The Wanderings of a Naked Brain
This month we'll be trotting the globe to open our minds! We soak up some naked brain wanderings, including visiting the banja, a Russian sauna, to be whipped by birch leaves. Plus, from the States, we'll meet the caring Robot trio, designed to help look after our increasingly elderly population, we'll visit a Brain Bank in New Zealand, keep fruit flies awake in Milan AND back in the UK meet a rocking professor who's addressing scientific gender inequality with music.
In this episode
01:56 - Visiting a Brain Bank
Visiting a Brain Bank
with Malvinder Singh-Bains, Auckland University
How a bank of frozen human brains is acting as a reference library, how a Hindu resolves conflicting religious and scientific beliefs...
In this show, we continue our quest, but this time, finding out New Zealanders are using a last quadruple approach to tackling Huntington's by looking at the human brain. We'll discover how a bank of frozen human brains is acting as a reference library and how scientists are creating human brain circuits in a dish in order to piece together the jigsaw of the disease. First up though, Professor Richard Faull and Dr. Maurice Curtis from Auckland University have set up a back of frozen human brains. This contains hundreds of brains from Huntington's disease patients and also, healthy controls from the general population. Their PhD student Malvinder Singh-Bains discussed her personal belief dilemmas with the project. She's been raised a practicing Hindu, a religion with strict funeral rituals. After death, Hindu bodies are cremated traditionally near a river, for example The Ganges and this cremation is important for transmigration of the soul from one body to another for reincarnation. Before this though, she took me on a tour of the research facilities.
Malvinder - Okay, now we're going to go into the Neurological Foundation of New Zealand Human Brain Bank. Long title but we call it the Human Brain Bank over here. If you just walk this way, and we have all our brain freezers isolated in rooms, no gloves on doors, so just through the door.
Hannah - We've entered into the brain bank room. So, it's got a massive freezer in here which is humming away. You might be able to hear it and there's also a fume cupboard over there where I'm presuming some dissection can take place into very clean conditions. Can you open up the brain bank and show us some of the samples?
Malvinder - I can, indeed.
Hannah - And the freezer is open up now and it's minus 80 degrees centigrade. So, it's keeping the brains in a very cold condition to preserve the tissue and all the proteins and the genes that are there.
Malvinder - Absolutely and we have a few of these freezers. So, we have the tissue stored and these columns that are kept in the minus 80 freezer and they're all designated with a number and they all code it specifically. We don't know who these cases belong to for security purposes and also for patient confidentiality. The tissue is kept in these biohazard bags. I just open up one of them. So here, we have one tissue block. We've designated it a case of H131. So, in this case, I picked out a normal one and we've also got the block number on it. So, SM4 stands for sensory motor block 4.
Hannah - So, that's sensory motor cortex. That's the band of your brain which runs kind of from ear to ear. If you imagine having a hair band or an Alice band, that's roughly about where the sensory motor cortex would be. The sensory motor cortex is involved in processing all of the sensory information that comes in through our bodies. So for example, sense of touch, sense of temperature and sense of self as well I think.
Malvinder - Absolutely. Sensory motor cortex is probably one of the most important cortical regions.
Hannah - So, can we open the sample without jeopardizing the integrity of the tissue, but open it and just have a quick look?
Malvinder - Absolutely. So, we have each of our blocks that are wrapped in foil. So, we snap freeze them using dry ice. I think this one has a few layers on it.
Hannah - We're unravelling now the block of human brain tissue.
Malvinder - So, this is a fresh piece of tissue and you can actually see the gyri.
Hannah - We can see, yeah. So, the human brain has these folds in it which almost make it look like a walnut and I can see now all of the gyri. So, there's like little folds coming into the brain which almost look like - I don't know - like a river that's flowing into the brain with little bits of blood which - that's how the brain gets its blood supply and the oxygen rushing to it and I can see that really intricate details are in this frozen block of tissue. It's quite awe-inspiring actually.
Malvinder - It's very real. When you see the brain this way, you'll know that this is such a precious gift from a person. You can even see the little tiny vessels on the top of the meninges. If you look very carefully, you can see little capillaries.
Hannah - And that's how the brain gets its oxygen through these little capillaries. It's through these vasculature which lies on almost the surface of the brain.
