Neuroimaging

My own view would be that the nervous system suppresses the motor system when we actually go to sleep. This is why we don't end up acting out more of our dreams, because of this region in the brain stem that stops the motor pathways going through. That will include some of the more complicated movements that make vocalisations happen, but you're still, in your dream, going to be talking and things, aren't you? So, that's why you would talk out loud sometimes - I guess there'd be a breakthrough of that suppression activity.

We put this to Professor Paul Fletcher and Professor Jack Gallant...

Paul - I don't know if that's a great metaphysical question. I mean, the brain scanner is looking at how the brain behaves when it is seeing something that isn't there, so it's not so much interested or able to see the content of that although as we've just heard from Jack actually, the possibility of seeing what the brain thinks is there is possibly something for the future.

Chris - Any comment on that Jack?

Jack - Yeah. I think there's growing evidence that when you have a visual hallucination, what's actually happening is the visual areas of your brain are being activated, essentially top down from inside out and the visual experiences you have in the visual hallucination are -since the brain subsystems were being operated in those cases are visual, then you both experience visual events and you could decode visual events because you're decoding from the same parts of the brain that are encoding visual information normally.

Chris - And hence, what you've got is this system where you think it's real because it's the same bit of the brain that would say, "Yup, I'm experiencing something" but it's just being internally generated.

Jack - Right.

Cancer is a disease caused by cells multiplying out of control. It's been known by many names through history - some of them unrepeatable on air, from people and families who've been affected by the disease. One ancient name is "the wound that does not heal", and today, researchers are uncovering many similarities between the controlled cell production required for wound healing, and how this process is hijacked in cancer.

 Now new results from a Cancer Research UK-funded team led by Professor Alison Lloyd at University College London have found an important link between nerve repair and how tumours may spread within the nervous system, and they've just published their findings in the journal Cell.

Our nerves are actually pretty good at repairing themselves, although it doesn't always work in the case of severe damage or crushing. For example, nerves can grow back through deep cuts, and it's possible to reattach amputated fingers, toes and even limbs, and have some regrowth of the nerves.  And this is all down to special cells called Schwann cells.

Schwann cells act a bit like insulation around nerves - like the plastic coating around electrical wires. Normally, they help the speed up nerve signals, but we know that they're also really important for directing repair.

When a nerve is cut,  Schwann cells start growing out into the wound, and start making "guide tracks" for the nerves to grow along. And here's where the new research from Professor lloyd and her team comes in, as they've uncovered some of the complex molecular signals that control the process.

The researchers were looking at exactly how the Schwann cells are controlled and directed into these "guide tracks" by fibroblasts - repair cells that gather at the site of a wound. The team discovered that fibroblasts produced a 'signal' molecule called ephrin B, which is received by 'receptor' proteins on the surface of the Schwann cells called EphB2, standing for Ephrin receptor B2.

It's this ephrin signalling that tells the Schwann cells to organise themselves into tracks, as directed by the fibroblasts, so the nerves can regrow, a bit like traffic police using special hand signals to direct cars into different queues on a road.

And, importantly, the scientists found that switching off ephrin signalling meant that Schwann cells couldn't repair nerve damage, proving that it's a fundamental part of the process. So these findings tell us something important about nerve repair, which will be useful for researchers working on techniques such as nerve grafts, which could repair damaged nerves after accidents or surgery.

So how is this linked to cancer? Well, we know that some types of cancer can spread along nerve cells - and the way they do this looks very similar to the way that the Schwann cells and fibroblasts move as they repair damaged nerves, and it's likely that the same ephrin signalling is involved.

Professor Lloyd thinks that cancer cells may be acting a bit like an unhealed wound, hijacking the signals that normally repair nerves. In a normal situation, the regrowth signals would be switched off when the nerves have grown across the wound. But in cancer, it may be that the signals don't get switched off and the cancer cells carry on spreading along the nerves, rather than ever settling down and 'healing'.  

So understanding how this signalling goes wrong, and how we can block it, could prove to be an interesting lead for future treatments that stop cancer from spreading.

