In my previous post "Cognitive Neuroscience Is Floundering, So the Kavli 2024 Neuroscience Prize Went to Low-Quality Research," I discussed how the million-dollar Kavli 2024 Neuroscience Prize was awarded to scientists for doing low-quality research work that failed to establish the boasts made in the prize announcement. Let us now look at two other cases of blunder in giving a big neuroscience research prize.
The Lundbeck Foundation issues an annual million-dollar prize in neuroscience research. The foundation blundered in its announcement of its 2023 Brain Prize. My complaint with the 2023 Brain Prize is not with the research done. My complaint is with how such research was sold as having relevance to memory that it does not have. The document announcing the prize made some claims that simply are not true.
The document announcing the prize goes wrong right at its beginning. We read Professor Richard Morris making these erroneous claims:
"In order to establish appropriate neural connections during development or to adapt to new challenges in adulthood through learning
and memory, brain circuits must be remodeled, and the new patterns
of connectivity maintained; processes that require the synthesis of new
proteins for those connections. The Brain Prize winners of 2023, Michael Greenberg, Christine Holt, and Erin Schuman have revealed the
fundamental principles of how this enigmatic feature of brain function is mediated at the molecular level. Together, the Brain Prize 2023
winners have made ground-breaking discoveries by showing how the
synthesis of new proteins is triggered in different neuronal compartments, thereby guiding brain development and plasticity in ways that
impact our behavior for a lifetime.”
We have here a statement of untenable neuroscientist dogma, the claim that learning and memory occurs when brain circuits are remodeled. There is no evidence for such a claim, and no one has any understanding of how a change in brain circuits could cause a memory to be stored. There are quite a few strong reasons why the claim above cannot be correct. One of the strongest is the speed at which humans can create new memories, which is a speed way, way too fast to be explained by some idea that brain circuits are being remodeled. Humans can learn new things instantly. If someone walks in and tells you that your father just died from a heart attack, you instantly form a permanent new memory of how your father died. It doesn't take minutes to form such a new memory, as it would take if it required a modification of brain circuits.
Beginning on page 12 of the 28-page document, we have long statements by each of the prize winners extolling themselves and their work. The first is a long statement by Michael Greenberg, who gives lots of nerdy jargon-filled discussion of the details of his work. Despite dropping a few little hints here and there weakly trying to insinuate that his work had something to do with memory, his long discussion fails to explain how his work had any real relevance to explaining how a brain could store or retrieve a memory. There is then a similar long discussion by Christine Holt, describing her life journey. She fails to explain how her work had any relevance to explaining how a brain could store or retrieve a memory. There is then a similar long discussion by Erin Schuman, describing her life journey. She fails to explain how her work had any relevance to explaining how a brain could store or retrieve a memory.
What went on here can be summarized like this:
(1) Some scientists made a little progress in understanding protein synthesis that goes on in synapses.
(2) Clinging to the untenable assumption that protein synthesis can explain human memory, such minor progress has been wrongly passed off as being progress in understanding how brains could store memories.
It's kind of like some scientists making a little progress in understanding cloud formation, and then some other scientists claiming this explains how extraterrestrials are constructing cloud bases in the sky. No, it sure doesn't.
There are several giant reasons why protein synthesis cannot explain memory formation. The first is that protein synthesis is a sluggish process typically requiring at least a few minutes, and often requiring many minutes. But humans can learn new things instantly. If someone announces to you how your child or your parent died, you will instantly form a vivid new memory that you will probably remember for the rest of your life. Memory formation could never occur instantly if it required protein synthesis in the brain or remodeling of brain circuits. The second reason why protein synthesis cannot explain memory formation is that memories can last for 60 years or more, but proteins in the brain are short-lived. The average brain protein has a lifetime of less than two weeks, as do synapse proteins. So the length of time that humans can remember is 1000 times longer than the average lifetime of brain proteins. Then there's the fact that no one has any understanding of how some fattening up of synapses or remodeling of synapses could ever be a process storing memories. The idea is no more logical than thinking that memories are stored when wind and snowfall jiggle around the shapes of snow drifts.
See my post "They Memorized Many Times Faster Than a Brain Could Ever Do" for many well-documented cases of humans memorizing at astonishingly fast speeds, speeds far too high to be explained as examples of protein synthesis. One example is the man who memorized a full deck of 52 playing cards in 14 seconds.
