Can we make a fake brain?

20 October 2013
Presented by Hannah Critchlow.

A special edition Question and Answer show: how do prosthetic limbs work? Can you train your brain? And is a brain transplant possible?

In this episode

01:32 - Introducing the Brain Panel

Who are our brains for this programme? Plus we find out their burning neuroscience questions.

Introducing the Brain Panel
with William (Bill) Harris, Katie Manning, Mike Edwardson, Cambridge University

Who are our brains for this programme? Plus we find out their burning neuroscience questions. Let's meet the brain panel.

Bill -   I'm Bill Harris.  I'm a Professor of Anatomy at the University of Cambridge and I study the early development of the visual system in fish mostly.

Katie -   Hi.  I'm Katie Manning.  I'm a PhD candidate in the Department of Psychiatry and I'm looking at the structural and functional connectivity in the brains of people with a genetic disorder called Prader-Willi syndrome.

Mike -   I'm Mike Edwardson.  I'm Professor of Molecular Pharmacology in the Department of Pharmacology here in Cambridge.  I'm interested in looking at structures of protein molecules.  So, I use a novel technique called atomic force microscopy.

Hannah -   And let's find out what their burning brain questions are, kick-starting with Mike and Bill, then Kate.

Mike -   How memories are formed and stored, I think is a really fascinating Burning questionsquestion and I'd really like the answer to.  I'm old enough to remember when England won the World Cup in 1966.  Younger people don't have that memory, so there's something different about what's going in my brain to what's going on in people's brains that don't have the memory.  I would love to know what that is exactly.

Bill -   My whole life, I've been interested in the question of how brains are built.  It's a very, very complicated organ and it has zillions of cells and zillions and zillions of connections.  So, how does that get built so accurately that it works?  That's the question that fascinates me.

Katie -   I think that brains are incredible in a way that they provide the interface between us and the world we live in: each and every one of us is different and we recreate our world and our understanding of everything by using our brain.  I think that's absolutely fascinating.

Hannah -   So, Mike, Bill and Katie's brains fire up when considering memory formation, nervous system construction and how our perception of the world is formed. 

Can we make a fake brain?

We posed this question to our brain panel. Bill - Well, we've been simulating neurons for a long time. the question is, how good are we at simulating a particular neuron and its fullness. It depends on which neurons you're looking at. All the neurons are different from each other and people have been trying to simulate different neurons and we can do it pretty well, but never to completion. The same thing with the brain - people simulate pathways in the brain, work out models for how information goes from one place to another and it's getting more and more sophisticated, but simulate a brain, which brain are we talking about - a frog brain, a human brain, you're brain? That may be more and more challenging.

Mike - There is a lot of interest now in trying to model whole brains but using super computers. So, there's a lot of funding just been awarded in Switzerland which is called a Blue Brain Project where people are trying to use very powerful super computers to model the whole brain. We're really at the beginning of that and I think it's going to be many years before useful data arise out of that project. Bill - When you say useful data, what do you mean by that? Because I think every model produces some data that's at least kind of hypothesis for what it might be doing so it's testable. So, models are valuable as far as they go and they throw up problems with our current understanding. So, I might argue that the Blue Brain project, even in its early phases will give you answers that may ring true or may not, and that lead to further sophistication of the model.

Mike - I think that's a good point. To be honest, I'm slightly sceptical about whether this is a good use of money and whether I would fund this or not. I think if it was up to me, I would probably fund far more slightly less ambitious projects. So, I'm actually slightly sceptical about how useful this will be.

Hannah - I mean, do we know enough about the brain in order to have the knowledge to simulate it in the first place?

Katie - So, there's a number of large multimillion pound projects going on at the moment and they're trying to map what's been called the human connectome, so using some of the newer imaging techniques that we've got to look at the brain to look at both the structural and the functional connectivity between different areas. We know quite a lot about this in some pathways and in some sort of networks within the brain, but we don't know in its entirety exactly how all areas of the brain work together, how the patterns of activity in one set of pathways might influence a pattern of activities in another set of pathways completely in all its complexity. Obviously, if we could, it would be a very useful way to perhaps be able to model what we might expect to happen in the use of certain drugs or certain medications in development.

