"This programme contains some scenes which some viewers may find upsetting" "OCD." "We hear those initials quite a lot these days." "We use OCD to describe our friends..." "Whenever he eats his dinner, he's always got to leave a tiny, tiny bit at the end." "He'll never finish it off." "My sister's got OCD." "She's very particular about things." "My boyfriend, he's quite OCD." "He likes everything to be kept in a neat order." "..we know OCD celebrities..." "I think David Beckham's a bit OCD, isn't he?" "That comedian, Jon Richardson." "Jon Richardson." "..OCD appears in BBC drama series..." "Bay four, please." "No, no, no." "I don't want her in bay four." "Bay three is free." "We haven't got time for this." "Can we just move her?" "Move this bed?" "I said, we haven't got time." "..we even use OCD to describe ourselves." "All my friends tell me I'm OCD." "The minute they've moved off my sofa," "I'll be sorting the cushions out behind them." "Always wash your glasses first." "OCD!" "I'm kind of a little bit OCD." "But just more relaxed OCD." "I'm not, but I think you are." "I like a tidy room." "Most of us use OCD to describe people who want things just so." "Or excessively perfectionist." "Fussy." "Quirky." "Funny, even." "The truth is much, much more serious." "Fear." "Anxiety." "Responsibility." "Fear." "Fear." "Death." "Terror." "Powerlessness." "Helplessness." "Despair." "I would put guilt in there." "Guilt." "Self-defeating." "And heartbroken." "Absolutely heartbroken." "My name is Uta Frith." "I'm a psychologist." "I'm a psychologist because I want to understand how the mind works and why it sometimes doesn't work very well." "And that's why I'm interested in OCD." "Because, by understanding the disorder, we might be able to work out how to overcome it." "But more than that, we will also discover more about how mind and brain relate to each other and perhaps come closer to revealing who we really are." "OCD is a disorder that affects between 1% and 2% of the population." "That's about one person on every bus." "That's about ten people in the average theatre audience." "It's 20,000 people watching this programme right now." "Nearly a million people in the UK." "I want to find out more about the reality of living with OCD..." "At the moment, the main thing that bothers me is the whole killing thing." "I keep thinking I've killed people." "My OCD keeps telling me I've killed people wherever I am and wherever I go." "..and discover the latest ideas about what OCD actually is." "One explanation is that this probably has to do with looking for hidden risks." "Dangers." "Hidden dangers." "Not overt danger, but hidden or potential risks." "I'll be learning about some extreme solutions to severe OCD." "Yeah, we have to move it down." "We never knew before DBS that we could change anxiety within a second." "It's unheard that you can induce or reduce anxiety with stimulation in a few seconds." "And exploring new research that sheds light on the brain circuits thought to be involved in OCD." "This was something that everyone had been dreaming about doing, to specifically activate one particular connection and then see what the impact of that was on behaviour." "First of all, so we're really clear," "OCD isn't about wanting things done in a particular way, being extra fussy about arranging things." "OCD stands for obsessive-compulsive disorder." "And this is what the International Classification of Diseases has to say about it." ""The essential feature of the disorder" ""is recurrent obsessional thoughts or compulsive acts."" "And it goes on to say that..." ""Obsessional thoughts are repugnant to the person who thinks them" ""and that the compulsions are what the person does" ""to try and get rid of these unwanted thoughts."" "We all have unwelcome and intrusive thoughts from time to time." "Have you ever stood on top of a cliff and thought," ""I could jump down there"?" "Or maybe seen a knife and thought, "I could stab somebody with it"?" "Well, these would be rare thoughts, very fleeting, very dream-like for us." "But for people with OCD, these kind of thoughts are a constant tormenting stream and make their life a nightmare." "If you pick up that knife, you don't know where you're going to go with it." "You make a cup of tea for someone." "Did you put bleach in it?" "Are you poisoning people?" "You might be." "I'd be chanting, "I'm clean, I'm clean, I'm clean." ""I'm super-clean, I'm super-clean."" "Trying to write a letter, trying to post a letter," "I have to check it a million times to make sure I haven't written anything offensive." "My pregnancy was very traumatic because I was absolutely convinced when I was pregnant that I was carrying a parasite, as opposed to a child." "Why is that person looking at me?" "Oh, God." "Did they see me look?" "Oh, God." "I need to ask them something." "I need to know something