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Show Notes
This is a ~52 minute discussion between Diana Moga (https://www.dianamogamd.com/), Alexey Tolchinsky (https://montgomerycountypsychologist.com/), Chris Fields (https://chrisfieldsresearch.com/), and I on topics related to autism, ketamine-assisted therapy, and the linking of these concepts to somatic biology.
CHAPTERS:
(00:00) Autism, trauma, ketamine
(03:02) Defining autism, social mismatch
(08:37) Sex differences, brain models
(13:14) Phenomenological pattern overview
(19:24) Neurotypical variation and spectrum
(31:25) Opposites, psychopathy, plasticity
(36:18) Morphogenesis, xenobots, immunity
(40:37) Supportive environments, stimming, movement
(45:26) Dimensional models, future experiments
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Transcript
This transcript is automatically generated; we strive for accuracy, but errors in wording or speaker identification may occur. Please verify key details when needed.
[00:00] Diana Moga: I am a psychiatrist and a psychoanalyst in Manhattan. I have a background in neuroscience. Hi, Chris.
[00:10] Chris Fields: Hi.
Diana Moga: Nice to meet you. I work a lot with autistic patients, and I work a lot with trauma and the intersection of trauma and autism, which is pretty much any autistic person who's going to come to see me has some form of trauma or other. It's a very high prevalence in this population. I've started to do ketamine assisted psychotherapy with autistic people because I think it helps address trauma in a way that's not accessible; it's much harder to access. I think it has more to do with a collapse in the inner psychic space and difficulty with one's inner world because of constant social trauma in life. So the ketamine creates a situation of trust and openness and lack of judgment. It also allows I think more synchrony between the patient and I. We're both in an altered state and we're able to put into words things that were not before accessible to language. We're all able to together get really curious about their inner life, which was difficult to do. So that's mainly what I do.
[01:25] Michael Levin: Very interesting. To make sure I understand. So you and the patient are taking the ketamine simultaneously? No.
[01:36] Diana Moga: No, I would not talk about that publicly.
[01:43] Michael Levin: Only because you said you're both in an altered state.
[01:46] Diana Moga: I'm essentially meditating when they are under. I'm much more receptive and much more attuned. The way that they express their experience. Recently, somebody was talking about their chest is a cage and it's empty inside. They associate with the house of their childhood, this dark house on a hill that's empty inside. They're a bird fluttering around and seeing the emptiness and the despair. I get a much more vivid access to aspects of their inner life that they otherwise would have a hard time pointing into linear language. It gives us access to sensations, bodily implicit memories, visuals. It's a dreamlike state. I'm in a more receptive state to receive that and we can talk about it. For example, I'm seeing somebody that I treated for nine years where I tried to get into his trauma with him. I knew that there was serious trauma there; he fled treatment and came back years later, but we could not get to it without the ketamine. It really can be make-or-break a treatment, specifically with autistics.
[03:02] Michael Levin: Would you mind saying a couple of words about what you think autism is to begin with, just the baseline, what you think is going on?
[03:14] Diana Moga: Alexi and I have been talking about that and with you guys a little bit as well. In the autistic community, we say it takes all kinds of minds, which I think you could relate to. I love that you say that as well. So it's a different kind of mind. It's a different pattern. I think there are changes happening all over the brain. The cerebellum is different. The sensory cortices, the thalamus, the frontal lobes, the connectivity is different across the board. It's really a different world experience, self-experience, other-experience. When you try and describe it in terms of buckets, you have social differences, which are considered deficits because they're different from the standard. You have communication differences, you have emotional differences, you have motor differences, you have sensory differences — you're describing basically all of human experience. So it's unwieldy and it's confusing for people, but it's really a neurodevelopmental difference that's there from the beginning. So it's not the same as a personality disorder. It shapes the way your world takes shape and it shapes how you interact with others. A lot of what we're seeing with autism in adults is a result of years of shaping of social interaction, which is not studied. I know it's a little vague. There are more specific ways to define it, but I think they're all problematic. For example, for a long time it was thought autistics lack theory of mind. What is theory of mind? It's all the experiments that are designed to study theory. The way theory of mind even started was what's the difference between a chimp and a human? Do chimpanzees have theory of mind? No. The chimp does not have a theory of mind because it cannot figure out what the humans are doing. It cannot figure out that the humans need help with the boxes. A chimp is very strong. A chimp would not need help with the box. Why would the chimp think that the human needs help with the box? It's very human-centric and very neurotypical-centric. Then the next paper was, does the autistic child have a theory of mind? The most consistent studies find that autistics do not have a theory of mind or have a weaker theory of mind. The problem is a lot of that is language dependent. If there are language deficits, that's going to be impaired. A lot of that is dependent on the social interaction. When the examiner leaves the room, there's one study where both kids perform equally because a lot of autistic kids want to figure out what the marble is. They don't care about what's happening in the mind of the other. So there's an intentional stance difference. I think it's a very different approach to the world. It's not as hierarchical. It's not as human-centric. Animals, objects, sounds, patterns are all important. But it creates social difficulty, social deficits, and real disabilities when you have to interact with a society that runs by certain rules and assumptions of what a mind should be.
