Another of its pages calls this collection "the largest collection of brains in the world that’s devoted to enhancing science’s understanding of psychiatric disorders" (which doesn't seem accurate, since the Dutch collection described below, existing for the same purpose, is twice as large). A page of the Lieber Institute entitled "Important Breakthroughs" mentions nothing very substantial about finding a link between brain structure and mental illness. 

    The site has a link to a "10-Year Anniversary Report" that fails to report much of any real progress in finding a link between mental illness and brains. We have in the report a page with a big headline of "KEY PUBLICATIONS."  The first publication listed in this report has a title of "Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance." It's a Questionable Research Practices study that used a sample size of only 13 subjects.  We read in the study, "The sample sizes were small and, because there were no similar prior studies, we could not reasonably estimate expected effect sizes or error rates." The study says, "Due to the small sample sizes and the number of tests performed, some of the associations observed may be spurious, so replication studies with larger samples are necessary to confirm and extend these findings." And this is what the Lieber Institute is offering as the first example of its work in their 10-year progress report?  The other three studies mentioned on the page only talk about claims of genetic differences. 

    The 10-year report has this not-very-wise comment on suicide:

    "There is certainly a genetic component to suicide, meaning that it can run in families. Twin studies, however, have shown there is more to it. Scientists believe epigenetics—the interaction of genes and the environment—is at play. Perhaps early trauma or illness can turn on specific genes, increasing a person’s risk of suicide. Until we unravel the biological mechanisms underlying suicide, it’s hard to fully understand, treat, or prevent it."

    The idea of suicide being caused by genes is nonsensical, as are all ideas of some idea or behavior being caused by genes. Genes merely specify low-level chemical information such as the amino acid sequence of proteins, not any tendencies to think or act in a particular way.  A gene may help make possible some physical action, but is never the cause of such an action. The idea of a genetic basis for suicide is nonsensical according to the assumptions of Darwinism. According to such assumptions, if there were any gene tending to cause suicide, natural selection would tend to weed out such a gene, reducing its occurrence of such a gene in the gene pool of humans. But suicide is still a widespread phenomenon, and it is estimated that 1.7 percent of people in the US die by suicide.  The person claiming a genetic basis for suicide is as misguided as a person claiming a genetic basis for homosexuality. It's the same situation in regard to homosexuality: if there were a genetic basis for it, we would expect (according to Darwinian assumptions) for homosexuality to be very rare or nonexistent. Instead it is estimated that 5% or more of the population is homosexual. 

    bad brain explanations
    Ignoring socioeconomic causal factors

    The 10-year Lieber Institute report says, "Lieber scientists ask what happens in the brain that makes some people take their own lives." That's a question making an implausible assumption, and what we should be asking is: what goes on in the mind or what occurs in a person's life history or current life situation that might make him suicidal?  There is no evidence that something occurring in a brain causes people to commit suicide. 

    The 10-year Lieber Institute report has a link to a paper entitled, "Genetics and Brain Transcriptomics of Completed Suicide." The "Brain Transcriptomics" part involves the ridiculous procedure of trying to analyze rates of gene transcription activity in the brains of people who have already died, using brains frozen 12 to 24 hours after death.  Gene transcription is greatly altered by death, and rapidly trails off in the hours after death. The idea that you can shed some light on what was happening in either the minds or brains of people when they killed themselves or beforehand by studying gene transcription rates in brains frozen 12 to 24 hours after they died seems likes nonsense. 

    A paper like this should not be taken seriously by anyone unless the authors followed a careful blinding protocol so that those analyzing the brains did not know whether any particular brain came from someone who committed suicide. We read of no such thing. There is merely a single sentence saying, "All diagnoses and decisions about manner of suicide were determined blind to any of the molecular data." That does not mean that people studying the brains were blind to whether suicide occurred. 

    Very ridiculously, the 10-year Lieber Institute report has a line saying, "Lieber researchers are looking at these biological snapshots of what occurred in the brain at the moment of suicide completion to determine what's different about these brains."  The brain of a dead person frozen 12 to 24 hours after he died is not a biological snapshot of what occurred in the brain at the moment of suicide. 

    The publications page of the Lieber Institute lists their top papers for the past nine years. We seem to find no mention of a discovery linking brain states and mental illness. Most of the papers mention only claims about genes. None of the papers listed uses the word "replication." What the Lieber Institute mainly seems to have in its research is gene analysis, particularly the weak borderline type of gene analysis called transcriptomics. Transcriptomics is some not-very-solid-seeming branch of inquiry that tries to analyze what genes were being used at particular times.  The idea of trying to use transcriptomics to study dissected dead brains is laughable. Gene transcription is greatly changed by death, and trails off not long after death. 