about them." "Now I need to know two things." "Because I have to have two things." "I can't have just one." "I can't have three." "I have to have four." "Richard and his girlfriend Kathryn are visiting relatives." "Car travel often takes a bit longer for Richard, as it means potential exposure to contaminants." "So I'd wipe up to here to make sure it's wiped where it touches across my chest and shoulders." "And that would be it." "That's the process I go through of wiping down the car whenever I feel like I've touched something dirty and then touched the car." "Inside, huge efforts have been made to accommodate Richard and his OCD." "As you can see, there are sheets on the chairs, there's sheets on the table." "Er, not what you'd expect when you walk into somebody's home." "Erm, but this is because of my OCD." "It's not an incredible hardship to put a few sheets on chairs, et cetera." "But I understand it's not the norm." "A fly coming into the room, landing on the sheet..." "If he's sitting on the sheet, the sheet has to be washed, he has to go up, his clothes have to go in the wash." "He showers, changes." "It saps the life out of me, to the point, kind of less than a week ago..." "..four o'clock in the morning and I had to shower and two o'clock in the afternoon, I finished." "And people say to me, "Well, just change," you know?" ""Just don't do it." "Just don't do these things." "Get better." "Do..."" "You know?" "And I wish for an hour that they could have the brain that I have, where they could just have to cope with the sheer amounts of thoughts that I have." "It's almost like Richard has two personalities." "He's got happy Richard and OCD Richard." "And happy Richard is the Richard that I know and love and want to be around all the time." "Erm, OCD Rich is unintentionally rude and mean and he snaps and..." "Yeah, it is hard to cope with because it's almost like he's a different person." "My main fear is anything that I feel is contaminated going into my body through food or drink, basically." "That's the main thing, because that can't be washed off." "That can't be bleached." "That can't be wiped down." "So what are you doing, Richard?" "Er, well, I'm going to make lunch in a minute and I'm just washing my hands first." "Erm, just making sure none of the soap splashes on the sides of the kitchen." "Erm..." "And I'm turning the tap off with my elbow..." "..so that my hands don't get dirty again after touching the tap." "And cos I can't use any paper towels or tea towels to dry my hands," "I'm flicking them dry." "Erm, and then..." "..getting out a plate." "Getting out the bread." "Then I have to wash my hands again." "Again, flicking it dry, living with the hardship of soggy bread." "And then making sure that my hands come out without touching the sides of the bread." "So I'm now obviously washing my hands again before I touch the sandwich." "What's your worry about the camera people being in the kitchen?" "Erm..." "Well, to put it bluntly, touching the side of the kitchen with your clothes or any part of yourselves and me never being able to eat in the kitchen again." "I haven't seen where the camera's been, so I can't visually check with myself, "Oh, it's clean."" "So I don't know, I've not cleaned it." "And that's the fear of... can I eat the food?" "Is the food contaminated?" "So, obviously, just making sure it's all going on the sandwich OK." "I would then fold everything away, put it back in the fridge." "Are you going to eat it?" "I'm not." "Because it would be too much for me, I think, if I'm being honest." "Erm..." "So this is a demonstration?" "Yeah." "I've not done everything exactly how I would cos it would take too much time." "And it's too much to deal with." "So what's going to happen to the sandwich?" "The sandwich will probably go in the bin, if I'm being honest." "I've got to figure it out in my head how I can throw it in the bin, making sure that the plate doesn't get contaminated by the bin, which is rubbish and, obviously, for me, a massive source of fear and..." "..contamination." "And you can see I'm getting uncomfortable and..." "..agitated." "This is where it's the hardest for me." "This is the biggest fear, the food and drink." "And this is every day." "I think you're avoiding getting rid of the sandwich." "Yeah, I'm really worrying about it." "Yeah, it's really bothering me." "Oh, honestly, I'm just really stressing out at the minute." "Can we stop, please?" "I'm sorry, can I, erm..." "Yeah." "RICHARD SNIFFS EMOTIONALLY" "You know why I'm doing this, don't you?" "Yeah, of course." "This is what people have got to see." "This is OCD." "This is how it affects people." "RICHARD SOBS" "Throwing the sandwich in the bin." "And this is my life." "And I don't get to go home and leave it at the job." "And I don't get to leave it at the door when I go anywhere, cos it follows