Bill - Let's say you look at a circuit in the spinal cord that's involved in walking. People have been studying something like that for quite a long time and understand to a medium degree of understanding I guess, the neurons that are involved. But it's not by any means complete how we walk faster or slower, how we change gait from walking to running, how we jump and hop and skip, what's the circuitry involved, what are the neurons involved? We don't even know those in a very small part of the brain. Similarly, when light goes into our retina and all the cells are connected up in the retina. We don't know what all the cells are doing. We know what some of them are doing, many of them are doing, but completion of this task, how far away from completion of the task is kind of hard to say.

Katie - I think that just because we don't have like fairly complex and in-depth models of a fully functioning brain in terms of software doesn't mean that people should think that we don't have useful models. So obviously, there's entire fields of neuroscience that are largely devoted to using software and using it to model the way that the brain works and that both helps us in developing theories that we can test and also, taking the things that we have learned and putting them together in trying to work out exactly what is going on by running different iterations of them.

Hannah - Along that line, there's a paper that was published actually last month. So, published in Nature, researchers at the Institute of Molecular Biology in Vienna, Austria managed to develop a 3D organ which resembled a 9-week embryonic human brain. They developed this from a human stem cells and it grew from 3 to 4 mm cubed. They think that they kind of seem to mirror some of the activity of a functioning kind of brain-oid they called it and may be useful in the future for trying to uncover more about Schizophrenia and autism for example.

Bill - I'm not sure what this little mini brain in culture has to do with modelling, simulating a whole brain. I'd take it has to do with getting a mathematical model that predicts the interactions and the activity of different things. This little mini brain made out of embryonic stem cells certainly has some wiring to it as bunch of neurons in a culture dish would if you put the dish together. And it may be a little bit more alike a real brain than a bunch of neurons in a dish that are randomly connected to each other. But that's such a far away from a real animal's brain or a human brain.

Hannah - But do you think some of the information that could come from this brain-oid could help to input into the computer simulations?

Bill - No. I would study real brain rather than little mini brains. Each one of which is going to be different from each other.

Is a brain transplant possible?

We posed this question to the brain panel. Katie - So in fact, the idea of transplanting brains did have some media attention earlier this year. An Italian neuroscientist wrote an article which had quite a lot of discussion suggesting that a brain transplant could theoretically be achieved by transplanting the whole human head onto a donor body. He proposed a method for reconnecting the severed spinal cords.

In this paper, he referred to the work in 1970s of Dr. White and he transplanted a rhesus monkey head onto the body of another rhesus monkey. The monkey was apparently able to see and smile and taste, and in Dr. White's words, 'bite' and he did this with the idea that eventually, human head could be transplanted onto a donor body. It might help people who had healthy brains but some degenerative illness of the body. So, while the animal awoke, it was reported to live for a very short time. It didn't really have any use of the body because they weren't able to reconnect the spinal cords.

Hannah - And has that study been replicated since the 1970s?

Katie - Well, no. It hasn't been replicated. Of course, the ethics of doing a research programme like that now would be very questionable. It just wouldn't be allowed.

Bill - The easiest part would probably be connecting up the blood supplies, but connecting up the broken nerves is a real problem especially in this central nervous system, the spinal cord. However, you can transplant brains in embryos. You can transplant an embryonic frog brain from one frog to another. You can transplant embryonic chick brain to a quail. Lots of brain transplants are possible. It's when you get to the mammals that it becomes particularly challenging because the nerves don't regenerate so well and they don't cross cuts. So, when you cut a nerve cell axon and you want that cut nerve then to be able to regenerate its axon and make connections with the appropriate targets, it has a really hard time doing that in a mammal.

Why can't the brain heal itself?

We posed this question to the brain panel. Bill - Skin cells replace themselves all the time. So, we're always making new skin cells. Most of our brain cells we are given just one of each and they have to last our lifetime. There's not a lot of cell replacement in the brain. So, the question then becomes, if a cell dies, it doesn't get replaced because we have no mechanisms to replace it in our brains whereas we have mechanisms to replace some skin cells or muscle cells, there's something intrinsic about the nerve cells that doesn't let them re-grow so well. The distances are a lot longer in an adult than they were when they were connecting up as an embryo. When you get a cut in the central nervous system, there's a reaction, an environment that makes it difficult for cells to re-grow through that injured environment and connect that properly. So, brains have a couple of challenges in the healing.