An equally great blunder of the Lundbeck Foundation occurred in the announcement of its 2016 prize. The announcement made this false claim: "The Brain Prize for 2016 was awarded to Timothy Bliss, Graham Collingridge and Richard Morris for 'their ground-breaking research on the cellular and molecular basis of Long-Term Potentiation and the demonstration that this form of synaptic plasticity underpins spatial memory and learning." No such demonstration has ever occurred.
The 2016 announcement page has no document justifying the award. We merely have the display of the video. At the start we have some dumb reasoning by one of the winners. Asked to describe his field of research, Timothy Bliss states this:
"Well, what I would say is, a simple question: how does the brain store information? How are memories stored in the brain? Given that we know the brain consists of a huge number of nerve cells and the connections between them, what happens to those connections when you lay down a memory? Something must happen, the brain must change in some way, because it now has this memory that it did not have before. Tomorrow I will look back on this day and remember this interview with you. And my brain has changed in some way, there has to be a physical change. So the question is: what is that physical change? And Long Term Potentiation is that physical change, a change in the efficiency of the connections between cells in a subset of cells which are stored in this memory."
What we have in this quote is circular reasoning, vacuous hand-waving, and a false claim. We do not know that memories occur by means of brain changes, and there are the strongest reasons for thinking that such an idea cannot be correct. The claim "something must happen, the brain must change in some way, because it now has this memory that it did not have before" is saying that the brain must be storing memories because it stores memories. No, we do not know that the brain stores memories; we merely know that people acquire and hold memories. If we are souls or spirits (and there are innumerable reasons for believing that we are), then memory may be a spiritual phenomenon or a psychic phenomenon rather than a brain phenomenon.
The term "long term potentiation" is a misleading term neuroscientists have long been using. What was called "long-term potentiation" in the first years of using that phrase is actually a very short-term phenomenon. Speaking of long-term potentiation (LTP), and using the term “decays to baseline levels” (which means “disappears”), a scientific paper says, "potentiation almost always decays to baseline levels within a week," while noting that even after considering LTP "we would be at a loss for a brain mechanism for the storage of a long-term memory." Another scientific paper says something similar, although it tells us even more strongly that so-called long-term potentiation (LTP) is really a very short-term affair. For it tells us that “in general LTP decays back to baseline within a few hours.” “Decays back to baseline” means the same as “vanishes.”
Neuroscientists have long been guilty of profoundly misleading behavior in trying to persuade people that so-called so-called long-term potentiation (LTP) is a "mechanism for memory." Experimentally inducing LTP requires artificial electrode stimulation which synapses do not naturally receive. Also, human memories can last for sixty years, but LTP is a very short-lived thing. So why do neuroscientists keep doing LTP experiments, and why do they keep mentioning LTP as if it had something to do with memory? There are two reasons:
(1) It always sounds better if you have some sound bite or catchphrase you can mutter when someone asks how something occurs, rather than saying, "I haven't the slightest idea how it occurs." When scientists can mutter the phrase "LTP" when asked about how memories are created, it makes them sound more knowledgeable, rather than sounding like people who have no understanding of a topic.
(2) LTP research is an easy-to-conduct "no way to fail" line of research that provides an easy way for a neuroscientist to add to his total of published papers. Scientists love these kind of "no way to fail" research opportunities. Similarly, theoretical physicists keep grinding out speculative papers about string theory or primordial cosmic inflation. If you have learned how to write such a papers, doing another such paper is a relatively easy and safe way to get another published paper.
There was "definition creep" in regard to the term LTP (long-term potentiation). Erroneously claiming that LTP originally referred to a long-lasting increase, a science paper describes how the term changed:
"Originally, LTP referred to a long-lasting increase in the synaptic response (potentiation) resulting from stimulation at high frequency (Bliss and Lomo, 1973). Over the years this term became fuzzy as it has been applied to pretty much any increase in synaptic strength regardless of the specific induction procedure."
The claim made by Bliss in the quote above is nonsensical. There are no signs that memories are written to brains, and if learned knowledge were to be stored in the brain, it would require some almost infinitely complex mechanism almost infinitely more involved than a mere "change in the efficiency of the connections between cells." Synapse strengthening cannot be memory storage. Complex and very detailed information cannot be stored by a mere strengthening of something.