me." "And this is my life and it's hell and I wouldn't wish it on anyone." "And I don't know how I'm still here..." "..cos if I was stronger, I'd have killed myself a long time ago." "OK, you're stronger than you think." "OCD is a modern term for a disorder of the mind that's been known for at least 2,000 years." "For most of that time, we were powerless to help." "We had no idea where the mind came from." "After all, when confronted with the body's organs, it's not always obvious what they do." "We still talk about "the affairs of the heart" and this is because it was once thought that the heart was the source of our emotion." "But it isn't true." "In fact, everything we are, our personality, our expediencies, the love we feel for others, it's all down here to the brain." "Saying, "I love you from the bottom of my brain" doesn't quite have the same ring to it, I admit that." "But the fact that it's true is an extremely powerful idea." "Once we realised that the mind comes from the brain, there was at least a target to aim at when it came to trying to change the fate of people with mental illnesses." "The early attempts to cure mental illness, including OCD, were actually pretty crude." "We shudder to think that in the early part of the 20th century," "Iobotomies were actually quite common." "And here we can see what happened to the brain." "You can see this dark, scarred area which happened because the surgeon put the scalpel through the eye socket and wiggled it about a bit and severed the connection of the front part of the brain with the rest." "And amazingly, sometimes this did relieve the symptoms of OCD." "And, of course, sometimes it didn't." "If, ultimately, we are to fix the broken mind, it seems that we must also understand the brain." "Here in Cambridge, they're hard at work pursuing that extremely audacious goal." "'I've come to see Trevor Robbins, who is an old friend of mine." "'Like me, Trevor is a psychologist." "'His group is undertaking a study 'looking at what is actually going on 'in the brains of OCD-affected people.'" "Trevor, you have done work on addiction, but how come that you're now turning your attention to OCD?" "So drug addiction used to be thought of in terms of things like dependence and withdrawal." "Still quite important, but what people have realised, people like Barry Everitt and myself, is that addiction involves compulsive behaviour." "And what do we mean by compulsive behaviour?" "We mean behaviour that really is performed, you know, almost automatically." "So you're talking about habits that happen outside our control." "You know, we have this distinction between goal-directed behaviour, where you perform actions for consequences." "So I show goal-directed behaviour taking up this." "You want a drink, you pick up your cup and you have a drink of coffee." "Or you take a drug to get an effect which you enjoy." "But then, goal-directed behaviour can become habitual or automatic." "You just pick up a cup without thinking." "Yeah." "You didn't want coffee particularly, you just did it." "Right." "And these two systems, the goal-directed system and the habit system are in balance in the brain, the brain systems, and we think both in addiction and in OCD, the balance is swung in favour of the habit system." "Ahhh!" "Too much habit and too little goal-directed behaviour." "The habit way of thinking can be induced by the drug dependency." "But it might also exist as a predisposition." "A way of thinking revealed by this deceptively simple experiment." "You have to work out the rule for correctly sorting these cards which, as you see, vary in shape..." "Right." "..colour and number..." "OK." "..of symbols, OK?" "That's wrong." "Oh..." "Leave it there." "Just take the next one." "That's correct." "'Trevor's first rule seems to be simply match by colour.'" "That's correct." "'Simple.'" "Correct." "Correct." "Incorrect." "'Trevor has now changed the rule." "'Could it be number?" "'" "Incorrect." "'So let's try shape.'" "Correct." "Correct." "Correct." "Correct." "I think you've learned it." "So what did you do there?" "Obviously, you found the rule, which is to sort by colour." "Sometimes by colour." "And then I surprised you by saying you were wrong." "You did." "I didn't really know quite what to do." "You showed a lot of cognitive flexibility, actually." "You weren't too rigid, Uta." "The problem in OCD is that they stick with it for much longer." "So they show, you know, a lack of flexible thinking here." "Not responding to change." "So you could actually say that OCD is a kind of addiction to certain types of behaviour?" "That's a good way of thinking about it." "I think it's a kind of behavioural addiction." "And the whole point of this project is to make the comparison with drug addiction to see whether OCD is another form of behavioural addiction." "On the other side of Cambridge