Historically, scientists thought that the most severe form of malaria, known as falciparum malaria, first spread into humans from chimps.   But now, by looking for the parasitic DNA in faecal samples from thousands of wild apes, including chimpanzees, gorillas and bonobos, Edinburgh University's Paul Sharp and his colleagues have found that, in fact, it was gorillas that gave us malaria rather than chimps.  He talked our own Smitha Mundasad through the work, due to be published in Nature this week.

Paul -   Before we set out on this particular study, there was one species of Plasmodium known to infect chimpanzees and that's a species called Plasmodium reichenowe which is quite closely related to Plasmodium falciparum - the worst cause of malaria in humans.  What we have subsequently found is that there are in fact six similar species of Plasmodium and we found three species of Plasmodium that only infect gorillas.  When we compare those different species of ape Plasmodium to the human species, all the evidence suggests that the human Plasmodium has originated by a jump from gorillas to humans.

Smitha -   What implications does that have now for our understanding of malaria?

Paul -   Well, the initial aspect of this of course is just that it satisfies our curiosity about where humans acquired their Plasmodium parasite from in the first place.  But ultimately, it can also prompt us, or others, to ask whether there are any differences between the strains that infect gorillas and that infect humans.  For example, it looks like only one of those six species has successfully jumped into humans and it looks like it may have only done it on one occasion.  These parasites are transmitted from ape to ape by mosquitoes and we would expect those mosquitoes also to be biting humans who live in close proximity to the apes.  So we would expect there have been many opportunities for those Plasmodium parasites to infect humans but most of those occasions, they simply aren't successful.  It looks like the gorilla strain that did make it into humans must've undergone some kind of adaptation - it would be really interesting to find out what that was.

Smitha -   Could these findings lead in some way to find treatments in the end?

Paul::  Any additional knowledge about what it is about these strains that allow them to infect humans or doesn't allow them to infect humans could lead to insights for therapies.  Perhaps the most important implication of the work is that it says that there are these other species of parasites out there that might have the potential to infect humans in the future.  And that would be particularly important if people were successful in curing humans of Plasmodium falciparum.  There's a possibility that we're simply opening up the niche for one of these other ape parasites to jump into humans.

Smitha -   Has this research thrown up any new questions?

Paul -   There are all sorts of questions that arise out of this.  We never find one of the chimpanzee parasites in faecal samples from gorillas and we never find one of the gorilla parasites in faecal samples from chimps.  Presumably there's something about whether these parasites can successfully infect blood samples of other species, and it would certainly be intriguing to figure out - what is that species specificity?  And of course, that then leads into the question of whether that specificity could change so that any of those parasites could infect humans in the future.

Smitha -   Do you have plans for further research?

Paul -   We do hope to look first of all at human samples to see whether any of these other ape species of Plasmodium have made it into humans.  We also want to look further at the ape samples because Plasmodium falciparum, although it is the most common form of Plasmodium causing malaria in humans, is only one of four or five different species of Plasmodium that infects humans.  We haven't really looked extensively at these ape samples to see whether the apes are infected by relatives of these other Plasmodium species that infect humans.

A satellite designed to measure the Earth's gravitational field with unprecedented accuracy may sound like something out of a James Bond film, but it is in fact a reality.  The European GOCE spacecraft or "Gravity field and steady state Ocean Circulation Explorer" has been doing just that and has recently sent back its first results.  Richard Hollingham finds out more...

Richard -   The launch of the dart-shaped GOCE satellite from the Russian Plesetsk Cosmodrome was in March 2009.

Helen -   It is definitely the Formula 1 of satellites, if you like.  It's designed to slip through the atmosphere as easily as possible.

Richard -   Eighteen months later, in her office at the National Oceanography Centre in Southampton, Helen Snaith is studying the first data from this sleek satellite.

Helen -   Its primary mission is to measure the Earth's gravity field at very small spatial scales.  It's to see the very, very small changes in the gravity as you go around the Earth, and ultimately, to be able to use that information to get to ocean circulation.

