Having done a neuroscience degree myself, I would double on your conclusion — I still have no clue how a brain works, apart of some simpler systems, like visual pattern recognition. I am out of the field for a single-digit number of years already, but in retrospective it is hilarious how all the literature in neuroscience is gently moving around the question of «guys, bit how all of it works»? People are happy to hack on single neurons or do some fishy fMRI studies instead. But of course, our tooling today is not adequate for this task.

> fish fMRI studies

Link for those curious about this comment:

(Neural Correlates of Interspecies Perspective Taking in the Post-Mortem Atlantic Salmon: An Argument For Proper Multiple Comparisons Correction)[https://teenspecies.github.io/pdfs/NeuralCorrelates.pdf]

As the first author of that paper, I approve of this link.

Am I reading this right: you compared fMRI studies in humans to a dead fish?

Still one of my favorite papers I was ever assigned in my cog sci grad program.

Nick checks out.

Well, I expected fishy as in dubious, not like literal fish.

So the f in fMRI stands for fishy? :-)

I did a minor in neuro and had a very similar experience. Fascinating and useful but it was always slightly alarming when the professor would answer a question with "I don't know.. no one knows. That is far beyond the limits of our capabilities to know." A reminder that scientists really do work at the edge of ignorance!

That to me is really how we need to be emphasizing education in science for young people.

We tend to give the impression that we’ve figured almost everything out, and so you’re just learning the facts of it all.

Really, we’ve carved out a little island in a sea of ignorance, and the foundations of the island are just our current best rough approximations that might collapse.

An example from the field I’m in — biology. It’s quite likely that if you worked at it you can describe a new species in your backyard. You don’t have to go to the Amazon rainforest, there’s scientific unknowns all around you all the time.

The major questions of biology have already been solved, though. The rest is filling in the details.

This doesn’t seem to be true at least for the nervous and immune systems. Probably also the microbiome we host. There’s lots of important stuff yet to be learned with those systems.

I read the parent's comment in terms of how we once viewed life being mysterious, talking about the "elan vital" before we understood DNA. This is often used as an analogy to our current struggle to understand consciousness.

My above comment was not ironic. What I meant is that we have already discovered the algorithm that gives rise to all biological phenomena: Evolution by Natural Selection.

We also have some grand principles that further unite the field, like the cell as the basic unit of organismal life, emergent properties of higher order systems, &c.

The remaining work is mostly 'stamp collecting' - looking at the details of the output of that algorithm. Of course those details are enormously complex. Kind of like mapping out the Mandlebrot Set after you already know the algorithm.

Well the stamp collecting is where the action is.

If you wanna cure cancer, resolve chronic diseases, conserve ecosystems under climate change, etc.

It’s cool to know that DNA exists and that life evolves by natural selection, but getting into the complex weeds of that fractal is where we discover that we know so little.

What? This very thread is about an article talking about the lack of accuracy in our model of the brain's mechanisms.

I suspect GP agrees with you and is making fun of what this guy[1] said to Plank.

[1] https://en.wikipedia.org/wiki/Philipp_von_Jolly

Famous last words of some biologist? :-P

> People are happy to hack on single neurons

This is where science communication fails, the general population and even the most curious people still think that there is such a thing as "Jennifer Aniston neuron", but in reality there is "Rachel from Friends neuron" that sits at the top of hierarchy where the signalling converges and then it's highly likely it isn't the only thing it's responsible for (OR gate), but finding what is the hard question. This is speculation stated at about 20min in this talk: https://www.youtube.com/watch?v=Y1ID0FQN9tg

Yet somehow Pharma can prescribe drugs that affect the brain's functions. How do they get away with that knowing so little about the brain?

Psychiatrists are doctors who prescribe substances that have been closely studied - but their effects may be easily and specifically understood, their mechanisms may not be.

Lithium is a great example - very effective treatment for bipolar. No one really knows why. Prescribed for decades as they've tried to figure it out because tests showed it was effective and relatively safe, just no one knew exactly what it was doing in there.

It's sort of how you can be a woodworker without knowing the cellular biology of trees, and without being an electrical or mechanical engineer who can build a table saw from scratch.

The discovery of it is pretty interesting.

Lithium-rich mineral springs have historically been touted for their healing properties. It was first used for mania in the late 1800s, with Denmark leading the way, but little was published about the medication for more than half a century.

https://www.verywellmind.com/lithium-the-first-mood-stabiliz...

This is a good argument as to why we should look closely at traditional medicines of various cultures. We (1) coevolved with this stuff and (2) have gone through generations of trial and error.

I'm a believer in modern scientific medicine, but think we often have it backwards. Before reinventing the wheel we should exhaustively test what we used traditionally. Maybe the reason we don't do much of that is that it's not possible to patent, and so there's no financial incentive to do so?

