A Chemical Mind

Nicholas Kircher

Stories of our fascination with the Brain: from medical mysteries, great triumphs and cautionary tales, to great discoveries and tragic failures, conspiracy theories, technology, and more; hosted by Nicholas Kircher (Published every Tuesday AU Time) chemicalmind.substack.com

  1. 4d ago

    How NOT to design a brain

    My good friend Tommy Blanchard wrote a great article the other week, on the question “Are humans (and biological organisms) simply wetware machines?” He gave a really good look at it with illustrations and everything, highly recommend reading it here: I just wanted to add some more interesting - for me - context to this point. In fact, I kind of want to do a loosey-goosey, unscientific look at what I’ve learned about the utter chaos of how the brain is put together by evolution. I think it really illustrates just how incredible these systems are, but also how mind-bogglingly complex and seemingly illogical, and how it might compare to a brain if we designed it like we might a computer. Prepare thyself. So the boss comes in to the office one morning. He rushes over to your desk. “Nicholas!” he says, breathlessly. “I’ve had a revelation!” Uh oh. It’s never good when the boss has had a revelation. “Since the brain is just too complicated to figure out, we should design a new one from the ground-up. It will be modular, maintainable, and debuggable!” You convey your misgivings for such a project, but their mind is made up. You’re now project lead for Brain 2.0 What now? Well you might start by analysing the existing behaviour of the current brain. In software engineering, when needing to do this, we often study the behaviour of the “legacy” version to identify each discrete “capability”, “feature” or “flow”, and map it to its own objective. Brain 2.0 should at the very least match the existing “legacy” behaviour. To know if it’s working, we have to formulate test criteria which the legacy brain should pass consistently to guide our work. The end goal should be for Brain 2.0 to also pass all those tests consistently. An example set of functions and features for a brain might consist of: * Sensory input processing * Language processing * Autonomic systems * Threat detection * Motivation state management * Bodily resource management * Memory * Motor function …and so on. Under each of these “feature buckets” we’d have to break it down into constituent parts based on what we understand of each set of behaviours or needs. For instance, “sensory input processing” is a very broad set of things. It includes vision, olfactory, tactile, proprioceptive and auditory inputs. We’d have to break each of these down into discrete modules. I’m already looking at it like: “Create a base schemata for modelling input data from a sensory organ, each sensory organ then extends that base with its own variations and needs.” This way, we have a basis for shaping the data for all sensory organs, and we can even add entirely new ones arbitrarily. Each sensory organ could have its information passed through a single module which would route the information to the correct destination for processing. So let’s say we get all this working, and now sensory inputs are coming in to the brain and informing it about the environment in which it finds itself. Furthermore, we have magically made motor control work, so our Brain 2.0 can respond to its environment via control of a physical body. But we’re running into problems. Something we need to consider is how to turn this discrete sensory information into a unified world model, but before we even get to that, we’re faced with a more serious challenge: compiling a world model directly from sensor data is slow. It takes time for signals to travel up nerve fibres, and yet more time to get filtered and processed, making it too slow to be viable when rapid near-reflex responses are sometimes required to avoid danger. To solve for this, we can borrow an idea from the legacy brain: its predictive model. The real human brain doesn’t feed sensory information directly into consciousness. Instead, it runs a continuous on-going prediction of the world, and uses sensory data only as a comparison to measure how accurate the prediction was, and to make corrections when necessary. The prediction is able to run ahead of the sensory input processing, making it ideal for rapid responses to potentially volatile environments since it doesn’t have to wait around for the data. So that’s what we’ll do with Brain 2.0! We’ll include a module for that as well! Notice what we’re doing here? We’re designing architectures, circuits, modules, patterns, and structures. We’re grouping things into neat, discrete boxes. We’re wiring things up cleanly and logically. The real human brain is nothing at all like this. Despite the way we often talk about it as though it were a modular architecture, it’s not really. It is a chaotic mess, worse than some ancient decades-old banking code base which has never been refactored. Change one thing, and you get unexpected side-effects all over the place, in ways that make no sense at all. Some people call evolution “The Blind Watchmaker”; quite frankly I think that’s an insult to blind people and watchmakers. It’s more like the proverbial infinite monkeys on typewriters, except also they’re blind and mildly deranged, have a total of 3 fingers, and for some unknown reason become obsessed with pressing only 4 keys on the typewriter: A, C, G, and T (or sometimes U instead of T, but no one knows why) Said monkeys never get even close to Shakespeare. Now, the universe didn’t really know what to make of this when it saw the crap these monkeys were coming up with. So in some strange act of madness, it invented a mechanism to interpret these long streams of 4-letter nonsense, and associated each letter with a nucleotide molecule: Adenosine, Cytosine, Guanine, and Thymine (or Urasil, depending on the monkeys particular whim) It is truly a remarkable achievement, then, that from such building blocks came all we see before us. Indeed, the legacy brain is a billions-of-years-old project. Every time evolution has demanded a new feature, or even a bug fix, our infinite blind and semi-deranged monkeys almost never clean up the old mess. Instead, they simply patch over the top of it. Everything becomes a patch on top of another patch. They live and die by one golden principle: if it increases survival and/or reproduction, ship it immediately and patch it over and over and over again. In digital computers, we would have electrical signals crossing wires and circuit pathways, transmitting digital information: a stream of 1s and 0s. By interpreting the specific sequences of 1s and 0s in a known way, we can derive its true meaning. Each processor that receives data knows how to interpret these signals in that way. In the wetware brain, things began much more simply. The earliest neural networks are thought to have been made out of highly multifunctional generalist cells, which combined sensory functions, inter-cellular communication and muscle contraction all into one, similar to the epithelial muscle cells still found in the modern cnidarian. Communication between these cells was necessary for rapid adaptive injury and stress responses. When damaged, a cell would release a flood of cheap, abundant signalling molecules into its surroundings to trigger coordinated, defensive/repair responses in neighbouring tissue. It was a rather crude but effective method of volume-transmission, and a bit like a mesh-network of light switches; damaged cell releases a messenger chemical, chemical binds to receptor on a neighbouring cell, cell activates a prepared response, and in turn releases its own chemical messenger molecules to recruit other neighbouring cells, and so on. This rapid cell recruitment and activation strategy proved highly successful, and the blind monkey that happened to stumble upon this particular configuration with its 4-letter alphabet was made to breed a whole new lineage of infinite blind monkeys. Then the scope creep began. These ancient multifunctional cells began specialising, separating the responsibilities of sensory receptor and muscle contraction into their own distinct cell types. Because these newly specialised sister cells became physically separated, and the traditional chemical messenger approach used before was too slow for communicating over larger cellular distances, a new type of cell which would bridge the gap between sensor and muscle contractor was needed: thus, the electrically-active neuron was born. Complex functionality first evolved within localised systems. Instead of a central brain suddenly appearing, small groups of these proto-neurons would connect up together in various parts of the body to control specific local reflexes. The Carribean Box Jellyfish, for example, has no central processing for sensory inputs, despite having 24 eyes. Instead, it has 4 separate “sensory ganglia” dangling off its body, each one processing input from 2 high-fidelity camera-like eyes, and 4 simpler ambient-light-sensors. These ganglia don’t communicate with each other, and have no world model. They continuously fire a regular pacemaker signal which controls the contractions of surrounding musculature for swimming. When one ganglia recognises an obstacle in the visual data from its 6 connected eyes, it changes the rate of the pacemaker signal, causing it to steer away. Over time, these networks grew to span even longer distances, and as organisms became more complex and evolved more sophisticated limbs and musculature, there was an evolutionary need for coordination and synchronisation. The Starfish’s approach to this problem was very simple. Each arm kept its localised network of nerve cells with all their localised sensory processing, but added peer-to-peer networking via a broadcast ring. When one of the arms detects food, a signal gets sent out to the other arms and degrades over distance. So the nearest neighbour arms will get a strong impulse, while the arms further away will get a weaker or no signal. The starfish will then crawl towards the food. The successes kept coming, s