[06:12] Michael Levin: Do you think that is part of the trauma that you mentioned that is so universal, is that because of the mismatch between that kind of mind and the neurotypical society that they're trying to embed in? If it was all, is it a stable strategy all by itself? If there was a population that was entirely that way, would that be fine or would there be issues? Is it a difference issue?
[06:42] Diana Moga: I love that question. That's not been studied enough, actually. I think there are ways to model agents interacting now. And if we could model a neurotypical agent and an autistic agent and a group, I think we would see big differences. But in general, autistic people get along better with other autistic people. There are easier ways of communicating. They function together better. And yes, it's much more nuanced than that. There are issues also with parents' expectations. Parents have a lot invested in their children, specifically in our capitalistic society. The way IQ developed, the way testing developed, the way school testing developed was all based on eugenics and generating productive members of society that can make money. So we're all very concerned about that. In other societies, it's not a problem if the child lives at home for the rest of their lives and helps to milk the cows. So parents have many expectations and much anxiety. When that two-year-old is not talking or walking, if they're on a different developmental trajectory and may talk at four but are just not talking at two because there's so much sensation and patterns and sounds to enjoy, the parents freak out. Then you start to have ABA and you start to have "now you need to smile." I'm seeing somebody now. I have records of reports. He's not smiling, not smiling today. Today was a good day. They smiled, they followed the rules. They're disobedient, they get punished harshly. There's a constant feeling of "you're wrong, you're wrong, you're wrong." That's not to say that autism is a big spectrum; it can come with inability to speak, inability to take care of oneself, it can come with profound deficits and disabilities, but so can neurotypicals; we can all have intellectual disability. I don't think that's what defines autism itself.
[08:37] Michael Levin: Is it more common in males? If so, do you have any idea why?
[08:43] Diana Moga: So this is an amazing story. There was a Russian psychiatrist in the 1920s, probably a psychoanalyst. She described in this hospital a group of boys and a group of girls with what exactly Asperger's described 20 years later. She said, in the boys, there's much more stereotypy, repetitive movements. There are more very abstract obsessions. There's a much greater complete lack of emotion. The girls tend to be moody, emotional. They have big reactions and big tantrums. They're disobedient. They hate following the rules. They're basically wild. They're different from the boys; they're less likely to have atypical interests. The interests are more typical: social interests, books, and they have much bigger emotions. She basically defined the female autistic phenotype, but she was completely ignored because she was a woman. Then Asperger and Kanner came, and the majority of their patients were boys. So all the studies were developed to study the boy phenotype. Therefore you confirm there are many more men than women, or boys than girls, but that's because that's how your questions were set up. And so now they're rediscovering the female autistic phenotype. It's much more equal than was thought. It used to be thought to be four to one. I don't think that. And by the way, some men have the female autistic phenotype, because brains aren't entirely female or entirely male.
[10:32] Michael Levin: Are there models of it, either animal models or AI kinds of models? For purposes of experiments and so on, do you think there are decent models for this?