There seems to be a good bit of different literature studying traditional cultural practices. Maybe it flies under the radar compared to flashy high-tech stuff. Below is a link to related articles about fermented beverages.

https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from...

I absolutely agree with this. We should go through the many cultures' lists of traditional medicines with the lens of modern chemistry and determine what compounds lead them to be effective pharamacologically.

You do realize what you're proposing happened and happens extensively?

I've read a decent chunk of that research, but it's often relegated to backwater low-reputation journals focused on alternative medicine and is largely ignored by mainstream science. For an example, see the research on various traditional sleep-inducing drugs.

It also doesn't make its way into mainstream practice among GPs and psychiatrists. As an example, which mainstream practitioner would ever prescribe or recommend curcurmin with piperine for any condition, aside from alternative medicine practitioners? Which psychiatrist would recommend EPA fish oil for depression? I could go on. The research that does exist is largely ignored.

Not in that way, no. Pharma, on the other hand, often looks into various remedies etc. in order to draw from and produce more distilled and controllable substances. Aspirin for example, from 'cook a tree bark and drink the solution' into a pill process. Penicillin.. etc.

I am by no means an expert in pharmaceutical studies, but I suppose they can afford a huge number of dead ends in the initial phase of research due to the massive wealth and in the end, they have to test only for two variables: efficiency and side-effects. An explanation on how it actually works, is a very nice extra, but is not required. The problem for Pharma is that at some point you require tests on human subjects, which is very expensive and dangerous.

A lot of original psych drugs were also discovered by accident, intending to address some other medical issue. For example MAOIs were found to have antidepressant effects during a trial to use them for tuberculosis. Development of SSRIs (e.g. Prozac) then came from trying to create a similar drug with less side effects.

Also, the many dead ends thing is true in general for pharma, but at some point there are too many dead ends for it to be profitable even given their bankroll. This is happening a lot lately with neuro-related drug development. In the last 10 years I know Amgen, Pfizer, Novartis, Eli Lilly have all had shut downs/lay offs in their neuroscience research divisions.

You might be interested in reading about Stuart Hammeroff who is an anesthesiologist and professor focused on studies of consciousness...

https://en.wikipedia.org/wiki/Stuart_Hameroff

They give random drugs to rats until something happens.

And then to humans

> fishy fMRI studies

Subtle, but I get it :D

Now is the perfect time to build models of 'how all of it works', just like Kepler did with Tycho Brahe' astronomical observations.

There is plenty, more than enough, data to work with, and many promising/proven models to build upon, need more good theorists in the field.

Saying "but we don't know much" is just being lazy.

> However the author appears to be arguing from a position that they (or someone) actually know how the brain works

Interesting that you had this takeaway, I didn’t get a sense of this at all. My takeaway was that the author presented modern findings (which constitute our present model for how the brain works, speaking nothing to a notion of some absolute correctness) to dispel older hypotheses that are disprovable based on the latest research. As presented, IMO, the author captures well that these modern findings are just a reference point against which to refute the stubborn tropes.

I had the same reaction to parts. This in particular:

> So why does the myth of a compartmentalized brain persist? One reason is that brain-scanning studies are expensive. As a compromise, typical studies include only enough scanning to show the strongest, most robust brain activity. These underpowered studies produce pretty pictures that appear to show little islands of activity in a calm-looking brain. But they miss plenty of other, less robust activity that may still be psychologically and biologically meaningful. In contrast, when studies are run with enough power, they show activity in the majority of the brain.

Another, more relevant reason, is that brain-scanning studies are in their infancy.

All of this seems really confused to me, or so simplified that it no longer makes any sense.

The simplest thing you can do in a scanner is have them sit there doing nothing while you acquire scans. In the end, you just have a 4d matrix of unsigned integers. For each voxel you can acquire an average over the scan and check whether it is significantly above zero using a t-test. Given enough data everything will be significantly greater than zero, including parts outside the head. Or you can compute a global mean to center all the voxles, and check which parts of the brain are significantly above the average, or significantly below the average. Extremely simple analyses (and so yes, there are lots more you could do).

In task fMRI, you have them do a task, and you use events in your task design as predictors of the BOLD, and then display a voxel map of either the beta values, or, more commonly, the T-values of those regression betas (or a contrast of those regression betas). In this case, you really aren't looking at activity. You are looking at correlations.

Those islands of activity in whole-brain analysis images in figures in papers happen because the result images are thresholded, e.g. at p < .05 false-discovery-rate correction for multiple comparisons. Personally, I think unthresholded images are better because they are more informative.