Katie - I think it's important also that the brain can adapt to induce to a certain extent. So, with other parts, the brain is working to take over lost functions from the damaged area even if that's not sufficiently as it happened before. And also, that the brain does have some fairly strong defence mechanism. So, when you make a cut in your skin, it might happen in everyday life - you're doing some cooking, slip with the knife. But the brain, it's protected. It's in the skull. There's two membranes beneath the skull and between that, there's a cushion layer so to speak of cerebrospinal fluid. And then even beyond that, you've got what's called the blood-brain barrier which helps to control some substances that can enter the brain. The brain isn't exposed to harm than in quite the same way as an organ like the skin in everyday life.

How do prosthetic limbs work?

We posed this question to our brain panel.

Mike - There are prosthetic limbs now that do respond to thought for example and how that works is pretty complicated. I've just been looking it up myself and as far I understand when you amputate the limb, say you amputate the lower leg, what you do is preserve the nerves that are supplying the bit that you chopped off by attaching them to muscles and parts of their remains. And then the limb is then basically responding to changes in the muscle that's being re-innovated. Their limb is being controlled by a computer and they're sort of learning that when a particular part of a muscle mass twitches, that's a signal to make a particular movement. So you can actually have a prosthetic arm with a hand which will allow you to pick up objects by replicating the movement that would've been there if the arm and the hand have been there.

Katie - My understanding is that it's sort of prosthetic limbs where they can receive some of the signals the brain is that it acts like a pattern analyser effectively. So, their nerves are reconnected to a muscle higher up and then as you think about doing something like moving your arm, opening your hand, closing your hand, those sorts of things, the computer learns. It has sensors in the prosthetic arm and it learns what those pattern of the muscle contractions in the higher up muscle, what that means in terms of what movement you're thinking of. As the sensors pick these up, the computer looks at the pattern of muscle contractions and reads that off as which movement is intended and then that creates in the prosthetic limb.

Bill - There's also been some progress in a kind of EEG control of prosthetic devices. For example, a patient in a wheelchair could control the direction of the wheelchair by thinking about it. Want to go right and the wheelchair turns to the right. It depends on the sophisticated ability to analyse electric patterns in EEG type recordings from kind of a bicycle helmet connected to the skull. Well, just a helmet you could wear that would pick up your brain waves and interpret them and then you learn to think left in a way that the wheelchair understands and it will go left.

Katie - The sort of very, very early research being done into actually using the electric signal of muscles contracting and sending signals back so you get a very rudimentary sensation or stimulation that could be interpreted as touch on the brain. So, using a prosthetic limb to actually get some sort of sensory feedback as well.

Was Einstein's brain different to mine?

We posed this to the brain panel. Katie - So, upon Einstein's death, his brain was removed and it was photographed before being dissected and the majority of the slides are now stored at the National Museum of Health and Medicine in Washington DC. The latest description of the structure of Einstein's cortex, the outer bit of the brain did suggest that cerebral cortex folding pattern was unusual in areas that might be related to cognition and mathematical reasoning. And it also had a slightly large area of one side of the hand control region which was thought to be linked to his violin playing.

Hannah - I heard that when he died, they performed this autopsy and there's some controversy about whether or not he did actually donate his body for medical research. They performed this autopsy and they fixed his brain with formalin and they cut it into 240 blocks, really small blocks and basically scattered Einstein brain blocks around the world to different researchers to study. Is that true?

Katie - That sound like that was largely what happened. I think the main researcher that had taken part in the dissection, he kept a lot of them, but he certainly did lend out slides and some of the tissue samples which is why not all of them are entirely accounted for today. We've often, I think over time, a lot of times when somebody who's been seen as having a superior intelligence dies, people have taken their brain to try and have a look at what makes somebody really, really intelligent. I think that's an interesting idea, but a lot of people have cautioned about the fact that everyone's brain is slightly different. And so, by looking at somebody's brain, you can tell whether the thing that looks slightly different on their brain to someone else's brain is actually functionally relevant whether it actually determines what made them more intelligent or what made them really good at a certain thing than anyone else.