  2. Jun 9

    The Myths of Serotonin & Depression

    TLDR: Serotonin has no association with depression whatsoever. Instead, some cases are thought to be caused by reduced neuroplasticity during chronic periods of stress (mediated by the HPA axis and cortisol), resulting in a reduction in BDNF (brain-derived neurotrophic factor). SSRIs might work not due to serotonin, but due to significantly increasing BDNF expression, which is likely why psychedelics can also help in some cases. Few molecules in the history of biology have travelled as strange a road as serotonin. It was discovered twice, on two continents, by researchers chasing two completely different problems; one studying why blood serum constricts vessels, the other studying a substance in the gut that makes smooth muscle contract. Within a decade of its chemical identification it leapt from a curiosity of vascular physiology into the centre of psychiatry, becoming the basis of a “chemical imbalance” myth that has shaped how hundreds of millions of people think about depression. Today, that simple story has collapsed under the weight of evidence, even as serotonin has turned out to be far more biologically important - and far more widely distributed through the body - than its early champions ever imagined. In this episode, we trace the rise and fall of the “serotonin hypothesis” of depression, dig in to its surprisingly broad function that modern research has revealed, and take a peek at the current leading theories for what makes clinical depression happen (oh, and why SSRIs work at all!) Get in on these insights early! Hit the button: In the late 1930s, the Italian pharmacologist Vittorio Erspamer, working in Pavia, was studying a substance concentrated in the enterochromaffin cells of the gastrointestinal mucosa which caused smooth muscle to contract. He named it enteramine. Over years of painstaking work he and his colleagues characterised its biological actions, and Erspamer correctly suspected it was an “indole”-derivative (an unpleasantly-oderous organic compound found in coal tar and poo.) Interestingly, the Italians also played a major role in the West’s discovery of Dopamine, but that’s a whole other story. Independently, at the Cleveland Clinic in the United States, a team interested in the vasoconstrictor activity of blood serum was trying to isolate the agent responsible for raising vascular tone. Some 10 years later, in 1948, Maurice Rapport, Arda Green, and Irvine Page succeeded in isolating and crystallising the target agent from beef serum. Because it came from serom and affected vascular tone, they coined the name serotonin. Rapport then went on to determine its chemical structure, publishing the proposed vasoconstrictor principle the following year. Shortly afterward, serotonin was chemically synthesised, and it became clear that Erspamer’s enteramine and Rapport’s serotonin were the very same molecule: 5-hydroxytryptamine. This double discovery is why the molecule carries two naming traditions to this day: pharmacologists and neuroscientists usually write 5-HT, while the popular and clinical name remains serotonin. Then, in 1953, serotonin suddenly became a rather important subject of study to those who investigated diseases of the brain when Betty Twarog and Irvine Page demonstrated that serotonin was present in mammalian brain tissue. This was the moment serotonin became a candidate neurotransmitter, and the timing couldn’t have been more extraordinary. It coincided almost exactly with the discovery that the powerful hallucinogen lysergic acid diethylamide (LSD) was structurally related to serotonin, and could even antagonise (promote) its actions on smooth muscle (as serotonin does.) The inference - that a serotonin-like compound could so profoundly alter perception and mood, and make you hallucinate like the devil - electrified the young field of biological psychiatry and planted the seed of an idea that serotonin governed states of mind. Even before receptors could be cloned, classical pharmacology hinted at serotonin’s complexity. In 1957, Gaddum and Picarelli, studying guinea-pig ileum, proposed that serotonin acted on at least two distinct receptor types, which they called the “M” (morphine-blocked) and “D” (dibenzyline-blocked) receptors. This early two-receptor scheme was the ancestor of what is now recognised as one of the most complicated receptor families in all of pharmacology, encompassing at least 14 distinct receptor subtypes today. The serotonin theory of depression did not emerge from a direct observation that depressed people lacked serotonin. It emerged, somewhat backwards, from pharmacology. In the 1950s and 1960s, clinicians noticed that certain drugs altered mood, and researchers reasoned backward from the drugs’ known effects on brain chemistry to a presumed cause of the illness. Two foundational papers framed the debate: Joseph Schildkraut proposed the catecholamine hypothesis of affective disorders in 1965, arguing that depression might be associated with a deficiency of noradrenailne at functionally important brain sites. Two years later, in 1967, the British psychiatrist Alec Coppen advanced the case that 5-HT, rather than (or in addition to) the catecholamines, was central to the biochemistry of affective disorders. Together these papers crystallised what became the monoamine hypothesis of depression; the idea that mood disorders stem from a deficit of monoamine neurotransmitters in the brain, such as dopamine, noradrenaline, and serotonin. The hypothesis gained enormous traction because drugs that increase synaptic serotonin can apparently relieve depressive symptoms. The decisive commercial and cultural moment came with fluoxetine (Prozac), developed at Eli Lilly and described by David Wong and colleagues as the first selective serotonin reuptake inhibitor (SSRI) to reach the market. Wong’s retrospective review traces the deliberate, two-decade evolutionary process by which fluoxetine was engineered specifically to block serotonin reuptake while sparing other systems. SSRIs supposedly work by inhibiting the serotonin transporter (SERT), thereby raising the concentration of serotonin in the synaptic cleft. The marketing logic was seductive and simple: if a drug that raises serotonin treats depression, then depression must be caused by too little serotonin - a “chemical imbalance” that the medication corrects. This framing was widely communicated to the public through advertising and clinical encounters, and it became one of the most successful pieces of medical folk-knowledge of the late twentieth century. And, as Psychopharmacologist Stephen M. Stahl noted in his 1998 paper, Prozac and similar agents are “among the most frequently prescribed therapeutic agents in all of medicine.” It turns out, however, this simple pharmacokinetic story was built on far shakier foundations than anyone believed at the time. Crucially, the inference is a logical error of the form of “the drug raises X, therefore the disease is a deficiency of X.” Aspirin relieves headaches, but headaches are not caused by an aspirin deficiency. Even at the time, serious problems were visible, such as the therapeutic delay, and a heterogenous pharmacology of anti-depressants. SSRIs raise synaptic serotonin within hours, yet clinical antidepressant effects typically take weeks to appear. This temporal mismatch suggested that the relevant therapeutic mechanism is not the acute rise in serotonin itself, but slower, downstream adaptations. For example, one such adaptation is the desensitisation of somatodendritic 5-HT1A autoreceptors (these are receptors that detect the molecule in the “extra-cellular space”, i.e outside or overflowing the synaptic cleft) in the raphe nuclei. Meanwhile, drugs with very different effects on serotonin can all have antidepressant activity, which is hard to reconcile with a single, simple serotonin-deficiency model. Something was clearly not right with any of this. The drugs definitely work; we just couldn’t quite figure out how. The empirical case against the simple serotonin-deficiency model was assembled most comprehensively in a 2022 systematic umbrella review led by Joanna Moncrieff and colleagues, published in Molecular Psychiatry. Together, they synthesised the principal bodies of evidence: * serotonin and 5-HIAA (its main metabolite) concentrations in bodily fluids; * 5-HT1A receptor binding; * serotonin transporter (SERT) levels by imaging and post-mortem; * tryptophan-depletion experiments; * and SERT gene associations and gene–environment interactions. Their conclusions were revealing. First, meta-analysis of the serotonin metabolite - 5-HIAA - showed no association with depression. A meta-analysis of serotonin in blood plasma showed no relationship with depression, either. Shockingly, it actually found that lowered serotonin was associated with the use of antidepressants - suggesting these medications might be doing the exact opposite of what we all believed. Then, further analysis of the largest and highest-quality genetic observations of Serotonin Reuptake Transporter - SERT - showed no relationship whatsoever with depression, and no gene-by-stress interaction. Not only had we been wrong about how these medications worked, we had been ass-backwards wrong. Upside-down looney-tunes wrong. We had been living in opposite land. The bottom line was that the main areas of serotonin research provide no consistent evidence that depression is caused by lowered serotonin activity or concentration. The authors wrote that the areas surveyed “provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations”; more provocatively still, “some evidence was consistent with the possibility that long-term antidepressant use

