Neurohacker, systems scientist, and philosopher Daniel Schmachtenberger discusses the questions at the heart of modern science which will allow us to unlock the secrets of the most complex instrument in the known universe: the human brain, and offers avenues to begin quantifying and hacking it.
Episode Summary
On a recent episode of my Head First podcast, I sat down with a systems scientist and co-founder of a neurohacking research group to talk through the hard problems at the edge of brain optimization. The conversation ran wide, from the philosophy of consciousness to the chemistry of acetylcholine. I want to pull out the parts that change how you should actually approach your own brain.
What does "neurohacking" actually mean?
My guest defined neurohacking as anything that optimizes the mind-brain interface and the function it produces. That covers cognition, mood, psychomotor skill, and general well-being. The framing I found useful was "sovereignty optimization," your capacity to make good adaptive choices.
That capacity has two halves. There is the input side, your sensory intake and information processing. There is the output side, your ability to act, which runs on impulse control, executive function, and emotional resilience. When difficulty hits, a resilient nervous system processes it and keeps learning. A depleted one shuts down.
The hardware and software are not separate systems. Your physiology shapes your subjective experience, and what you focus your attention on changes your physiology back. Both keep changing each other through experience-dependent plasticity. If you want a deeper read on this loop, I cover it in Biohacking Plasticity.
Why does the same symptom have completely different causes?
Take anxiety. When the research describes anxiety, the presenting complaint is the same word for very different brains. My guest laid out the causal possibilities clearly, and they match what I see in the brain maps.
Anxiety can be physiogenic. A gut microbiome disrupted by a parasite picked up traveling can drop GABA and serotonin production in the gut and drive inflammation along the enteric nervous system. A minor head injury that a CT or MRI misses can still show up on a QEEG as a measurable shift in the EEG. Mold exposure, methylation differences, and genetic predispositions all sit on this side.
Anxiety can also be psychogenic. Early childhood attachment patterns produce a different neurological and psychological picture than acute adult trauma. The approaches that help are different too.
For one real person, anxiety is often a confluence, a causal cascade where several of these factors stacked over time. This is why anxiety is better understood as a cluster of symptoms with multiple possible roots than as a single disease with a single fix. I break down the circuits involved in Biohacking Anxiety, and the QEEG side in Neurofeedback for Anxiety: What the Research Shows.
Is personalized brain medicine even computable?
I work with brain maps every day, and I am humbled by how little any of us fully understand. My QEEG gives me one slice. It captures less than half the EEG, only the dipoles oriented to the skull, averaged across several minutes. That means it emphasizes traits and largely misses states. I look at roughly 30 to 40 features and read those. It is a powerful tool with hard limits.
The reason no single tool solves the whole problem is mathematical. The total information in a human system exceeds conscious working memory by a wide margin, which is itself the tightest bottleneck in human performance. The genome operates through combinatorial dynamics across tens or hundreds of thousands of interactions, not single SNPs. Layer on the epigenome, the transcriptome, the proteome, and the microbiome, most of which is non-human DNA, and you reach what computer science calls an NP-complete problem. The system is also chaotic, so any model projected forward in time diverges from reality.
The practical takeaway is not despair. Brute-force big data alone will not crack this. You have to understand the dynamics of causation in a complex adaptive system well enough to model what actually matters. That is the modeling work worth doing.
What is "homeo-dynamics" and why does aging fit it?
My guest preferred "homeo-dynamics" over homeostasis, and the distinction is sharp. Life is not stasis. You hold a dynamic range across many axes, and health is the capacity and resilience to stay within those ranges when stressors push you out.
Insulin makes this concrete. Insulin rises when you eat sugar, cells take up glucose, insulin falls. Push that system to the top of its range chronically and it stops varying. On the way there you get insulin resistance, fasting insulin climbs, and blood sugar swings further out of balance, which cascades into every system that depends on it. The same pattern shows up in the brain as neuronal insulin resistance, sometimes called type 3 diabetes, where brain cells cannot use glucose well despite adequate blood levels (de la Monte & Wands, 2008).
Here is the reframe worth holding. Aging is not disease. Disease is when a metric leaves its effective range and a pathophysiologic cascade follows. Aging is the decreased capacity to absorb a stressor and stay in range, which raises susceptibility to disease. Someone can have every marker inside the healthy band and still be fragile, less able to sit in the healthy basin of the phase space when stress arrives. For more on when this fragility accelerates, see The Critical Aging Window.
Can the brain regenerate what it lost?
The old dogma said you do not make new neurons and that neurogenesis happens in only a few regions. That is wrong. We now find neurogenesis in the adult hippocampus (Eriksson et al., 1998), and we are learning how to support pluripotent stem cell production, differentiation, neuroprotection, and synaptogenesis.
A self-generating system that built its own tissue should be able to rebuild it. The capacity often drops or switches off for various reasons, and those switches are likely modifiable. The same logic applies to clearing senescent structures and protecting cells from becoming senescent in the first place.
There is a catch the gerontologists name antagonistic pleiotropy (Williams, 1957). A mechanism that protects you when young can harm you when old. Telomere shortening blocks runaway replication and cancer in youth, then in age it stops fibroblasts from clearing themselves and creates a pro-cancer environment. You cannot simply reach in and switch one thing on. Crank telomerase and you risk cancer.
Why does targeting one variable rarely work?
This is the daily frustration of my work. Neurofeedback is not me dialing a neurotransmitter up or down. When you perturb a system, the system reorganizes, and the response is hard to fully predict. The honest move is to raise system resilience rather than chase a single target.
So at the cellular level the general supports matter. Improving the NAD+ to NADH ratio, supporting mitochondrial biogenesis, raising ATP production efficiency, upregulating the Krebs cycle, and protecting mitochondria from senescence all help the complex work cells do go better. These are broad supports with broad effects.
This is exactly how I frame neurofeedback for people. We build more resources across the regulatory domains of sleep, stress, and attention first. That is resilience. Get someone sleeping well and thinking flexibly, and the specific complaint they came in for often sorts itself out along the way. Then, if needed, the coaching targets the remaining piece. The interconnection is also why medical specialties have struggled with complex illness. A structural knee problem can drive chronic inflammation, and those cytokines cross the blood-brain barrier to affect neural circuits, while the pain itself feeds sympathetic load into the brain. If you want the sleep foundation first, start with Biohacking Sleep and the SMR Neurofeedback protocol.