Hannah - Suppose, humans are always looking for patterns aren't they? They always want to see some reasons, some kind of basis. Yeah, Bill.

Bill - If Einstein was particularly good at algebra and mathematics and well, maybe he wasn't just so good at something else, but do we even know which part of the brain is involved in algebra? I don't think so.

Katie - Generally, as we're moving away from understanding particular discreet regions of the brain as being involved in doing this exact task and understanding the brain more is networks of different areas which work together and that sometimes these networks will overlap and sometimes they'll be slightly different. That it's actually the recruitment of lots of different brain areas that give rise to abilities to do things.

Hannah - I have heard that Einstein's brain may have had more glial cells. So, these are kind of the supporting cells that help secrete factors like cholesterol for example that help nerve cells to connect with each other. This is obviously just one observation from one study that's been published, but do you think that could be true?

Bill - Again, I find it hard to think that Einstein was more brilliant at every aspect of every bit of life than everyone else. He had certain fantastic abilities that's for sure and he was a good violin player. But was he fantastic at everything? No. You're probably more fantastic at some things than he was. Maybe you could dance better than he could. And so, there's a part of your brain that maybe we should fix and scatter around the world when you die.

20:05 - A Quick Tour around your Brain

How many brain cells does it contain? How heavy is it? And how does it work? We take a quick fire science tour round your brain.

A Quick Tour around your Brain
with Simon Bishop, Naked Scientist

How many brain cells does it contain? How heavy is it? How much fat? And how does it work? We take a quick fire science tour round your brain with Naked Scientist Simon Bishop.

Simon - Your brain weighs about 1.5 kg,

Hannah - That's about the same as a bag of sugar or your typical cauliflower -  it looks like one too.

Simon - Your brain makes up about 2% of your total body mass

Hannah - Even though it's not that heavy, it's a greedy hungry beast your brain, consuming about 20 % of your daily energy quota

Simon - What's using all this energy? There's almost 100 billion nerve cells up there.

Hannah - that's over 12 x the world population in terms of nerve cells in your head

Simon - These cells use electricity to send signals by pumping charged ions in and out of the cell. They then communicated with other cells by releasing neurotransmitter chemicals -- like dopamine and serotonin

Hannah - Each nerve cell is connected to between 1,000 to 10,000 other nerve cells, and it's through these connections that they send the signals through the brain network.

Simon - So, in total that's almost 1 × 10 to the 14 connections in your brain, or about 100 trillion.

Hannah - The human brain is the fattest organ in the body - over 60% of it is fat.

Simon - This fat wraps itself around the nerve cells and helps to insulate the electrical signal, making communication along nerve cells faster and stronger.

Hannah - Nerve signals can reach up to 120 metres per second, or 300 mph.

Simon - Contrary to popular belief, we don't use only 10% of our brains.

Hannah - It is true that we can only use a few specialised brain circuits at a time, but the rest of the brain is constantly ticking over, ready to be put to work.

Simon - You can find out more about how nerves work in our latest Science Scrapbook, at
www.nakedscientists.com

Can you exercise bits of your brain?

We posed this question to the brain panel. Katie - So, there are a few areas of the brain where new neurons can form right throughout life and the hippocampus which is involved in memory and learning is one of them. There is evidence that the hippocampus can become bigger as a result of certain experiences. Exercise is one of them. It can help to generate new neurons. Typical example of this is the hippocampus size in London cab drivers and they have to learn the entire London roadway system and pass a complicated test called The Knowledge. Eleanor McGuire, the researcher who's looked at this a lot, has followed a group of successful and unsuccessful taxi driver trainees and she showed that an increase in the posterior hippocampus was associated with those that did pass the test and went on successfully has become the taxi drivers.

Hannah - So, just by training, just by trying to pass this knowledge test and kind of exercising their navigation, spatial reasoning skills by navigating through London in their black cabs, they actually grew one part of the hippocampus. But was this at the expense of another part of the hippocampus or another part of the brain?

