Christof Koch  
You lose almost everything. It’s a close cousin to near death experiences. You lose yourself, there’s no more you, there’s no more self, the external world totally disappears. And then people report different things. You know, sometimes it’s it’ just a feeling of ecstasy, sometimes terror, sometimes both, sometimes a light, sometimes people have some other strange what William James called ineffable experience — pretty powerful stuff.

Rachel Tompa  
That’s Christof Koch, chief scientist of the MindScope Program at the Allen Institute, describing the psychedelic called 5-MeO-DMT, also known as the toad, because it’s excreted from desert toad glands. The toad came up in the course of an interview for our last Lab Notes episode, which you can find on alleninstitute.org, or your favorite podcast platform. I was interviewing Christof about why the brain is so hard to understand and we got off on some tangents about psychedelics, consciousness, comas, and near death experiences. It was too much to pack into the last episode. But it was also too interesting to just leave on my computer, and I thought you all would like to hear it. I hope you’ll listen through to the end, because after we talked about consciousness and psychedelics, Christof got into some fascinating stuff about how we could actually put a number on consciousness in a mouse or human brain — work that’s going on right now in the laboratory.

I’m Rachel Tompa. And this is Lab Notes, a podcast from the Allen Institute.

Christof Koch  
We’ve learned vastly more over the last 10 years than ever before in the history of humanity about the brain…

Rachel Tompa
One of the best parts of my job is doing an interview like this, where I’m talking to a brilliant scientist about one topic, and then the conversation goes to a lot of different and sometimes weird places.

Christof Koch  
You know, in an engineering sense, to build brain machine interfaces. Again, this would have been impossible 50 years ago. So there’s certainly progress…

Rachel Tompa  
When Christof and I were talking about why the brain in general is so hard to understand, he said some aspects of the brain are even harder to understand than others. Consciousness, which we can define as experience — your experience both of yourself and of the world around you — is one of the hardest to pin down, he said. I asked him, so why is that?

Christof Koch  
Well, so the challenge posed by consciousness, you know, the ancient mind-body problem is that ultimately, you don’t have access to my consciousness, right? And I don’t have access to your consciosness. I don’t feel what you feel, I don’t see what you see. Although I can infer what you see, you know, because you’re looking at the Zoom box, and I see something similar and your brain is very similar to mine. And I can ask you, do you see me? Or am I frozen, right?

Rachel Tompa  
As an aside, this is something I used to agonize over as a kid. How do I know that what I see or hear is the same as what everyone else sees or hears? How do I know I’m not hallucinating, maybe just a tiny bit, or that I might be seeing colors in a different order than everyone else? This sense of possibly being more alone than I knew in my own brain just completely freaked me out.

Christof Koch  
And so in a sense, that’s the, the limits of life that I never know, I can live with somebody for 20 years, I never know what they feel about me because they can all of course fake it. And we know that people have affairs, they are undercover spies, you know, that go long term. And so you’ve, this is what makes, philosophers call this first person aspect. Science typically studies the third person aspect, you know, I can take a brain of a mouse and poke it, put it in the scanner and record from the individual neurons, etc. But consciousness is about how the system feels from the inside. So that’s always been the big, the big challenge.

Rachel Tompa  
It’s a strange quirk of being social creatures that we can’t know what it’s like to inhabit a mind that’s not our own. Even as we rely on other people for our survival, when we’re surrounded by others, we are in that sense, still completely alone. Humans have this great capacity for empathy, which is putting yourself in another’s shoes, but it’s still the shoes you imagine someone else is wearing.