Richard -   We'll talk about that in a second, but let's look at the first results.  You've got some of these early results through, up on your screen here.  It's an image of the Earth, but it's a lumpy, bumpy, multi-coloured, almost like a rock-like Earth.

Helen -   This is an image that's been generated to show just how lumpy the Earth actually is.  If you looked at the Earth, it's not completely smooth.  We all know it's not completely smooth.  We have mountains.  We have oceans.  We have valleys.  But they have an effect on the gravity field as well.  So the gravity field isn't the same all the way around the Earth.  When you do maths, let's say in your school, you get taught that acceleration due to gravity is 9.8 metres per second squared.  Unfortunately, that's not strictly true.  There are very small changes as you go around the Earth.  If you go over the Himalayas, there's more mass, there's more mountains, there's more gravity.  So things are pulled towards them.  If you go over deep trenches in the ocean, there's less mass, there's less gravity, and things aren't pulled towards them as much.  It's these small changes as you go around the Earth that we're trying to measure with GOCE and which you can see exaggerated an awful lot on this image.

Richard -   Okay, so you have a map of the Earth's gravity field which is what the satellite is producing.  You want to use that to work out ocean currents.  How do you make that leap?

Helen -   Because the gravity field isn't the same everywhere, the water in the oceans isn't being pulled down to the same level everywhere.  So, if the water was completely still and there were no ocean currents, it would be a bumpy surface.  But if you put a ball down on that surface, it wouldn't roll anywhere.  It would stay where it is, which is a slightly strange concept to be able to get your head around, but this is where we're coming from.  What we're trying to calculate now is the difference between that nice smooth steady state - that if there were no currents, this is the shape of the sea surface - and what we actually measure - the difference between those two is what's being caused by the ocean currents.

Richard -   So the only way you can work out really the impact of the ocean current or the height of the water as a result of these ocean currents is by removing the gravity from that.

Helen -   Exactly.  That's precisely what we want to do.  We can use an altimeter - satellite altimeter - to measure the precise height of the sea surface at any given time when the altimeter flies over.  What we don't know is how much of that height is being caused by the gravity field or that change in height.  With GOCE, we can start to get a handle on that.  That's what we're really interested in.

Richard -   Okay, you're interested in it.  Why is it important to learn or work out where the ocean currents are and what effect they're having?

Helen -   The ocean currents are a really important part of the heat transport system of the ocean.  What we're trying to do is to monitor those currents and see how consistent they are, how strong they are, whether there's changes in those currents.  To be able to do that, we need to be able to monitor them globally.  Satellites give us one of the few options we have of being able to look at the currents everywhere in a consistent way.

Kat -  So if you could tell us a little bit about what fMRI can actually tell us about what's going on in the brain and what it can't actually tell us yet?  I think some people think it's maybe a magic mind reading machine.  Where are we at the moment with this technology?

Paul -   Well, as we were just hearing from Dr. Gallant,  fMRI is a way of looking at which different bits of the brain respond when people are asked to do things or when they're having particular experiences.  From my perspective, it's very interesting because we can start to look at the areas of the brain that become active when somebody's experiencing quite unpleasant symptoms that co-occur with mental illnesses.  So for example, a hallucination where somebody is perceiving something that isn't actually there; for example hearing a voice when there's nobody around or seeing something that isn't there. Or delusions where they believe very strange things, often very unpleasant things such as their neighbour is trying to kill them or something.  And fMRI offers us a way of putting them into the scanner and looking at how their brain is behaving in this sort of setting.

Kat -   So, how are you actually doing this in practical terms?  What's your research involving?

