Neuro thinkery 2.0

I've now completed the aforementioned med school class and started thinking about research again. While the med school course focused on problems like "A patient walks in with X symptoms, what part of their brain is acting up?" my research is more focused on a specific portion of the brain and what it does normally. My hope is that studying this portion of the brain will bring out some general principles that apply more generally, but we'll see about that.

Rather than dive into explaining what I'm studying just yet, I thought I'd give a very brief introduction to the overall idea of how brains work we (people who study this stuff) think brains work. And before I get into that, I need to point out that I am going to be glossing over how we know most of this stuff. That is actually something that I want to go back and cover at some point because it's really cool, but for now I will stick to what we know rather than how we know it. Because of this I will also stick to subjects where there is a very high level of certainty that we're right because often the details of how we know something also helps clarify the limitations of that knowledge. Lastly, I'd just like to mention that I'm going to be sticking to the low level of how neurons work and interact rather than big scale anatomy like I talked in the previous post.

Ok, enough of the preamble. So as most of you probably know, the main interesting cells in the brain are called neurons. They stand out compared to the rest of the cells in the human body because of their very long projections (scientists like to call them "processes") that connect one part of them to some distant part of the body. For example, if you can feel the tip of your big toe, that is because there is a cell (actually many cells) that extend from the tip of your toe, up to your spine, into your spinal cord, and all the way up to your brainstem. So if you're six feet tall there is cell that is at least five foot six running almost the entire length of your body telling your brain if there is pressure, heat, vibration, or whatever on your big toe. But how does it do that?

Ooooh, pretty neurons! Fun fact: the sensory neurons I'm talking about all look like the one on the bottom right here

First, one of the sensors on your big toe has to be activated by a stimulus. As an example, let's say you bump your foot into something lightly enough that you aren't in pain. After all, we don't want you to be in pain during this example. Then there are tips of certain neurons that are designed to detect the pressure from the bump, and others that will detect the vibration in your skin. The tips of these neurons are excited by the stimulus. Different types of sensors are excited in different ways, and to be perfectly honest it isn't too important how those different sensors work other than to say that the toe-bumping excites the tips of some neurons.

What does it mean for the tip of the neuron to be excited? It means that some super-tiny specialized holes in the cell open up. First, some of these holes allow sodium (or calcium, but I'll stick to sodium for simplicity) into the cell. Sodium, when it is floating around in water/cells/your body, has an electric charge. So after some sodium enters the cell, there is a change in the electric field across the edge of the cell. Now if there is a small amount of sodium, then it might leave the cell, or it could spread out enough that there isn't much of an effect. If there's a bunch coming into the cell all at once, then the electric field will actually open up more sodium-holes and let more into the cell, creating an even bigger electric field, which leads to a loop of more sodium, more electric field, and more holes opening up. When the electric field gets high enough, a second part of the sodium holes closes up and stays shut until the cell has reset, and to help reset the high electric field opens up some potassium holes, that do the opposite of what the sodium did. Just to throw in a few vocab words, the edge of the cell is referred to as the cell membrane; the holes in the cell membrane are called sodium/potassium/calcium channels depending on what they let through; the electric field across the membrane is called a membrane potential or membrane voltage; and the spike in membrane potential from the sodium is called an action potential. One final note just for accuracy: though calcium can help start raising the electric field, it is always sodium channels that open up when the membrane potential gets high enough, causing an action potential.

Now the process I just referred to begins at the tip of a neuron and spreads down it. In the case of your big toe I guess it's actually spreading up the neuron until it gets to your brainstem. When it gets there, the neuron releases a chemical called a neurotransmitter into a bunch of tiny gaps connecting to different neurons in the brain. I'll try to touch on how those neurons react in the next post. At some point, though, it's important to remember that we scientists really lose track of the effects of individual neurons firing in the sea of thought action and memory that is the human brain. For now, it just helps to know that the sensory neurons act a bit like electric cables, sending little pulses of information when they are stimulated.

What your doctor knows about neuroscience

I have nearly finished taking a first-year medical school course on neuroscience, though I am actually a graduate student myself. As a result I have a weird perspective on the course. So, the very first thing we learned is that the brain is made up of white matter and gray matter. When you dissect a brain (which was a surprisingly non-surreal experience) you can see parts that are lighter and parts that are darker. In general, the surface of your brain is grey matter, and then more towards the inside is a lot of white matter.