The type of evidence typically given for an LTP involvement in memory is bad, unconvincing evidence. An animal's brain will be scanned; the animal will be taught something; and then the animal's brain will be scanned again; and (using a looser definition of LTP as merely "synapse strengthening") some scientist will claim that some synapse was strengthened, and that this was memory storage. But the fact is that many synapses strengthen while many other synapses weaken, with this occurring all the time, regardless of whether you are learning anything. So showing some synapse strengthening occurring somewhere when an animal learned does nothing to show that such strengthening was memory formation. Similarly, my front-yard germaniums can grow while I learn about some type of scientific research; but that sure doesn't show that my geraniums stored such new learning. In a PhD thesis, a scientist says, "While LTP is assumed to be the neural correlate of learning and memory, no conclusive evidence has been produced to substantiate that when an organism learns LTP occurs in that organism’s brain or brain correlate."
Bliss later in the video (at the -2:48 mark) makes the untrue claim that if you block an NMDA receptor, an animal "learns much more slowly, and cannot remember what it has learned." The statement is false. A 2014 study was entitled "Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories." And a 2011 study found this:
"We found that inducible knockout mice, lacking NMDA receptor in either forebrain or hippocampus CA1 region at the time of memory retrieval, exhibited normal recall of associative spatial reference memory regardless of whether retrievals took place under full-cue or partial-cue conditions. Moreover, systemic antagonism of NMDA receptor during retention tests also had no effect on full-cue or partial-cue recall of spatial water maze memories. Thus, both genetic and pharmacological experiments collectively demonstrate that pattern completion during spatial associative memory recall does not require the NMDA receptor in the hippocampus or forebrain."
A 2024 study states that it "failed to demonstrate a role for NMDARs [NMDA receptors] in excitatory CA1 and DG neurons in learning about temporal information." A 2011 study tells us that rodents without NMDA receptors are "impaired in a variety of
habit-learning tasks, while normal in some other
dopamine-modulated functions such as locomotor
activities, goal-directed learning, and spatial reference memories."
We have in the video no true statements convincingly backing up the claim that so-called long term potentiation has anything to do with memory. What we mainly have are false claims, hand-waving, and circular logic.
The 2011 Brain Prize of the Lundbeck Foundation was announced with the false claim that Gyorgi Buzsaki had discovered that memories are replayed while you sleep by means of "hippocampal sharp wave ripples." This is an example of what is abundant in modern neuroscience research: the spread of groundless achievement legends. The claims made in the video on this announcement page are speculations not well grounded in observations.
A look at Buzsaki's main paper on this topic (the 2015 paper "Hippocampal Sharp Wave-Ripple: A Cognitive Biomarker for Episodic Memory and Planning") shows a very long paper that has a long discussion of experiments with rodents, but never mentions any decent study group sizes. Alas, it's another example of Questionable Research Practices low-quality science. Mostly Buzsaki just vaguely refers to "mice" or "rodents" without telling us how many mice were tested (whenever this happens you can be 90% sure the study groups sizes were way-too-small). Rarely Buzsaki does tell us how many mice or rodents were used, and in such cases we learn of way-too-small study group sizes such as only 4 rodents or 9 rodents. We have no mention in the text of any blinding protocol being used in these experiments. No robust evidence is provided of memory replay or memory consolidation.
Buzsaki defines a sharp wave-ripple as a little brain-wave blip lasting less than a tenth of a second. With this definition describing no pattern of any decent length, he is able to see "sharp wave-ripples" under innumerable conditions, attaching all kinds of deep significance to these fleeting blips. What is mainly occurring is runaway pareidolia. It's like someone assigning deep explanatory significance to every time he has the slightest skin itch.
Similar Questionable Research Practices occur in a 2017 paper by Buzsaki on sharp-wave ripples, in which the study group is a way-too-small size of only five rodents. And it's the same deal in his 2024 paper on this topic, in which the study group size is a way-too-small size of only six animals. The paper used no blinding protocol.
In the video on the page Buzsaki makes groundless boasts that tiny fragments of memories are replayed in the brain over and over again in the brain, claiming to have identified this. Such a boast is unfounded, and his research on this topic did not follow sound research practices. Many of the main claims made by the narrator in the video are groundless or untenable claims. The claim of Buzsaki that these tiny tenth-of-a-second ripples are the tiniest memory recall fragments (rather like individual frames from a 24-frames-per-second movie) is a groundless claim that is not credible.