[10:48] Diana Moga: I think there are partial models. I think Alexei can speak more to this. For example, there's a knockout mouse where they affect the thalamus and differences in sensory gating — basically more bottom-up sensory information coming in, less gating. And that's a model a lot of us are simpatico with, that our brain doesn't curate information quite as much, we just let a lot more in. Then it's harder to process all of that. Some things might be slower, but we're also going to see details that other people don't see. That mouse model develops seizures, cerebellar ataxia, certain kinds of things seen in some autistic kids, but not all. There are a lot of syndromes that look like autism. A lot of different diagnoses are combined. It's a huge umbrella. There's not really one autism. There are a lot of different developmental differences that come up with a social deficit or social disability in our world and therefore are called autism. The FEP model is that it's essentially not enough prediction and too much sensory precision. Alexei understands the details of that better than I do. That's another model. There was a movement-based model coming from Northern Europe; a center has developed a lot of models of motor differences. The emotions are more intense, less coordinated, and that creates friction in social interactions. The kid is in another child's space, or their whole mind gets organized based on a motor system that's too intense. There are ways of thinking about it as lack of cohesion or integration; early studies showed increased connectivity in local regions and decreased connectivity across distal regions. There are models of lack of cohesion or integration of different modalities of sensation, motor, speech, et cetera. I don't think it's been modeled by computers, but that's a neuroscientific model. Alexei, we've been listing some. Are any others coming to mind?
[13:14] Alexey Tolchinsky: First of all, very grateful that Mike and Chris you are joining in this effort because what I thought we could do is I learned so much from Diana and I've done both psych evaluations and treated in therapy patients with high-functioning autism. I haven't worked with low-functioning autistic patients. I am very grateful, Diana, because I learned so much and I was driven by some stereotypes and biases, theory of mind issue or social deficit. And now we're finding more nuance that perhaps there's a deficit of fluid or spontaneous theory of mind, but it's not a global issue. Boys and girls problem and the consequences of trauma and disproportionately how much children in the autistic community get bullied in school; they were targeted. If there's bullies, they pick the neurodiverse kids. But what I thought we could do is I asked Diana to write phenomenological patterns of what it sort of feels like by the patients. We just wrote them as a list without trying to infer why, how, or draw connections. We have a list now which I can read briefly, just the list of maybe 13 patterns now. Some are pediatric. We've seen them very early on at 12 months. Some are more later on, and they come together in interesting ways. I see connections, which is why I thought about you, Mike, and you, Chris, because you're fantastic at doing scale traveling from lower scales to higher scales in space and time, and we need a biologist and computer science and mathematical and physics mind to see how we could try to connect the dots here. There have been prominent theories of autism, Frith and Frith in England about the weakness of central coherence and other ones, but they don't do enough. They describe a part. That's one component why I thought it would be fantastic to hear your thoughts. Another one is treatment, because what Diana is doing with ketamine — I see inflexibility and difficulty to change; something is very hard in regular treatment. When Diana and I talked, one of the mechanisms of plasticity in ketamine is mTOR, and we have talked so much about mTOR, Mike, in your work on stress — adaptive and maladaptive — and also in plasticity; that's another thing. There in that regard we could do experiments. In fact, I may have sent some. Both biological experiments with the specific underlying mechanisms of that plasticity, and ketamine or MDMA, but we could approach mTOR through 5HT or from nutrition and other things and indeed do animal experiments. I can just read you the list of patterns to see how it sounds.
[16:13] Alexey Tolchinsky: Is that okay? Sure. Pattern one is challenges with fluent or spontaneous theory of mind tasks when a person is in the state of higher sensory load while having no such challenges in the state of low load. The second pattern is over incorporation, attending closely, paying much attention to many stimuli in the environment and possible challenges with deprioritizing some stimuli and focusing attention on higher priority ones. Pattern #3 is not prioritizing social stimuli over other ones. Pattern 4 is difficulty disengaging or shifting attention away from, and related heightened ability to hyperfocus on something. Some people may describe it as challenges with attentional flexibility. Pattern five is difficulty with joint attention with a caregiver, which affects learning and parenting. This we see very early. Pattern 6 is again weak central coherence. Individuals with autism tend to focus on details rather than see a big-picture gestalt. That's a difficult part to go into the higher abstraction level and to conceptualize. Pattern 7 is what we call concreteness, difficulty in processing more abstract or metaphorical content from neurotypical individuals. Pattern 8 is a style of doing one thing at a time. These are, again, differences in how neurotypicals process things, who may more flexibly think about several things at the same time. Pattern 9 is challenges with transitions and changes in childhood, such as going to recess after class. Pattern 10 is the experience of struggling to connect different modalities such as sensory exteroceptive modalities, interoceptive data, and proprioceptive data. Diana mentioned it. I've added a few from pediatric specialist Jodi Bleiberg. This is what we observe in children as well: differences in cognitive flexibility compared to neurotypical kids. They tend to be a bit more black and white, rule-oriented, and staunchly logical. Pattern 12 is proclivity to interpret or explain emotions or social reactions from a logical standpoint. Some might say that it's a proclivity to be right over being together with a person. The 13th one is a bit more coarse-grained or logical perception of emotional states. They can identify "angry," but shades of gray like "irritated," "irritable," or "annoyed" may be more difficult. So this is a long list, but how does it sound to you?
