Titans of Science: Trevor Robbins
Titans of Science continues, where we talk to some of the major movers and shakers leading the way in their respective fields. This time we’re hearing from Cambridge neuroscientist, and expert on obsessive compulsive disorder - OCD - Trevor Robbins...
In this episode
01:10 - Trevor Robbins: What makes people tick?
Trevor Robbins: What makes people tick?
Trevor Robbins, University of Cambridge
In this edition of Titans of Science, Chris Smith chats to Cambridge neuroscientist, and expert on OCD, Trevor Robbins...
Chris - Trevor Robbins was born in London on the 26th of November, 1949. He attended Battersea Grammar School and then he read psychology at the University of Cambridge. Here he graduated with first class honours before embarking on postgraduate studies. He is a leading authority on the frontal lobes of the brain and the role that they play in mental and behavioural disorders like depression, drug addiction, OCD - that's obsessive compulsive disorder - and ADHD, attention deficit hyperactivity disorder. He's also an expert on degenerative conditions like Parkinson's and Alzheimer's. Trevor's currently the director of the University of Cambridge Behavioural and Clinical Neuroscience Institute and an emeritus fellow at Downing College in Cambridge. He has in the past served as the president of the British Neuroscience Association. In his spare time, he likes to play chess and has represented both England Juniors and the University of Cambridge back in the day. You certainly need your frontal lobes for that, Trevor.
Trevor - Especially when you get old like me. Unfortunately in chess you peak when you're in your late twenties and then when you get older you get worse. But I used to be a pretty good player.
Chris - As in you could give Kasparov a run for his money?
Trevor - I played someone called Mikhail Tal who was the world champion many years ago, and I got crushed by him in a simultaneous exhibition in London many years ago.
Chris - Let's kick off with one of the things that you're really interested in and that's OCD. This I think is trivialised a bit. People tend to just say, 'Well it's my OCD kicking in' as they reorganise things on the table in front of them, for example. But for the people who have this, they're absolutely plagued by it. Can you just paint a picture of what a day in the life of someone who's got that is like.
Trevor - It's a disaster. It's a really severe and disabling disorder. Imagine that you perform a ritual like washing your hands because you are scared of getting germs, but instead of washing your hands and then drying them off and going off to work, you feel compelled to keep on washing your hands and then they're still not clean enough. You're checking: 'no, not clean enough.' So you have to get the bleach out and you're using bleach on your hands and damaging your hands and spending hours and hours and never actually leaving your house so that people at work think, 'is he ill? What's going on? He can't hold down a job.' Eventually your whole life collapses. Personal relationships, everything goes. People become suicidal with severe OCD and they have to resort to very strong treatments, which surprisingly can be quite effective, but nevertheless are quite invasive.
Chris - And thanks to you, we now have a much better insight into why this is happening and what we can do about it. You talk about those treatments and we'll come back and talk about those in a bit, but let's, let's wind the clock back a bit. First, I mentioned that you got to university here in Cambridge, became very good at chess, what led you into psychology? That's what you studied here to start with. Why did you embark on that in the first place?
Trevor - Well, you know, actually Chris, I'm a failed molecular biologist because that's what I was really interested in. I did study biochemistry for a while as well, but I was inspired taking a course in experimental psychology to go the other way, to study the brain. I got very interested in what makes people tick: motivation. I was going to be a clinical psychologist, but then did well in the exams and you get this offer to do a PhD. So I did a PhD in very experimental work associated with the effects of drugs on the brain and behaviour, and I was particularly interested in drugs of abuse like amphetamine, which caused a lot of compulsive like behaviours. I guess that's where it started.
Chris - Perhaps you could just orientate for us the different bits of the brain that we're going to talk about and where they fit together to make the brain tick as it were.
Trevor - Well, amphetamine is a drug that releases dopamine in the brain. I think a lot of people have heard about this chemical messenger, which provides signals particular for structures in the brain called the striatum, which is right in the middle of the brain and has been associated with Parkinson's disease and the expression of motor behaviour. But I also think it's to do with emotions and thoughts. For a long time I studied how dopamine works in the striatum and its relevance to Parkinson's disease, for example. But then I got interested in what controls the striatum. It's a bit of the brain, but does it have a kind of supervisor? And the supervisors are your frontal lobes. These are the bit of the so-called cortical mantle of the brain (the outside bit, the huge bit of gray matter in the human brain) and the frontal lobes are right in the front, just behind your eyes, Chris. They send projections to the striatum, connections which control the striatum, and in a sense maybe control compulsive behaviours.
