Neuroscience Research Is Floundering, So a Huge Cash Prize Recently Went to Weak Research

Inaccurate press accounts hailing low-quality research are a central part of the social construction of groundless triumphal legends in neuroscience. Another key element in the social construction of such groundless triumphal legends occurs when the unwarranted claims are repeated in the papers and textbooks and college lectures of neuroscientists and psychologists. A lesser element in the social construction of such groundless triumphal legends is when big prizes go to researchers who did poor research guilty of Questionable Research Practices. Then the researcher can start boasting, "It must be true -- my research got a big prize!"

John O' Keefe published papers in the 1970's and after claiming to have detected "place units" in the hippocampus of rats. The papers also used the term "place cells."  The claim was that certain cells were more active when a rat was in a certain spatial position.  Greater activity during some type of observation is not representation. My eyes may widen if I see a naked woman walking down the street, but that is not a case of my eyes representing the naked woman. It has always been a case of misleading language when neuroscientists attempt to pass off claimed higher activation in some neurons as an example of representation. Real representation involves the use of symbolic tokens. Neuroscientists cannot find any symbolic tokens in the brain, other than the symbolic tokens in DNA that represent amino acids. 

The "place cells" papers of John O'Keefe that I have examined are papers that do not meet standards of good experimental science. An example of such a paper was the paper "Hippocampal Place Units in the Freely Moving Rat: Why They Fire Where They Fire."  For one thing, the study group size used (consisting of only four rats) was way too small for robust evidence to have been produced. 15 animals per study group is the minimum for a moderately convincing result in animal studies looking for correlations.  For another thing no blinding protocol was used. And the study was not a pre-registered study, but was apparently one of those studies in which an analyst is free to fish for whatever effect he may feel like finding after data has been collected, using any of innumerable possible analysis pipelines. 

The visuals in the "place cell" studies done by O' Keefe compared wavy EEG signal lines collected while a rat was in different areas of an enclosed unit. You can see what I'm talking about by looking at page 1334 of the document here. The wavy signal lines look pretty much the same no matter which area the rats were in. But O'Keefe claims to have found differences.  No one should be persuaded that papers using analysis so subjective show robust evidence for an important real effect.  We should suspect that the analyst has looked for stretches of wavy lines that looked different when the rat was in different areas, and chosen stretches of wavy lines that best-supported his claim that some cells were more active when the rats were in different areas. 

When I looked for later "place cell" papers by O'Keefe, I saw papers that seemed to just continue the same Questionable Research Practices. Specifically:

• A 1993 paper co-authored by O'Keefe was entitled "Phase Relationship Between Hippocampal Place Units and the EEG Theta Rhythm." The paper used way-too-small study group sizes of only three rats and two rats.  No blinding protocol was used, and the paper was not a pre-registered study. We have some wavy-line analysis that seems extremely subjective and arbitrary.
• A 2008 paper co-authored by O'Keefe was entitled "The boundary vector cell model of place cell firing and spatial memory." The paper used a way-too-small study group size of only two rats. For example, we read "Twenty five place cells were recorded from the two rats."  No blinding protocol was used, and the paper was not a pre-registered study. We should chuckle when the paper says that "we followed 11 cells for time courses varying from a day to the duration of the experiment" and confesses ungrammatically that " it is difficult to draw firm conclusions from such as small data set."  There are millions of cells in the brain of a rat. Paying attention to only a handful of such cells seems like ridiculous cherry picking. 
• A 2012 paper co-authored by O'Keefe was entitled "How vision and movement combine in the hippocampal place code." The paper used a way-too-small study group sizes of only six mice.  No blinding protocol was used, and the paper was not a pre-registered study. We have some data analysis that seems extremely subjective and arbitrary. 
• A 2014 paper co-authored by O'Keefe was entitled "Long-term plasticity in hippocampal place-cell representation of environmental geometry." The paper used a way-too-small study group sizes of only three animals.  No blinding protocol was used, and the paper was not a pre-registered study.

Studies like this are generally not good evidence unless a very stringent blinding protocol is used, and studies like this almost invariably fail to follow any kind of blinding protocol. It's easy to find the failure: just search for the word "blind" or "blinding" in the text of the paper, and note well when it fails to occur. 