[19:13] Diana Moga: Coordination in motor issues, which I think we have to add because it's described by every study.
[19:23] Alexey Tolchinsky: Very interesting.
[19:24] Chris Fields: Can I ask a meta question, you've both used the phrase neurotypical, which occurs throughout the literature, my question is, what do you see as the range of variation in the population that's considered neurotypical? And how large is that range of variation compared to both what you would consider the center point, if that's even definable, between the neurotypical population and the autistic population? And also, how large is that range of variation compared to the range of variation that you see in the population that's considered autistic? So how easy is it to separate these two populations?
[20:43] Diana Moga: So what Francesca Hupp's research shows is that there's these three buckets that go together, communication, social, cognitive, and motor sensory, or however she divides it, they tend to travel in families. So they'll see traits of a certain cognitive style traveling in one family, and they'll see traits of a social emotional style in another family, and then they'll see traits of motor sensory issues in another. When these buckets come together, you get an autistic kid, but you can see in their grandparents and their genealogy traits. So these traits are human traits. They're part of the population. It's just that when you combine them together, it's treated as a syndrome. You get a syndrome of a number of traits coming together. So that means the variability is huge and it's hard to separate. I've worked in camps with autistic kids before and I've interacted with autistics, but I don't treat autistics with high service needs. I have autistic adolescents to people in their 70s. I've seen the range for some years now. The saying is "you've seen one autistic" — they're just as different from each other as neurotypicals are from each other. They all have character. We all have character. There are definitely different types. There's a more social type that's the ADHD; we call it ADHD and autism together because the ADHD piece is seeking novelty, chaos, and excitement all the time. The autism is needing consistency, calm, and repetitive behaviors so that you know what's going on because it's overwhelming. If you put them both together you get very excitable social autistics who then need a lot of time to recover because they're completely burnt out. So that's a type that I see. There are definitely different little types, but it's very variable. The DSM criteria that we have do distinguish an autistic person from a neurotypical person, but you can't see it. People really try to determine if they look autistic or not. You can't see it because there's also high masking, which is the way that the person mimics; there's a lot of mimicking and mirroring social interactions in girls, and they learn how to be excellent actresses. If you ask them how they do it, it's a very intentional way of doing it. So that's one big difference: the autistics will look neurotypical and do the neurotypical things, but it's all cognitive. It's all thought through. They initiate the interaction and plan to copy what the other does, or if they smile, they'll smile too, whereas it's much more intuitive for a neurotypical person. I think all of it has to do with a bigger cognitive load, essentially. You can distinguish them, but psychometrically the actual metrics are hard, because the ADOS misses a lot of autistic women. I have a very impaired autistic woman who was not picked up by the ADOS. There's not a good standard to tell the difference all the time. I'm not aware of any MRIs or EEGs or anything that predict; the medians are different, as in anything else, but you can't separate out individuals.