  3. May 28

    The Myths of Dopamine

    I know you’ve heard of it. “Dopamine.” It’s supposedly a chemical in the brain that causes pleasure, right? I mean, everyone says so. Even Harvard says so, and surely we can trust Harvard, right? No, sadly, this most perpetuated of common wisdom is perhaps the most common medical myth of our time. If you thought dopamine had anything to do with feelings of pleasure, it’s time to set the record straight. To do that, we need to start at the beginning of the story; the story of how dopamine became so misunderstood. While you’re here, check these out: In a sterile room of a McGill University laboratory in 1954, a surgical mistake birthed a fascinating discovery. James Olds and Peter Milner were attempting to study the neural mechanisms of learning in rats, using a microelectrode embedded into the midbrain reticular formation. When it came time to test “rat number 34”, the electrode slipped, misaligning by a fraction of a millimetre, and embedding itself into the septal area. Like the others, this rat was placed into their operant conditioning box and given a lever which, when pressed, delivered a fraction of a volt through the electrode into the brain. Unlike all the others, however, this particular animal became utterly transfixed by this device. It pressed the lever again, and again, and again. Soon, it was pressing it thousands of times an hour. The rat ignored food, it ignored water, and it ignored females in heat. It would actively stimulate its own brain until it collapsed from exhaustion, and starved to death. Olds and Milner concluded they had stumbled upon the mammalian brain’s “pleasure centres.” The pathways radiating from these regions were rich in a specific neurotransmitter: Dopamine. Thus began one of the most persistent biological myths, one that has survived for over 70 years despite rigorous scientific falsification, embedding itself in the popular consciousness, and even today being repeated in academic research as an axiom that “everyone knows” without any citation or reference. Look again at that article from Harvard; do you see any citations? This idea - that dopamine was “the brain’s pleasure chemical” - was further crystallised in 1978, when researcher Roy Wise formulated the “Anhedonia Hypothesis” after observing that administering the dopamine receptor antagonist (blocker) pimozide to rats caused them to stop working for food. To the naked eye, the rats behaved exactly as if the food had been removed entirely. Wise argued that blocking dopamine systematically eroded the “hedonic impact” of the reward itself. In this paradigm, dopamine was pleasure incarnate; chemically turning off dopamine meant chemically disabling the capacity for enjoyment. It was a neat, beautifully simple and consumable theory that resonated deeply in the minds of scientists and laypeople alike, and helped to invent many of the most ridiculous pop-psychology fads we see today. That anhedonia hypothesis held for a decade, until neuroscientists Kent C. Berridge and Terry Robinson fundamentally broke everything about the model in 1989. Berridge reasoned that if dopamine was the quintessential chemical of pleasure, a rat stripped of all dopamine should exhibit a total absence of hedonic response. The question was: how do we really test “hedonic response” with confidence? Using the neurotoxin 6-hydroxydopamine (6-OHDA, or “oxidopamine”), Berridge selectively destroyed 99 percent of the dopamine neurons in the rat striatum. Predictably, the rodents became entirely aphagic (refusal or inability to swallow). They refused to seek out food and would rapidly starve unless they were artificially fed via gastric tubes. However, Berridge also introduced a novel metric originally designed by Grill and Norgren in 1978: the “taste reactivity paradigm.” It turns out, rats give off a remarkably consistent signal of receptivity to taste through their facial expressions. It’s so consistent, in fact, it can be used as an empirical measurement. Given something sweet and delicious, rats exhibit rhythmic tongue protrusions and relaxed facial muscles: the “positive” response. When given something bitter and yucky, they gape with mouth open wide, jaw dropped, and corners of the mouth retracted, followed by a sequence of physical aversive reactions: the “negative” response. When given something entirely tasteless, such as room-temperature water, only rhythmic mouth movements occur, without either the tongue protrusions of sweetness or gaping from bitterness: the “neutral” response. If dopamine really was the chemical responsible for pleasurable sensations, blocking or destroying dopaminergic neurons should result in the total elimination of the “positive” response to sweet or delicious-tasting substances. In fact, that’s exactly what Berridge had been expecting to find: that all taste reactivity would become either “neutral” or “negative,” regardless of what was given to the rats. So when Berridge manually pipetted a sweet sucrose solution directly into the mouths of these dopamine-depleted rats and recorded their facial micro-expressions in slow motion, the results were… confusing. The rats still exhibited the same rhythmic tongue protrusions and relaxed facial muscles as would be found in the unmodified control rats; the positive pleasure response. So then what, exactly, was dopamine-depletion doing to them? If they still experienced pleasure, why were they so... depressed? Berridge and Robinson spent the subsequent decade proving an idea: that dopamine does not mediate “liking” (hedonic impact, pleasure). Instead, it mediates “wanting”. They believed dopamine in the mesolimbic pathway supports an unconscious tagging system that makes reward cues fundamentally attractive, propelling the organism’s behaviour toward an objective. They called this “incentive salience.” The dopamine-depleted rats still liked and enjoyed sugar; they merely stopped caring for it one way or another. They stopped pursuing it. They no longer particularly wanted it. It turns out there is a distinct difference in the brain between liking something and wanting something. True pleasure, or “liking,” is actually fragile and remarkably localised in the brain. It is mediated by isolated “hedonic hotspots” predominantly driven by opioid and endocannabinoid signalling in the nucleus accumbens shell and ventral pallidum. By contrast, the dopamine-driven “wanting” system is massive, robust, and highly susceptible to sensitisation. This neurological divergence explains the bleak reality of severe addiction. As Berridge noted, the dissociation of wanting and liking means a drug addict can reach a neurobiological state where their mesolimbic system, driven by dopamine, is so heavily sensitised to a particular sensory cue - in this case, a drug - that they possess a desperate, overwhelming want for it, even if subjective tolerance is so high that they no longer like the experience of taking it. Furthermore, in 2025, Berridge was able to demonstrate conclusively that it is possible for an organism to want something that they severely dislike by directly manipulating the mesolimbic pathway with electrical stimulation: using this mechanism they were able to cause rats to feel an overwhelming motivation to bite on an electrified rod, causing them pain and discomfort. Clearly, we can like things we don’t want, and want things we don’t like. It has been scientifically proven that you both want and like articles just like this one; subscribe! Here’s another fact about dopamine you probably didn’t know: your eyes use dopamine to signal the brightness of light entering the retina. Your brains motor cortex uses dopamine to gate movement signals for fine motor control. In fact, dopamine is used in lots of completely different ways throughout the brain and body; it makes no sense whatsoever to pin any one function on it. Suggesting dopamine is the brain’s pleasure chemical is not only specifically wrong, it’s also wrong in general. It would be like suggesting radio waves are how software engineers communicate cat videos with each other. Sure, if you follow enough reductionist reasoning, you can reach a level where cat videos are indeed carried across the internet which sometimes includes radio waves, but would anyone describe “the internet” explicitly as a “system for transmitting images and videos of cats?” Don’t answer that. (On that subject, this is one of my earliest youtube videos:) Anyway, you get my point. Sometimes people watch other sorts of videos on the internet, too. Not me, though I’ve heard rumours of it happening. So, if dopamine really isn’t relevant to the phenomenon of pleasure, why has the myth been so persistent? My only guess is that it lets us quickly and easily explain away things like addiction, ADHD, depression, “youths” (get off my lawn.) It makes it easy to say that drug addicts are just out to get “high”, that it is a choice they make  - choosing to seek pleasure even to the detriment of all else  -  which they could change if they really wanted to, if they simply “took responsibility for themselves.” It allows us to pretend ADHD isn’t real, that such people need to “be responsible”, as if it’s all just a choice they make to pursue only “enjoyable things”, or that it’s only a childhood phase one grows out of: because, you know, being a “grown up” means you start making “good choices” and “doing the hard things” which is the antithesis of ADHD, right? It makes it easy to wave away depression as merely an absence of joy, to say “come on, it’s not that bad”, as though the cure were merely to realise that butterflies and rainbows exist, and allow all the joy to flow back into the brain just like that. These simplistic explanations may allow us to forget a