In general, there is nothing scientific about using nicknames such as "place cells" to describe cells. The justification given for the use of such a term is based not on observations of permanent features of any cells, but on subjective judgments of how the cells behaved at particular moments. That's as unscientific and subjective as saying that certain people have "fear eyes" or "sorrow eyes," based on subjective judgments of how their eyes looked at particular moments.  

Although O'Keefe's "place cell" papers were not at all a robust demonstration of any important effect, the myth that "place cells" had been discovered started to spread around among neuroscience professors, aided by the use of a catchy memorable catchphrase: "place cells."  O'Keefe even got a Nobel Prize in 2014. The Nobel Prize committee is normally pretty good about awarding prizes only when an important discovery has been made for which there was very good evidence. Awarding O'Keefe a Nobel Prize for his unconvincing work on supposed "place cells" was a very bad flub of the normally trusty Nobel Prize committee. Even if certain cells are more active when rats are in certain positions (something we would always expect to observe from chance variations), that does nothing to show that there is anything like a map of spatial locations in the brains of rats or mice. 

This year something similar went on. A 2.5 million Euro prize was awarded to psychologist Christian Doeller for his work on what he calls "grid cells." Granting this award is a very bad error, because Doeller's work on so-called "grid cells" is just as weak and unconvincing  as O'Keefe's work on so-called "place cells."

On the page announcing this award, we read these claims:

"How do human thought processes and the brain work? The psychologist Christian Doeller has been exploring this question for decades. He is a leading memory researcher and his work has led to ground-breaking findings in the field of neuronal spatial cognition, which is the ability of human beings to orient themselves in a physical space, and to apprehend and navigate it. Doeller demonstrated that spatial contexts can also be recoded into abstract categories and that they therefore form the neuronal basis of thinking and decision-making. Among other things, Doeller developed imaging analysis methods that allowed him to detect, for the first time ever, signals in the human brain that correspond to the grid cells. These are cells that were originally found in rats and that provide the animals with a system of coordinates that enables them to determine their own position."

The middle sentence here (in boldface) makes no sense. If "spatial contexts can also be recoded into abstract categories," that does nothing to show a "neuronal basis of thinking and decision-making." The claim about "a system of coordinates" that allow animals to "determine their own position" is spurious and groundless, and does not match any well-designed and robust neuroscience research.  No one has ever discovered any coordinate or any number or any letter of the alphabet inside a brain by examining brain tissue or brain scans or EEG readings of brain waves. No one has any coherent and credible tale to tell of how any such thing as a "system of coordinates" could exist in any organism's brain. 

On the page announcing this award, we have no direct links to particular papers written by Doeller, and no mention of the titles of such papers. There is an "information system GEPRIS" link that takes us to a page from which you can access two papers co-authored by Doeller, which are discussed below:

• There is a link to a project called "At first glance: How saccades drive communication between the visual system and the hippocampus during memory formation." But we have no link to a paper, and Google Scholar makes no mention of such a paper. 
• There is a link to a project called "Episodic integration under stress," and there is a link for a paper, one entitled "Stress disrupts insight-driven mnemonic reconfiguration in the medial temporal lobe." That paper has a good study size of about 60 humans. But it does not say anything about grid cells. Nor does it do anything to establish a "neuronal basis of thinking and decision-making." The paper does nothing to show a "mnemonic reconfiguration in the medial temporal lobe." We have some psychology test involving stress and memory. The paper draws no clear link between mind states and brain states. 

I looked on Google Scholar for other papers that Doeller might have authored on so-called "grid cells." I find these papers:

• "Evidence for grid cells in a human memory network." This 2010 paper co-authored by Doeller includes a poorly-designed experiments with rats. one using a way-too-small study group size of only 8 rats. The term "grid cell" is used without any justification, and without any proper definition of what such a term means. The closest the paper comes to defining the term "grid cell" is when it says, "Grid cells recorded in medial entorhinal cortex of freely moving rodents fire whenever the animal traverses the vertices of an equilateral triangular grid covering the environment (see Fig. 1a), and may provide a neural substrate for path integration." But neurons in brains fire between 1 and 100 times per second. So it makes no sense to define a grid cell as a cell firing whenever some point or line is traversed. All neurons in the brain of rats and humans are continually firing. After some statistical gobbledygook that smells like "keep torturing the data" and "see whatever you are hoping to see" pareidolia, the paper claims, "Our results provide the first evidence that human entorhinal cortex encodes virtual movement direction with 6-fold symmetry, consistent with a coherently-oriented population of grid cells similar to those found in rat entorhinal cortex and pre- and parasubiculum." We should always be suspicious when neuroscientists claim to have found "the first evidence" for something. That amounts to a confession that at the time their paper was written, no other evidence for the claimed effect existed.  Figure 3 gives an example of how unconvincing the paper's evidence is. We have some fMRI brain scan data purporting to show changes in brain activity. But if you take a close look at the scale, you will see that the differences are only small fractions of a half of one percent.  The differences being graphed are about 1 part in 400. These are negligible differences that are not convincing evidence for anything. Anyone "noise mining" a brain scan and free to search any of 1000 little areas looking for such differences would be able to find such differences, purely because of random fluctuations.
•  "Grid-cell representations in mental simulation." This 2016 paper makes  this untrue claim: "Electrophysiological recordings in freely moving rodents have demonstrated that positional information during navigation is represented by place cells in the hippocampus (O’Keefe and Dostrovsky, 1971) and grid cells in entorhinal cortex (Hafting et al., 2005)." The claims are untrue; no such things were demonstrated. O'Keefe's work on so-called place cells is not convincing because of the poor experimental practices I discuss above. The Hafting paper was guilty of Questionable Research Practices such as the use of fewer than 15 subjects per study group, the lack of a control group, and the lack of a blinding protocol. The authors of the paper "Grid-cell representations in mental simulation" then discuss some experiment they did while having a small number of people doing some imagination task while they had their brains scanned. The results are not any convincing evidence for either so-called grid cells or for brains being involved in imagination. The study group size is not that bad (24 subjects). But nothing in the paper does anything to give any convincing evidence for "grid-like representations" in the brain. We have no pre-registration of a hypothesis to be tested and an experimental protocol to be followed, and no blinding protocol. 
• "From Cells to Systems: Grids and Boundaries in Spatial Memory." This is a review article by Doeller, one containing many unfounded claims about research done by him and others. The paper claims, "The background firing rate of place cells is very low, effectively zero." But contrary to such a claim, very many sources tell us that all neurons in the brain continuously fire, at a rate between about 1 and 100 times per second. 
• "Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe Maps Visual Space." This 2018 paper lacking any blinding protocol claims, "Our findings provide first evidence for a grid-like MEG signal, indicating that the human entorhinal cortex codes visual space in a grid-like manner." Again, I must emphasize that we should typically have little confidence in neuroscience researchers claiming to have provided the first evidence for some claim, as such a confession about "first evidence" is typically an admission that the claim is not well-replicated. The term "grid-like" is so flexible that almost anyone looking for something "grid-like" in a large body of data can find it somewhere. No convincing evidence is presented here that brains are representing visual space. It's just more pareidolia in which neuroscientists eagerly seeking grids claimed to have found something "grid-like." Similarly, give eager cloud analysts thousands of photos of clouds, and if the analysts are eager to find "grid-like" patterns, they will surely be able to find them somewhere. 

Reviewing Doeller's work, I fail to find anywhere any convincing evidence for anything like representations in the brain of visual space or anything non-genetic, or anything like convincing evidence that justify the use of the terms "place cells" or "grid cells." Failing to use pre-registration, his papers typically seem to involve someone being free to analyze brain data in endless number of ways, with the analyst then announcing that after using such-and-such an elaborate gobbledygook rigmarole scheme of convoluted analysis, something "grid-like" was supposedly found. Typically there is a stink suggesting noise-mining, pareidolia, and "keep torturing the data until it confesses." None of the gathered brain data does anything to naturally suggest any such thing as neural representations of the subject's position or orientation or what the subject is seeing. But when neuroscientists are free to slice, dice and massage data in endless possible ways, they may get data to produce the faintest whiff of a suggestion of something, whenever neuroscientists are eager to conjure up such a suggestion. 