[24:15] Alexey Tolchinsky: A little bit to what Diana said, Chris, so first of all, recently I've heard people say something like, oh, it's a spectrum, therefore we're all on the spectrum. Individuals in the autism community take a big issue with that. They're saying, "No, you're not; just don't do that." Now, it may not be easy to define. We have a whole methodology of neuropsychological testing. I spoke recently with the top neuropsychologist in our area, Jodi Bleiberg, who's fantastic. She gravitates slightly away from ADOS because it's too simple. Many things are very operationalized, manualized. It's just one of the tools we use. It's a play-based assessment of a child, and it is normed, Chris, from 12 months. So right now, the kid may get diagnosed at 12 months. To answer your question with a little data, there are studies that are very interesting on eye tracking in infants. Individuals with autism tend, on eye tracking, to look at mom less. Then when parenting starts, the big thing in parenting is joint attention, where mommy says, "Look over here." That is also a difference between an infant and a mom in a child with autism and a child without. It's not just vision; now they're doing studies on audition, mom's voice, but again, paying attention, because this is an absolutely crucial interaction. We have this fantastic psychologist, researcher and analyst in New York City, Beatriz Beebe, and she studies this complex dance between an infant and a mom. It works differently when the child has autism. Then it leads to other consequences when they're four or five in preschool and kindergarten. It may not answer your question fully, but there is a difference. We're approaching how to get better in doing it. The tools that we have are imperfect, but eye tracking shows some promise. With adults, if you walk into a room and there's a painting with a social scene, neurotypicals tend to follow the line of sight. They look at this guy who's looking at this woman, and this woman is looking at that woman. A person with autism may start examining the pattern on the couch.
[26:47] Michael Levin: It sounds like a little bit of the frame problem, Chris.
[26:52] Chris Fields: In the sense that the frame problem is basically a boundary drawing problem, yes.
[27:07] Michael Levin: Well, in terms of...
[27:10] Chris Fields: When listening to or reading the set of typical patterns of behavior, none of those sound very atypical to me. My question is, how atypical are these atypical patterns? If you were to take one of these and ask, say, 10,000 people at random, would you get a bimodal distribution? Would you get something that looked like a normal distribution with a long tail on one side? How atypical are we talking here? Maybe that's not an important question at this point.
[28:21] Alexey Tolchinsky: The issue is also a quantitative approach. I will tell you, though, that in my much more limited experience than Diana, when I did school visits as part of the evaluation, the kid stands out. When you see elementary school kids, the neurotypical ones have a big range of emotions. There's this and that and the other, and you see a more constrained range where it was anger, happy, and sometimes they express it in something said happened and they're smiling, so the kids stand out sometimes. But again, because we're talking about the spectrum and there's a level of functioning, when it's low-functioning autism, it's going to stand out very much. When it's high functioning, it stands out differently. But you can qualitatively, and I realize I'm saying something contrary to what Diana, but I'm saying early on, pediatrically, in my experience, I saw the difference. And again, if you have stereotypy and repeated movements like rocking and other things, then it stands out quite a bit. Sometimes you see that in perhaps slightly lower-functioning cases.
[29:30] Diana Moga: Chris, I think you bring a really good point, though, because I don't think it's that atypical, except that our society has become so specialized and so hyper-social and so overstimulating, most of us would not have gotten picked out. My grandfather loved classical music and worked as an editor and had his obsessions and his little world and you couldn't change a light bulb or drive a car, but it didn't matter. He was perfect. Nobody would have ever called him autistic. But today's standards, probably he would be because he would need to buy things online and communicate with a bazillion people if he tries to buy something or have a simple interaction. So I think it's just a tail end of the population that also is getting left out of the game in some ways and getting very bullied in other ways. But sometimes it's Bill Gates and Elon Musk, and girls' repetitive movements could be picking their nails and curling their hair. Nobody sees that. But you don't have any friends. And so that's the cumulative not having any friends, struggling to date, struggling to become independent, not understanding why things are happening, why people are dropping you, or why you're not part of a crowd. Or you're smart enough, but you can't get a mentor and your projects don't work as well because people get turned off by you, but you have no idea why. So it's this cumulative experience of being on the tail end or on the margin, but not really understanding why you are. And then of course with trauma, the best predictor of not developing PTSD is social support. So now once you get hit by trauma and you don't have the social support, that's it.
[31:23] Chris Fields: Okay. Thank you.
[31:25] Michael Levin: If we think about the different axes on which you pick whatever the most important axes are on which this population is different, is it possible to go in the opposite direction? Is it conceivable, or in fact, is there a real counterpart that basically is to neurotypical what neurotypical is to autistic — that goes in the opposite direction? Does that exist?
[31:53] Diana Moga: Good question.
[31:56] Chris Fields: There's that old paper by Crespi and Badcock from long ago in Behavioral and Brain Sciences where they argued that autism and psychosis were two ends of the spectrum where neurotypicals were in the middle. And I think that's largely been discounted now. I never hear people talking about that, although I'm not all that familiar with the literature. That was at least an early proposal in this.