Christof Koch  
However, science is up to it I believe. It has shown, so for instance, we can systematically ask people what they do. We do this it’s called psychology. It’s called sensory psychophysics. We can show people various visual stimuli and ask people what they see; we can train a monkey or even a mouse to tell us what it sees. And by and large, it agrees with what we expect from our own brain and from our own experience. Not always of course. I can have hallucinations where you’d say what what are you seeing there’s clearly no one there. But then, we know something is wrong and that the brain of the person who hallucinates is different from the brain of a person, like most of us, who doesn’t hallucinate. So, science is up to it. My brain like your brain, that relationship aspect, right? It feels like something. That’s what consciousness is. There are scientific theories of consciousness around that are being tested right now. It’s very popular — there’s this foundation that is sponsoring a so called adversarial collaboration where two different theories of consciousness are directly being tested. Some of those experiments in fact, are happening here [at the Allen Institute]. There’s a lot of excitement right now around the idea of, of studying the what’s called the neuronal footprints of consciousness.

Rachel Tompa  
The neuronal footprints of consciousness, scientists want to know what happens in our individual neurons that gives rise to consciousness. Take any experience, say the experience of eating a sweet popsicle on a hot summer day. Christof and his colleagues want to know: What are the neurons and brain circuits responsible for that conscious feeling? An even more general way to put that is, how does the physical matter of a brain give rise to non-physical feelings, to the mind? There are a few different scientific theories of consciousness that scientists are working to prove or disprove. I’m hoping we’re going to get deeper into some of those theories in a later episode. But for now, let’s just say that the theories make different predictions about what is going to happen in the brain when you or a mouse are having a conscious experience.

Christof Koch  
It’s difficult to test that but they make some very different predictions about where in the brain, the neuronal activity of consciousness is, where you can find the footprint of consciousness. Let’s see if I look at something and I can see it, where is that activity that correlates with my conscious seeing this thing? And is it in the back or in the front of the brain? What’s its timing, if I look at it shorter or longer? What is the timing of these neural footprints with respect to my own experiences? So that’s how these these two theories are being tested in, in 500 subjects using fMRI, EEG, MEG. And in these two other species, non-human primates and in mice. There are other ways of testing these theories, you know how to, for example, if you think about psychedelics, psychedelics can rapidly can rapidly, can dramatically expand your consciousness you know, if you’ve ever tripped…

Rachel Tompa  
No comment listeners.

Christof Koch  
…or it can also shrink it. You can also have this near death experience where the outside world completely disappears, your body is gone, time is gone, space can also be gone. When everything is gone, except an intense bright point of life and a feeling of ecstasy and agony, of terror and ecstasy. So we know that psychedelics can manipulate consciousness with some degree of lawfulness. So again, we can study this in animals, in mice, and also in human volunteers.

Rachel Tompa
It’s interesting, I hadn’t heard that perspective on psychedelics before that they can actually change your consciousness.

Christof Koch  
Yes, it does. So I mean, you can read the literature you can, you know, read accounts of psychedelic experience. So the classical, The Doors of Perception, Aldous Huxley, he took mescaline, but something like mescaline, your ego is reduced. But the world is still there, you’re still there, you still have your memories, etc, you can still talk etc. But then you’re primarily focused on the outside, the world becomes wonderful, you’re just looking and you’re utterly fascinated — you sort of realize this transcendence. You realize how beautiful the world truly is. And you can spend like 10 minutes just gazing at the, as I do now at Lake Washington and the way the wave moves, I can look at the tree, I can be totally captured by the transcendent beauty of the foliage, of the canopy. And so and people of course, typically feel very good under these experiences. They come back, happier, more content, less self-centered. Grateful just for being, grateful for existing, grateful for being able to experience this because we take it for granted, existence. But of course at night in deep sleep, I don’t exist. For me, I’m not there. I’m just gone in deep sleep. During anesthesia, I simply don’t exist. And of course, if I die, I also don’t exist anymore.

Rachel Tompa
The Doors of Perception is a short book written by Aldous Huxley in the 1950s about his experience taking mescaline which is the active ingredient in peyote. Huxley describes it as putting him into “a state of pure contemplation.” Let me just read you a little bit from the book where Huxley is outside and he sees a chair.