in part of Addenbrooke's Hospital," "Trevor's team are looking at what happens in the brain when people are demonstrating cognitive flexibility." "And in this instance, there's really good motivation for learning quickly." "So we're ready for the first shock?" "I can't avoid it!" "It's quite annoying." "I can't avoid it." "At this point, you can't avoid it." "So next we'll be setting up Anna and she will be set up with two sets of these on her left wrist and her right wrist." "The experiment is designed to see what cognitive flexibility looks like in the brain of OCD patients, compared to volunteers without OCD." "Today, Anna is one such volunteer." "What she's going to be seeing is three squares that are going to be shown here on this screen in a minute." "This picture means that Anna will shortly receive a shock to her left wrist, which she can avoid by pressing the left foot pedal as soon as possible." "And this one means a shock to the right wrist, which she can also avoid by pressing the right one." "If she presses on time, she will not be getting any shocks." "And it will be perfect avoidance." "So right now she's getting that and getting the shock." "Left wrist and the shock." "After she's got used to avoiding the shocks, one set of electrodes are removed." "Like most of the volunteers without OCD," "Anna stops pressing the associated foot pedal straight away." "So what about OCD patients?" "They find it very hard and very many of them, they will continue to press, even though they know." "So you've communicated with them and they say," ""I know I don't need to press any more."" "But they can't stop." "They can't stop." "And afterwards, they rationalise this, just like they do in everyday life." "So what do they say?" "They say, "Well, I did it just in case." "" It seemed better to me to press." "" I thought I really should still press."" "So they see relevance to this pressing." "On its own, this tells us little more than the card-sort test." "It's what the scanner reveals that's really interesting." "These OCD patients who keep pressing, even though they don't need to..." "You can see in the brain this region that is hyperactivated while they keep pressing." "So we have a direct link here between the behaviour and the brain." "Annemieke's experiment identifies a specific area deep within the brain." "But that's not the end of the story." "To find out more about this brain area," "I've come to St George's Hospital Medical School to see consultant pathologist Paul Johns." "So what we have here is a preserved human brain specimen." "So this has been immersed in preservative solution, an embalming fluid, essentially, and it gives it this firm, rubbery consistency." "The fresh brain, as we call it, would actually have a very soft sort of jelly-like consistency." "To think that this is the essence of a human being." "That's right." "Some people say the appearance of the brain is disgusting, but I think it's an absolutely beautiful structure." "Oh, no!" "It's absolutely amazing!" "And, obviously, this is the seat of a lifetime of memories and thoughts..." "Everything." "Yes, yes." "..and behaviours." "In terms of obsessive-compulsive disorder, the part of the brain that's been most consistently implicated is the basal ganglia." "Right." "The basal ganglia can't be seen from the external surface." "In order to show that, we'd need to actually slice into the brain." "So I'm going to use the brain knife." "Oh..." "And we're going to cut quite close to the mid-line." "Yeah." "A short distance away." "Yeah." "And we're going to make one longitudinal slice through the brain." "And then we can see the internal anatomy." "Oh, this is amazing!" "Yeah, absolutely beautiful." "What we have here is this dark, grey structure, and this is the caudate nucleus." "What we find is that the connections to the basal ganglia are arranged in a set of loops." "So the one that we're interested in in obsessive-compulsive disorder begins here, in the orbital cortex." "The basal ganglia are a collection of structures sitting, as the name suggests, at the base of the brain." "They receive widespread connections from different brain areas and project back to the same regions to form closed loops." "The basal ganglia help to select among competing thoughts and behaviours." "People with OCD, hyperactivity in some of these loops makes it difficult to filter out certain types of thought." "One explanation is that some of the basal ganglia loops that pass through the caudate nucleus are part of a kind of safety checking mechanism." "And a real ancient mechanism." "Probably an evolutionary ancient mechanism, that's right." "And this probably has to do with looking for hidden risks." "Dangers." "Hidden dangers." "Not overt danger." "Mm-hm." "But hidden or potential risks." "And this is where the checking comes in." "So, for instance, if