[32:24] Diana Moga: That was Simon Baron-Cohen's book too. Simon Baron-Cohen's theory is that psychopaths have high cognitive empathy. They can understand. They have very good theory of mind. They understand exactly what's going on in the mind of the other. They have no affective empathy, so they don't feel any of it. They couldn't care less, and they can manipulate people. Autistics have the opposite. We get hit by a wave of emotion. We have very high nociception, so we really feel what a little bug is feeling, or an animal, or a child, or a human. But then there's so much intense stimulation, it's hard to quickly come up with possibilities about what's going on. We consider too many possibilities. Anything could be possible. We can come up with 10 stories, so we can't intuitively quickly act on, this is what's going on, this is what they need sometimes. We have high affective empathy, but sometimes low cognitive empathy. He said we're on the opposite end of the spectrum. But humans are not that simple. I would say politicians are the opposite: the social maneuvers, the social movers and shakers.
[33:30] Chris Fields: Just meaning Newton probably are psychopaths.
[33:33] Alexey Tolchinsky: Many are. With Mike's excellent question, if we take Isaac Newton — no friends, no lovers, no wife — physics. One interest, narrow interest, intense, and that's it. Immanuel Kant or Grigori Perelmann, who proved the Poincaré hypothesis. There's just mathematics. And in kids, we see that there's this Lego and he is like rocket scientist in Lego, but there's nothing else. And then it moves to dragons and there's encyclopedic knowledge of dragons and there's nothing else, hyper-focused in one narrow thing. So perhaps it's just like Diana Express, when somebody is a mile wide and an inch deep and they're very social, hyper-social, center of attention, everything, but you ask them about mathematics and they know this much. Maybe, but I can see both in this domain: somebody is very different from that, but we don't tend to. And again, it's a matter of fit and adaptation. If the story of Sherlock Holmes, for example, he sounds slightly Asperger-ish, but these individuals make for exceptional forensic investigators because they notice things that a very social-oriented person doesn't notice, like whatever play from Staffordshire on your shoes or something. But then the other ones are really preoccupied with social context and they don't look at that. I don't know if that answers your questions.
[35:04] Diana Moga: Another axis, because you're talking about broad versus vertical deep. mTOR is the regulator of resilience versus plasticity. When is it time to rebuild your organelles and reinforce the membrane versus let's change and be plastic. My intuitive sense from what I read is autistics are actually hyperplastic. There's a high coincidence of loose joints too. There's sometimes a physical hyperplasticity where a lot of us are double jointed. EDS (Ehlers-Danlos syndrome): over 50% of autistics have this. So we're put together in this kind of loose way. That's the word: loose central, weak central coherence. So the rigidity is required to hold us together. So if you have a person who internally is very rigid, in the sense of I know who I am, I know what I want, I know what I'm going to do about it, that's the opposite, because we're indecisive. We could be anything, we could morph into anything, we could take on anything, and it gets too much and then we fall apart.
[36:18] Michael Levin: That's super interesting. That reminds me of Bongaard and Pfeiffer's morphological computation. This notion that you can't separate the controller from the body, that a lot of the cognition is actually happening in the body. And the plasticity is an issue both mentally and physically. That's incredibly interesting.
[36:45] Diana Moga: That was a long-standing theory that the mind is put together from a body metaphor that's very loose and plastic.
[36:53] Michael Levin: So I wonder, as we flesh out some of the behavioral studies of xenobots and anthrobots and all these things, which we are doing. We're setting up all kinds of behavioral tests; we can quite readily modulate tissue stiffness and actually see if there is an effect. I know what's going to happen. People are going to look at those papers and they're going to say, "Well, that's just physics." They're going to say, "You've made it more squishy and so now it tends to go this way." That's why everybody always says it's just physics. But I think it's an interesting idea to connect those.
[37:31] Diana Moga: I think that we're a different pattern. And if it doesn't become reified as the right pattern and the wrong pattern, that's why I would love to see modeling of agents interacting together, because if you make somebody looser, they might end up needing to be more separated from the group. I love your experiment of stress sharing. That ability of the cell to communicate to the others, it's distressed because it belongs in the head, not the tail or the arm or the limb, and all the cells just move around for it. If we could have that, autistics could communicate clearly, then if other people accommodated, we could all have more stress levels. We're so individualistic.