Malvinder - You can even see the separation between the grey and white matter. The grey matter contains all the bodies of the cells of the neurons and then the white matter contains all their processes. So, all the connections come through the white matter here and it's just very distinct. We haven't even stained the tissue. You can get so much information just from one block.
Hannah - It's beautiful, thank you. A quick question, would you donate your brain for medical research for this type of study?
Malvinder - Absolutely. I think the care that we take into the processing of every single block of tissue and just the brain as a whole, we treat these brains like as if it was our grandparents or our parents and I would certainly donate my brain with the knowledge of how well we treat the tissue here. With the Indian culture, certain different cultural groups amongst Indians, the Indian population, we have beliefs that the blood of our body is sacred and our organs are sacred, that the tissue is sacred. This is why when a person passes away, we practice the art of cremating so in other words, giving everything back to the earthy, so sending our ashes into the ocean and then passing on to the other side. So, the sensitive topic tissue donation i.e. leaving a part of yourself on Earth is very, very different for Indians. So for me, I've actually had an internal cultural battle as well. I actually wasn't allowed to donate blood at a point. And now...
Hannah - Because of your family's wishes.
Malvinder - Yes, because of the cultural commitments and also, the family understanding that blood is sacred. I brought my parents to the centre and showing them firsthand what we do and also, my parents can see how precious the information is, it's as almost as if that knowledge has armed them with the understanding that we can actually learn so much from what we have.
Hannah - Thanks, Malvinder.
08:34 - Birch Leaves in the Banya
Birch Leaves in the Banya
with Dr Andrew Irving, Dundee University, Dr Mark Cunnigham, Newcastle University, Dr Jamie Ainge, St Andrews University
I took a little interval to immerse myself in Russian culture. Andy Irving took me to the banya. And what, exactly, is one of those? A sauna, including getting whipped by birch leaves. All in the name of getting in touch with the local traditional and demonstrating how our body and brains regulate temperature, or so I was told....
14:36 - Is your sleep bank in the black?
Is your sleep bank in the black?
with Gero Miesenbock, Professor of Neural Circuits at Oxford University
Ever been up all night partying and then crashed out completely the next day? That's your brain sleep bank getting out of the red....
I caught up with Gero Miesenbock, Professor of Neural Circuits at Oxford University to find out what he's discovered from sleepless fruit flies.
Gero - So, flies actually sleep more than we do. They're quite lazy to spend about 16 hours a day of sleep and their sleep is usually concentrated during the night. They are active but they also take a very long siesta in the afternoon. So, they're most active in the morning and in the evening. It was actually controversial for a long time until about 14, 15 years ago where flies would actually sleep. But I think now, the evidence is quite clear, but you might wonder how does a sleeping fly look like. How do you know that the fly is asleep? It's similar to how I would know that you are asleep. First of all, we don't move or we occasionally twitch when we sleep, but there's no walking around or running around or flying around. Second, we don't support our body weight well. A fly obviously won't lie in bed, slump in a chair, but it also sort of crouches on the floor when it's asleep. The third criteria is that it has heightened sensory arousal threshold. So, like you and I when we're asleep, it takes a louder noise, a brighter light, a little shake to wake us up, right? And the same is true for flies. The fourth criterion is that, if you take away sleep, if you keep a fly forcefully awake, it sleeps more during the following day. So, it has to make up for that sleep deficit. And this, being able to make up for a sleep deficit is also the central theme of the research that I presented today. It's widely thought that we have two control mechanisms in our brains that regulates sleep. One is the body clock which will be familiar to many of you and the other one is the strange device that senses that you've got enough sleep or not. And that then determines that if you haven't got enough sleep, put it to sleep.
Hannah - And so, the body clock in the brain for example is as little kind of cluster of nerve cells. It's a region called the suprachiasmatic nuclei that's got about 10,000 I think nerve cells in there. So, about the size of a pinhead and it's, if you imagine, sticking a pencil up your nose, it would kind of eventually hit the suprachiasmatic nuclei and that's the human brain body clock that will regulate whether you need to go to sleep or when you fall asleep and when you don't, and when you're awake. And then there's also - you're saying - a second system called the sleep homeostat which can cause you to compensate for lack of sleep if I haven't slept very well last night for example, hopefully, I'll be able to get aligned tomorrow.