Chris - Different animals have different sized ones. We have a very characteristically overdeveloped front part of our brain. How does that manifest then in the way our brains work compared to say a laboratory rat?
Trevor - That's a really interesting question. First of all, I should say the frontal lobe has many different areas. There are 20 different areas, and we're trying to understand how they all work together, like a committee, to control behavior. Now, our relatives, the non-human primates, monkeys, they have similar bits of the frontal lobe. Not quite as well developed as us, but more or less the same thing. If you saw a monkey brain frontal lobe, it would be quite similar to a human one. Now you ask about rats, rodents, they don't seem to have all of the components of the frontal lobes. They have some of them, some of the ancient parts of the frontal lobes, but not some of the more modern parts, which probably give us our cognitive sophistication.
Chris - Does that mean then that these disorders that you are interested in don't manifest in a rat? They are unique to us and animals like us, like monkeys?
Trevor - I think some aspects of these disorders you can study in rodents particularly. So for example, I mentioned the striatum, well the striatum in the rat is pretty well conserved, similar to the human striatum. So to the degree that compulsive behaviour depends on the striatum, yes indeed, you can study this in other animals. But if you are interested in the frontal lobes, frontal cortex, really the full component of the frontal cortex, you probably need to study this in non-human primates or in humans.
Trevor Robbins: What causes OCD?
Trevor Robbins, University of Cambridge
In this edition of Titans of Science, Chris Smith chats to Cambridge neuroscientist, and expert on OCD, Trevor Robbins...
Chris - What do these different bits, you said there are multiple areas of the front part of the brain, what are these different areas doing and how are they controlling that core region, the striatum, to produce the behaviours that we see both in health but also in disease?
Trevor - This is the million dollar question. The frontal lobes in general exert what's commonly called executive function. In other words, it's a set of operations of controlling functions which affect behaviour in different ways. One of these is called working memory, which is our ability to remember phone numbers and then act on them. Another function is a very important one, inhibition. In other words, stopping you blurting out stupid things or stepping out into the road or making a stupid purchase. Another aspect is cognitive flexibility, the ability to organise your time to multitask, to switch effectively from one activity to another. And very importantly, two of our main controllers over behaviour are the so-called goal-directed system and the habit system. This cognitive flexibility has to constantly balance these two systems in order to optimise our behavior.
Chris - And how does that age and grow? Children characteristically do not have a lot of those things that you just mentioned, those traits, whereas hopefully you and I do, some of us more than others. So how does that change with age then?
Trevor - It's absolutely key because the frontal lobes, the frontal cortex, is the last bit of the brain probably that develops. And it doesn't really properly mature, I suspect, until you're about 25.
Chris - People say that this happens at different rates in boys versus girls. Is that true or is it just that all of us have still got a lot of growing up to do until we are in our mid twenties?
Trevor - There are subtle differences in boys and girls, but overall the point is that the frontal lobes aren't very operative very early on, for example, when you are three or four. That's an age where actually compulsive behaviours often begin to emerge. They may go away as the child develops and their frontal lobes mature, but in some cases they may persist. Now, the fact that we get more rigid as we get older is probably because the frontal lobes are diminishing in their role. Indeed the frontal cortex is one of the most vulnerable regions of the brain to ageing. So basically then you release all of these behaviours, which previously you've been able to regulate and keep under control.
Chris - So a person who gets dementia, for example, and it affects the volume of the front part of the brain, is that why people often say they seem to regress and they become childlike in some behaviours? Is that sort of unleashing what's always there, but it was previously kept in check by the frontal lobe?
Trevor - Well the most graphic example of that is the so-called frontal dementia, which is distinct from Alzheimer's disease. It's another kind of dementia and it's often expressed behaviourally in very outrageous ways. So for example, one way it's expressed is if you are eating in a restaurant with a relative who's got frontal dementia, they may lean over and grab your steak from your plate. Or they may do unmentionable things in public. So they completely lose their inhibitions because of the relaxation of the frontal lobes and as a consequence of its degeneration.
Chris - Why does that part of the brain burn out more quickly then? Has that evolved? Is that an evolved trait or is it just because it's so busy in your average person that it does clap out rather like a car being driven with the pedal to the metal all the time?