[38:21] Michael Levin: Go ahead, Alexia. I was just going to say that the ketamine, it's not obvious to me in the end what we are and aren't going to be able to get our hands on, because obviously there's a lot of access issues to some of these compounds. But we're working on it, and I'm very interested in trying some of these things in morphogenesis assays, what does it look like to be on that spectrum in gene expression space? Are there a set of diseases actually that are because of those kinds of trade-offs in the way that you would process, let's say, chemical signals, for cells and things like that?
[38:59] Diana Moga: There's a lot of immune issues; they call it mast cell degranulation syndrome. A lot of inflammatory and immune issues also in autistics, very prevalent IBS. So your immune system is more sensitive too.
[39:14] Michael Levin: If you get a chance after, at some point, if you want to send me any of those papers that describe some of that stuff, I used to have my students do this by hand, but then we made a tool, and it's on the web to do this, where you take a neuroscience paper and you do a find-replace. Everywhere it says neuron, you say cell. If it says millisecond, you say minutes. Most of the time you get yourself a developmental biology paper. It doesn't take very much to pivot it and everything works out. Thomas O'Brien has added to that tool: you can map things into economics; there's a whole dropdown of disciplines you can map into. It would be interesting to take some of the descriptions that you've put out today and turn them into other spaces. What does that look like as a developmental biology paper, as an immunology paper, as a signaling paper? Then go back, because as you're saying that there are immunology aspects of this that have been characterized, treat that as the ground truth and come back to say, were we able to recover any of those actual facts, any of those observations? That would be really fun.
[40:37] Chris Fields: I think another interesting exercise might be to go down this list of behavioral patterns and, keying off something you said, Diana, suppose you had some generic organism that behaved in this way or exhibited this pattern. What would the right kind of environment for that organism be? Think about it from the environmental side of the question as well as the organism side of the question.
[41:23] Michael Levin: Yeah.
[41:26] Diana Moga: In humans, phenomenologists and embodied cognitive philosophers who are writing and thinking about this very much in terms of how the interactions need to happen differently.
[41:40] Chris Fields: If you could share some of that, some pointers to that literature, that can be brilliant.
[41:48] Diana Moga: Hannah Jager is one of the big. She's in Dyager. I can't remember where she is. Nordic country. I'm happy to send it.
[41:58] Alexey Tolchinsky: What we did was assemble a library of papers and continued to populate it. That's already ready on Google Drive. We sent access to you, Mike and Chris. You can launch the bot to try to reclassify neurons into something else. It's ready. Another thing is in terms of environment. There's a famous animal researcher, Temple Grandin, who is a big name in the autism community. The interesting part about her is she has a hugging machine at home made of pelts. She has a remote control that hugs her with precisely the intensity or the pressure that she wants. Her science is the environment in which she feels good and well. Sometimes there are books by individuals with autism such as "My Life with Asperger's" by Robinson or "Born on a Blue Day" by Daniel Tammet. Robinson was into radio electronics and mechanical things; give him that and he's happy. He's married now, and it's a fascinating book. That is when the environment matches your prediction: there's not a lot of change and you feel contained. I am trying to answer, Chris, your question, but we do have some qualitative narrative human accounts of when the person feels well enough, adapted, adjusted. We have very sad stories where society is trying to change you and fix you, particularly in ABA, where we're going to coach you out of it or fix you. It doesn't end well; they try to make you fit our expectations.
[43:47] Diana Moga: Dance. I saw one girl who started dance therapy at the age of three for severe tantrums. She was never diagnosed, but the parents just had an intuitive way with her of what's going to help and what's going to calm down, painting, being very receptive to the motor sensory, the non-verbals, the way that the person is in the world, and finding creative ways and allowing that to be. She's a great dancer and the tantrum stopped. A lot of us are very intense movers. Ultramarathon runners are a lot more autistic. I do Ashtanga six days a week, yoga, swimming, intense motor things that help you feel coherent in the body and make you feel stronger mentally as well. A lot of room to play and to experiment. That's the funny thing: a lot of us autistics say that neurotypicals are very rigid because what's the problem with stimming? Why can't we not stim? Why is that an issue?