  4. May 7

    Saving "Disorder"

    Note: I am not a doctor (I didn’t even finish High School) and none of this should be taken seriously let alone be considered medical advice, or in any way accurate, rational, logical, grammatically correct, or even comprehensible, and should probably be ignored by all of humanity. Anyone taking this too seriously might want to get checked out for Autism ahem I mean ENT J/P. I’m not usually interesting or popular enough to be written about, but on occasion it happens. This time, it was due to a post I made about being accepted into a “secret society of neurodivergents” at my new workplace: (If you can’t see the light-hearted, tongue-in-cheek nature of this post, you should perhaps consider therapy) I got into an interesting discussion in the comments, challenged on whether ADHD is just a personality profile, and what exactly makes it pathological. I think we had a good discussion about it. Turns out, however, the same individual went to the trouble of interpreting this as me being self-diagnosed, and decided to turn me into the poster boy for everything that is wrong with the kids these days and all their social-media-driven self-labelling rainbow-67-skibidi-toilet nonsense. Apparently I’m not who I think I am? Take this fellow, Nicholas Kircher, who posted about being added to a ‘secret’ AuDHD group. Now, those not up with the lingo, this Frankenstein word is a fusion of Autism and ADHD, two of the most conflated and error-prone ‘diagnoses’ of the last 15 years. The authors take issue with the whole neuro-divergence thing, and seek to un-diagnose me. They paint me as having succumbed to some tiktok fad, joined a bandwagon, been “influenced” into self-diagnosis. Nicholas and the rest of the Neurodivergent bandwagon Which, lets be honest, is pretty funny considering my history (and I don’t even use tiktok.) The whole thing is horrifically over-cooked, and although probably not meant to be mean-spirited, it definitely smells like self-righteous silliness. This might be a valuable teaching opportunity. Then again, it might not. Time will tell. So I am posting today to send the whole thing even more over-the-top than is necessary, or responsible, or even legal. For one time only. After this, I’m not spending any more time on the subject, as we all have better things to do. Example of a better thing to do: subscribe! First, some history about me and my situation, because nobody asked (and perhaps if anyone had asked, the original article could have been significantly improved, and maybe a lot shorter): I was diagnosed with ADHD and Autism Spectrum in the year 1999 - the same year The Matrix came out - when “Social Media” didn’t even exist yet, and MySpace was still a good 4 years away. Back then, my diagnoses were known as ADD-Inattentive and Aspergers Syndrome. Why was I diagnosed? I was nearing the end of primary school. I’d already repeated one grade, and was failing another. I’d had no success in making any in-school friends or proper connections with others, and I fidgeted incessantly at all times. Some developmental goals I was reaching, but many I was hopelessly behind in. I was not absorbing anything being taught, I was constantly getting lost in time and in space, and for nearly every activity in class, I would somehow draw a blank when instructions were given, having no idea what was happening or what we were doing. I almost never remembered to do homework, or quite frankly anything else unless it was squarely within my “special interest” bubble, and when I did remember or was reminded, I could rarely get it started, and even then I didn’t last more than 5 minutes before I’d crash and burn, hard. I didn’t even complete the IQ test I was given by a psychologist, and never got a score. (I like to joke that I got a zero) I came home every day to my mum - who was suffering in the throes of a chronic illness - sobbing intensely, because I could not understand why I could not do what all the other kids were doing with apparent ease. Every unqualified person and their dog seemed to have an opinion on why this was. The greatest hits: * he’s lazy, * he’s faking (for attention, apparently) * he has a bad/lazy mother, * he needs to take more responsibility for himself, * he’s not being punished enough (bring out the lash), * he just needs to apply himself, * he just needs to pay more attention (duh), * he’s a designer moron Wait, a “designer moron?” Yes, friends, that was the term used for me by some of my extended family after I received my formal diagnosis. They, too, thought all this fancy label stuff was just to hide the simple fact that I was an idiot. Growing up with a single mum, she worked hard to find a way to help me. She was the only person in my life for a long time that gave a s**t, and she refused to give up on me. I saw several different specialists as we searched for some explanation that actually made sense. Most of the opinions we got in those early days were nonsense - like mum being told she needs to take “parenting classes” - while some of them were outright scams. However, two interesting leads came along. The first: perhaps I was having “absent seizures”, a kind of epilepsy that causes a blanking of conscious awareness, without the typical shaking/motor movement symptoms commonly associated with epileptic seizures. Thankfully that one can be pretty definitively tested, and it came back negative. The second: maybe I have some combination of attention deficit, and/or Asperger’s. This one was - and still is - far from having a definitive test, and very few specialists in Australia at that time were well equipped to diagnose either of them. We got a lucky break however, and managed to get in to see perhaps the leading specialist in these two psychiatric conditions in the country. My mum remembers the moment he came to a conclusion about my case: “Mrs Kircher, I see a lot of kids brought in who are suspected of having one of these conditions, and the fact is, most don’t have it. In the case of your son, there is absolutely no doubt in my mind that this diagnosis fits.” Since that day, it has been re-evaluated at least 4 separate times by independent specialists for various reasons, each time being re-confirmed. So let’s just get one thing absolutely clear before we do anything else: I am not one of your guinnea pigs for hypotheses about self-diagnosis. And back to the beginning, when we mix personality types of both individual and cultural, where the US is an amalgamation of dozens of cultures, what is neurotypical? Ironically, for Nicholas and the rest of the Neurodivergent bandwagon… They are. Currently, 20% of the US population and a whopping 53% of Gen Z self-identify as neurodivergent. 53% self-identify. Read that again: self-identify. One person’s self-identity is not the same as my psychiatric diagnosis. I’m not self-diagnosed, I’m not Gen Z, and I’m not American. Could have spent 5 seconds to find all that out, but instead of “doing the hard things,” why not just make assumptions and roll with them? And that is also a very typical human behavior because doing hard things is… hard. I bet. What’s more, I’ve lived my whole life with people casting all kinds of aspersions about whether I’m “really” this or that or the other thing, or whether I’m just bereft of moral fibre and/or character, based on some 5-second observation they’ve made of me. This is not the first time - not by a long shot - and won’t be the last. As the New Zealand pathologist Dr Temple-Camp said: “That’s the thing about opinions and arseholes, isn’t it, gentlemen; everyone’s got one.” So I asked Nicholas how he defined typical, but in answering my question, he skirted with vague statements about holding a standard job, maintaining social connections, and navigating daily life without significant distress. Which I’d like to find a single human who does this with frictionless ease. I didn’t realise I was expected to provide some sort of DSM-version of the definition of a word that arose originally as a joke. The term “neurotypical” was actually coined in the late 1990s by the autistic community, specifically by the autism rights group Autism Network International (ANI). It was created as a satirical counterpart to the idea that people with Autism were “neuro-defective.” They wanted a neutral word to describe non-autistic people (whom they playfully referred to as having “Neurotypical Syndrome”) to shift the framing away from autism being a “disease” and neurotypicals being the “healthy default.” The author’s actual question was this: What, specifically, is Neurotypical because neither Level 1 Autism, nor ADHD are divergent, given the quantities they exist and they can be easily explained by Personality proclivities, not pathologies. The reason I ask is people keep trying to tell me I’m both Autistic (I’m not, I’m analytical, disagreeable, and not nuerotic) and ADHD (I’m not, I’m Intuitive, fast thinking, and middling contientiousness.) What I’m saying I’m an ENT J/P… which is one of sixteen personality categories, totally neurotypical… Here’s the actual part of my much longer response to their overall comment that partially dealt with the author’s specific question, framed within the context of how neurological conditions and personality constructs relate and differ: So if you’re able to hold a standard job, maintain social connections, and navigate daily life without significant distress or the need for specific accommodations, you may still exhibit traits common to people with Autism or ADHD without being impacted by the symptoms which make it pathological. A diagnosis is only necessary when the underlying neurological factors create barriers to typical functioning. I wasn’t even trying to explicitly define anything, merely explain how one m