“The sun was shining and the shadows of the laths made a zebra-like pattern on the ground and across the seat and back of a garden chair. That chair — shall I ever forget it? Where the shadows fell on the canvas, stripes of a deep but glowing Indigo alternated with stripes of an incandescence, so intensely bright that it was hard to believe that they could be made of anything but blue fire. I was so completely absorbed in looking, so thunderstruck by what I actually saw that I could not be aware of anything else. It was inexpressibly wonderful, wonderful to the point almost of being terrifying. This is how one ought to see, I kept saying, this is how one ought to see, how things really are. And yet there were reservations. For if one always saw like this, one would never want to do anything else, just looking.”

I think this is a really important point about consciousness. Our brains limit our conscious perception by design to keep us focused on the important tasks of survival, and not to be lost in contemplation of flowers when a saber toothed tiger attacks. More consciousness is not necessarily a good thing.

So do different people have like different levels of consciousness? I mean, if drugs can expand or contract your consciousness, are there people who would have naturally a more expanded state of consciousness than mine?

Christof Koch  
Yes. So during the lifespan it changes. Well, it’s a good question. When were you first conscious? What was your first conscious experience? Which is different from asking, what is your earliest memory? Because of course, we all have childhood amnesia and so typically, we don’t remember things before three or four. But were you first conscious, let’s say in third trimester in your mom’s womb, or were you first conscious when you exited through the birth canal? You came into this cold, loud noise, a world with all those lights, etc. right before you weren’t aware of that. And then you cried. Was that, in fact, the first time you became conscious? Or is it a little, you know, in the next several weeks? What will happen at the other end of life, you know, as you lose consciousness for for the final time? And there’s no doubt different people will have different levels of consciousness. So for instance, when you’re, before puberty, you may have no experience of sex, you may have no experience of love, you know, romantic love and attachment. That is a great expansion of the gamut of possible experiences. Right now, suddenly, you  really greatly care about someone else in a way you didn’t do before, you have sexual feelings. When you discover you know, art, when you discover drugs, when you discover alcohol, smoking, all of those are new experiences that can in general, expand but also towards, you know, your later stage of life, for example when you get dementia, that can also shrink what you’re conscious of. Yeah, so I think it can differ, just like other traits, like intelligence, or emotional intelligence, etc, can vary across people and across species.

Rachel Tompa  
At this point in our conversation, I asked Christof if there was anything else he wanted to talk about — a standard closing question in any interview. And that’s when he told me about this really cool research underway at the Institute and elsewhere.

Christof Koch  
I’m clearly as you can tell, passionate about this about this subject and the progress. OK. Let me finish off by talking about one particular experiment that we’re doing here that has direct relevance. So what I and some colleagues of mine are trying to build is a conscious meter. Okay. This will be the first practical tool that comes out of the ancient mind-body problem that goes back at least you know, you can read Aristotle on the psyche, De Anima. And he talks about consciousness. This is 2300 years ago, okay? It’s been primarily philosophy. But now it’s a term for scientists to study it. And we want to build a conscious meter. What is this device? This device is a clinically useful device that would test in patients, either anesthetized patients or patients with so-called disorders of consciousness. So these are typically patients that are in what’s called a vegetative state, sometimes also known as behavioral unresponsive state.

Rachel Tompa  
One of the most famous cases was Terry Schiavo. This was a young woman who had a heart attack in 1990 and was left unconscious. She was found not breathing and with no pulse. She was eventually resuscitated but had severe brain damage from the lack of oxygen and had no consistent responses to external stimuli, what’s known as a persistent vegetative state. Basically, there was no hope that she’d come back to consciousness. Her husband, who was her legal guardian, wanted to remove her feeding tube after several years, when it was clear she wasn’t going to recover. But her parents, who were very religious, took the case to court to stop him and it turned into a massive amount of litigation all the way to the Supreme Court. The case was in litigation for seven years in the end until her feeding tube was finally removed, and she died in 2005.