you may have dirty hands, the idea normally enters your head, it would enter anybody's head that there are germs there, there might be contamination, so then I should wash my hands." "And then, when you do that, that provides a kind of closure." "You have checked that the germs have been dealt with and you feel satisfied that you've checked and it stops there." "That's enough." "But in a pathological case there is no stop." "Exactly." "It just doesn't stop." "There's no natural stop." "It's easy to assume that the relationship between the brain and the mind is all in one direction." "It starts with the brain and it ends with the mind." "But what's more fascinating to me" "But what's more fascinating to me is that we now know that the mind can change the brain." "So when it comes to treating mental illness, it's just as valid an approach to work with the mind as it is to interfere with the brain." "While I was studying psychology in Germany," "I heard about some exciting new research being carried out at the Maudsley Hospital in South London." "And I was lucky enough to be accepted for a course that was then called abnormal psychology and we now call clinical psychology." "But I wasn't the only foreigner there." "Another was a young doctor called Isaac Marks." "Isaac had studied medicine in his native South Africa and had come to the UK to pursue a career in psychiatry." "In the 1960s, traumatic and invasive treatments like lobotomy were slowly giving way to the first psychoactive medicines, some of which also had troubling side effects," "like the surgeries they superseded." "Meanwhile, Isaac Marks and his colleagues were embarking on a radically different treatment for anxiety disorders called behaviour therapy, which focuses on treating the mind, rather than fixing the brain." "I remember a patient who had agoraphobia..." "..and I suggested to her that she could perhaps try to go out and meet her fear, so to speak." "And she became extremely angry with me and said," ""But, you idiot, that's my problem!"" "And she got so angry with me she left the consulting room and went out." "Oh...!" "We found that she could actually go out and still survive the experience." "That's remarkable!" "And she then did this a few times and she lost most of her fears." "So why is behaviour therapy so specifically useful for the treatment of OCD?" "Well, in obsessive-compulsive disorder, the rituals are usually engaged in, it appears, to switch off the anxiety produced by particular circumstances." "Of course, they don't succeed in doing that switching off." "That's right." "So, for example, if they touched the outside door handle outside a toilet, they might then feel anxious and go and wash their hands for half an hour afterwards." "And we teach them to not engage in any ritual, in any washing, for at least half an hour or preferably an hour." "But to experience the anxiety during all that time?" "In order to experience the anxiety, which will then gradually diminish and the desire to wash their hands will diminish." "The challenge in treating OCD is the many forms it can take." "What if you can't stop counting the number of times that you blink?" "You get embroiled in it." "You start to count, and then you try to stop yourself counting." "Even when you stop yourself counting you know, um...it's there." "Initially, I was convinced that I was HIV-positive." "Is the iron off?" "Is the oven off?" "Did I lock the door?" "Why is that piece of rubbish there?" "Should I touch it?" "I think I should touch it twice." "If you don't do this, your family are going to die." "The promise of behaviour therapy and CBT is that any fear can be confronted and overcome, however extreme it might be." "For Sophie, that's pretty extreme." "At the moment, the main thing that bothers me is the whole killing thing." "I keep thinking I've killed people." "Mm." "My OCD keeps telling me I've killed people, wherever I am and wherever I go." "I have to always check behind me if there are any dead bodies, and stuff like that...yeah." "I've come back to the Maudsley Hospital where I trained and where Isaac first practised behaviour therapy, to see how the people who work here now are treating OCD." "Today, I'll be observing one of Sophie's CBT sessions with her therapist, Laura, from behind a two-way mirror." "And what were the rituals he was trying to get you to do?" "Oh, different things," "like tapping things and stuff like that, which I haven't done in a long time, but I refused to do them, so..." "Gosh, what a bully." "Laura is helping Sophie see her OCD as something separate to her - a bully, who she can resist." "How did you feel when you, sort of, didn't do what he wanted you to do, then?" "Um...in that moment, I was very anxious, but I just tried to ignore it, tried to ignore the OCD." "When we did a measure after seven sessions, she was still in