Trevor - I think you've answered it Chris. I don't think we know absolutely for sure, but it's probably to do with the fact that the frontal lobe uses a lot of metabolism and therefore is very vulnerable to energy demands.
Chris - Now returning to where we started, which is the link with diseases, you've explained all these important jobs it does and that normally it holds our behaviour in check. So how does it allow some of these conditions to manifest then like OCD?
Trevor - Well, our hypothesis would be that the weaknesses develop in its function basically. There's evidence in some cases of reduced grey matter in the frontal lobes. There's also evidence of what we call impaired connectivity. In other words, its connections with other regions, which you can measure in humans with brain scanning. And so because of these failures of communication over other areas, then you are going to get this dysregulation of behaviour.
Chris - Talk us through then, if one subjects people who've got these sorts of conditions like OCD to the sorts of brain scans you're talking about, what is wrong with the connectivity that means they tend to have the problems that bother them?
Trevor - Well that's again another million dollar question. We think that there's actually an imbalance in the frontal lobes and some of the areas become overactive and some become underactive. That's basically the story. As a means of therapy, one wants to rebalance the functioning of these regions. Now the region that becomes underactive is precisely this area that mediates what we call inhibition and cognitive flexibility and affects, as I said previously, the ability to switch between your goal-directed system, which is in another part of the frontal lobe function, and the habit system, which is a bit more primitive and depends more on the striatum, for example.
Chris - If you ask someone who's got this problem and they are getting to the stage where they're washing their hands with bleach, if you say to them, 'Do you think that's a sensible thing to do?' Do they know it's not helpful to do that, but they just can't stop it? Or does the nagging part of them think, 'No, I really am doing some good with this bleach?'
Trevor - That's an interesting question. I think probably both of those in different patients in a sense. So in other words, one patient would say, 'Well of course I know it's stupid to do this, but I just can't help myself.' Another patient might believe perhaps early on in the disorder that it's actually goal directed. But our hypothesis is that there may be a transition from that state to the more compulsive state where you just simply can't control it.
Chris - But why in some people is it contagion on their hands? They're worried about germs, but they're very happy with all other aspects of their life. Whereas another person, they'll be worried about thieves breaking into their house and stealing things. If there's something fundamentally wrong with the wiring in the front part of the brain, shouldn't they have all these problems all the time?
Trevor - I think they do. There's a lot of symptom substitution in OCD. You might start off with somebody who's worried about germs, but then you may show a transition to having checking problems or hoarding problems even. I think these symptoms can be substitutable and I think there's a general tendency to be compulsive, which is expressed in different ways. Now, that's a hypothesis, but I think there's some evidence to support that. It arises from this being a general problem, but why they fixate on particular things initially is probably due to specific experiences. If you are a bit compulsive and you experience the pandemic, for example, you might become focused on germs and that might exaggerate your existing tendency already to be a bit worried about germs. So, I do agree that's an interesting issue: why precisely did you get these particular symptoms? But I think they can generalise to some degree as well.
15:39 - Trevor Robbins: When does OCD appear?
Trevor Robbins: When does OCD appear?
Trevor Robbins, University of Cambridge
In this edition of Titans of Science, Chris Smith chats to Cambridge neuroscientist, and expert on OCD, Trevor Robbins...
Chris - When do you think it starts? Have you got evidence that even youngsters have got this but it doesn't manifest in a way that would be visible to their parents, their friends and so on? And it's only as they become adults it gets worse? Or is it that you're fine until you're in your mid twenties, thirties and then you've got a problem?
Trevor - It can occur quite pretty early on, in four and five year olds, and some parents I know have been concerned about that. Now it's really important that it's detected early because I think there's evidence that the longer it's untreated, the worse it gets. This is a real problem because it's very often not picked up until adolescence or even in adulthood. Very interestingly, sometimes you have adult patients who suddenly say, I've got OCD, and you interview them and you realise actually they had problems earlier on, but they didn't surface, they weren't referred to the appropriate clinicians, and so it festered and became full-blown perhaps as a consequence of some experience.
Chris - To what extent are all of us able to have these symptoms? Because I go around people's houses, for example, and I might see that all the CDs are in alphabetical order. The pencils will be on the side in a very specific way. The books will be nicely organised on the bookshelf. There's an innate human tendency towards being organised, isn't there? So to what extent is OCD just a manifestation of this but taken to extremes and is it therefore just a variant of normal?