Gero - Exactly. You're probably normally not aware that there's two mechanisms that influence your sleep and waking because normally, these two mechanisms operate in sync. So, when your body clock says it's night time and you should go to sleep, your sleep homeostat which is this other mechanism - the one that determines whether you've got enough sleep - your sleep homeostat also says, "You've been awake all day, so please, go to sleep now." But as you know, there are certain situations where you can dissociate the two things and they start fighting against each other. One such situation is, if you've pulled an all-night - either for work or because you've been partying - and then you will have no trouble usually going to sleep in the morning even though your body clock will tell you to stay awake. There's also another frequently experienced situation which happens after intercontinental travel. I for example then suffer these extremely painful situations where my sleep homeostats screens over fatigue, but I still can't go to sleep because the body clock keeps me awake. So, there's these two brain mechanisms. I think of the sleep homeostat is actually holding the key to the big mystery by every animal that has been looked at needs sleep to survive. That's a fact. Every animal needs to sleep. It will die without sleep. But nobody really knows what sleep is for. There's various ideas around, but nobody has really gotten to the heart of the problem. I don't think that by studying the circadian clock, you will. I view the circadian clock as an adaptive mechanism that makes sure that you do your essential sleeping at times when it hurts you least. I mean, taking your brain offline is obviously a risky thing to do. You are more vulnerable and you also have a cost of lost opportunity because you could be working or giving interviews. But if you time these inactivities so that they interfere least with your lifestyle then that's an advantage.
Hannah - And so, the region of the brain that's involved in this sleep homeostat is almost like a bank account which measures whether you've got credits or deficits in terms of the sleep and whether you need to compensate or makeup for it.
Gero - The bank account is a very, very good analogy. The one that I use often is the thermostat on your living room wall. So, the thermostat measures temperature and switches on the heating if it's too cold. The sleep homeostat measures waking time and puts you to sleep if you've been awake for too long. So, it's a similar feedback system, a regulatory control system that determines whether you need to go to sleep and make sure that you get enough sleep.
Hannah - So, you're investigating this in the fruit fly. Are you keeping the fruit flies up, partying all night and then messing with their bank system so they're massively in the red and then trying to figure out how the brain senses that they need to put some sleep credit into their bank account?
Gero - That's exactly what we do, except we don't keep them awake all night partying. It's more sort of a Zero Dark Thirty, if you've seen that movie about torture in Iraq. It's more of that approach for a sleep deprivation like the secret service would do. What we have is, we have our flies in sleep monitors and we rattle them all night. So, whenever they try to nod off, the heavy weight drops down and rattles the whole apparatus. And so, they can't go to sleep. We found mutant flies that cannot put in these extra few hours of sleep. So in them, the sleep homeostat is broken. So, you sleep-deprive them and they don't sleep more and also their basal sleep. So, if you just measure how much they sleep during a regular day as I said before. A normal fly sleeps about 16 hours. These mutant flies, they sleep only 7 or weight. There's a result of this chronic sleep deprivation. They have severe cognitive impairments. How do you measure cognitive impairment in a fly that you can't talk? You test its ability to learn and remember. Like humans, if you sleep-deprive flies, they don't remember their lessons well. So, cramming before an exam is never good.
Hannah - And there's many mental illnesses that were associate with sleep destruction. So for example, Alzheimer's, dementia, even depression, and lack of motivation for example. And so, it's really crucial that we try to understand this bank of sleep monitor that we have on our brains. How on Earth are you measuring this in this miniscule fruit fly brain with their very small circuits of nerve cells in their brain whilst you're rattling and keeping them awake?
