Dr. Daniel Toker (5:32)

Thank you so much.

Dr. Samantha Yamin (5:33)

You've been doing all sorts of really cool stuff, so I want to get into some of your research. But first, where or how is consciousness controlled in the brain? Like, is there a consciousness spot?

Dr. Daniel Toker (5:43)

It looks like there's not really a single consciousness spot in the brain with some potential caveats. So there are some highly vulnerable areas where if you damage those select spots, you will become unconscious or go into a coma. That doesn't necessarily mean that that's where consciousness lives. That just means that that's like a crucial bottleneck probably for these larger networks that are involved in it.

Dr. Samantha Yamin (6:09)

Can we even measure it? Can you detect when someone's in different states of consciousness, like besides sleep?

Dr. Daniel Toker (6:16)

So there is a lot of work trying to sort of non invasively detect consciousness, which is interesting, but also really clinically important because you have a lot of patients who might present as if they're, you know, not conscious or unresponsive, but it could be that they're just not able to report on what they're feeling or seeing. So there's something like locked in syndrome, where they look like they're vegetative, but they're actually fully aware. And so if the patient can't tell you if they're conscious, how do we know if they are and if they can hear us? So, for example, some patients, you can ask them, hey, imagine playing tennis or something. And. And so part of the brain called the premotor area, which is involved in motor planning. So if someone told me or you this, like, that area would light up because we're imagining the sort of movements that we're gonna go through. And for most vegetative patients, or if a patient is actually vegetative, nothing happens. But a small subset of patients who can't respond, that part of their brain will light up, which tells you that they can hear you and they can do what you're asking.

Dr. Samantha Yamin (7:17)

Is there like a pretty concrete definition for consciousness, like a lack of responsiveness, for example?

Dr. Daniel Toker (7:23)

Probably the gold standard for disorders of consciousness Is this behavioral test called the Coma Recovery Scale Revised. And that tracks things like, you know, can they follow something with their eyes and can they do basic commands? And it's obviously not perfect, but it's still the best we have.

Dr. Samantha Yamin (7:41)

Interesting. Okay, I want to dig into your research now because one of the many things that you do is growing organoids in the lab with brain cells and tissue. So can you share for everyone, like, what is a human brain organoid and you know, what is the strength and weakness of it as a model? Like, are they conscious? Should we be concerned about that ethically? Where, where are the lines there?

Dr. Daniel Toker (8:04)

So a brain organoid is basically this thing that we grow out of stem cells. So stem cells we can now induce. So we can take your skin cells or your, your blood cells and we can turn those into stem cells and then we just give them factors that coax them into becoming brain cells and we just sort of grow them in a clump. And then depending on what factors we give them, they can model different parts of the brain. And so some people will use this term like lab grown mini brains, which most people don't like because they're not really brains in a dish. They're just kind of brain like tissue in a dish. Right. And so there are now ways of growing certain types of brain tissue in a dish where they start to create electrical oscillations. So, you know, in a human, you typically measure an eeg, but if you can access actual brain tissue, it's what we would call a local field potential. And certain types of brain organoids will generate these electric waves that kind of resemble our brain waves. And that could be really useful for studying things like epilepsy or coma, which have these very well characterized changes in our brain waves. We take skin cells from someone with epilepsy, then their organoids will be, will have certain features that you'd see in an epileptic brain, so they're more electrically active. You'll have a bunch of neurons firing together. So you get these big spikes of electric waves like you would do in an actual patient. And then what's helpful is you can maybe see what drugs might help this brain behave more normally, or what is happening at the circuit level to drive these changes.

Dr. Samantha Yamin (9:46)

People who have concerns about these potentially being sentient or ethical concerns, what do you see as the kind of clear line or how do you reconcile that?

Dr. Daniel Toker (9:58)

Yeah, I think things start to get murkier when you give the organoids sensory input, which there are people doing. You can have. There's that Paper where organoids learn to play pong. I think if we're starting to allow them to interact with their environment and they can start learning, that's when I think things get a little murkier.

Dr. Samantha Yamin (10:22)

Important thing to keep in mind, but for the purpose of your work, you're mostly looking at electrical activity to figure out how cells fire differently. Now, outside of the dish, you have a recent preprint using different AI and machine learning models to produce biologically realistic simulations of both conscious and comatose brains in humans and other species. I'm curious, like, why are you making these in silico or computer models? And how good are they at modeling consciousness potentially?

Dr. Daniel Toker (10:52)

As, you know, a lot of biology and neuroscience research depends on animal models. And most animals can't really go into a coma. I mean, some can, but. So, for example, pigs can go into a coma. A rat can't. It'll either. If you give it a severe brain injury, it either dies or wakes up. And so we can't really model these disorders or diseases. You can with epilepsy, but, you know, coma, you can't. And so we're sort of limited to what you can learn from an MRI or a PET scanner or autopsy. So we can't really dig into these brains to see what's going on. And so with this work, we thought, what if we develop a whole brain model that can accurately capture what's happening in these different states and then dig into the model to see what changes there to drive this coma like behavior? And can we then verify that in real brains? But, for example, you know, there's this pathway through the basal ganglia, which we normally think of as more involving motor behavior. There have been some ideas about how they might drive coma, but there's certain sub pathways within that. And the AI was saying, hey, I think this particular one is the more relevant one to look at. And then. So we looked at actual brain scans. Where you look at it was a diffusion tensor imaging scan. So this lets you look at bundles of connections in the brain. And it did actually turn out that this specific track of connections that the AI was pinpointing did seem to be more selectively damaged in these patients. So there's some connection back to real data.