What separates a real nootropic from a smart drug?
We spent real time on definitions, because the field is sloppy with them. Three categories matter.
A brain nutrient is something you would normally get from diet that supports neural function and often sits at suboptimal levels. Tyrosine, the amino acids, omega-3 fatty acids, B vitamins, and vitamin D fall here. There is a large gap between medical deficiency, where acute pathology appears, and optimality. Plenty of people sit in that subclinical gap, including vitamin D deficiency in Southern California. Stress and dietary restriction burn through B vitamins faster, which is why a vegan or a high-stress life can need more.
A nootropic, by the original definition, is a compound that improves some aspect of cognition above baseline without meaningful negative side effects (Giurgea & Salama, 1977). That last clause is the whole point.
A smart drug is the override. This is where modafinil, Adderall, and methamphetamine live. They have real effects and real costs.
The original definition matters because it is a hill I am happy to die on. Modafinil with a significant side-effect profile is not a nootropic. A presynaptic dopamine agonist like Adderall can raise focus while simultaneously decreasing working memory, which is not the total intelligence anyone actually wants, and it brings anxiety, irritability, and depersonalization. Because it overrides an internal regulatory system, it also erodes regulatory independence and produces a comedown.
When is the risk worth it?
Western medicine runs on a risk-benefit ratio built for disease, where the risk of not treating justifies some treatment risk. Optimization above baseline flips that math. If your function is already good, why accept real side effects for a small supra-baseline gain? Trying to remedy a genuine deficit can justify more risk. Chasing a marginal boost on the chance it suits your chemistry does not.
The honest exception is citizen science. Some frontiers cannot run through formal trials for ethical reasons, and dedicated self-experimenters advance the edge. The useful response is to give those people better quantified-self tools and then aggregate what they learn. If you want the evidence-based framing of cognitive gains, I cover it in Biohacking Intelligence.
How do you build a stack that respects the whole system?
The design principle my guest described for their formulation is the opposite of single-molecule override. Map the full regulatory process for a target, address the rate-limiting steps, and aim for a broad set of positive effects without the downregulation and crash.
Acetylcholine is the clearest example. You can supply racetams and choline donors, but the donors differ. Citicoline acts more centrally, alpha-GPC more peripherally. Run the conversion path from uridine to CDP-choline to phosphatidylcholine to acetylcholine and you get different peak plasma times, so combining several smooths the curve instead of spiking it. You also have to ask whether acetyl groups are rate-limiting, whether B5 is limiting the acetylation, whether you need an acetylcholinesterase consideration, and how much NMDA upregulation the acetylcholine load can support before cellular energy becomes the bottleneck.
Then glutamate. Many racetams have AMPA-modulating, or ampakine-like, properties. Noopept gets called racetam-like and ampakine-like even though its structure is neither, since it lacks the pyrrolidone ring. It upregulates acetylcholine and glutamate uptake at the relevant complexes, acts as a precursor to cycloprolylglycine, and is neuroprotective and anti-excitotoxic by clearing excess glutamate from the synapse. The thinking here is systems-level, not single-target. Psychedelic microdosing has interesting effects but sits outside the legal frame for a formulated product, so the constraint there is regulatory rather than physiological.
What I want you to take from this
Optimization is not a matter of finding the one lever. The brain is a self-organizing regulatory system embedded in a body that is itself a web of regulatory loops. Build resilience across sleep, stress, and attention first, identify and reverse the specific causes of dysregulation where you can find them, and treat anything with a real side-effect profile as a treatment, not a daily upgrade.
If you want a starting point this week, pick one regulatory domain and measure it. Track your sleep for two weeks before you change anything, or get a QEEG brain map to see your actual traits rather than guessing at them. The map tells you where the leverage is.
References
- Monte (2008). Thctf1 transcription factor of Trichoderma harzianum is involved in 6-pentyl-2H-pyran-2-one production and antifungal activity. doi:10.1016/j.fgb.2008.10.008
- Eriksson (1998). Development of the histaminergic neurons and expression of histidine decarboxylase mRNA in the zebrafish brain in the absence of all peripheral histaminergic systems. doi:10.1046/j.1460-9568.1998.00394.x
- Williams (1957). Brucella suis infection of a child in Eire. doi:10.1016/s0140-6736(57)90165-4
- Giurgea (1977). [Epidemiological study of chronic cough and obstructive ventilatory dysfunction in a rural area]. PMID 204972
Full Transcript
[Music] welcome to another episode of head first with dr. hill today's guest is Daniel schmuck Tim burger who is a co-founder and R&D director of the neuro hacker collective which sounds kind of exciting so Dan is going to tell us all kinds of cool things today and dig into his history a little bit and some of the projects he's working on so welcome to the show today Daniel thanks for having me it's good to be here with you yeah happy to have you so first of all what is this collective of neuro hackers you are assembling it sounds like a you know sort of pie-in-the-sky big project where you're hit you're aiming for a lot of world-changing goals but can you unpack a little bit for us what your your approach here yeah so by neuro hacking we mean anything that can optimize the mind brain interface and the function thereof so this is cognitive and psychomotor and health and well-being and so we could roughly define it as well-being optimization but even larger than that we think of it as sovereignty optimization people's capacity to make good choices right to be adaptive which is a function of intelligence of agency of sentient soul together and there's obviously a kind of human software right psychology here and there's human Hardware physiology involved and we know that's a software hardware divide in humans is a plastic one it's continuously inter affecting each other and so you know your work with neurofeedback is neuro hacking the other people you've had on the show to discussing meditation etc is all in that space so we're interested in all categories of technologies that can meaningfully increase the homeostatic capacity the dynamics as you like to call them yeah of the human neuro regulatory system and thereby increase people's capacity for complex thinking emotional resilience etc and the reason why collective is anyone that is doing meaningful work here we want to figure out how we can participate at a research level and at a you know information product level etc so like us walking here together is is awesome shape koshering information in the space that's great so you say sovereignty it's an interesting way to way to frame that agency what do you mean by I mean what what kinds of things are bottlenecks to human agency that appear to be a mere affected by things we can do to the brain like what how can we affect agency in tractable ways what are you saying what are you exploring yeah so by agency here we mean the the actuator capacity of a complex system the ability to act on and in the world okay send chance is kind of roughly related to our scent our sensory input capacity intelligence to our information processing of that sensory input so that those exist in a closed-loop take in information about the world which is internal and external sensing process it to inform choice make choice get that about that choice recursively upregulate and so on the agency side on the capacity to act obviously that requires the capacity to have good information and information processing so there's good choice in forming it right it also requires impulse control yeah yeah one can actually have executive function and all that they now come to bear it also requires the it on