Paul -   Well the first thing is, I'm not actually terribly interested in trying to map the hallucination to the brain.  I think that would be a lovely thing to do, but the problem is, if you lie somebody in the scanner, and they're having hallucination, you can get them to indicate when the hallucination occurs, and you can watch what changes in the brain are occurring, but you don't actually know whether those changes are the course of the hallucination which would be very interesting, or whether they're actually a consequence.  For example, if I'm hearing a voice, my brain will respond to that voice even though it's not causing that voice. Or there may be a compensation; so, a hallucination would be very unpleasant and that the changes we see in the brain might actually be a result of somebody trying to suppress the unpleasant thoughts and connotations.  So I'm much more interested in trying to use functional imaging to try and test particular cognitive or psychological models of how the hallucination occurs, what computations in the brain may be disturbed as a prelude to hallucinations or delusions.

Kat -   So you're trying to sort of strip out some of these variables.  How are you actually doing that?

Paul -   Well, we're taking as our starting point an acknowledgement that actually, pretty much all of us live in a fantasy world where we are hallucinating quite a lot of the time.  We're creating our own reality.  The reason being that if we were to try and sample all of our neural inputs at once, all of the sensations that are impinging on our brain, we would be totally paralysed by information.  And a consequence of that is we start to take shortcuts and we start to process the world, not so much as a result of what is there, but of what we expect to be there.  And I think we can think of our brains as being a very delicate balance between what we're predicting to see, or hear, or feel, and what we're actually experiencing through our neural apparatus. And my belief is that we can start to understand some of the symptoms of mental illness by looking at this balance and by acknowledging that there's a very important signal in the brain that almost pervades all neural firing which is the mismatch between what we expect and what we've got, the so-called 'prediction error.'  And so, what we can do is look at how prediction error firing in the brain occurs in people with and without hallucinations and see if that is disordered in some way.  For example, do they appear to show surprise or prediction error by things that should actually be highly predictable or contrarily, do they show an absence of prediction error when there should be something surprising occurring.  So we can use imaging to test this and in so doing, try and understand the basis of these experiences.

Kat -   So I understand that you're using a drug called ketamine to try and make people hallucinate.  My friend have this when he broke his leg.  Doctors gave it to him and he said that the doctors were fine putting his leg back together, but they were all talking backwards.  What can that tell us about hallucinations in the scanner?

Paul -   Well, the big advantage of ketamine is that you can control it.  You can control the dose that somebody gets.  You can infuse it, you can keep them at a particular level for a certain amount of time, and you can watch how their brain responds.  You're not reliant on the chance and randomness of normal hallucinatory experiences.  So we use ketamine as a way of producing very temporarily these experiences and seeing what it does to the brain as a way of trying to understand how the hallucinations or delusions might arise in the context of mental illness.

Kat -   And so, what do we think about what is going on in mental illness when people are having these hallucinations and delusions?  What's actually going on in their brain?  What have you found out so far?

Paul -   Well what we seem to be finding is that people with these experiences are actually getting false signals in their brain that the world around them has become surprising, and is sort of baffling their expectations.  They can have very strong expectations about what they're about to see or hear, and even if what they do see or hear actually fulfils those expectations, nevertheless, their brain is telling them that it is wrong.  And so consequently, they have to keep changing their predictions, rebuilding their models of the world, trying to understand the world in new, and evermore often bizarre ways.  And I think there's good evidence emerging across our work and a series of other studies elsewhere that this may be a fundamental deficit in certain mental illnesses.

Kat -   And so, really briefly to touch on this, we sometimes hear about some great creative artists, very creative people who are also judged to be mentally unstable or mentally unwell, do you think maybe that some people who are extremely creative are slightly unhinged in this way that their hallucinations are maybe coming to the surface more?

Paul -   I think that's a very interesting point and certainly, people have played with that idea.  My own feeling is that up to a point, the sorts of processes that might be deranged in hallucinations and delusions, up to a point, actually, having a slight derangement in those could be advantageous because it might lead you to look at the world in very new, and salient, and original ways that might actually give you insights that perhaps you wouldn't normally get by just predicting the world and it always fulfilling your predictions.  So I think there may be a link there, but I have yet to actually draw it and so, I wouldn't want to speculate too much.

Kat -   Absolutely fascinating then, a line between genius and madness.  That was Cambridge University's Professor Paul Fletcher.