  5. Jan 23

    The Erotic Button: A Case-Study

    Addiction Resources: https://chemicalmind.substack.com/p/addiction-support-resources Ko-Fi Link: https://ko-fi.com/dopamine Note: This is a true story, taken from one of the many fascinating case reports of medical literature. This is a fairly famous example in the annals of addiction neuroscience, and it reveals in stark colours the counter-intuitive nature of addiction. She couldn’t stop herself. She had to push the button. She kept it on all day, dialling the power knob between 75% and 100% in rapid bursts. All she could do was blast the electrodes buried deep in her brain, triggering an experience she called “pleasant discomfort,” a kind of “erotic sensation” as though her g******s were sending signals to her brain at kilowatts of intensity. By all objective measures, though, she was disintegrating completely. She would exhibit the physical symptoms of stroke. She would become extremely thirsty. Her verbal IQ would drop by a whopping 25 points. She even developed an ulcer on her index finger, the one she used to tune the power dial rapidly. This was not a particularly pleasant experience. Indeed, it was painful. And yet, she stopped going outside. She stopped talking to other people. She even stopped bathing, and eventually, eating. She could not pull herself away from the button. There were times when she’d beg for her family to take it away, and they would; only for them to give in when she went through inevitable withdrawal symptoms, and demanded its return. It was an addiction like any other; except this was not chemical. It was electrical. In 1954, James Olds and Peter Milner released a remarkable study that would go on to shape our understanding of addiction. They implanted electrodes at various locations into the brains of rats, and gave them a series of levers they could press to stimulate the different electrodes. The behaviour of the rats demonstrated the existence of specific locations in the brain which, when stimulated, could produce profound addiction: the rats would go to stimulate them again and again and again, until collapsing from exhaustion. Such experiments would have been completely unethical if done in humans, and would never be approved by a review board. So, how had this woman, in the 1980s, ended up in the position of one of Olds’ and Milner’s rats? Years earlier, the 48-year-old New Yorker had suffered a herniated disc right at the base of her spine, between L5 and S1; an excruciating experience, leaving her with severe sciatica. Pain would surge through her legs like a bolt of lightning. Her lower back was in constant agony. The pain and suffering was constant and intractable. Eventually it became too much; she obsessed about finding a way to halt the pain. Although of limited effect, so far, opiates - specifically, methadone - was the only thing keeping her functional at a basic level. That wasn’t ideal. She had a history of alcohol abuse, and knew the dangers of addiction all too well. So she had turned her body into a veritable pin-cushion, subjecting herself to any and all ideas, in search of an alternative. She had seen so many specialists. They tried pharmacological treatments of all kinds, including antidepressants, atypical analgesics, and more. Every drug wore off quickly. Massages and exercises had no effect. Acupuncture was useless. Cognitive Behavioural Therapies made no difference. The TENS units - skin-conductance electrical stimulators of nerves - achieved nothing. They tried surgically removing the back plates of 4 of her vertebrae to relieve pressure on her spinal cord. They denervated the area at the base of her spine, and even severed specific nerve fibres in her spinal cord they believed were transmitting pain signals to the brain. All of it failed. All this medical science, all these doctors and specialists, all this money, and they were at a loss. Here they were - in the 1980s - and they had no idea what was wrong or how to fix it. One well-meaning specialist had an idea: if we can’t seem to solve it from the nerve side, perhaps we can find another way through the brain itself. Pressing the button below will instantly cure all ailments, guaranteed! (note: not actually guaranteed, but it might work?) Electricity for pain management is, remarkably, far from a new idea. There really is nothing new under the sun. The first written description we have found of using electricity to manage pain was by the ancient Greeks, where both Plato and Aristotle described the use of the “Torpedo Fish” - a kind of electric ray, after which the submarine weapon is named - as an aid in curing ailments; but it was the Romans who wrote specifically about its use in treating headaches and gout. Some 2000 years later, in the 1950s, we began to seriously experiment with delivering electricity directly to the brain. The implanting of electrodes directly into neural structures could bypass faulty central nervous system wiring, not to mention all the chemical filtering which made pharmacokinetics such a challenge. Early experiments with this method as a treatment for chronic pain seemed to yield some positive results. Deep Brain Stimulation (DBS) was, indeed, originally meant to treat pain. Later, people like José Delgado would begin experimenting with the technique to treat movement disorders, epilepsy, and paralysis. DBS has a storied and controversial history. José Delgado, among others, would become the targets of crazy conspiracy theorists like Peter Breggin, who for their own political purposes ran a campaign of lies designed to paint Delgado in particular as an evil mind-control villain, eventually chasing him out of the United States. Despite this, by the 1970s, DBS for pain was quickly gaining traction, with companies like Medtronic setting up its neurological division for manufacturing devices to control electrode stimulation. Case reports started to come out showing positive results for pain with electrodes implanted into the thalamus. So, although still quite a new treatment, it wasn’t as hare-brained an idea as it might seem to us today, though it still sounds utterly counter-intuitive: stimulating a brain region that is signalling pain in order to suppress that pain. However, it was based on a historical precedent, or perhaps, neurological dogma: that stimulation mimics ablation (destruction). The thinking was that with electrical stimulation, based on this precedent, they could use it as a reversible alternative to destroying those neurons entirely. If it worked, we might never need to surgically damage or destroy anything in the brain, whether in cases of severe intractable epilepsy or chronic pain. It could eliminate the use of lobotomies, which were still popular in the United States at the time. So in ~1979, specialists handling the case of this woman’s intractable pain decided to give it a try. They made 2 attempts. First, they implanted an electrode in the right Posterior Medial Thalamus, the region of the brain mostly concerned with your emotional response to a sensory input, e.g being startled by sudden sharp pain. When they turned on the electric current, she felt a warm flush spread across the left side of her body, and the pain dissipated. For 6 months, this seemed to work remarkably well. However, like everything else, it was only temporary, and soon the device gave her no relief from pain at all. They left the electrode in place, dormant, and continued to pursue other treatment options. Four years later, they made another attempt. The target this time was the left Ventral Posteriolateral Nucleus, the region which helps to determine what a sensation is (touch, pressure, temperature, pain) and where it’s coming from; it then relays the information to other regions of the brain relevant to that specific sensation. Again, it seemed to have a reasonable impact on the pain. She initially reported a tingling “paraesthesia” down her left side, but that was it. For a few months, the pain became manageable again. Then, there was something else. She had begun to experiment with the settings on the stimulator. She found that by manipulating the controls in a certain way, she could induce these peculiar “erotic sensations,” and reported this to the clinicians shortly following the procedure. Unfortunately, this did not ring any alarm bells. When the pain inevitably returned a few months later, her need for stimulation didn’t end. Indeed, it was only beginning. She found herself continuing to need more and more stimulation. She would keep the device on, set to 75% power, and every few minutes rapidly turn the dial between 75% and 100% power. It brought her to the edge of climax, but never over the precipice. She was always just out of reach of satisfaction. During these intense stimulations, her body would writhe in severe discomfort. The left side of her face would droop as though she were in the throes of a massive stroke. She would experience paroxysmal atrial tachycardia, and the most extreme thirst leading to psychogenic polydipsia (compulsive water drinking to the point of toxicity.) There’s simply no way this could have been pleasure she was experiencing, and even if there was, it would have paled in comparison to the devastation and pain being inflicted upon her body and brain. Somehow, she managed to continue like this for 2 years. Her addiction was so total, she spent most of that time in complete inactivity, save for occasions when her obsession with stimulation drove her to tamper with the device in an effort to further increase its amplitude. IQ tests she performed shortly before and shortly after implantation of the electrode, and again by the authors of the case study 3 years later, reveal the utter devastation wrought on her brain. Initially scoring 99 both before and after implantation on full-scale IQ - a reasonable score - by the time of the case study, she had lost a whopping 11 points. Her memory qu