the you know kind of choice making side of it requires the capacity to think through things using different frameworks right critical thinking frameworks systemic thinking frameworks lateral thinking etc but also in the agency side emotional resilience is a key factor so that as one is working with things and difficulties come they can process that physiologically and psychologically in ways that empower them to continue to learn rather than get shut down and so when we look at the physiology of that we know a lot about how dopamine about how adrenal hormones about how you know many different aspects of neural chemistry and physiology are involved in one sense of drive one sense of reward dynamics that can predispose dysfunctional or more functional patterns of human behavior increased sense of capacity psychologically physiologically etc so again we're back to this somewhat soft division between the software and the hardware so on the hardware side things as you said like impulsivity or executive function I think you'e Bleakley referred to working memory essentially which is from my perspective the biggest bottleneck in human performance and one that appears to be the least responsive to change but also ways of thinking about emotional regulation and decision-making criteria I'm much more familiar with the physiology side you know the biohacking idea is on the brain not the mind largely what are you seeing of some interesting ways that we can get into cognitive change so the core psychological brain mind question right is at the core of the philosophy of neuroscience the philosophy of line the philosophy of science itself right because the brain mind gets into the brain physics and the question of what is consciousness what is physics how do they interact is there bi-directional causation beyond the scope of what we're probably going to dive into here but it's definitely at the core of what's informing the whatever you do okay so how in any model of philosophy of mind however we address this it's clear that what's happening physiologically is affecting one subjective experience and what's happening one subjective experience is being mirrored on you know affecting the physiology side and so we can obviously modify brain chemistry the whole field of Psychiatry is focused on this right second row pharmacology and not just pharmacology but neuro tech in general sure sure to affect cognitive and psychological predispositions and capacities we can also do practices that are involving one's direction of their own attention and subjective experience whether we're talking about cognitive behavioral therapy CBT DBT other psychotherapeutic processes or even what we call more kind of mindfulness processes of proprioception pay attention to various sensations in the body parts of the body and what's the changes as I'm sure you've done a lot of on physiology EEG processes and then what's the capacity for neuroplastic changes in the connectome with enough time and input in there so it's not only that the division between hardware and software is soft it's they are both Co evolving all the time and interdependent and changing each others you alluded to yeah yeah I mean I have to say I'm a I'm a reductionist in this space a little bit so for me the mind is simply the part of the brain that we are aware of and experiencing and and I kind of don't go below that I have a somewhat of a Buddhist perspective where I don't really believe in consciousness I believe in moments of consciousness but not the overarching I like if the brain falls over from my perspective that's it there's there's there is no mind outside of the the coupe Oriole boundary of the skull so to speak even though I know that there are non-local phenomenon that we're observing now in the brain and I'm sure you are deeper into this idea of begin the physics affecting consciousness I've just saw a saw paper last week that showed that water has some strange kind of non-local I hate to use word but quantum tunneling in microtubules apparently under some conditions it appears like water molecules have a superposition and can be in more than one place at once inside of cells this is getting very quickly out of the realm of anything we fully understand but do you think that we are getting to a place where we're starting to run up against the you know the edge of wander said science and we're off in the quantum you know weeds or is there something here that we're making actual progress in you know actionable understanding of the brain both so quantum mechanics brings us to the limit of understand ability not just what we currently understand that the upper limits on epistemology have measurability them yeah and even beyond measurability the upper limits on ontology Reitman Heisenberg's theorem doesn't just say we can't know what it is because of measurement issues it says it's and it depends on which interpretation of quantum mechanics but standard model interpretation its fundamental nature is not yet defined independent of an observation dynamic that observation the subject object interaction Arco defining at the level of quantum particles mhm it's a very philosophically weird thing for us to think about using the intuition that we have from traditional larger particle physics yeah now we have historically kind of written that off as just super weird phenomena that happens only below atoms then cancels itself out at the level of atoms and so we don't have to worry about it the topic of quantum amplification are there quantum phenomena that then affect the behavior of things at a mesoscopic level at a Newtonian physics level or right uh-huh so this is you know the work of Stewart Kaufman the work of other people at Santa Fe Institute of complexity science the work of people like Stuart Hameroff have really shown quite clearly the quantum amplification does happen which means that the non-deterministic right a causal phenomena at a quantum level are affecting macroscopic behavior at the level of brains that still follows probability distributions but not determinism and I so this is this is a very interesting very important weird topic and the whole topic of microtubules microtubules in neurons and specific and superposition dynamics and quantum information processing is one of the like kind of interesting cutting edges in the field the work of Stuart Hameroff and Roger Penrose kind of open that space up and the work of dr. honor bond there's a few people kind of working in that space and it is only scratching at the surface of what we can claim to know well but there's already application happening and things like transcranial ultrasound that were based on the philosophy from there that seemed to be having positive result so it's a super interesting field interesting that's oh it's wonderful thanks for unpacking that just a touch for us I would say one more thing about that yeah the Buddhist perspective the kind of John Cyril idea of that the mind is what the brain does [Music] this is one interpretation of Buddhism right there different schools as yours I'm sure have very different interpretations here obviously the foundational idea of what's real in Buddhism coming from Vedanta was that consciousness is what we actually have a stronger sense of no ability on than physics mm-hmm right sure sure and so their model was well I know that I'm experiencing something there's an experiencer here I don't know that what I'm experiencing is what I think it is but in an almost kind of Descartes like way there is some witness that is witnessing changing phenomena that is prima facie real right so their model is be was reductionist in the opposite direction either that that consciousness is an emergent property of physics which is where physicalism science has gone they saw the rest of universe as either not real or an emergent property of consciousness and that that kind of idealism physicalism divide is right at the heart of what we're figuring out when we're studying consciousness via objective methods in brain science but correct if i'm wrong but you know old school you know early pali buddhists wouldn't consider consciousness a phenomena outside of momentary experience i mean i nietzsche impermanence the nature of reality is transient so even consciousness the I always even fall back to the metaphor classic metaphor ship of theseus you know a thought experiment here's a model ship if I