 Because I'm studying the limbic system, the amygdala and all these emotion-related areas, it was a natural outgrowth of that to start talking about disorders in these models. So it's not just about successful filtering, but also what can go wrong. There's many ways that things can go wrong. And that allows us to not just ask what are the correlates, like which area is involved, but why. So in the case of schizophrenia, it's again this circuit involving the TR and this thin layer of inhibitory neurons and the thalamus and the cortex. So we were just focusing on what else we could say about this three-area circuit. It's a generic circuit, so for different systems you have the same kind of motif. We call it a circuit motif. So schizophrenia is a very complicated disorder and no one has really found a definitive cause or even a definitive correlate. But in recent years, one line of research experimentalists have uncovered is dysfunctional inhibition. So there's local inhibition in the cortex and tamping things down. Then there's the TR in itself, which has been linked with schizophrenia. So we thought let's look at this circuit and see what it can do and what can go wrong. So when you're making a computational model, you need to fix a behavior that is tractable. Modeling hallucinations would be cool, but it's very difficult because we really don't understand how language is generated. So getting to that is too complicated. So what we found, I was quite intrigued to learn that a few years ago that one of the most readily identifiable symptoms of schizophrenia is disordered eye movements. So schizophrenia patients and sometimes their close relatives have an inability to fix their eyes on a target. And for instance, you could have a dot on a screen that's moving around and healthy controls. They can follow along that dot just fine, going in a figure of eight, for instance. Whereas with a schizophrenia patient, their eyes will often be quite erratic. And there was a paper showing that a machine learning method involving a couple of eye movement tasks just using those could tell schizophrenia patients and their close relatives from controls with something like above 95% accuracy. So it's a diagnostic symptom, very useful for at-risk populations and for the patients themselves. And so the question is, well, what's producing this symptom and might that shed light on other symptoms? So I set up a circuit involving a simplified version of the three brain agents, Cortex, TRN, Thalamus. And I made a simple eye tracking model that uses this kind of circuit to maintain a target at the center of attention. And what we saw is that disrupting a couple of different classes of inhibition could produce this erratic behavior. And so that's something that experimentalists can now maybe work with. We showed that different disruptions could look vaguely similar but also have differences. So this ties into the idea that schizophrenia and potentially other disorders may not just be one disorder. They may be a family of disorders with different causes that seem outwardly similar. And I think this is very important going forward for the field. And I think the field is more and more acknowledging this. So apart from that diversity of causes story, one idea that we elaborate in the discussion section is the idea that going off track is maybe a feature of other symptoms of schizophrenia. So one symptom is having disordered thoughts. So it may be that if you can't track a dot, if that similar disruption is going on elsewhere, you're not able to follow the context-relevant set of thoughts. So the same disruption going on in an analogous circuit might prevent someone from holding on to the line of thinking and sort of jumping from one thing to the other. So it's an interesting way of looking at how a simple local circuit disruption can have these widespread effects in different systems. Okay, this example was, now I'm thinking my imagination is roaring about all these other potential diagnostic methods that don't yet exist, that we're going to be able to figure out and leverage machine learning to be able to more effectively figure it out. And then also when you're explaining this potential that something as complex as a schizophrenia could potentially be a myriad of different involvement in different brain regions. Exactly. This is very complicated. And this is all the way to when humans are even in the womb and then they're born and there's foundational infrastructures that get laid out during that time period and how that interplays with their adolescent and adult life then. Okay, I have a question as we get into depression, I want to ask about schizophrenia. I've had several conversations with people about how we may all be the spectrum of schizophrenia, potentially from a good schizophrenia to a bad, potentially schizophrenia, and what we've created with hyper realities where like a Santa Claus is kind of like a hyper reality. We've made up a story and we call it real and then some people tell their kids that that's real and there's cookies and stuff and sliding down the chimney with presents and all this kind of stuff, reindeer, etc. And then it almost gets, you know, in a sense there's these two competing realities that are then occurring. And some people even say one of the greatest measurements of intelligence is one's ability to abstractly reason multiple perspectives, multiple variables on a given issue. And so when you're doing that, what you're doing is you're trying to see how like a low socioeconomic status person sees the world, how a rich person sees the world, how someone from India, how someone from Pakistan, how someone from different countries, also different genders, different religions, how people see the world, right? So if you're trying to balance all these