Trevor - It's an extreme variant of normal. It's a very maladaptive, disruptive version of normal. But I think this is correct. Our hypothesis is that there is this general trait, if you like, which we can call compulsivity. And actually there are questionnaires, you can measure yourself on a compulsivity scale, Chris, and see what your score is. I think it does begin by looking at your overall map of activities. Suppose you've got hobbies, for example, stamp collecting or something like that, and you spend most of your waking hours stamp collecting. Well, that's probably okay. It's fairly adaptive and quite normal. But then if it starts intruding into other behaviours like going out and getting your shopping or even going to work, then you realise you've got a problem. Now, let's go back to something a little more obvious, like internet behaviour for example, going on the web and gaming, gambling behaviours, dare I say porn related behaviours, these are potentially serious disorders when carried to extreme, but of course we have most of these tendencies ourselves initially in the way that we organise our time.
Chris - Is there a genetic element to it? If this is a wiring thing and the brain wires itself up following instructions and recipes from our genetic code, does this therefore run in families?
Trevor - Well, let's begin with OCD. OCD certainly runs in families and there is a genetic basis. We don't know as much about the genetic basis as we do for something like schizophrenia. One of the problems in general with these psychiatric disorders is that they probably have many genes of quite small effect. You can't really talk about a single gene as you can in some diseases like Huntington's. Each of these genes, it's like a hand of cards and together they produce this behaviour which makes it particularly hard to study actually.
Chris - Presumably it's also hard to study because if you grow up in a household where people are behaving in a certain way, you've got to disentangle children copying their parents away from something they're innately compelled to do?
Trevor - Precisely. We've done a lot of studies where we've studied OCD patients and their first degree relatives and you know what? Their first degree relatives tend to be a bit cognitively inflexible and a bit disinhibited. And even the first degree relatives may have some small brain changes, which may be more pronounced in the patients, but they're in the same direction. I definitely think that there's a family basis of this, but as you say, teasing apart the genetic part from the environmental part is tricky. I think both are probably important.
Chris - If we've got some genetic leads we can follow, we've got some magnetic resonance imaging leads we can follow, we can begin to look at mechanisms, and if you've got mechanisms you can begin to think about how we put things right. What is emerging in terms of the best way to manage these sorts of conditions?
Trevor - Let's talk a little bit about genetics again. Some of the genes associated with OCD seem to be related to a chemical messenger in the brain called glutamate. Glutamate is very important for the excitatory part of your activity in areas like the frontal lobes. You can actually measure glutamate and its partner GABA, which is its opposing inhibitory influence, using a technique called magnetic resonance spectroscopy. That's simply based on measuring with a huge magnet the way that chemicals resonate under that magnet. You can then measure actually how much you've got of each of these neurochemical metabolites if you like. Now we did a study recently using the seven Tesla magnet here and showed that patients with OCD have an increased level of glutamate in part of the frontal lobes. And moreover, this increased level correlated with their symptom severity. It correlated with a questionnaire which measured how compulsive you are. We even found in healthy volunteers as control subjects a similar result, even though they're not as compulsive as OCD patients. And we also showed with an experimental test that measures the bias to habits, a relationship with this increased glutamate level. So we would argue that one thing one needs to do is to improve this balance of glutamate and its partner GABA in the frontal lobe, and there may be pharmacological ways of doing that,
Chris - Have people not also experimented with electrical stimulation where you put deep electrodes into the brain and use that to drive different patterns of activity. That seems to give some people relief?
Trevor - Absolutely. Neurosurgeons actually still perform what we call cingulotomies, which are removing a bit of this hyperactive region of the frontal lobes, and it actually works. It's the only bit of psychosurgery that's ever seemed to work. However, there's a gentler way of doing that, as you've mentioned, using so-called deep brain stimulation. Very fine electrodes are put into the brain - as used in Parkinson's disease a lot to unblock the system - and there's a similar rationale with OCD and it works. It can only be given to patients where nothing else works: cognitive therapy, drugs. They're desperate because they're performing rituals most of the time. We were lucky enough to be in the first UK study recently with Queen Square London where some patients experienced an enormous relief of their symptoms. I think one lady was confined to her house with her OCD, but after deep brain stimulation she was able to go out and interact socially and even get a new boyfriend and go on holiday. That's what I call a real clinical effect.