replace one plank is it the same ship how about two how about three at what point is this capital I self the same if every seven or eight years all the molecules my body are completely different and have been replaced you know this is where it fundamentally breaks down for me personally in terms of consciousness but would the you know the Vedanta approach say that there is a cohesive sense of consciousness or is it emergent property of just you know having a meatsuit so Sanskrit has a lot more words that have a lot more specificity in their definition than just consciousness and self-awareness and they're actually very key distinctions in their philosophic system okay and again there are different interpretations and in these systems but the Buddhists traditionally say that the foundation of reality is neither self nor non-self because that distinction doesn't exist at that level that the rational distinction of the concept of self other than self is more superficial than the foundation of reality right it's its ontological a less primary okay so the idea that it's non self or the idea that it's self are inadequate so what we think of as self is self other than self division right they talk about a foundational oneness beyond division it would be neither of those concepts right not self nor non self that's different than the traditional way that is spoken about in Vedanta which is that at the foundation of all of it there is consciousness with a capital C that is that is different than self right that can hmm this is basically if you think about it almost in terms of a unified field of physics as a field of potentiality for dynamics to occur in quantum foam to emerge from etc that there is reference happening but it's referenced within the only thing there is other self reference and that the foundation of what we think of as self referentiality happens at the level of Unified Field interesting now I'm not saying this is what I think but this is some of the kind of interpretations there I will say there are real problems with most of the models of physicalism there are real problems with these models and this is why these are unsolved famous problems in philosophy and you even see like you'll see a couple physical lists like the classic debate that Sam Harris and Dan Dennett had under Sam wrote has become free will was that Dan fundamentally said consciousness isn't real maybe is a radical limit Avista it's an illusion but freewill is real and Sam said consciousness is fundamentally real an emergent property of brain but freewill is available is a core disagreement on the most foundational concepts of existentialism of what actually is both being physicalists and having the same kind of critical thinking background agreeing on a lot of other things so it's part of why these have been so hard as they're beyond our current tools of knowing my pistol my logic tools when we do science we are studying third-person things that's very sure do so when we try and study consciousness which is first-person by looking at the third-person core correlates we're actually doing a category mistake mmm by assuming that they're the same thing also when we assume causation when we get to the level of things that are for sure via Bell's Theorem a causal our intuitions get off right and so these are fascinating and tricky areas what we can say at the level of what's probably useful for people right now is that we can do things with our own subjective experience of self so what we focus on we put our attention and the meaning we give to things that has a real effect on brain and physiology and we can do things to our physiology that are not obviously utilizing our subjectivity that will affect our subjectivity and there can be recursive effects between subjective and objective that can either depending upon how you do them have the potential of being virtuous cycles in more adaptive evolutionary directions or vicious cycles and so learning how to use both the conscious direction of our thought awareness attention and what we do with our physiology in mutually reinforcing adaptive ways is I think what we're interested in wow it's quite heady stuff no pun intended till you taste like a philosophy a guy he read you have a philosophy background yeah yeah tell us about that what is your when he's returning been there uh so I was home-schooled growing out okay and all the sciences and all the philosophic traditions were what I was fascinated by and so a particular home school didn't have curriculum so I just got to study what I wanted to know was interdisciplinary science system science and the various philosophic traditions because the the impulse to study science was impulse to understand the nature of reality we live in sure better yeah which is a philosophic impulse right science is a method of knowing that correlates to a particular philosophic system right philosophical system usually a logical positivism or the idea that reality exists objectively objective stuff is real we can measure it get the same results so science is a subset of philosophy it's a particularly useful meaningful one it doesn't happen to be an exhaustive one of all sure assurance yeah yeah and so fortunately got to study many different Eastern traditions and Western traditions and my early and then you know deeply in my kind of method of understanding any new discipline is I like to start by going to the edge of what the hard problems that are not understood and you know believe may be unsolvable and then understand the range of opinions on that and why and then go back and understand the core axioms of the field in light of recognizing where they might actually have limits Oh injury all right so let's so with that perspective with this lens into you what are the hard problems you bump up against and enjoy bumping up against in the biohacker neuro hacker world what are the what are the growth edges I mean I I see people acquiring tools and technologies and ways of modifying their physiology and their minds constantly and I provide some of those tools a lot of the time we're operating a space we really don't fully understand you know what we're doing it's this summer between art and science and I'm sure half the things that biohackers do are completely irrelevant and a certain percentage is probably working counter to what they actually want to do what do you find the hard problems are in neuro hacking or by hacking so neuro hacking bio hacking and what the hard problems are in medicine and we kind of looking at that as medicine moving from dysfunction to function how can bio hacking generally thinking of it is trying to enhance function build on previous baseline we think of that as one gradient some of the hard problems that are not like philosophically hard problems and of maybe unsolvable ax T or n stemming limits but like the Holy Grails of the space yeah one of them has to do with complexity okay and so when we're trying to look at what's going on for an individual person say we're trying to look at addressing anxiety for someone is their anxiety primarily physio genic or psychogenic and what causes in each of those if we just look at physio genic physiologic causes we see a whole good body of work on the ability for microbial imbalances in the gut to cause anxiety anxiety predispositions because of decreasing the total amount of gaba produced in the gut or serotonin producer in the gut or inflammation on the enteric nervous system or whatever so if someone went traveling the third world got a parasite microbiome got off has never restabilized afterwards know that could be a tier one cause of anxiety that no amount of no tropics or CBT or DBT assures yeah yeah or if they had minor head trauma where the cat scan or the MRI didn't show anything but maybe a qejy would or maybe a SPECT scan which is this you know functional fire hydrant sure went off how we're going to address that that might require neurofeedback that might require neurogenic chemistry right that's going to be totally different again if they were exposed to mold or other forms of cytotoxic sure that can cause anxiety it so there can be genetic predispositions there and then you can we can continue to populate there can be methylation disorders right there surely thousands of different things and then the confluence of those things right and then if we're looking at the psychogenic side event we're