  6. Jan 9

    Sacrificing yourself to save your life

    “The common conception that the brain is primarily for thinking, or other cognitive processes, is potentially misleading... neuroscience may benefit from a theoretical structure that centers on basic questions of how the brain coordinates and efficiently regulates the body.” What if our entire understanding of the purpose of the brain is wrong? By default, we have come to believe the main task of a brain is to think, to wield intelligence, to learn and remember and feel. Is this not what our own brains do the most? It turns out it’s not nearly so simple, and by focussing on just our own perceptions - our conscious mind - we have completely ignored perhaps its most fundamental role: regulation of bodily systems to keep us alive. I’m talking about the system of allostasis, or predictive regulation. Unlike homoeostasis, where the body reacts to problems when they arise, allostasis is all about predicting the bodies needs ahead of time and adequately preparing for them, regulating internal systems to manage energy and resource-use. It’s tasked with efficient logistics planning, ensuring the supply is available at times when demand is predicted to rise. This makes for a very obvious evolutionary purpose to the brain: it likely evolved as a means of managing the complex biochemistry of large multi-cellular organisms, and consciousness arose from the eventual complexity of its allostatic functions. Although not a new idea, allostasis seems to be going through a bit of a revival. According to an article recently published in Neuron Volume 113 (Issue 24), Jordan Theriault et al. argue that thought and consciousness might be a case of exaptation, a kind of happy accident of evolution which turned out to be useful in its own right. If we adopt this "allostasis-first" lens, the very things we traditionally call "the mind" - our emotions, awareness, even sensations - appear to be low-resolution readouts of our metabolic state. Your mood, for instance, may function as a low-dimensional "allostatic barometer," a summary of how efficiently your brain is managing your body’s internal energy budget. Even "stress" loses its purely psychological weight. In this biological framework, stress is simply the brain predictively issuing commands to deliver glucose and oxygen to your tissues in anticipation of a metabolic outlay. It is a value-neutral preparation for action should action be necessary. This is not to suggest that these barometers and predictions are always correct. Like any sensor, they can be fed faulty data or be improperly calibrated. Like some safety systems installed on aircraft, a bad sensor can kick off a distinctly inappropriate response (see: Boeing 737 Max) Still, this regulatory priority is etched into the very architecture of the human cortex. The brain is organised along a structural gradient that stretches from a "limbic core" to our primary senses. At this limbic core, signals are abstract and low-dimensional compressed summaries of the body’s collective needs. As these signals flow outward toward the motor and sensory systems, they "decompress" into the specific particulars required to move a muscle or adjust a heart rate. Simultaneously, the firehose of raw sensory data coming from the world is compressed as it travels inward. It is stripped of its noise and categorised into meanings, with the most salience being placed on its allostatic value, i.e “what does this sight or sound mean for my survival?” Ultimately, this shift in perspective dissolves the artificial wall we have built between the mental and the physical: we are not merely a mind inhabiting a body. The mind and body are a unified system. What happens if we look at cognitive decline using this allostatic lens? Take Alzheimer’s, one of the main examples cited in the paper: the perspective shifts from a system breaking down, to a series of desperate, yet calculated, sacrifices. Higher-order cognition uses up a fair bit of energy, but is non-essential for staying alive. It also produces a lot of waste products, due to the rather-inefficient method of anaerobic metabolism of glucose products into ATP (up to 15 times more inefficient than the aerobic alternative.). These waste products need to be removed regularly, mostly via the bloodstream, otherwise they can build up and cause havoc. However, as we age, our vascular health naturally declines and becomes less efficient at this waste-removal task. So when a system is faced with a situation where the waste produced by this high-energy, higher-order cognition begins to out-pace the brains ability to remove that waste, the authors suggest we might be forced into an “allostatic trade-off”, with the allostasis mechanism automatically rationing the amount of glucose supplied to the brain to reduce the overall demand on the vascular system. If brain waste clearance is compromised, then it may be allostatically beneficial for the brain to downregulate glucose metabolism by restricting the transport of glucose into neurons and across the blood-brain barrier. Consistent with this, in older adults, glucose uptake and glucose transporter density (GLUT1 and GLUT3) decline following amyloid accumulation but before the appearance of cognitive decline. That trade-off might allow the body to physically live longer than it otherwise would, but at what cost? Put your email in this box. Just trust me. Alzheimer’s results in the gradual destruction of the inner self; cognitive ability, memories, beliefs, even volition, eventually slip away. However, the allostasis model does suggest that approaching Alzheimer’s as an energy-management syndrome centred around glucose and the function of the vascular system in general might lead to better treatments. Perhaps, if we work on improving vascular system health, as well as finding ways to clear up debris as we presently do, this combined, systems-driven approach might give us a fighting chance. Everything psychological that a brain accomplishes—sensing, perceiving, thinking, feeling, deciding, acting—can be considered a means to the end of its core ongoing task: coordinating and regulating internal bodily systems, as an organism navigates a constantly changing but only partly predictable world. The mind is a prediction machine. That’s its purpose: to predict what happens next, what’s coming down the pipeline, where and when we need energy levels to be at their highest readiness and when we will need to rest. The mind is all about forward-projection, and from birth it is continuously training against the incoming data to identify sequences and patterns in time. As a fellow Substacker mentioned recently, it’s possible that consciousness arises only when the subconscious mind is inadequate to the task of managing one particular system in a particular context. Take breathing. You breathe autonomically, and are entirely unconscious of it most of the time. However, now that I’ve mentioned it and brought it to your attention, it will have entered your conscious awareness. You’re now aware of the action of your diaphragm, as it works to expand and contract the lungs. You can now choose to alter its action, slow it down, speed it up, or hold your breath for a period of time. This also happens at times of physical exertion, or when your head is underwater, or your conscious mind perceives the air around you to be unsafe to breathe: your conscious mind takes over to analyse the situation and decide when and how to take your next breath. Soon, likely in the next few minutes, it will return to subconscious autonomic action, and your conscious mind will focus on other things. If allostasis is the brain’s primary job, then it must prioritise the body’s internal state over external data. This leads to a phenomenon called sensory gating. Emerging evidence suggests that our distance senses - vision, hearing, and touch - are synchronised to our internal rhythms. We’re not perceiving the world at a constant, steady rate; the brain “samples” the environment in time with the cardiac cycle. In fact, so much about our perception is aligned with such cycles. For instance, during systole (when the heart contracts and pumps blood), we are statistically slower and less accurate at detecting visual or auditory stimuli. The brain actually suppresses external input during these moments of high internal pressure, effectively “blinking” our sensory awareness. We saccade - rapidly move our eyes - more frequently during systole, but we fixate and actually process the world during diastole, when the heart is at rest. Breathing acts in a similar way, functioning as a global “oscillatory pacemaker”. It synchronises neural signalling across the brain, impacting everything from memory consolidation in the hippocampus to how we process emotion and make decisions. Self-regulation isn’t a silo, either. Humans are social animals, we have evolved to “outsource“ some of our allostatic regulation to others. This is known as Social Allostasis, and resembles the concept of co-regulation. When we are in close, trusting relationships, our companions help regulate our heart rates, breathing, and even our core temperature, effectively reducing the metabolic “tax” on our own systems. The sense of safety these relationships provide allows us to operate at a reduced level of vigilance. This explains why loneliness is so physically toxic; without a social network to help distribute the load, our brains can remain stuck in a highly costly state of vigilance, which eventually wears down the system. In the context of Alzheimer’s, it’s one way to explain why strong social support shows a slower rate of cognitive decline; the social environment can help regulate a struggling internal energy budget. In short: we see and hear with our hearts, think with our lungs, and heal with our friends. Thank you for joining me on today’s short dive into some new resear

  7. 12/24/2025

    Can A Pill Change Your Morality?