the severe range at 30, but after 14 sessions, she was down to 18, which is the cut-off between mild to moderate, um...and my hope would be, at the end of treatment," "she'll be down in the mild range, if not the non-clinical." "So I know you said this is the thing that worried you the most..." "Yeah." "So I managed to get hold of a bit of a rope." "Mm-hm." "Does that make you..." "How anxious do you feel, looking at that?" "I don't like it, but..." "Do you want to give that a go round my neck and make sure that is a long enough piece of rope to strangle somebody?" "Just stand up?" "Laura is working on Sophie's obsession that she might have killed people, and she's brought along some potential murder weapons." "This is where it's serious." "She has to do something that, in her mind, would be, like, the worst possible." "Definitely, you could?" "Yeah." "You reckon you could with that?" "Yeah, yeah." "Brilliant!" "What we can see here is the procedure that was initiated by Isaac Marks in full progress." "It's all about confronting your fears." "It's all about experiencing that maximum of anxiety, which is almost unimaginable." "Remind me why we're doing this, cos we know it's going to make you feel anxious, don't we?" "Yeah." "To tolerate the anxiety." "Yeah, absolutely." "And to, uh..." "..just practice, um...ignoring OCD and not listening to what it says." "Absolutely." "How have you been getting on with the loop tape?" "Yeah, I've been sometimes playing it." "Yeah?" "Yeah." "To help Sophie tolerate her anxiety in the real world," "Laura asks her to listen to a looped recording of herself repeating her darkest fears." "Are you ready?" "OK..." "Rather than the natural response of avoiding her anxieties," "Sophie is about to face them head-on." "All right, are you all set to go?" "Yeah." "All right." "I'll see you back at the clinic." "Go on - go for it." "'You have just strangled somebody." "You've just killed somebody." "'You've just strangled somebody." "You've just killed somebody." "'You've just strangled somebody." "You've just killed somebody...'" "This task is designed to make Sophie as anxious as possible." "'You've just strangled somebody." "You've just killed somebody." "'You have just strangled somebody...' She is actively thinking about her fears in public, while having to hand the tools she would need to act on her intrusive thoughts." "'You've just strangled somebody, you've just killed somebody..." "The whole exercise is to help Sophie learn that her anxiety will eventually subside, even when it's extreme, and that nothing bad will actually happen." "'You have just strangled somebody.'" "Fantastic - how are you feeling?" "A bit more anxious." "Yeah?" "Really well done." "You've done a really great task, cos you're saying you've got lots of worries now about having killed somebody." "Yeah." "And you keep looking at what you were carrying around in your bag on the table - you had the rope there and you've got the belt there." "Really well done." "What's so heartening is that here's this young woman who has been through hell for a very long time and now, due to behaviour therapy, she's getting her life back on track." "And that's absolutely marvellous." "I thought I was going to be like that for the rest of my life." "I genuinely thought that that was my life," "I was never going to get better, cos it was that bad." "It's wonderful to see that behaviour therapy has stood the test of time." "The approach of helping the mind to help itself has been beneficial to many people who, like Sophie, struggle with OCD." "It's as good an indication as we're likely to get that brain and mind are two sides of the same coin." "But as effective as behaviour therapy can be, some patients don't respond to the treatment." "Nanda lives in the north of Holland." "Her OCD appeared in her early teens and has plagued her life ever since." "I was in high school and I was walking with one of my classmates to the supermarket and she said to me, "You have bad breath."" "And I was so shocked by that and from that moment on, I was obsessed with it." "Nanda's days are spent at home, with the curtains closed - alone, worrying." "When I touch something - doesn't matter, it can be anything " "I worry about there's something landing on my body or clothes that looks strange, or smells bad." "For example, I worry about, um...food between my teeth, or snot in my nose or around my nose." "I worry about the hairs of my eyebrows - are they in the same direction?" "My obsessions as well as my compulsions together," "I spend half of my day...yeah, and time." "It's so strong, it feels like you're fighting against some kind of monster or something." "Nanda's obsessions and compulsions are all-consuming." "She is unable to work and has abandoned most of her hopes and dreams." "I would like to have children, but I decided not to have children