Gero - First of all, how do we measure sleep in a fly? We measure sleep by putting individual animals into glass tubes that are about 5 cm long and these glass tubes gets bisected by an infrared light beam and then when the fly walks up and down the tube, it crosses the light beam every few seconds or so. And we simply count how many beam breaks occur over time. sleep in flies is defined as any pause. There's no beam breaks for at least 5 minutes. So, it's not that flies have extremely fragmented sleep. They tend to sleep in shorter bouts than we humans do. But there's many episodes of sleep that extend for many, many hours. The project that we did started with a post doc (Jeff Donley) looking for flies that had neurons in their brain that could be activated artificially. He found that when he activated a specific small group of neurons, just about 12 cells in each hemisphere of the brain out of 300,000 of cells, when he turned on these neurons artificially, the flies would nod off. They would go to sleep. And then he looked at some of the genes that were active in these neurons and he found one that when it was mutant, (11:10) the fly is insomniac and also, unable to compensate for a sleep deficit. At that stage, a second post doc tried the project and he had the fabulous (11:21) skill of being able to insert a tiny, tiny glass tube into the brain of these flies and actually measure the electrical currents from these neurons. What he discovered was that in the mutant flies, there neurons were electrically silent. As I've told you before, Jeff discovered these cells because they become electrically active when a fly is sleeping. So, if you can switch these cells on, you'll sleep less.
Hannah - And that's exactly how the human brain works as well using - if we scale it up a bit, that's 100 billion nerve cells or so in the human brain but we use as electrical activity, electricity essentially that uses to switch a light on in your house in order to switch on particular areas of the brain and nerve cells in the brain switch on a circuit. So, the same kind of thing is going on in this fruit fly to switch on sleep using a very discreet 12 nerve cells within their brain.
Gero - Yes, brains are devices that run on electricity. That's something that was discovered about 230 years ago in Italy by Luigi Galvani who showed that when he touched a frog's slumber nerve to essentially a battery, the frog's legs twitched. So, this showed for the first time that all information in the brain is encoded in the form of electrical impulses. So, strings of electrical impulses represent what we see as stream of electrical impulses emitted by your ear as you listen to this podcast are then interpreted by other structures in the brain. Streams of electrical impulses are fired in my brain now hopefully as I'm trying to make sense and explain what's going on and also, streams of electrical impulses control the movements of the muscles that are important for me to produce the speech. What was surprising was that there's also dedicated cells whose streams of electrical impulses encode the need to sleep.
Hannah - And there's particular genes within these fruit flies that render those particular subset of nerve cells sensitive to electrical impulse. If you don't have the right version of those genes and you basically can't get sleep.
Gero - That's correct, yes.
Hannah - And so, does a similar thing happen in humans that suffer from insomnia?
Gero - So, there's a homologous structure of nerve cells in the human brain. These are also neurons that are electrically active while we sleep. These neurons like those of the fly that we have studied are the targets of general anaesthetics. So general anaesthetics activate these cells. As you know what the effect of general anaesthesia is, it puts you to sleep.
Hannah - And so, have you basically found the bank of sleep that can figure out whether you're in credit or debit for sleep?
Gero - I think we have found an element of the bank. We don't know whether it's the actual area that the account is kept, right where your balance sheet is being monitored. What we know is that what these neurons do is that they convey the message that you are in debit and that you need to go to sleep. How credit and debit get accounted is one of the pressing questions for future research. We'd love to be able to discover what actually is monitored in the brain to determine how high or how low your sleep balance is.
Hannah - What are the next steps for your research in the fruit fly in order to find out more about how problems with sleep might possibly lead to Alzheimer's for example, so problems with learning and memory, and problems with mood and depression?
Gero - In terms of learning and memory, this is a problem that's relatively straightforward to tackle in flies because we know how to measure their ability to learn and to remember. Now, they also and can control their sleepiness or their sleep deficit. So, what we are now trying to do of course is link these two processes in a series of very simple experiments. As far as something like depression is concerned, that's much trickier because we don't really know whether flies do get depressed or whether they're anxious, or whether they have any kinds of emotions like that. I think it would be surprising if they didn't have an element of fear or anxiety, but there's no well-established way to measure that yet.
Hannah - In terms of the gene that your post doc formed in the lab, is there a human homologue for that that's involved in insomnia?
Gero - There is many human homologues of this gene. Unfortunately, at this stage, too many. We don't know exactly which one the right gene is to look for and to my knowledge, nobody has really linked any of these genes to insomnia in humans, but that may just be because nobody has looked for an association.
Hannah - ; So, one of the things that you're really excited about or about your future work in your lab, can you mention some of the exciting studies that you're looking forwards to conducting?