Things such as neuron firing rates (picked up by EEG devices) or tiny variations in blood flow rates in brains (picked up by fMRI scanners) are randomly fluctuating data. Anyone eagerly analyzing some large body of randomly fluctuating data hoping to find some desired correlation or pattern will always be able to find little bits of "superior activity" or "increased activation" here or there, about as good as the weak evidence Doeller gives for his so-called "grid cells." But that's not decent evidence of something being represented in the brain. Similarly, someone eagerly analyzing thousands of pictures of clouds in the sky and hoping to find something that looks like the ghost of an animal will be able to find now and then some shape that looks a little like an animal. But that's no evidence for any real representation of animals shapes in the sky. 

The term "representation" is enormously misused and abused by neuroscientists, who abundantly use the term in an imprecise way, without any adequate warrant.  Assumptions underlying Doeller's papers are implausible. If there were to be increased firing in some cells when some subject was in some area of a grid (as picked up by an EEG), that would not actually be a representation of the subject's surroundings. And if there were to be a tiny bit more brain activity in some tiny fraction of the brain when some subject was in some area of a grid (as picked up an fMRI machine), that would not actually be a representation of the subject's surroundings.

The fact that Doeller has got some 2.5 million Euro prize for his weak research is a commentary on how little progress is being made in trying to substantiate "brains make minds" claims and "brains store memories" claims. When a top prize goes to research this weak, it shows you how badly neuroscientists are failing in their attempts to substantiate their untenable dogmas about brains, already discredited by so many facts discussed in the posts of this blog. 

To get an example of some robust grid-related science, you can look at the periodic table shown below:

Credit: National Institute of Standards and Technology (link)

There's no pareidolia going on in the periodic table shown above, no "see what you were hoping to see" noise mining like in papers about so-called grid cells. Nature really does have the number of elements listed in this table. Each of the listed types of elements really does have a number of protons exactly equal to the number shown in the top left corner of the square representing the element. Each of the listed types of elements really does have an average weight equal to the atomic weight shown under the element's name in the square representing the element. 

We may contrast this rock-solid good-as-gold example of robust science with the socially constructed will-of-the-wisp legend-mongering pareidolia dross of "place cell" papers and "grid cell" papers producing no robust evidence of representations in any brain cells, papers that engage in unjustified cell-nicknaming that is not at all robust observational science. 

Below is a relevant quote from a scientist:

• "Neuroscience, as it is practiced today, is a pseudoscience, largely because it relies on post hoc correlation-fishing....As previously detailed, practitioners simply record some neural activity within a particular time frame; describe some events going on in the lab during the same time frame; then fish around for correlations between the events and the 'data' collected. Correlations, of course, will always be found. Even if, instead of neural recordings and 'stimuli' or 'tasks' we simply used two sets of random numbers, we would find correlations, simply due to chance. What’s more, the bigger the dataset, the more chance correlations we’ll turn out (Calude & Longo (2016)). So this type of exercise will always yield 'results;' and since all we’re called on to do is count and correlate, there’s no way we can fail. Maybe some of our correlations are 'true,' i.e. represent reliable associations; but we have no way of knowing; and in the case of complex systems, it’s extremely unlikely. It’s akin to flipping a coin a number of times, recording the results, and making fancy algorithms linking e.g. the third throw with the sixth, and hundredth, or describing some involved pattern between odd and even throws, etc. The possible constructs, or 'models' we could concoct are endless. But if you repeat the flips, your results will certainly be different, and your algorithms invalid...As Konrad Kording has admitted, practitioners get around the non-replication problem simply by avoiding doing replications.” -- A vision scientist (link). 

The paper here ("Investigating the concept of representation in the neural and psychological sciences") says this: "Neuroscientists and psychologists do not appear to have a precise idea about what kind of brain structure or pattern counts as representation." 

There are no components in the brain that have a physical structure resembling a grid. No electron microscope photos of anything in a brain show anything looking like a grid. This is one of the reasons why it is misleading to be using the term "grid cells" to refer to claimed grid resemblances that only arise after convoluted dubious data analysis has been done by scientists.