Dr. Samantha Yamin (12:34)

Oh, cool. So you're feeding it data from humans, and you're seeing if it can pick up patterns for different states of consciousness that, you know, because you know what the humans were experiencing. And then you could give it simulated data and see if it could start to identify based on the training on the human Data.

Dr. Daniel Toker (12:50)

Yeah.

Dr. Samantha Yamin (12:50)

Oh, my gosh. I got it. Wow, that's super cool. Yeah. And you could see how that'd be useful too, like even in real time clinical settings, to detect maybe how a patient's faring in a given moment if they're not being monitored 247 with an actual person.

Dr. Daniel Toker (13:06)

Yeah, exactly. I mean, you could just record their eeg, feed it to the AI. The AI can output how awake they are.

Dr. Samantha Yamin (13:14)

Okay, last, last thing, I just want to ask you. What drew you to neuroscience? And especially because you have a bit of a unique route. You went the route of, like, math and computation, and clearly you're integrating all these things in your work. But was there a certain draw or something that brought you on this path?

Dr. Daniel Toker (13:31)

I think I first started thinking about it in 10th grade anatomy and physiology, where we just started learning about, like, here are neurons and here are different parts of the brain. I just was sitting there in class and it just kind of hit me. Oh, my God. All my conscious experience comes from chemical reactions. What? I never stopped thinking about it. I think historically in consciousness research, there's been a lot of, like you said, the really high level stuff like FMRI and eeg, like, how's the entire brain acting? And, you know, how is glucose metabolism and the whole brain going up or down? But we don't really know what's happening at the circuit level. In things like coma, we do for seizures at least. So that's a case where people, people have done work at all the scales, from the EEG down to the single cells, but not in coma, because we don't really have those animal models. So part of my sort of dream with making these organoid models, if we can get them to look like they're in a coma like state, we can start figuring out at the level of single cells what's going on. And if we can figure that out, we can find targets for new medicines.

Dr. Samantha Yamin (14:40)

That's the real goal of neuroscience, is to be able to connect these big, complicated things, like at the smallest of levels. Dr. Daniel Toker is a neuroscientist at UCLA. You can find him at the Brain scientist on Instagram and TikTok. He's so much fun to learn from and follow, so be sure to check him out online. Thank you so much for being on our show, Daniel.

Dr. Daniel Toker (14:58)

Thank you for having me.

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As kids, we're taught about the five senses. Touch, taste, seeing, hearing, and smelling. But I want you to try and experiment for a second. Close your eyes, reach your arms out wide, and now with your thumb, touch the tip of your nose. Did you get it on the first try? If you did, that's because most of us have an awareness of how our bodies are positioned in space. But what sense allows us to do that? Well, it's not one of the traditional five. It's a different one called proprioception. And our ability to understand proprioception tells us that maybe the five senses aren't that cut and dry. Those familiar five senses gather information about the external world, but there's also senses that track what's going on internally. These are called interoceptive senses, and they gather data that we don't consciously think about. Things like heartbeat or blood pressure. Other interoceptive triggers are harder to ignore, like hunger or needing to pee. It makes sense if you think about it. If our brains are actively processing every single signal within our bodies, it would be a total information overload. But those senses still exist. So how many senses are there really? Well, it sort of depends on who you ask. Some say the five, but others say we have 10 or even 20 or even 30 more senses. The answer really depends on how you define a sense. You could go strictly by the specific sensory receptors in our bodies, like those for taste, vision. Other people argue you define a sense at the level of the brain. Then you might include our sense of time, our awareness of where our body is in space, or even learned skills like echolocation. It all shows that five senses is more of a simplification than the whole story. The echolocation is an interesting one because it relies both on hearing and a learned skill. The lines become even more blurred when you think about people who have conditions like synesthesia, where the stimulation of one sense triggers a response in another sense. People with synesthesia can see music or taste colors. Imagine listening to Beyonce and being able to see her songs as different colors, as muddied as the waters may seem. When it comes to understanding the senses, it's a really important field of study. Looking further into proprioception, for example, can have huge breakthroughs in treating pain or building better prosthetics for amputees because we can better understand how our internal receptors like pain communicate with our brains. While we're still debating on the actual number of senses the human body has, I'm betting on there being more than five for Warner Bros. Discovery Curiosity Weekly is produced by the team at Wheelhouse DNA. The senior producer and editorial correspondent is Teresa Carey, our producer is Chiara Noni, our audio engineer is Nick Kharisimi and head of Production for Wheelhouse DNA is Cassie Berman. And I'm Dr. Samantha Yamin. Thanks for listening.

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