saying someone who had anxiety since childhood because of kind of attachment early childhood attachment stuff of parents versus only after a very acute trauma even if dealing crowder are sure they're they're different psychologically they're different neurologically and there are different best practices and therapies to address all these things and for one particular person's anxiety we might be looking at some confluence of some number of these factors right where there was a causal cascade and then that person with anxiety maybe also has a sleep issue or not or maybe also has some autoimmunity or so as we're trying to help them are we how do we factor all yeah certainly complexity and personalization yeah is this possible I mean I I work with brains every day and I am humbled every day by how little I actually understand and my strategy for dealing with that is you know maslow to a man with a hammer every problems a nail my hammer is neurofeedback in meditation and to some extent nootropics but I view the brain as a regulatory machine and when I do a QE G and see something off and it matches symptoms it's you know it's a little bit more skill than being a mechanic perhaps but it's that that approached it to be let me go region twins wake this and see what happens I would I mean I'm working on integrating lots of different information systems so that I can you know do visualization do big data do a better sense of what's happening but even that will have a fraction of the type of the degree of things you're talking about right is it a solvable problem can we actually bring in personalized medicine if you will personalized psychology track data this way I mean is this being done can we do it I think we're getting enough information about the the individual data points you can do a methylation analysis you can do a theta beta ratio you can do you know a blood flow imaging or something but these measurement tools are limited by the tool space that they are using and qejy gives me one thing because me less than half the EEG only the dipoles that are at right angles to the skull and it's a 10,000 foot population average of average deg across several minutes so you're missing states completely only emphasizing traits and the this you know 30 or 40 big features in the Q EEG that I look at and then I operate on in terms of intervening but it's I default back to that because I can't do everything because I can't hold everything in my mind and I can't ask everyone all the right questions to tease out what might be going on because I just don't understand the brain fully I mean as you say probably none of us do are we getting to the place where we're going to be able to aggregate and analyze and extract meaning from this complexity or is the complexity because I've secured our ability to know what's real I know it's important yeah I do believe we are starting in the next few years okay having an exponential curve this is a Kurtz wily and predicting here sorts out in a different direction than rank much of what we hear about what is going to happen with brains from singularity okay as you said we can't hold it you can't hold it on your brain okay total amount of information exceeds our conscious processing by a lot mm-hmm because of working memory limits mostly right yeah there's a storage limit the brain as far as we can tell but there is a working memory limit for your ability to consciously you know try to make sense of not just how many different metrics but the relationships between those mixture or ideal material relationships so say we start looking at the genome most things aren't affected by by snips right by one snip there's very few things that are mostly we're looking at dynamics combinatorial dynamics across tens or hundreds of thousands three effects essentially right and but that's that's a lot when you look at you know three billion base pairs yeah and then we have to deal with the fact that that doesn't tell us which ones are actually coding right we have to look at the epigenome for that which is not something we do well right now so we have to look at the transcriptome or eggs Omega proteome which is all stuff that is emerging but hard and that's just the human genes which is not actually the majority of the genes we carry around or actually art ours are human right so so if you think about it this way right when you're saying the brain is regulatory system it's a top-down regulatory says right the bottom-up regulatory system is the code layer the genomics the microbiome except I romics right they are creating a distributed bottom-up regulation of individual cell function right and routine code is sure sure that bottom-up regulatory capacity is what led to the the evolutionist top-down regulatory capacities that get to control larger groups of cells and tissues working together in coordination the feedback relationships between the bottom up and the top down regulatory systems and all the dynamics in between is where we're what I think we're starting to do is map the human as a cybernetic organism okay right as a regulatory organism Plex adaptive system science and kind of systems modeling to understanding that better and it is what in computer science is called a np-complete issue it's an uncomputable issue okay there's an uncomputable amount of information yeah we're not just going to brute force big data and machine learning and figure it all out well to chaotic system we have we do not have infinite precision therefore any model that steps into time far at all diverges from the chaotic system and so yes chaotic meaning there's some fundamental unpredictability there our measurement limits and then there's there is uncomputable complexity and so what that means is rather than just depend on brute force computation we have to understand the dynamics of causation and a complex system better so we can compute the things that actually seem like they would make sense to happen right that's the modeling part I think the modeling part is key and that's it neuro hoc are what we're really focused on is taking models like cybernetics right like complex adaptive systems and like information theory and putting what we understand from human biology and medicine into those more complex models to understand dynamics better right complex dynamics and getting to the place where we can start to aggregate tremendous amounts of data there and that of it is has progressively better sensitivity and specificity and then be able to process that data where you know right now for the most part when we look at a biometric we look at someone's hemoglobin or their vitamin D or whatever we're looking at in relationship to a reference range sure but when we look at someone's someone has a kind of dynamic homeostasis right I actually really like it we're at homeo dynamics it's a better word because the stasis is nonsense as you mentioned sorry I need your response right here the word homeostasis sure life is not stasis we have these homeo dynamic yeah and then thriving health has to do with the homeo dynamic capacity and resilience across all of those homeo dynamic axes right mm-hmm aging is decreased homeo dynamic capacity across some of the axes does that mean decreased range of variability in actually decreased capacity to have a stressor right some things that's trying to create deviation from homeostasis and the ability to stay within the homeo dynamic range so then if which means less resilience so to be concrete things like insulin or cortisol rotla to insulin rises when you consume sugar right when you know it's a signaling molecule cells suck up the glucose insulin goes back down to chronically pretty sure the insulin system to the top of its range eventually it stops varying and we call that type 2 diabetes and on the way there the kind of syndrome X dynamics where fasting insulin levels raise you get insulin resistance at the level cells now you take sugar and in your blood sugar is going to go further out of balance no longer causing more effect on other systems are affected by blood sugar so more than pathophysiology so we're defining here aging is not disease because disease we'd actually say is the deviation from homeostatic range or homeo dynamic range where some metric actually goes out of effective range and then you get a pathophysiologic cascade okay so aging is not that it's the increased susceptibility for that so it's