Gero - I think sleep is a wonderful and exciting process because it's deeply mysterious and I think we have now sort of gotten into the stage where you can see the fork lifting a little bit. You can see the underlying mechanisms, the nuts and bolts, the wheels impacting with another gear, and so forth. So, it becomes more like clockwork rather than just a mystery. They're just very exciting. They've also recently found a way in which arousal promoting substances can actually alter that sleep switch. That's something that's very interesting. So, the general problem that I find myself thinking about more and more is the representation of time in the brain and processes that require time to unfold. So, sleep obviously is something that occurs on a regular temporal rhythm. If you think of, for instance the sleep homeostat having to monitor changes that occur gradually over many, many, many hours, it's not really clear how neurons do that, how they change the activity over many, many, many hours because as I've said before, information is encoded in tiny, very short impulses, electrical impulses. So, how can such a tiny electrical impulse that lasts a thousandth of a second be used to represent information over timescales of hours. A related question that we are currently studying is how information is represented over timescales of a few hundred milliseconds to a few seconds or minutes. And in order to gather that problem, we study how flies make up their minds. You probably know if you are faced with a difficult choice, you think long about the hard choice then about the easy one. We've recently discovered that flies take a moment too and we found neurons that are involved in that. Again, we found a gene that interferes with the process. And so, we can now study what's happening during these few seconds while a fly considers its options and then makes a choice which fundamentally is a problem that's similar that you have to hold information in your mind over time-periods, that alarmer than the impulse of a single cell.
Hannah - It's how the fly decides to stay, taking information in for a longer period of time until it makes its decision because it's a tricky decision that it's based with. So, it's abiding its time to collect more information before it makes its decision and you're trying to figure out what's going on in the brain in the fly when it's doing that.
Gero - That's exactly what we're trying to do.
Hannah - Will that information also give us some concept of the perception of time within our own minds?
Gero - I'm not sure. Possibly.
Hannah - Thanks to you Gero Miesenbock, Professor of Neurocircuits at Oxford University.
23:14 - Meet the caring Robot trio!
Meet the caring Robot trio!
with Professor Goldie Nejat, University of Toronto
Meet Brian: he encourages those with Dementia to eat. Casper helps with food preparation and Tangi who helps people get together for bingo!
Hannah - Hello. I'm Hannah Critchlow reporting from Washington DC for this special Naked Neuroscience podcast in partnership with the International Neuro Ethics Society and the Wellcome Trust where we'll be taking a journey into the future to explore how brain research will shape our future society. In the last episode, we welcomed in the era of the brain. We discussed the colossal cash injections that will allow us to peer into the human brain as never before and we start to discuss how, as a society and as scientists, we should best make use of the data that comes out. In this episode, we meet Brian, the robot who's helping the elderly remember to eat.
Brian - Hi. My name is Brian. You look very nice today. Please join me for lunch. Today's menu includes some pasta, apple slices, and water.
Hannah - And Tangy who encourages people to get together to play memory boosting games.
Tangy - Congratulations! You have won Bingo. Great job!
Hannah - And we discuss the ethics of robots in warfare.
Barbara - People are concerned about who is responsible if for instance, in the context of warfare, one of the robotics that's being used is out of control or is doing something that it wasn't planned to do because we've all had the experience of computers going badly wrong.
Hannah - All to come...
First up, with a growing elderly population whose cognitive abilities are declining, could robots help jog memories and support elderly people in their daily activities whilst also keeping them socially active? I met Goldie Nejat. She's director of the Institute for Robotics and Mechatronics at Toronto University. She spoke at the society's evening public lecture on how robots can help the elderly.
Goldie - The ideas that we're trying to design are socially assistive robots that can help the elderly. Robot can engage people in recreational activities, memory games, as well as help them with activities of daily living that they may find difficult to do on their own.
Hannah - And these are 3D walking, talking robots that can also emotionally and socially engage with the elderly?
Goldie - So, the idea is to have natural communication between a robot and a person. So, just like we display expressions through our face and body and through what we say, the robots do exactly the same thing and they're embodied in their environments so that they have a better engagement tool with people. So, the person can be engaged looking at a physical 3D robot in front of them.