[44:51] Michael Levin: Fascinating. That sounds great. Let me take a look at the papers. I think we'll do some translation and we'll also think about some experiments that we can actually do. I think that would be really interesting. Super interesting. Thank you for this. I appreciate it a lot, and thank you for making that connection, Alexei. I learned a lot. I was really not aware of a lot of this, so that's awesome. Very interesting.
[45:26] Alexey Tolchinsky: Do you have to go, Mike, or do we have another few minutes?
[45:29] Michael Levin: 5 minutes, but let's keep going. If you guys want to keep going, we absolutely can.
[45:37] Alexey Tolchinsky: We'll end, but you have to go. Chris, you had some thoughts about dimensionality. Maybe you can say briefly what you thought after looking at the patterns, and say a little bit more about this dimensional approach you had.
[45:51] Chris Fields: One of the dimensions seems to be this context-switching dimension. And then another one seems to be this, what's called loose central coherence, but there were several representations of that in the list. I'm intrigued to hear about the physical correlates in terms of lack of tight coherence because so much of problem solving seems to be done by the motor planning system, which, if it is used to loose connections, might connect to the way problem solving works as well. I think we could pursue that kind of dimensional approach. I would think that applying a similar way of thinking to the population that counts as typical would be useful if we do that kind of dimensional way of thinking. How good are typical people at context switching? I have no idea whether that's been measured.
[47:26] Diana Moga: There's a paper that measures that.
[47:28] Chris Fields: Okay.
Diana Moga: There's a virtual reality paper where they alter the bounciness of the ball. The autistics are slower to adjust to the change in the bounciness of the ball than the neurotypicals.
[47:42] Chris Fields: Okay. So those seem like two fairly clear dimensions. The social, non-social dimension seems more difficult to me to get a handle on. But people have been trying to do that over the years without too much consistent success.
[48:10] Michael Levin: What we, and this is something that we were talking to Tom Pollack about, is we could make anthrobots from tissue samples. We have social dynamics among Xenobots and anthrobots. They do have collective behaviors. We could look at simple models of that. That's a possibility. We've got our SEMA effect. The attention thing is super interesting. We're still struggling to quantify that in some cases. I would love to know how to say, okay, here's how much attention the cell is paying to XYZ. So measurements of those are still worked out. But as far as the behaviors, we absolutely have collective behaviors that we could measure. I think some of the information theory metrics could get a handle on collectivity, on causal emergence of the group. Actually, has anybody done that in humans, watching human behaviors of autistic hybrid and neurotypical groups doing stuff and doing PID or some kind of causal emergence metric on that?
[49:31] Diana Moga: There are studies that look at groups, but I don't know if they do that specifically.
[49:34] Michael Levin: Because there's cool new math that's been developed over the last 10–15 years that basically captures the extent to which the whole is more than the parts. And so it might be really interesting to apply that math. In fact, if the data are out there, it might not even need to be new experiments. You might just be able to grab the data and we could do it. Federico computes this stuff all the time. There's a paper.
[50:03] Diana Moga: On social synchrony that's different.
[50:09] Chris Fields: It sounds like the context may be an incredibly important variable in thinking about group problem solving.
[50:18] Michael Levin: But maybe that's part of the issue that you raised, Chris, about finding the environment to match the kind of mind: you could imagine, okay, here's my data set. Now, what would the environment have to have been like to raise the FID to whatever level? And so then you could certainly do simulations. You've got your data, keep that fixed. Here's the behaviors. That's how it's going to be. Now, the question is, what do you need to put around it to make this coherent? I think that would be a super cool study. That would be really interesting. Let's look at the data. And I wonder, too, if we look at—if we build classifiers around that data, could we say that, OK, here's an evolutionary process of a search for something? Is it some kind of evolutionary track? We could say, does that have features—what does a more autistic looking evolutionary track look like? So I was exploring this environment. I did or did not find what I was looking for. I got stuck on some local maximum. Could there be one? Once we're looking at behavioral data, I'm motivated to track it across various really weird problem spaces. We might find that this kind of spectrum actually has uses well beyond traditional behavior.
[51:50] Diana Moga: That's part of what confounds researchers and studies: development can look so different. Somebody can start by looking very autistic, nonverbal and can end up being Asperger's and writing books. It doesn't seem there's a good way to predict how somebody is going to end up. If you catch it at different timelines, it looks very different.
[52:13] Chris Fields: Yeah. Amazing.