increased susceptibility for disease because someone could have all of their markers within homeostatic state range mm-hmm but more sensitive to them being able to go out of range from whatever stresses so they're less label to sit in the in the in the healthy basin of the phase space so to speak right okay sorry and so what we're interested in here is how do we where someone already has disease dynamics going on how do we identify specifically what caused deviation from homeostasis on which dynamics what was the causal cascade that happened and how do we specifically reverse it like we mentioned with the anxiety are we are we keel ating neurotoxins or are we fixing the gut brain access or those are very different things that require specific addressing of what the causal cascade was so this is not let's say going to insulin the insulin insensitivity that cells experience after high levels of insulin that's not the disease itself that is the failure of the dynamic range correct and we call these diseases things like diabetes and Alzheimer's or other things because of the failure now there are some people who get type 2 diabetes who did not consume too much carbohydrates relative to what they burn but they are deficient in chromium or vanadium that are nary to actually have insulin process that receptors so there are other dynamics that can go on which is why we actually have to understand what are what is the entire causal phase space of what can cause an imbalance all the things that could be involved and this is what we've sucked at at medicine so far is dealing with complex causation yeah feud causation straightforward right so injury pretty straightforward and so we're going to be able to address that in a clearer way but where the causation is either delayed in time right so something happened and it led to a slow deviation from homeo dynamics over the course of years or decades it's hard to assess what it was yeah or where it's multifactorial there's many different things going on and where it's a combination of some multifactorial set that's different for different people so I don't think ms is a disease I think it is and I don't think Alzheimer's is a disease or anxiety I think they are conditions where some cluster of symptoms and biomarkers come together what we call with that but the actual causal etiology going into it can be radically different from one person to the next so Laurie syndrome less of a disease a cluster of symptoms that may have multiple causal features interesting I saw a study out of UCLA a couple weeks ago that suggests Alzheimer's insulin insensitivity if you will can be reduced simply through behavioral mechanism to a bunch of people off of all the meds off of anything instead of doing specific intervention they said let's do lifestyle things and did you know paleo diets and exercise and lo and behold symptomatic Alzheimer's individuals showed recovery of some function this is fairly magical things there was a study out a couple weeks ago showing that even in people with type 2 and type 1 diabetes who have no beta islet cells essentially anymore in their pancreas producing insulin short period of fasting if it was 12 or 24 hours a very short period seems to cause a read if ur enchi a ssin of non beta islet cells into beta islet cells to produce insulin right that flies in the face of what we thought of in the disease model diabetes where it's either autoimmune or it's toxic from the sugar essentially that kills in some person cells once they go on to gone that does not appear to be accurate is this the kind of thing that your your listing is the main thing that the idea that we don't produce new neurons right that was an old idea driven we realized you know Genesis happens and it can be up regulated yeah and that it was only in three places and now it's pretty much everywhere you look in the brain we're finding new actually button stem cells so and so can we increase pluripotent stem cell production and their differentiation throughout the connectome and can we increase neural protection and synaptogenesis and yeah like we're learning a lot about how that works any when you have a system that generated itself it's a self generating system the idea that it just could not generate those tissues that it originally generated again doesn't make that much sense obviously capacity to do it and then the capacity decreases or turns off for some reasons those then likely are modulated to turn on again so sure when we think about life extension how do we increase progenitor stem cells hmm how do we increase the rate of purging senescence structures how do we protect cells from senescence these are all things that happen already sure they can start happening in at suboptimal levels for a lot of reasons we can support them happening in optimal levels and maybe even beyond previous genetic optimality right just to give us discrete example the gerontologist teach courses in aging is a term aging called antagonistic pleiotropy the idea that a mechanism that is healthy at one point in life is harmful another point in life and the telomeres you know the shortening end caps that prevent replication forever when you're young prevents cancer from running away with yourselves when you're old keeps fibroblasts in your collagen from cleaning themselves up and they become homes for a pro cancer environment basically so this kind of thing we're identifying where the natural arc of development may not be optimal for long term performance and turning these things back on and controlling it I mean from point of view telomeres you know for a long time that was of course the Holy Grail in antisemitism years you know ridiculously it would probably just cause huge amounts of cancer so we can't simply reach in and turn one thing on I mean this is something I struggle with a neurofeedback it's not reaching in and dialing up and down different neurotransmitters or different you know brainwave ratios when I perturb a system the system reorganizes and I'm never quite sure how it's going to reorganize this is uh you know little frustrating sometimes so if we think of it as increasing system resilience right homeodomain capacity because it is a self-organizing system and the complexity is well beyond what we're going to understand in a momentary view right we're never going to factor all of the dynamics happening probably even in one cell but we can understand the dynamics that are involved in its some of the key ones in its own regulatory dynamics and how we can increase its regulatory capacity and so in general do we see things like redox signaling decreasing inefficiency in cells yes yeah so this is why all the nicotinamide right aside stuff has been so if you can up regulate the NAD+ NADH ratio there's a lot of cool things that happen yeah do we see a CP decreasing inside of cells yes do all the things that cells do need those chemicals sure yeah if we can support mitochondrial biogenesis if we can support ATP production efficiency and krebs cycle upregulation yep if we support protection of the mitochondria so they don't become senescent right these are key things that what exactly is that going to do what is going to help the complex dynamics of everything the cells are doing happened better and so I think those are one of the key things we so you know we were saying earlier there are specific sources of pathology right causes of deviation from homeostasis that we want to identify specifically in Reverse you have the Jin's toxins deficiencies etc then there are general system dynamics that support system resilience and we want to support those even though the effects of that are going to be general increase well-being in crossing systems so EEG regulation is going to produce you know how much is it going to affect a particular gastrointestinal dynamic well it depends on what all the causal dynamic oh yeah it should move it in the right direction to the degree that it's creating better sympathetic parasympathetic you know ratio dynamics etc yeah so we want to in general support the homeostatic processes that are fundamental and get better at diagnosing individual sources of pathology and reversing them this is great I mean this actually ties into how I often frame there a feedback for people and they say oh how to do this and I'll say well we're probably going to give you more resources and all the regulatory domains