    Coffee Fund: https://ko-fi.com/dopamine Note from Author: Yes, the title is slightly click-bait; but only slightly. Welcome to another deep dive. Morality (from Latin moralitas ‘manner, character, proper behavior‘) is the categorization of intentions, decisions and actions into those that are proper, or right, and those that are improper, or wrong. Let me ask you a simple question: would you ever commit murder? We need to dig deeper. Let’s clarify a bit: would you ever commit murder if you knew there would be no negative consequences? What if the proposed victim had brutally abused and murdered your children, and would not face justice in any other way? If you answered either “Yes” or “No” to any or all of these, you’d actually be wrong. The only possible answer to these is “maybe”. There is no way to know what you will or will not do in any future situation. However, if I were to ask: “is it ever morally acceptable to commit murder?” the answer is quite simple: No. Morally, it is never OK to commit murder, despite some backward parts of the world remaining committed to capital punishment (which is, indeed, a type of murder.) The distance between what we know as being morally right or wrong and our commitment to that moral judgement in our actions can be vast and incredibly dynamic. One easy example is this: is it ever morally OK to lie? Technically, the answer here is more of a “maybe,” but even so, you negatively judge those that you believe to have lied for personal gain, while simultaneously fudging the information on your résumé. Don’chya? The presence of a moral sense is consistent with a focus of human evolution on mechanisms of individual behavior that maximize survival in social groups. Evolution has promoted social cooperation through emotions against harming others, a need for fairness and the enforcement of moral rules. Mario F. Mendez, The Neurobiology of Moral Behavior: Review and Neuropsychiatric Implications (2009) Our moral values feel universal and immutable. We struggle to talk about them or think about them in any other way. We disdain others who don’t share our moral values, and often dehumanise them entirely. The Imperial Japanese in WWII believed dying for the emperor was the single highest moral good a human being could achieve on earth. Compared to the Yankee boys in the Pacific who, although ready and willing to fight and avenge the attack on Pearl Harbour, would have preferred to be home and warm and safe and at peace. They could not comprehend each other at all, and saw each other as less than fully human. When starting and waging war it is not right that matters, but victory. Close your hearts to pity. Act brutally. Eighty million people must obtain what is their right. Their existence must be made secure. The stronger man is right. The greatest harshness. A troglodyte with a toothbrush moustache. Interestingly, that brutality Hitler spoke of to his Generals shortly before the war, was never intended for to the soldiers of the nations at war with him (except for the Russians, of course.) No, that brutality he spoke of was meant only for a specific subset of people: those considered “racially impure” or “defective”, such as Jews, Gypsies, Slavs, the disabled, and many more men, women and children. The Germans would go on to murder millions of them with industrial efficiency. Considering the fairly frequent self-justifications made by officials, they knew it was wrong. Hitler knew they would know, and demanded they operate with black hearts regardless. Despite having some of the most potent chemical weapons ever made (even to this day) and having mass stockpiles of them ready to be used, Hitler refused to deploy them on the battlefield, not out of fear of retaliation, but as a moral judgement. Imagine that. The Japanese saw it as quite acceptable to decapitate captive enemy soldiers with a samurai sword, and did so frequently. They saw this as building up their own “Sei-shin”, or “Fighting Spirit”. The Allies saw this as barbaric; they preferred to do their slaughter from a great distance and with superior technology, such as the fire-bombing attacks on Japanese cities which burned alive around half a million men, women and children. Indeed, it was perhaps this idea that the Japanese had deliberately crossed some kind of universal red line into immorality in their waging of war which may have helped to loosen the Allies own inhibitions on morality, allowing them to adopt one of the most barbaric war-fighting tactics: terror-bombing. More recently, there have been debates about how pharmacology may one day provide “moral enhancement”, in which certain drugs could re-enforce a specific set of moral ideals and behaviours. The problem is: whose moral ideals and behaviours, exactly? It’s hard for many people to imagine that simply changing the balance of certain chemicals in the brain and body could change how we make moral decisions, but in fact, they already do. Research in 2014 found that we already have such drugs, and they’re already impacting our morality so much more than we could imagine; beta-blockers for example were found to significantly reduce racial bias in tests with only a single dose. So, if certain drugs can strengthen our moral inhibitions, there must be others which can weaken them, right? Press this button to get your fix! Weakening the Will In the late-2000s, a teacher from the UK was caught downloading sexually explicit images of minors. During the investigation and trial, it was found that the medications he was on - to treat his worsening Parkinson’s Disease - had been a direct cause of this paraphilia which had not been present before treatment. The medications in question - primarily dopamine agonist levodopa, but also the many others which contribute to overall dopamine agonist effect - have long been linked to the development of various psycho-social/sexual disorders, but this was a fairly landmark case which essentially found that a psychoactive medication was the causative agent of a persons offending. This leads one to wonder: how exactly does this occur, and in what circumstances? As far as I am aware (IANAL), individuals that go on drug-fuelled binges and commit crimes are considered responsible for their actions under the law. The reason is fairly straight forward: despite the mass of information put out about the impact on decision making by various drugs - alcohol, cocaine, methamphetamine, PCP, and more - choosing to take them anyway means you assume full moral and legal responsibility for your actions while under their influence. However, in a case like this, the substance was medically necessary (quite literally life-saving), properly prescribed, and the potential influence on decision-making was not widely known. All medications which have an effect can influence us in one way or another; even placebos which have no biological or chemical effect can change our perceptions and decision-making. Paracetamol reducing pain can result in a better mood, with decision making patterns that would be different to those made while in pain. Beta-blockers like Propanolol inhibit instant amygdala-driven fear responses, significantly reducing things like racial bias. Then, there’s dopamine. I’ve long been fascinated with the Nucleus Accumbens (NAcc). It’s a tiny little blob of brain cells (two of them actually, on both sides of the brain). It’s essentially the seat of motivation and goal-directed valuation. My friend Kent C Berridge developed the Incentive Salience theory of motivation, in which the NAcc plays its part by calculating how much value something has. This calculation is done using dopaminergic neural circuits running along the mesolimbic pathway. When we think of an action that might have some value - regardless of morality, consequences, effort, or any other cost - a signal is sent out along that pathway. The stronger the signal, the greater the potential value. Inhibition then acts to counter that signal. It is essentially subtractive, performing the other part of the Volition Equation, which is to subtract cost - in effort, risk, social standing - from the original value, thus weakening the signal. In order for an action to be taken, this signal must run the gauntlet of our inhibitions, and remain strong enough to clear a minimum threshold. Anything below that threshold is dropped. Morality can play a part on both sides of the Volition Equation; either adding or subtracting, so on the one hand, doing the “morally right thing” can boost the motivating signal. On the other, it can slam the brakes on behaviours and actions which might be detrimental to those social measures. Morality evolved to help us maintain conformity with a group, and as a core part of our own sense of self. So, while moral behaviour is an obvious benefit when in a group context, we still often exhibit moral behaviour when alone. Sometimes, this need for conformity can work against us, and lead to horrible and dramatic consequences. Drugs of Brute Force A teenager is hanging out with his friends one day, when one of them - a leader in the group - brings out a crack pipe. The teenager has never seen one before, but he’s able to make an inference on what it’s likely to be. He’s been told, by his parents, teachers, the government, and others, never to try it, because one hit is all it takes to cement a permanent addiction and lead him into a life of ruin, destitution, and early death. His friends, however, are all jovial about it. “Nah that’s all b******t, I can stop whenever I want to. I just like having fun, it feels f*****g awesome. C’mon don’t be a p***y.” The attitude of his in-group - the group with whom he identifies - significantly reduces the inhibitory effect of anxiety about the potential dangers, and his need to prove himself a bona-fide member of his in-group - a core part of