Let's take a concrete example. You have a subject do a task where they have to choose between two gambles varying in risk and reward. Then, for each voxel, you predict the BOLD time course using a series of events (time of presentation of gamble options) with magnitude equal to the coefficient of variation between the two gambles. So now, for each voxel you have a beta value showing how CoV predicts BOLD. You notice that anterior insula on both cases has the highest beta values. You threshold at conventional statistical signficance, after correcting for multiple comparions, and all the spurious, or less important, correlations drop out of the image, and you are left with two bright spots on a map pin-pointed on the left and right anterior insula. See: in this anaylysis, not all "psychologically and biolotically meaninful activity" is being examined or looked at. For example, button presses events show up localized in the motor areas too, but they weren't looking at those. But they could have, if we were interested.

The issue here is the brain of test subjects aren’t simply doing exactly one thing at a time. Your ears don’t turn off because you’re doing a memory task in an MRI.

As such it’s impossible to say what subset of brain activity is directly related to some activity rather than some related mental processes.

Not necessarily. For one, most fMRI studies will have a resting state scan to establish a baseline of what an individual's brain is doing in an MRI setting when it's not really doing anything in particular (typically having the subject stare at a fixation cross and letting their mind freely wander). Then, for the actual task, stimuli are presented and responses are recorded at very specific times with that fixation cross in between with enough time for the brain activity to return to that resting "baseline" before the next stimuli.

There's a lot of signal processing theory, regression analysis, etc. that goes in to it. With that said, the issue that arises is that only the strongest correlates may surface or be observed. There may be a lot of brain activity that overlaps or looks identical between that resting state (baseline) and the stimulation state, but can't really be included because a distinction can't be made, which goes back to your final point. That, however, doesn't mean that there aren't actual subsets of brain activity that we can attribute to a specific activity.

For example, if you're in an fMRI and I show you nothing but a fixation cross, then show you a sad image at a specific time for a specific interval, then went back to the fixation cross, and also showed you a scrambled version of that same image, I can (oversimplified) run a diff check to see what's different between the three. From there, I can remove the overlap between the three from normal baseline activity and activity specifically related to visual processing (scrambled image) to reveal what's specifically different with that sad image. If I see that the amygdala has much higher activity during that sad image compared to the fixation cross and the scrambled image, I can conclude that it has some role in emotional processing (well not really in this example because you'd also need a ton of images, including neutral images, with different orderings of each to really be confident; also really couldn't make that conclusion, just present the correlation because...science).

The point is that there are methods to isolate activity related to a specific activity/stimuli/response/etc. However, it's currently very difficult, if not impossible, to make distinctions in those overlapped areas.

Note: this is obviously an oversimplification of neuroimaging research and analysis

The brain is doing multiple things at once. But that doesn't mean its impossible to subset brain activity related to specific activities.

I think I wasn't fair in this comment, because it suggests that it is easy to do, when it actually isn't. For example, a cogntive control task might have an easy and hard condition. You'll end up with significant activation all over the brain for either of them, and their contrast will still have significant differences between the conditions all over the place too (e.g. SMA, pSMA, Anterior Insula, Anterior Cingulate, Posterior Cingulate Cortex, visual and motor cortex, cerebellum, etc. etc. etc.). Because the brain is doing all kinds of things during the task, and any "subroutine" is still going to involve communication between lot of places. But if the idea that function isn't localized, i.e. going back to a naive connectionist paradigm, then, sorry, no. The distribution of activations we get are often quite stereotyped, and if we are more careful and specific with our models we can localize function often even better.

I don’t think your point is more relevant than theirs.

It’s expensive to run brain scanning studies, so studies have smaller populations or lower resolution data collection in response. Yes, brain scanning studies are new, but we’ve been doing fMRI studies for nearly 3 decades and it’s still expensive. Had that cost been scaled back, we’d have more and/or better data because grants are (very) finite.

I'm upvoting your comment but can you clarify on left brain/right brain? I thought split-brain/callosal syndrome showed us that a lot of our ideas about left brain right brain functional divide were true.

Edit for clarification: I was not expecting folks to respond to this by linking split-brain experiments; I am specifically referring to split-brain experiments showing us that our ideas about left brain/right brain were correct. This was in reply to "I'd agree with this author that they are oversimplified and generally incorrect - I'd add the left brain right brain divide to the list" -- I want to know what this person thinks, thanks.

See Ian McGilchrist’s 2009 book The Master and His Emissary:

> McGilchrist digests study after study, replacing the popular and superficial notion of the hemispheres as respectively logical and creative in nature with the idea that they pay attention in fundamentally different ways, the left being detail-oriented, the right being whole-oriented.

[1] https://en.wikipedia.org/wiki/The_Master_and_His_Emissary

Without listing the actual misconceptions some people have, it's hard to say 'the left brain/right brain divide' is a misconception since I was already aware of this understanding that they just observe in different ways, not that "left brain is creative and right is logical". I grew up with the internet, though, so my understanding didn't solely originate from grade school science books that might be simplifying this phenomenon.