Hannah - Do they look a little bit like a person or more like a robot? Are you almost tricking the elderly into thinking that they're interacting with a person?
Goldie - So they all look very robotic. So you can actually see the metal, the wires, the plastic, and that's done on purpose. And even with the Brian robot, for example, when it moves its arms you can hear the motors, there's noise, and that's all done because we want to make sure that people understand these are robots they're interacting with. We're not trying to fool them into thinking that these are people.
Hannah - And we're now going to hear a little sample of the type of prompting and encouragement that the robot Brian can give whilst trying to help the elderly remember to eat when they've got Alzheimer's.
Brian - That's good helping of food you have there. Please take a bite.
Goldie - So, Brian prompts a person through the steps of eating by encouraging them to, for example, to pick up their utensil, bring the food to their mouth, tells a joke during that time and the idea is that during the interaction, the robot is happy when the person's doing it. It displays facial expressions, happy big smile, excited voice, and gestures, body language. It gets excited, does a little dance when the person eats properly and the same extent, we also do a few different expressions where the robot will get sad if a person get disengaged in eating. So, if they get distracted and look away, the robot tries to reengage them by getting sad that they're not interacting with it anymore. And so kind of, that's the idea of how we display expressions too when a person's interacting with us. The robot uses that to keep a person engaged in eating.
Hannah - Some people with Alzheimer's might not remember how to make a meal and so you've developed Casper to help with that?
Goldie - Yes. So Casper and the idea is that when it's meal time, for example, Casper can go find the person, bring them to the kitchen, and really prompt them through the steps and make it a fun activity. You know, recipe finding, what they wanted to make and then go through the steps and show videos of how to exactly make the food, and then so that the person will enjoy eating the food after and they have some encouragement to do so.
Hannah - And then Tangy is a robot that assists with playing bingo.
Goldie - Yeah. So Tangy is a group robot. So the idea is that it facilitates a few people, you know, five to ten individuals playing a bingo game and the robot provides encouragement, calls out the bingo numbers, help if someone forgot to mark for example, a bingo number.
Tangy - B12 was previously called, please mark this number on your card. Wow! You are getting close to having bingo.
Goldie - And then again, celebrates with the person when they win bingo.
Hannah - And how do the elderly react to these robots? I mean, we're talking about a generation that weren't brought up with computers. So how do they react? Do they really engage with the robot?
Goldie - The robot engagement or interaction with the person is very natural. The person doesn't have to learn how to use the robot for example, right? It's pretty much the same way we interact with a person, another person. So the idea here is that the robot is engaging and displays expressions and behaviours similar to how we do. So that learning curve is gone. So this whole idea of using technology that you've never used before, the ease of use of the robot promotes its acceptance.
Hannah - And one part of the reason for studying this, is it to try and replace care as human social interaction, humans that would normally help and support these activities for the elderly and is that ethical?
Goldie - That's a very good question. So robots are being designed, in our case, to help the healthcare professionals. So we do actually - a lot of our interactions is with the healthcare professionals themselves to find out what they're needs and wants are. And really, we're trying to design robots as assistants or tools that they can use so they can focus their attention on, you know, high-level tasks that they need to do and not only they can do and the robot can supplement them. A lot of the jobs, there's a lot of turn-over rates because go in they're very overwhelmed and they leave the job. So the idea is that we help use the robots to minimize stress and the workload that they have, and especially since we have this growing population of elderly people, right? And we need to take care of them find a way. So we want to assist both the elderly individuals, right? To benefit, but as well as the healthcare professionals in helping them do some of this repetitive tasks that the robot could take over for them.
Hannah - And at the moment, how much would Casper cost?
Goldie - I should mention they're all kind of at the research and development stage. So the good thing about our robots is that we're trying to use off-the-shelf components, right? A lot of the sensors can just be easily purchased and integrated, so we've kept the costs down in designing and developing these robots. So to build something like Casper or Brian has cost us, maybe five to ten thousand dollars to do. And the idea is that as mass production happens of these robots, we can keep the cost affordable so that people can buy them.
29:10 - Sexism in Science
Sexism in Science
with Professor Tim Bussey, Cambridge University
Tim Bussey, professor, budding rock star and performer explains how he's addressing scientific gender inequality.....
Transcript to follow...