I will give you a quick look at how claims of a relation between sharp wave ripples and memory consolidation involve appeals to junk science. The paper "Hippocampal ripples and memory consolidation" tells us this:
"More recently however, several studies have revealed a
correlation between SPWRs [sharp wave ripples] and memory. Ripple occurrence rates were shown to increase during the hour
following a training session on an odour-reward association task [51]. A similar increase was observed in rats
learning a radial maze task, concomitant with a significant
improvement in performance [52]. Also, the intrinsic
ripple frequency increased after a change in the task
contingency, such as a variation in the minimum delay
to receive a new reward by lever pressing [53]."
Every one of the references is to a low-quality science paper guilty of Questionable Research Practices. Reference 51 is to a paper "Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning." The paper used way-too-small study group sizes such as only six rodents, and failed to use any blinding protocol. Reference 52 is to the paper " Reference 52 is to a paper "Hippocampal Sharp Wave/Ripples during Sleep for Consolidation of Associative Memory." It's another piece of Questionable Research Practices shlock that uses way-too-small study group sizes such as only four or five rodents; and again we have a complete failure to follow a blinding protocol. Reference 53 is to a paper "Frequency of network synchronization in the hippocampus marks learning." This is also low-quality research with study group sizes such as only 3 rodents or 9 rodents, without any blinding protocol being followed. None of these studies provide any good evidence for any relation between memory and sharp-wave ripples; they merely provide evidence for how low are the publication standards these days for journals publishing neuroscience research. No rodent-using experimental neuroscience research trying to establish correlations should be taken seriously unless it followed a blinding protocol and also used at least 15 or 20 subjects per study group.
Poor research practices are the norm in
today's dysfunctional world of neuroscience
Brains have a great deal of signal noise of many types, and the abundance of such noise is one of many reasons for disbelieving that the brain is the source of human thinking and recall which can occur with incredible accuracy, such as when people perfectly recall very large bodies of text and perfectly perform extremely difficult math calculations without using tools such as computers, pencils or paper. Claims about sharp-wave ripples are made by brain wave analysts analyzing EEG readouts. The analysis of brain waves obtained by EEG devices is an area of science where bad methods, pareidolia and junk analysis is very abundant. There is an abundance of people trying to use fancy statistical methods to try to extract identifiable "signals" or "signs" from data that is very noisy and polluted. Muscle movements abundantly contaminate EEG readings. Unless a study is very carefully designed and includes things such as a blinding protocol and adequate study group sizes assuring good statistical power, you will typically have some junk paper that is suitable only for tasks such as lining bird cages and wrapping fish.
A junk-quality article "How the Brain Decides to Remember" in Wired Magazine recycles an article on the Quanta Magazine web site, a site notorious for its credulous puff pieces parroting unbelievable boasts by scientists. In a misleading puff piece about Buzsaki, we have all kinds of claims about scientists establishing grand things they did not actually show, such as the claim that "In 2009 and 2010, two papers, including one led by Zugaro, showed that sharp wave ripples were involved in consolidating memories to endure over the long term." One of the references is to a low-quality science paper "Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat" that used only a study group of only five rats. The other reference is to an equally low-quality paper using only seven rats.
It is frequently pointed out to neuroscientists that experimental studies involving mice are generally worthless unless they use at least 15 or 20 subjects per study group; but neuroscientists keep senselessly continuing to use ridiculously low study group sizes. Why do they do that? Because it allows them to "mine noise," and report false alarms that would vanish if a decent study group size was used. It's rather like someone trying to prove his prophetic powers by publishing a test in which he correctly predicted whether merely four consecutive coin flips were "heads" or "tails," conveniently failing to publish a larger test of his powers involving how well he predicted 15 consecutive coin flips. You can get all kinds of false alarms when you use tiny sample sizes.
See the paper "The Case Against Memory Consolidation in REM Sleep" for a rebuttal of claims that REM sleep has anything to do with memory consolidation. The paper states, "We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or
consolidation of memory."
The awarding of neuroscience prizes plays a large part in the social construction of groundless achievement legends claiming that neuroscientists did grand things they did not actually do. Often the judges who award such prizes are people who did similar research as the research being awarded, and the judges are often doing themselves favors by helping to legitimize poor quality work similar to the work that the judges themselves are performing.
The Lundbeck Foundation announces its annual Brain Prize on some page with a video. Since the page will have no link to a scientific paper, it then becomes a bit difficult for anyone to dive into the relevant research papers, to find out what whether the research followed good practices. But with some work, you can find when the prizes were awarded foolishly. You can look at the video, find the main scientists mentioned, find the research topic, and look up the authors and the topic on Google Scholar. You can then read the papers and see whether they were merely more examples of the low-quality schlock that is so predominant in today's neuroscience research.
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