Now, scientists know exactly what white and gray matter are, but rather than get into the details, I'm just going to simplify by comparing to a computer. In the computer, there are chips, where information is processed, and then there are wires connecting the chips. So in the brain, the gray matter is like the chips, and the white matter is like the wires. There is white matter that goes from the top of your head all the way down to the bottom of your spinal cord, and some that goes from your toes all the way up to your brain in a single cell. Pretty cool, right? And of course, you need those long bits of white matter, otherwise how are you going to control your toes and feet? So all of this white matter is carrying pretty specific information. When you're outside of the brain, or in the brainstem, it is pretty easy to figure out what type of information all of those white matter wires are carrying. After all, you can see what they're connected to. Do those fibers go to a particular muscle? Do they come from sensors in your skin? Figuring that part out is pretty easy, so over the years scientists and doctors have figured out what goes were. In essence, they've figured out the wiring diagram of the body and brain.

For doctors, knowing that wiring diagram is great! With just a bit of knowledge about what areas of the brain are associated with what, they can then figure out what has become disconnected when you have a stroke, an aneurysm, hit your head, or whatever. This is particularly helpful when they scan your brain in an MRI machine and maybe they find two weird things in there at once. Is just one of them the problem? Maybe you only need one surgery, maybe you need two. If they know their wiring diagram well, then they can figure it out.

So I'm not trying to minimize how great it is that we know this wiring diagram, but given what I've learned I'm absolutely astounded at how little we have been taught about the computer chips! As an engineer, I'm picturing trying to learn about a computer by only being taught about the connections between the chips. That would gloss over everything that made it really a computer! You might figure out that the hard drive seems to store information if you looked on the signals on the wires. You might even figure out that the hard drive is long-term storage while the RAM is short-term storage. But you wouldn't have the faintest idea that a computer could run Word, Excel, and your game of Solitaire at the same time. That isn't to say that no one is working on figuring out what the gray matter does. A bunch of people are. I am. But to most medical doctors, they don't really have to care too much. And that's fine for them, just don't necessarily trust them to have deep insights about the brain.

I hope I have done justice to the wiring diagram. As a start, it is absurdly useful, especially to medicine, but from a perspective of trying to build a deep understanding of the brain, it does very little. It helps direct research a lot by telling us where we should stick our electrodes to study specific behaviors. Putting those electrodes in the wrong places would be a huge waste of money, so that is no small contribution, but the diagram also makes us miss connections sometimes when we're too focused on a specific area. For example, a lot of vision processing happens in the back of your brain (the occipital lobe), but if you focus too much on that area then you would miss how lip reading effects audio processing and how the associated sounds might also effect your vision.

One final endnote. No one in any neuroscience field that I've talked to has the slightest idea what is going on with Obama's BRAIN innitiative. In many senses we've already mapped out the brain (see above). In other senses we aren't even close (if you count the gray matter). And in some other senses (this is probably worth its own post) it doesn't even make sense to try to map out the brain because it's changing all the time. The initiative has the feel of Obama either trying to build a legacy out of nothing or just wanting to fund brain research and having no idea how to phrase it to sound intelligent to both the public and the scientists at the same time.

Failures of imagination

I mentioned this in my last post, but it deserves its own post. Failures of imagination have been a big deal and I believe that any scientist, or really anyone making long-term plans should be aware of this kind of thing. They were first described by Arthur C Clarke in an essay called "Hazards of Prophecy". I highly recommend reading the whole thing, but here are a few good parts.

 The second kind of prophetic failure [ed: The first one what he calls a "failure of nerve"] is less blameworthy, and more interesting. It arises when all the available facts are appreciated and marshaled - but when the really vital facts are still undiscovered, and the possibility of their existence is not admitted.

 He then goes on to describe how a philosopher, Augustus Comte tried to suggest that astronomy should only be limited to discussions of the solar system, ignoring the distant stars. Little did Comte know, the spectroscope, which allows for the analysis of stars' compositions, was invented shortly after his death. While Comte's mistake is understandable, it is important to remember that you should never believe that something like a spectroscope can't be invented. Or as Clarke put it:

When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.

Another, slightly less optimistic example of a failure of imagination is that of the biologists who predicted massive, thorough understanding of many human diseases as a result of the human genome project. These scientists were so stuck on the Central Dogma of Molecular Biology (that DNA makes RNA, and RNA makes proteins) that they could not imagine how little we knew. Therefore, they thought that simply sequencing the human genome would open up medicine to innumerable discoveries. As we now know, sometimes DNA gets regulated (but we don't really know how), and RNA gets modified (which scientists other than me seem to understand somewhat) and proteins can do all sorts of crazy things that are quite hard to predict.

I know scientists, particularly the ones that get a lot of popular press, are awful about this sort of thing. If you see it happen, you should yell at them, yell at the media, and yell at me if you want to.