    What do you do when you can't find differences in brain size or brain structure to explain mental differences? Maybe you look for differences in genomes. But the genes in genomes merely specify low-level chemical information such as the amino acid makeup of proteins,  and have basically nothing to do with mental states. What do you do if you cannot find differences in genomes to explain mental differences? Then maybe as a last resort you do some studies on the will-of-the-wisp, ever-changing kind of thing called "transcriptomic profiles." Since transcriptomic profiles are ever-changing, and it is possible to get a separate  "transcriptomic profile" for any of 20,000+ genes, you will have some very noisy data allowing you to see pretty much anything that you want to see. 

    Apparently no drugs or treatment for mental illness have yet resulted from all this studying of 4000 brains.  On a page of the Lieber Institute we read this

     "Seven years of operations, we have made considerable progress in identifying and developing a promising set of novel therapeutic targets including two that could be in clinical trials within two to three years. In addition, we have four promising leads that could introduce two new drugs into Phase II clinical trials by 2021."

    That isn't a report mentioning that any drug had yet been developed by such brain studies. We hear of four drugs "out-licensed for further development," but we don't hear of any drug that has been federally approved. Apparently all this annoying the families of just-deceased people for a brain donation isn't getting much of anywhere in establishing a link between brain states and mental illness. 

    The Lieber Institute publishes a free online magazine called neuroDEVELOPMENTS. In the March 2019 edition we have the very untrue claim that "the genome guides construction of the brain." The human genome (DNA and the genes in it) do not guide or specify the construction of either any human organ or any human cell. The claim that DNA is a blueprint telling how to make a body or any of its organs or cells is a grotesque lie that materialist scientists have been telling for 70 years.  For a long list of quotes by scientists and doctors saying that DNA is not a blueprint, program or recipe for building a body, see my post here. 

    Elsewhere in the world is an even bigger collection of brains, one that also has failed to substantially support claims of a brain basis for mental illness. The Japan Times tells us this:

    " Countless shelves line the walls of a basement at Denmark's University of Odense, holding what is thought to be the world's largest collection of brains. There are 9,479 of the organs, all removed from the corpses of mental health patients over the course of four decades until the 1980s. Preserved in formalin in large white buckets labeled with numbers, the collection was the life's work of prominent Danish psychiatrist Erik Stromgren...The brains were collected after autopsies had been conducted on the bodies of people committed to psychiatric institutes across Denmark. Neither the deceased nor their families were ever asked permission."

    We hear not one word about any discovery that came from studying these brains. A CNN story on the basement filled with brains tells us this:

    "A 2012 study found that roughly 40% of Danish women and 30% of Danish men had received treatment for a mental health disorder in their lifetimes – though Werge estimated that number would 'almost certainly' be higher if the same study was done today. (By comparison, that same year, less than 15% of US adults received mental health services.) 

    I don't think Danes are any more prone to mental illness than Americans, but it seems from the numbers above that Danish authorities have some great enthusiasm for diagnosing people with mental illness, particularly women. We may only wonder how many of the brains in the Danish collection were taken without permission from women who were wrongly put in mental hospitals. The CNN article also fails to tell us of any progress in understanding the cause of mental illness from studying such brains. A web page of the University of Odense describes the collection of brains, but fails to mention any progress that has come from studying the brains.  There is no link to any papers that were produced using such brains. 

    There is another brain collection called the Human Brain Collection Core (HBCC). The collection is described here. The collection seems to consist of about 1000 brains, 700 from people who were diagnosed with mental illness. 300 of the brains are from normal people. We seem to have the same kind of method as used by the Lieber Institute. The families of people who recently died are asked to donate the brain of a family member, with a time pressure element of "we must act fast." We are told "there is no direct benefit to the family for allowing the donation." I guess such "grab the brains without paying a cent for them" stinginess is what we might expect from research neuroscientists, who nowadays pay meager  "chump change" wages to volunteers for scanning their brains in medically unnecessary brain scans that might expose them to health risks (as discussed here). 

    Related to this collection is a "Selected Publications" page, apparently listing the best results obtained from studying these brains. None of the papers listed have impressive-sounding titles making it sound like any brain structure or brain condition has been found explaining mental illness. Most of the papers merely refer to obscure claims about genetics and genetic transcription.  

    Of about 46 papers listed, the paper that sounds the most like something reporting a link between brain structure and mental illness is a paper entitled "Accelerated hippocampal biological aging in bipolar disorder." The paper does not report any differences in the hippocampus size or structure for those with bipolar disorder. The authors tried to look for some epigenetic difference, and initially found "Groups did not differ for epigenetic aging acceleration when considering the entire sample." After using the old "slice the study group into a smaller group, looking for statistical significance" trick, the authors were able to report a very marginal  statistical significance of just barely better than the minimum of p < .05, something that smells like p-hacking.  We can't tell how large the sample size is, because the authors haven't listed it in the abstract, and the paper is behind a paywall. This does not at all qualify as any brain difference explanation for bipolar disorder.