Christof Koch
There are thousands of patients like this. This is not rare, these people used to die very quickly but now with emergency room physicians, you know, emergency rescue with helicopters, and better medical care, we can pull them back from the brink of death, but then they may hover in this state. And the problem is up to 30 to 40% of these patients are actually there, there’s someone, there is still a mind there, but they’re unable to communicate because the damage to their motor system is so severe. So there’s this procedure, which is you pulse magnetic pulses into the cortex. And you measure the reverberation using a high density EEG. So it’s a little bit — think about you have a bell like the Liberty Bell, and you hit it with a hammer and you listen to the sound it makes. And then you look at the complexity of the sound, a normal brain that’s awake, or sleeping, but in a dream, or under drugs. Those brains have high complexity, reflecting the high complexity of consciousness. When normal volunteers are in a deep sleep, or you can take volunteers, you anesthetize them with different types of of anesthetics, then their complexity becomes much lower. And so now you can do this procedure at the level of individual subjects. It can predict in normal people with 100% specificity and sensitivity: Is this person right now conscious or is this person unconscious? And, of course, the challenge is to apply this to these patients in this vegetative state. And this procedure does indeed show that 25% or so of these patients are misclassified, at least according to the signature of the complexity, their brain is as complex as your or my brain when we are either in wakefulness or having a conscious experience during dreaming. We’re doing some similar experiments, because we want to understand the underlying neural circuits, here in the MindScope Program. We’re doing something very similar with mice,  where we have EEG electrodes, on the mice, on their skull, just like in humans, and then we have Neuropixels recordings.

Rachel Tompa  
Neuropixels is this really cool new technology that lets scientists record the activity of hundreds or 1000s of neurons in one experiment. It’s a different kind of measurement than the EEG, which is looking at overall brainwaves using electrodes placed on the scalp.

Christof Koch  
We stimulate them with an electrical pulse, it’s similar to the way it’s done in humans. And then we can see, we can compute their complexity just like we can do in humans. And we see when they go into dreamless sleep, it goes down, when we anesthetize them it goes down. But the advantage is, of course, we can now also study the detailed circuits involved in that. So that’s pretty cool. And we’re now thinking about how to take this idea and to, you know, to make a reliable device, get it FDA approved, and get it out there in the world, into emergency rooms. So we can help, we can give some more diagnostic certainty to loved ones of these patients to say yeah, either your loved one is truly not there anymore. They’re alive, but they’re not conscious, or there is somebody there, but they are unable to communicate.

Rachel Tompa  
So is it known of those 25% of people who are still conscious, do we know if they are more likely to wake up from their vegetative state?

Christof Koch  
Some subset of those do. So because you also want to, the first question when you get called, you know, your loved one is in the clinic. First question, is there anyone there? I mean, are they alive? But then the next question is, is my, let’s say Dad, is he there? And the second question is, will he come back? And so complexity will also predict the likelihood of the patient recovering. Now, if you ask them afterwards, they don’t typically remember anything. They’re sort of I mean, partly you’re getting lots of drugs, you know, you’re not a normal person that just happens to be in a sleep like state, right? It’s a very abnormal state. It may well be that the brain goes into some sort of stupor, you know, and sort of shuts down so typically, people when they recover they don’t have memories. Oh, yeah, I heard you having that discussion. And you know, I was trying to communicate — that’s, that’s typically not the case.

Rachel Tompa
That’s just in the movies.

Christof Koch  
Yeah. Well, it’s different for anesthesia. This may happen during anesthesia, but not in these in these cases.

Rachel Tompa
All right, great. Anything else you want to bring up?

Christof Koch  
No, life, death consciousness. Did we miss anything?

Rachel Tompa  
Psychedelics? We got a lot.

Christof Koch  
Psychedelics, that’s right.

Rachel Tompa
I don’t know about you all, but I learned a lot from that conversation. You can subscribe to Lab Notes on your favorite podcast platform and visit alleninstitute.org to hear updates about Christof’s consciousness work and other news from the Allen Institute.

I’m Rachel Tompa. Thanks for listening.

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