of sleep stress and attention and what that means is resilience right and we can probably reach in and do more specific things for you but let's see what happens first when we bring the resilience way up and get you sleeping like a rocket will and being creative and flexible let's do that for the first few weeks and then we can go in and try to target the thing you think you care about me and usually the thing that they really want to work on sorts itself out along the way towards just building everything that the complexity of the interconnectedness of everything is again why specialties have failed at complex illnesses yeah but it's also so fascinating because you know we can look at a structural issue right like a postural issue or osteoarthritis that's causing can continues inflammation within the inflammatory molecules right cytokines can cross the blood-brain barrier cause neural inflammation and damage to neural circuits yeah also where the continuous pain dynamic is causing sympathetic feedback into the brain which then is going to cause effects on all the things the brain is regulating for helps on perspective life and what needed fixed was a structural issue in a knee right right and or mold in the environment or a runaway process of dysfunctional information processing in the brain from a particular psychologic meaning making pattern right so can can structural issues and joints or psychological patterns of focus and meaning making or things going on in the gut or affect any other system in the body yes this is what's fascinating is why trying to separate neurology and gastroenterology and oncology has a pile here yeah and so now it's how do we synthesize what we understand about the parts to understand what happens for whole systems and what happens across systems so now you're doing this at the Niraj collective this idea of bringing in different aggregate data types and modeling and trying to figure out what is the meaningful inflection points for these models where you know what wears change happening that's very you know high level and and those are the kind of projects that frustrate PhD students for you know 20 30 years yeah I think it's great I'm you know I'm incredibly noble pursuit to enter those big questions I also know you guys are doing something's a little bit more okay here are some things we can actually do this a product you've produced called qualia which is Ana tropics is that is it an entropic space okay do you consider it in tropic or is it more than that is that a good frame for it is that too limiting I think that's a fine frame as you know the term no tropic is a little bit loosely defined in terms of how its generous yeah how do you define it well I would I would in general start by making the distinctions between brain nutrient no tropic and smart drug which are apparently used kind of in relation to each other yeah it's worth distinguishing so brain nutrient means something that you'd normally get from a dietary source that's critical to some part of neurologic function that can often be a suboptimal levels precursors like tyrosine all your amino acids fatty acids vitamins minerals that are part of neural dynamics and when we talk about medical deficiency we're talking about a level at which acute pathologies happening below that level there's a pretty huge range between medical deficiency and optimality hmm right and so we can call that subclinical deficiency or sub optimality and so there's heaps of brain nutrients that depending upon what kind of tests we do we see in suboptimal levels all the time right okay vitamin D is a puck sure yeah even in Southern California even in Southern California and and because it's not at a level four you know rickets right someone has a you know thirty vitamin D traditional medical process hasn't addressed that but when we you know have deeper insight about where optimality occurs it's a far away way which is why the vitamin D supplementation is meaningful same would be true with omega-3 or tyrosine or Nick cetera so brain nutrients that are either hard to source adequately in diet or where modern lifestyle has used them faster so if we're talking about Heidi or stress lives where B vitamins are in a process faster or whatever those are meaningful or you're a vegan if you are eating anything with s B vitamins in it so tight you know any kind of dietary limitation yeah things to address nootropics starting with you know defining piracetam as that field is some chemical that can increase some aspect of cognitive function beyond baseline without meaningfully negative side effects thank you for including that last piece the original definition essentially I this is one of the axes I love to grind you know I'm all over the new trophic forms and things and I can't tell you the number of times I have to resist reaching through the computer and throttling some kid who thinks that modafinil is mini trophic yeah nothing with our people with a significant side effect should be considered and I'm guessing you have the same perspective I do if your performance is already relatively good why would you risk side effects for small incremental improvements Supra baseline improvements you're trying to remedy a deficit that okay maybe you need to risk some things to get a problem sorted out but I don't understand the incredible marketing and consumer push to seek for you all of these drugs and compounds that have someone have very very significant side effects on the off chance that they're going to be you know designed for your sort of your chemistry and give you that little boost I don't understand the the philosophy feel behind that this idea that you can you can reach for something that might not be unilaterally good just in case it might you know that's that seems very um non nootropic you know to me so to speak so the topic of risk benefit ratio yeah is core to Western medicine right and it's partly why we only have a disease model and we don't have an optimization model is because in the disease model there is a risk to not treating the thing right pain problem so some risk of a treatment seems warranted sure and you have to make sure that the risk makes sense to possible benefit if people are already generally healthy and this also why longevity research hasn't you know had a lot of support until recently or any kind of optimization which provides been left to biohackers is how much risk can we justify for how much benefit beyond baseline right it's actually a really deep question and it's a question that should be answered individually within a range that is reasonable for the field as a whole to pursue now I think bodybuilding and steroids is a classic example of this okay so can people perform in fundamentally increased ways with anabolic steroids that they couldn't otherwise obviously right you know otherwise you wouldn't ban them in sports is it and you know were the people who are really pioneering this risking their health and if many of them experienced the downsides of that already totally yeah and for them at least knowing that quite clearly for many of them it was worth it because that's what they want to do right like the same reason anyone would do anything that was not a smart longevity decision for what the passages where and then the field of steroids itself evolved from a lot of that experimentation to where the you know that some of the Psalms today have compared to the early anabolics have radically more benefit for much less risk yep partly evolved by kind of the citizen science happening in that space that just for ethical reasons couldn't happen in formal ressure sure so it's a very interesting topic right it is a place where citizen science is always going to be advancing the front edge and I would say all of the Psychonauts working with deep psychedelics are in the same place and so one of the things we really like is for people who are for whatever reason inclined to do their own research give them better quantified self tools and learn from that if it's outside of what we can do formal research on and then you know be able to take the formal research from the crowdsource to get a very big level essentially that's great now with regard to what the appropriate risk benefit dynamics are yeah so you mentioned modafinil and take it further methamphetamine definitely increases certain cognitive capacities and it kills the flu virus it