I get minor strokes every couple of months.

Each time I lose feeling in right side of body, and lose the ability to write. Not 100%, but close enough. Typing is fine however, if slow. Critical thinking goes to crap. Talking is fine. I can still draw, though my motivation goes to crap.

Is weird what stays and what goes.

Last time I looked writing is a left brain activity. Which controls right side.

Usually the right hemisphere is linked with comprehending speech/writing, rather than producing it, so it's interesting that you lose the ability to write. Is your speech affected at all? It could be because writing involves a bunch of other more domain-general brain functions too I guess.

I think he's talking about motor control - how the left hemisphere is responsible for controlling the right side of the body and vice versa.

Correct. Right side body is numb, cold and weak. So I assume issue is left side of brain.

I can read and speak well enough. Thinking is harder, so I tend to stay quiet.

My best understanding (which, it's been a while since I took classes about it) is that there are some functions that tend to be more lateralized to one hemisphere or another -- with language being the prime example. However, some people do show more balanced functioning, and in some cases (more frequently among left-handed people) the lateralized functions can even be flipped from "normal".

However, there's left-brain/right-brain in terms of "some functions of the brain tend to be more on one side or another", and then there's left-brain/right-brain in terms of a pseudoscientific personality test about whether you're more of a "logical" thinker or "artistic" thinker, blah blah blah. There's no evidence for that. It's just mumbo-jumbo Buzzfeed-style quizzes to make you feel good about yourself.

More accurately, in right-handed populations subjects there is good correlation between localized brain insults and specific functional deficits. The association between brain insult locations and specific functional deficits is less strongly correlated in left-handed people and certain other subpopulations. These are also very much tendencies and not predictors for individuals.

aha, thanks!

My son has total agenesis of corpus callosum and he is 100% asymptomatic. We discovered accidentally in the last ultrasound the doctor did and confirmed with magnetic resonance.

The brain is complex.

Edit: https://en.wikipedia.org/wiki/Agenesis_of_the_corpus_callosu...

Look into corpus callosum separation (split-brain) and some of the experiments that have been performed after this procedure. Fascinating displays of two separate consciousnesses. Sam Harris' Making Sense Podcast #234 had Iain McGilchrist to discuss this in some detail.

That is what I am referring to :)

I would further add that those oversimplified concepts of how the brain works have hung around because they are useful for us as an abstraction to think about how our brain works.

They may be bad abstractions at a lower level of detail, but for general purposes they seem to be useful enough.

What are they useful for, though? The usefulness of wrong models, and why they hang around so long, mainly seems to be to provide income to people selling solutions.

Solutions offered based on bad simple metaphorical models have the benefit of being intuitive, so they stick around.

Theory-theory is the Efficient Market Hypothesis applied to common sense.

They are useful as a standard way to talk about the brain. If I say I am 'right-brained' in casual conversation, most people in my culture know what I mean.

Left/right divide is a myth-myth. Check out "Master and His Emissary" for the enormous amount of evidence about left/right divide.

The mirror neuron system is also a myth-myth. While there aren't "mirror neurons", per se (e.g., biochemically different), there is a system of mirroring and it is very important

I think there are a lot of myth-myths where basically the general public ran with a wildly pseudoscientific interpretation, and then the scientific community decides to dismiss the entire thing (at least outside of whatever subfield, although I've sometimes seen it within too).

Speaking specifically to left vs right brain, in popular media I've mostly seen it presented as logic vs creativity, which completely disregards that people can be creative verbally, and that certain quantitative/technical things are very non-verbal.

Obviously you know this, but the brain does localize some functions to either hemisphere, just not in the way most people think it does. My vague memory from having taken a class in psycholinguistics is that people with aphasia who've had some part of their brain damaged are good evidence of this localization.

https://en.wikipedia.org/wiki/Wernicke%27s_area https://en.wikipedia.org/wiki/Broca%27s_area

Yeah, and the amygdala has specific functions. Not that it's the only piece needed for that, or that it's not good for anything else.

The evidence for more advanced brains in higher mammals is also plainly there.

The author seems to be over-stating all this stuff in order to reject it.

And it's also the case that even though certain brain functions are linked with specific locations, the brain can still use plasticity to re-organize things and adapt to damage. And when you're doing any language related task, there are always going to be other more domain-general brain functions involved too, which aren't as localized.

What surprised me most about the replication crisis was that neurology actually seemed to be more affected than psychology in how non-reproducible it was.

What about using the RB/LB as a metaphor for teaching? I feel like it helps me build a ladder of abstraction for certain concepts as a music teacher. Of course I add the disclaimer that this is not ACTUALLY how your brain works, but all that neuro-jargon isn't really helpful for understanding syncopation...