perspectives and see them all, so do you see kind of where I'm coming in this term and how do you feel about all of that? So I just started reading a book sort of from left field compared to the neuroscience side. It's called The Sublime Object of Psychiatry. It's a kind of a more humanities approach to schizophrenia. So it describes schizophrenia as a sublime object and what they mean by that is it, schizophrenia has been defined by various fields including biological psychiatry and psychoanalysis as sort of beyond understanding, meaning that you could maybe study it, but you could never empathize with a schizophrenia patient. It's a very strange book but very interesting because I have, you know, people can relate to this. They're like, yeah, the person when the schizophrenia patient is describing their hallucinations or their overarching world theory, you can kind of make sense of parts of it, but the whole thing you just, it's very hard to understand what's going on with that person. So if I understood what you're saying correctly, perhaps some of these people are kind of torn between so many perspectives that they end up with this mosaic idea that is a product of perspectives that don't even sit well together. It's a fun speculation, but you know when you're talking about disorders, you have to remember there's a lot of suffering involved in this. And so you wouldn't wish this on anyone, especially the psychosis side of things in catatonia. And then there's also a way to, as one potentially experiences a psychosis from this mosaic of worldviews let's say, there is a way to live with that in a gentle way, in a way that creates almost a deeper degree of empathy for different worldviews in that sense. And so although it can at times feel like it's a big taking on the burden to be able to relate to all these different worldviews, at the same time it makes one super well-rounded in that sense. So it's a good, another way to view this is just the way that we use the social media culture. Because when you take a look at people's profiles, it's only almost exclusively their best selves. And so then that becomes, you know, what's real in this sense? What is actually you? Because is you really only your photos of you looking your absolute best, traveling, having the best meals, the best people? Is it real? Yeah. So because you're definitely not posting when you feel anxiety, when you feel depressed, or when you're feeling a lack of love. So here's again this idea of what is reality and how can, how do hyper realities, how do balancing different worldviews into a large mosaic, how do these things relate to schizophrenia? It's a fascinating question if we're in a simulation or not. Yeah, these are very, very hard questions. But what you said about empathy I think can help maybe ground this in something. So I read a few years ago a fascinating paper on schizophrenia in different cultures. So I believe it was called Hearing Voices in Africa, in Ghana and China. It was an African city and an Indian city. Excuse me. And the, I discovered it through a blog called Neuroanthropology. So the point of the paper was that it's widely believed that schizophrenia is a fairly universal disorder affecting around 1% of people worldwide. But the specific manifestations of it can be quite different. So meaning the content of the hallucinations is different. So in different parts of the world, like for instance, apparently in the West and in America, a lot of the voices are potentially giving sort of violent instructions of some sort. Whereas apparently in India, the voices sometimes are a motherly voice telling you to clean up your room. So there's that difference. Then there's also the way in which society responds to the person having hallucinations. So the paper talked about how in certain tribes, they frame this having of hallucinatory voices in terms of possession. So a spirit is possessing you. And interestingly, you might think, wow, that's unscientific, it's nonsense. But this may actually help reintegrate people into society because when the person is not hearing voices or acting weird, their belief is well, they can come join work because the spirit isn't with them today. And allowing people to be in society and be a productive member of society is really important. And one of the things you read, for instance, in that book I mentioned earlier, is that schizophrenia is sometimes defined in terms of inability to contribute to useful work. So there's a capitalist element to who we decide is incapable of being useful. So the way that society responds... And in one sense, because if you give them a big paint kit. I often wonder if, this is a popular idea, that in earlier generations people who were prophets or maybe shaman might have been what we would now call schizophrenia patients. So how the culture responds is important. And also how they tell people, so for a long time in America, there was an instruction to patients to ignore the hallucinations. Whereas what you said about empathy is very relevant because some places they instruct patients to listen to their... not act on everything that the voice tells them to do if they're telling them to do things. But you could, in the spirit of empathy towards people outside, these constructed people that may exist in you are in a sense perspectives. They might not be correct or accurate, but as with most people, people just want to be heard and given some kind of consideration. You don't have to act on every piece of advice you receive, but giving them the time to be heard is a great way to diffuse frustration and tension, rather than ignoring people. So empathy towards oneself may be important too. Or one's selves. Yeah, yeah. This has been such a fascinating back and forth on schizophrenia. I really am so interested in it.