23:25 - Trevor Robbins: Can AI detect mental health disorders?
Trevor Robbins: Can AI detect mental health disorders?
Trevor Robbins, University of Cambridge
In this edition of Titans of Science, Chris Smith chats to cambridge Neuroscientist, and expert on OCD, Trevor Robbins...
Chris - When you were doing these sorts of studies, you're using MRI scans. You put a person in a scanner and you're interrogating which bits of the brain are talking to each other. Often it is painstaking and it takes absolutely ages because you're looking for very subtle signals. We've now got tools like AI, haven't we? Are you beginning to look at those images now through the lens of AI to ask it to spot some of the more subtle things we might have missed?
Trevor - I think this is definitely the future. You can get so far with the rather sophisticated analyses that have been done already. However, putting two and two together often requires something as clever as AI to notice that a change here and a change there are actually related to one another and part of the same general circuit. So I think that's definitely something in the future.
Chris - Since presumably if we can see what circuits are doing to each other, we might then have some drugs which are discreet for those circuits and which, which might help to rebalance that, that imbalance that you've spotted that little bit better and with fewer side effects.
Trevor - Yeah, I mean that would be the great aim and we've certainly ourselves been developing this idea using a class of drugs which may reduce glutamate for example, in those areas where it's more active. I mean that would be an interesting approach. But there's a general problem with drugs, as you know, that the receptors for these drugs are often all over the brain and so that's what leads to the side effects. You know, you might be normalising something in one area but overdosing or whatever another area, and that is problematic. So how do we get that specificity? You can't necessarily rely on where the receptors are. Maybe you can get lucky about that. In the future, we may need to use techniques such as chemogenetics. Chemogenetics of course are only used in animals at the moment, but with this technique you can take a pill which activates or inhibits a particular neural circuit in the brain.
Chris - I've not heard of this. How far down the track is that?
Trevor - As I said, it's only been used in experimental animals so far, like mice. But what one has to do is to put a virus in the brain, a benign virus, that is done actually already in Parkinson's disease in some cases. And that puts a receptor in the brain, which has been engineered so that it doesn't respond to anything normally, but you put it in a particular circuit and then when you take a pill, a pill that's designed specifically to activate that receptor, you can achieve an excitation or an inhibition of that circuit. And it's the way of really analysing in minute detail, which circuits are in control of different behaviours. We are not going to be able to do that in humans <laugh> for quite a while yet because potentially it involves surgery. But it's a very interesting approach, particularly for severe patients. It's obviously more specific than something like deep brain stimulation, for example,
Chris - Any notable figures back in history who were affected? Because when one looks back in the history books, once we see what we think is a modern phenomenon, we then begin to see evidence that perhaps other people had this back in the past. Anyone stand out?
Trevor - Martin Luther, the Reformation, he was an obvious OCD patient, if you look at his biography. Kurt Gödel the famous mathematician. Howard Hughes, of course the great filmmaker, who had this problem with germs. His entire staff spent all of their time cleaning the house and cleaning his food and so forth. Charles Dickens had a bit of OCD. Samuel Johnson, Andy Warhol, Cameron Diaz, the actress. So it's interesting that in many of these cases people have been able to cope with this problem and be pretty effective in life, but many of them really are on the cusp of OCD and didn't really have a full blown diagnosis. Another example is David Beckham.
Chris - It slightly troubles me that if we were to go down the path of offering people help, we might have not had Charles Dickens and we might not have been able to bend it like Beckham.
Trevor - Well, indeed it becomes an issue about when these behaviours become excessive, but it's up to really the people and their relatives to understand that and then to get some help.
Chris - And in the years ahead. Now looking back at where you've come from and where we've now got to, what are the questions that you would really like to, in the years you have left on Earth, see answered in the OCD and frontal lobe space?
Trevor - What I really want to do is to achieve effective treatments. I wouldn't say cures, but you know, near cures for OCD. That would not only give me a lot of satisfaction to help people, but it would also serve to confirm some of the theories that I have about how the brain works. And I think that dual motivation is very important to me. I'm very interested in how the frontal lobes control behaviour, how neurochemical systems modulate this function and how this develops. And also its relationship to philosophical issues. For example, free will, which is clearly very important here.
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