  8. 11/29/2025

    Gods in a Machine

    If you’re interested in further discussion on neuro-integration from all aspects and angles, I’ve set up a discord server here. Come join the fun! WARNING: The following contains MANY spoilers for the show Pantheon (2022) from AMC. You probably haven’t seen it yet, but reading this article will make you want to see it, so I highly suggest you watch it first if you care about spoilers. If not, let us proceed. On the 30th of November 2022, the technological landscape tilted on its axis. OpenAI released ChatGPT, and suddenly Generative AI was the only thing anyone could talk about. We became obsessed with Large Language Models, transformers, and the eerie ability of a machine to predict the next token in a sentence. Just two months earlier, in September 2022, a show called Pantheon aired on AMC. While the rest of the world was about to lose its mind over a chat bot, Pantheon was quietly laying out a roadmap for something far more profound: Computer-Simulated Human Consciousness, or “Uploaded Intelligence” (UI). It contained some of the most realistic depictions of mind uploads, and the potential effects on society, that I have ever seen. It grapples with the hardest philosophical questions head-on, such as the true meaning of consciousness, personality cults, the consequences of immortality and digital death, self-copying, and the universe-as-simulation theory. I don’t think many people saw it when it came out. (I didn’t) Yet there are so many fantastic, mind-bending, life-changing things about AMC’s Pantheon not just in its philosophy, but also the way it depicts cyber-security, software engineering and big data concepts; not to mention the cut-throat world of big tech both within and beyond Silicon Valley. It’s not perfect, but it’s easily the most accurate I’ve ever seen from a show of this kind. Watching it today makes it feel somewhat prophetic, but likely was the result of extremely good footwork by the producers and their team, getting the most up-to-date picture of the inner world of big tech at the time, between 2021 and 2022. Facebook became Meta at the end of 2021 as a result of Zuckerberg’s Metaverse strategy, and you see a lot of those ideas were depicted in Pantheon. We also see clear depictions of things Generative AI are doing today: chat interfaces with digital intelligence, for instance. The digital intelligences in Pantheon weren’t artificial neural networks, but fully scanned and emulated human brains. They call these “Uploaded Intelligence”, or UI (which is confusing in tech, since UI stands for User Interface, but we’ll roll with it.) In the show, a UI is created by laser-scanning a biological brain, layer by layer, down to the stem. The brain is destroyed in the process - vaporised - but stored apparently in its entirety in digital form. This is a human mind, stripped of its biological substratum which is replaced by silicon. The entire connectome is then reconstructed digitally, presumably with simulated sensory receptors; the rest of the central nervous system is not included in the actual scan. Somewhere in between all that, there is some magic fairy dust that allows the full emulation to happen, but since that is still one of the great millennium-type problems of our time, I don’t expect them to have that bit of detail. At one point in the show, a UI produces an 80-page patent in seconds. Although GenAI today would likely screw that up with hallucinations, you can see the resemblance. It feels eerily prescient. However, we’re not here to talk about GenAI, and neither does the show: the real focus is on the Uploaded Intelligence and the ability to fully simulate a human being computationally. This requires a few major assumptions: * The brain - that is, the cortex and brain stem - constitutes the entirety of who we are as individuated conscious beings * An individual’s behaviours, emotions, and cognition, can be simulated in their entirety from a scan of the cortical network using classical and quantum computing platforms Before we can even begin to tackle these assumptions, we need to understand what it is to compute, to be intelligent, and to be conscious. I Am, Therefore I Compute When we perform a mental task, sometimes we are conscious of the effort expended to perform it. Other times, we are unconscious of that effort, and an input gets processed and turned into an output which is re-integrated with our conscious awareness sometime later. To us, these results arrive as flashes of inspiration or insight; that is the moment of reintegration. In truth, the brain was likely working on that problem for a period of time without you consciously being aware of it. These unconscious computations are presently done in our biological circuitry. Technically, the physical medium of computation doesn’t matter, and could be electronic. However, there is an inherent problem in viewing the brain as equivalent to electronic circuits. Classical computing and electronics are based on gates. Gates allow you to perform simple, but exact, operations on incoming electrical signals. For example, an OR gate takes 2 inputs, and so long as at least one of those inputs is receiving a signal, the OR gate outputs a signal. A simple way to model this would be like: 0 OR 0 = 0 1 OR 0 = 1 0 OR 1 = 1 1 OR 1 = 1 The number 1 denotes an electrical signal, while 0 is no signal. Meanwhile, an AND gate takes 2 inputs, and only outputs a signal if both inputs have a signal: 0 AND 0 = 0 1 AND 0 = 0 0 AND 1 = 0 1 AND 1 = 1 Gates like these feel intuitive to us. They follow a simple logic. They’re also exact and about as deterministic as it gets. They have no hidden influences outside the two expected inputs which can affect the result; so 0 AND 1 should never result in 1, just as 2 + 2 should never equal 5. Brains, and biology in general, are nothing like that. The thing about biological computation is that it is fuzzy. For most of us, doing novel arithmetic in our head is a combination of heuristics learned from repetition in similar tasks, which we use to get a sense of approximating a value; then more heuristics refine it down until we have a value in mind that we feel confident enough about. Let’s do a quick experiment. Solve the following 2 problems: * What is half of 10,000,000? * What is half of 8,626,400? Which one required more time/mental energy, the bigger number or the smaller one? If we followed a purely computational way of thinking about things, our expectation should be that the bigger number would be more computationally expensive to calculate than the smaller one. However for the human brain, it’s not dependent on the size of the numbers we’re working with, but on their composition. In the first problem, although the number was larger, its composition was vastly simpler, made almost entirely of zeroes. To solve it, we could reduce it by 6 decimal places, and then the problem becomes “What is half of 10?” The second smaller number had many more non-zero digits, meaning we could not reduce it in the same way. Instead, our natural inclination is to solve for each non-zero digit separately: “What is half of 8? What is half of 6? What is half of 2?” and so on. 1 problem instantly turns into 5. “Therefore, our brains are not computers, therefore, our brains cannot be simulated by computers.” Woah hold up there cowboy, not so fast. Plenty of things which are not computers are simulated on computers literally all the time in every field ever; we just haven’t simulated literally everything in the universe that exists. This argument, that the brain is not a computer and therefore could never be modelled by one, always drives me a little insane: just because it doesn’t follow gate-based logic does not mean it is not performing computation, and does not mean that it cannot be simulated computationally. It is, and it can. The problem here is one of dimensionality. To simulate the human brain, you need way more than merely its connectome. We know this from simulations of C. Elegans, the Nematode Worm whose species all have exactly the same number of neurons: 302, no more, no less. We have been working to simulate its entire set of known behaviours for decades computationally, and we have made progress; but consider how incredibly simple C. Elegans is, and yet we still haven’t figured it out? How complicated can a near-microscopic worm possibly be? Some have reached the conclusion that the complexity is not in simulating the worm, but rather, simulating chemistry itself. Chemistry is, in my opinion, the most sophisticated and most powerful phenomenon in the physical universe. Chemistry is like the operating system, the essential firmware, upon which the software of human minds can run. Even firmware requires something firmer: hardware. That’s quantum mechanics. That’s effectively the architecture upon which the Firmware must execute. Indeed, if the answer is that we need to simulate chemistry itself, then think of our predicament this way: Imagine you were trying to simulate a classical gate-based Turing machine on some highly exotic computer, and you only managed to implement AND and OR gates; then you proceed to try running DOOM on it (as is tradition.) You wouldn’t get very far, would you? Technically, we can build a complete computing machine using any combination of “NOT” operator with “AND” or “OR” gates, but we don’t even know the NOT operator exists, let alone what a universal Turing machine even is. That’s more or less where we are in the grand scheme of things when it comes to simulating all of chemistry. I Am, Therefore I Intellect Another very common assumption made by just about everyone is that the ability to think implies intelligence. It’s also extremely common to conflate intelligence with emotion, with motivation, with the survival instinct. This is part of the problem which has often taken debates on simulated

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About

Stories of our fascination with the Brain: from medical mysteries, great triumphs and cautionary tales, to great discoveries and tragic failures, conspiracy theories, technology, and more; hosted by Nicholas Kircher (Published every Tuesday AU Time) chemicalmind.substack.com

Information

  • Creator
    Nicholas Kircher
  • Years Active
    2025 - 2026
  • Episodes
    34
  • Rating
    Explicit
  • Copyright
    © Nicholas Kircher
  • Show Website
    A Chemical Mind