Katie - I think it was at the expense of the anterior hippocampus.

Hannah - Which is the region that wasn't involved in this navigation and spatial reasoning kind of skills?

Bill - If you pay attention to a certain kind of activity, you may use more for that and at the expense of something else. Blind people I think use their visual cortex - sighted people would use it for vision and blind people can use part of their visual cortex for other tasks, perhaps auditory tasks.

Katie - Yeah, probably the point is that the brain isn't able to infinitely grow. There are size constraints, but there are also constraints on what you choose to do with your time and we tend to choose to fill our times with the things that we enjoy and the things that we're good at.

Why does coffee make me sleepy?

We posed this question to the brain panel...

Mike - It depends on the time course. I'd be surprised if somebody would drink a cup of coffee then immediately feels sleepy. But I think it's perfectly reasonable to feel sleepy a little bit later on because, what's happening when you drink coffee, is that caffeine blocks the action of a "tiredness transmitter" in the brain called adenosine.

Adenosine progressively damps down brain activity as it accumulates during the day, contributing to sleepiness. When we go to sleep, the adenosine is flushed out from the brain again so that we feel rested and refreshed when we wake up.

If you block the effect of adenosine with caffeine, then you will feel more awake. But, later on, when the coffee effect wears off after it gets eliminated, which takes 4 hours or so, the adenosine is still there, and then that may kick in and make you feel sleepy. But I don't know of a circumstances where you would drink coffee and then suddenly feel sleepy.

Bill - Except, perhaps, if you had a strong association with coffee as a thing that you took next to going to sleep. Like children hear nursery melodies and they're put to sleep by it. If you had a routine in which you drank coffee and then went to sleep, it may be a signal to sleep and would help you get to sleep. Is that possible?

Hannah - Or maybe he associates coffee with incredibly boring activities like being in the office?

Katie - Feeling really tired?

Is taking Ritalin linked to addiction?

We posed this question to our panel of brains. Mike - What's happening here is that there's a link between - I'll probably be corrected but there's a link between the gambling and the ADHD. ADHD people are over represented in compulsive gamblers and I think that's well established, but I think the connection with Ritalin is much well established.

Hannah - So, you're saying that people with ADHD are possibly more likely to become gamblers?

Mike - That seems to be the evidence, yes.

Katie - And I would agree with that and I think that cause and effect can often be very difficult to disentangle. So, a lot of research has shown in those children with ADHD are much more likely to go on to develop substance abuse problems. Actually, a recent study that was done at UCLA looked at children with ADHD who were given medications like Ritalin and children who weren't given medications and they found no difference in the risk for developing substance abuse later in life. So, it seems to be something to do here with the ADHD rather than the medications.

Hannah - And that seems to make sense as well because the typical presentation of ADHD is the person may be slightly more impulsive and more likely to take risks. So for example, they might enjoy gambling or they might be more likely to abuse substances or go for substance of abuse in the first place.

Katie - Yes, that's true.

Bill - Does that mean the people who took Ritalin for their ADHD didn't get an improved outcome in terms of their gambling later? If you correct the ADHD with Ritalin, doesn't early training help you later in life?

Hannah - I think there's been some papers published where quite a lot of child ADHD cases are then taken off their medication early 20s and then they're not continued to be treated as adults, and it's at this point when they're off their medication that they're then more likely to become addicted to drugs of abuse for example or have problems with gambling.

Katie - With people with ADHD, it seems to be a case of some disrupted reward systems and attention control disregulation. This is what the Ritalin tries to address. In fact, one study that used Ritalin - a study done in Cambridge - that used Ritalin in people with frontal temporal dementia, so elderly people who are starting to become less able to use their cognitive control capacities actually found that giving Ritalin to individuals with frontal temporal dementia actually decreased their risk taking behaviour.

Hannah - And that's all we've got time for I'm afraid. Thanks to all of the listeners who got in touch with their questions and to Professors Bill Harris and Mike Edwardson, and doctorial researcher Katie Manning from Cambridge University for taking on your questions.

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