Neuro thinkery

I have a lot bubbling around in my head on the subject of neuroscience. I am well aware that I'm not really an expert on the field yet, but no one really understands what is going on in the brain very well so I don't feel too bad writing about my mostly uninformed thoughts on the matter.

When I think about the current state of the field of neuroscience, I usually try to put myself in the shoes of a Pre-Darwinian biologist. Back then, there were simply a mess of animals with a mess of characteristics that seemed to have some semblance of an order (usually assumed to be divine) but that order wasn't very clear. Some things were easily measured, such as nose length, number of legs, skeletal structure, and overall size, while other key aspects of animals, particularly their DNA, were completely immeasurable.

Now how does that compare to neuroscience? Well the thing is that neuroscience is attempting to explain something that just makes absolutely no sense from the perspective of any of the other hard sciences. While a physicist can explain how particles move and behave to no end, he never has to ask himself how the particles feel about their movements. A biochemist never has to ask about how a paramecium feels about its internal chemical reactions. Yet once you enter your own head, you are without a doubt capable of feeling things. That is to say that you subjectively experience the world, or to put it another way, you have qualia. The question is how in the freaking hell qualia arise. It's the thing that everyone would absolutely love to explain, yet no one expects to be able to do it. After all, all of our tools for the task are completely useless. If we borrow from physics, there is nothing there that explains subjectivity. Physics, as far as I can tell, explicitly denies subjective experiences of quantum particles on up, as it should. After all, when your theories make accurate predictions out to something like 40 decimal places, why would you bother adding subjectivity into the mix?

The trouble is that everyone who reads this is currently undeniably in the process of having a subjective experience, and that evidence right there says that something big is missing from our current knowledge of the universe. Sitting in my comfy apartment, it completely looks like modern physics chemistry and biology have absolutely no way to explain how a creature can have anything like a subjective experience. So how does that compare to the Pre-Darwinian biologist? To anyone before Darwin, the ridiculous diversity and order to the life on Earth appeared completely inexplicable using then-modern physics. There was no process that could possibly create both a cat and a dog, let alone a tree and a flying squirrel. Many smart people assumed that there must be a gap between then known physics and this crazy diversity. And the order! Resources are decomposed, others are generated by bacteria, still others are nutritious seemingly designed for human consumption. Yet all of it can be explained by noting three things: things reproduce, the copies are not always identical, and the ones that survive to reproduce again will proliferate more than those that don't.

So this raises the question, is the problem of qualia a physics-breaking problem, or is it one like the diversity and order seen by the Pre-Darwinian biologist. I personally don't see how a set of neurons like the ones I model could possibly have a subjective experience, which makes me intuitively believe that the problem is physics-breaking. However, in an attempt to avoid a failure of imagination I actively try to ignore my intuition in this case.

tl;dr: Physics, chemistry and modern biology don't appear to explain qualia at all. Maybe there's some nuance like evolution that bridges the gap, or maybe we need an entire paradigm shift.

[I should note that I read Edelman and Tononi's A Universe of Consciousness five years ago or so, and I probably lifted some ideas from that book unintentionally]

Sci-fi Idea #1

I'm titling this post Sci-fi idea #1 in the hopes that there will be more than one. It's a bit like having a first annual event. How do you know it will be annual yet? You don't, but you hope. So I was reading Atlas Shrugged for the first time in years and I got to chapter four, which begins like this

Motive power—thought Dagny, looking up at the Taggart Building in the twilight—was its first need; motive power, to keep that building standing; movement, to keep it immovable. It did not rest on piles driven into granite; it rested on the engines that rolled across a continent.

If you don't know, the Taggart Building is the main office of a giant railroad company, and that got me thinking: what if there was a building that actually did rest on engines, roll across the continent or some other fantastic idea like that?  So idea #1 is a kinetic building. The stationary part of the structure would sit high above the ground, and the legs would move so that as someone approaches they would get out of the way. Now what I'd really like to see is a city full of these things so that anyone can get to any building by walking as the crow flies.

And of course once you're thinking about moving buildings and cities of moving buildings, the really crazy ideas start to fly. What about a city that migrates? What about a city that reorganizes throughout the day? You could have neighborhoods that have restaurants next to them at dinner time, bars late at night, and office buildings during the day.When buildings are as free to move as humans, the ideas behind transportation would get very interesting.

So, if any sci-fi writer wants to take this idea and run with it, go for it. Or (way more likely) if someone wants to point me to some sci-fi with a good story where this has already happened that would be cool too.

Hello world!

I'm making this blog because I know I need to write more, and this helps me do that. I also figure that if I have stuff to share this is a good place to do that. Topics should include some discussion of neuroscience, some sci-fi ideas (though I don't read enough of it), and some pondering about the life, the universe and everything. Cheers!

-Danny