has a number of positive medical credentials yeah and it has very real side effects and so if someone is in a combat situation and then you have stay awake a little bit longer they have meth might make sense right part of how those drugs were developed yeah for general use for your midterms you know it's not a good idea now if we look at how much off-label adderall and modafinil and redbull and whatever right you know happens for those purposes this was one of the main reasons we decided to make quality was not only are the down regulation and side effects pretty significant of most of those but even the positives are fairly narrow mm-hmm right so if you have if you use it a presynaptic dopamine agonist right like adderall you will get increased focus but you might actually get simultaneously decreased working memory we would have seen on that is clear which is not the kind of total intelligence that we're interested in it as well as you know anxiety irritability depersonalization all those other dynamics and then of course because it's an external override of an internal regulatory system yeah regulation independence you know and so what we're really interested in I'm what I'm sure you've been interested in the in the space was can we understanding this system more completely and nowhere near total completely but more completely right we're not just trying to a single molecule intervention can we have a much more comprehensive set of positive effects rather than a narrow set without the negative effects in real time and without down regulation so that when someone gets off of them they're not experiencing addiction come down but if anything experiencing long-term upregulation of the capacity of their system so that's obviously that's the design principle with which we approach the whole space quality and all the products and development so follows your first product then yeah what's in it I haven't dug into the ingredients at this point so brain nutrients and no tropics okay and so as you know when people start in the no tropic space usually they dive into a seagull calling for sure shirring and so rasa Tam's and some choline donors that are like the the foundation for memory augmentation sensory nerve motor nerve you know acuity etc so but which rasa thames you use are going to have a bunch of other differential effects and rasa taking impress them are very different creatures oh yeah and also are we going to address the ability for the acetylcholine once it's produced to get across the synapse are we looking at acetylcholinesterase inhibitors are we making sure that the acetyl groups aren't rate limiting for the choline that's there that people aren't getting over cholinergic we look in different choline donors central phenoxy is going to act on the central nervous system more than alpha GPC on the peripheral nervous system if we look at the conversion of uridine to Citi choline to phosphatidylcholine LDPC to acetylcholine you're also going to get different peak plasma times when HMS Eagle : kicks in so if you want to be able to have less of a spike and more of a continuous process you might put a number of those so we focused on like with acetylcholine we're looking at what is the whole acetylcholine regulatory process so and how can we address any of the rate limiting factors and make sure that we're we're acting on peripheral nerves were reacting on central nervous system differentially more is what we want to be doing it the kind of pharmacodynamics and kinetics of so not just where it's acting but how long it's operating for and those curves are things that would really look at how much acetylcholine we're producing it so that you've also got not just a siedel donors which is why people love alkar right seal quarantine and one of the reasons and today I know what protein doesn't kreb cycle is b5 is often a rate limiting factor for the synthesis rather the acetylation of choline so you know what are the right ratios of those things together and then how much acetylcholine support for how much NMDA upregulation and then where do you get rate limiting effects in terms of the total cellular energy to process more acetylcholine and then all of that just acetylcholine yeah then we look at glutamate and typically it's pretty common that rasa terms of am packing light properties yeah certainly uh any rs.10 does and you kept which reviews know I always get confused new pep seems to have race at am like properties could not be a race at am correct I mean I look at the structure and doesn't have a protein ring that's correct so it called racetam like and am packing like okay as of up regulating acetylcholine uptake in the NMDA complex and up regulating glutamate uptake at the AMPA complex but it is actually not structurally either of them okay but it's very interesting it's a precursor to cyclopropyl glycine it is neuro protective it's anti excited is anti excitotoxins the way that it brings excessive glutamate outside of the synapse so it's a very interesting molecule a new pepsin quality as well great now there are plenty of things that we would have in qualia if there was different regulatory dynamics okay but you know so we're working within both the general well-tolerated space the effective space the and the legal space sure yeah people micro dosing LSD or psilocybin has a lot of neat effects we can that's that arising right um not yet not yet so actually that's face of the appropriate legal categorization of medicines as its base that we have worked in and intend to more because it's important so more political legal and regulatory not at the physiology but at the body politic exactly interesting so when you look at say two men offend being over-the-counter hmm as a legacy thing in the toxicity of it came to hair to pot having been illegal for and still illegal and so many plays for so long it's just nonsense right right and we can look at the whole history of why those nonsense decisions were made but they're not just nonsense they're really bad for people yeah because pot doesn't cause liver damage and acetaminophen does and it but it addresses the same pain dynamics of people using it man yeah but you can put a few minutes on it with opiates and that prevents people from taking all the opiates and overdosing in theory that's that's of course the title three vicodin kind of approach is to combine to seem innocent to avoid to to say hey it's going to kill you if you take too much don't take too much and so then people take too much and get liver damage right right so it's not a good idea but maybe they didn't that wasn't well thought out right so um it's been heady stuff Daniel thank you so much for sharing a video wisdom where can people find out more about you other projects do you have going on how can they dig into the the the Daniel list that that we have here in front of us a little more if they have had their interest sparked as far as the topics were talking about here neural high kinetics neural hacker calm okay a good place to go check it out great publishing more information there and I want to say that the work that you are doing and neurofeedback and the fact that you're scaling it with quality control and with the systems that allow that to happen that's one of the areas that if you hadn't done it we would have eventually got into because it's critical and we think it is one of the really most meaningful neuro hacks that has the least the least damage box really small downside is if done well right yeah yeah it's real super high reward possibility so I'm excited too look at if there's a way we can partner and support what you're doing I'm sure there is we're both in Southern California so we should very at least try to work that great so can they fall can folks while you on Twitter Instagram LinkedIn what's the what's if there's one of you know follow you and here so you drop wisdom and see all the things you do what's the best way to do that Facebook is probably best Facebook all right great so today's guest has been Daniel spectrum Berger of the neuro hacker collective we packed more into this hour than I think most shows we've had I'm going to go back and listen to myself and look up a few terms which is great so I rarely have to stretch myself that way I really appreciate it so folks it has been another show of head first doctor he'll take care of your brains and we'll see you next week [Music]