because, um...that's impossible with my OCD." "I can hardly, erm, provide for myself and look after myself, so...yeah, I'm not able to look after a child." "I have followed through therapy for 14 years now, but my OCD is still here." "Over the years, Nanda has exhausted all the treatment possibilities." "Except one." "She's preparing to travel to Amsterdam for a treatment called deep brain stimulation" " DBS." "For the treatment to work," "Nanda must undergo a five-hour operation to implant electrodes into her brain." "The electrodes generate a magnetic field that reduces the electrical loop that's implicated in OCD." "The effect can be tuned to suit the individual patient and is, unlike traditional surgery, reversible." "The DBS, it sounds extreme, but actually, I think it's quite..." "It's more natural than the medication." "I'm actually not nervous at all about it, no." "I'm very excited about it." "Actually, I was more nervous for this interview with the BBC than the surgery itself." "In the UK, deep brain stimulation isn't routinely available for the treatment of severe OCD, but here in Holland, psychiatrist Damiaan Denys has prescribed the surgery for nearly 50 of his patients to date." "DBS helps 60% of our sample and helping means that, in some cases, there is complete remission." "In 10-15% of the cases, there's no obsessive compulsive disorder any more." "It completely disappears which is, I mean, huge - it doesn't exist in psychiatry." "That's a huge effect." "So deep brain stimulation is not just important because it's a treatment - it, as well, changes our view on psychiatry, the pathophysiology of the disorders." "Because traditionally in psychiatry, symptoms, from a neurobiological perspective, were associated with neurochemical substrates in brain areas." "Right." "What we see with DBS is that psychiatric symptoms are associated with electrical activity in circuitries." "So this is a complete new paradigm in psychiatry." "It's a new way of seeing disorders and seeing symptoms and their neurological roots." "So this could even have implications for the treatment of, say, depression?" "Sure." "Schizophrenia?" "Yes, of course." "I think it changes our perspective on the neurobiology of psychiatry in general." "It learns..." "Because we never knew before DBS that we could change anxiety within seconds." "It's unheard that you can induce or reduce anxiety with stimulation in a few seconds." "And that's something that's related to electrical phenomena, because it goes so incredibly fast." "It's the morning of Nanda's operation." "THEY SPEAK IN DUTCH" "I've been invited to observe proceedings." "You are Uta?" "I'm Uta." "Nice to meet you, finally." "It's just nice to say hello before the big event, the big day." "Yeah." "Yeah, I'm very excited about it." "I'm not..." "I'm not nervous at all." "This is good, isn't it?" "Yeah." "This is very good." "You should be relaxed." "I'm happy about it, yeah." "Neurosurgeon Rick Schuurman will be performing the procedure." "The trick is that we're going to implant through one borehole in the skull." "We go straight down into the intended target, and this on both sides." "Now, in order to navigate this electrode to the right position, uh, we have a frame that we will mount to the head of the patient." "So the next step now is to get an MRI scan." "Because the frame is fixed to Nanda's skull, its precise location relative to her brain will be used to guide the electrodes to an exact spot in the basal ganglia." "But, of course, plunging electrodes through Nanda's brain is not without risk." "To find the best path through the brain to the target, there are couple of criteria." "First of all, we want to end up in the right space, of course." "Roughly, it will go in here." "But we have to check whether that route is possible at the cortical surface." "Mm-hm." "So I can change the path and put it a bit more to the side." "Be safe." "Just a bit further away from that vessel." "This is the predetermined path towards the target." "It should enter here." "So we mark it...there." "What we have to do is enter the skull here with the electrode and I have to make an incision that is not going straight over the electrode, but curved around it." "Now here, I cannot curve like this, because then it will be visible..." "Mm-hm." "..which is not good in any patient, but especially in this patient, in whom the perception of her body image to the outside world is part of the obsessive-compulsive disorder." "Same on the other side..." "So, we're going to make the borehole at the place where we put the marking on the skin." "DRILL WHIRS" "There's one." "Rick fits plastic covers over the holes he's made in Nanda's skull." "They will hold the electrodes in place and re-seal the holes." "And here is the gyrus that we were aiming for." "We make a very small hole in it, just large enough to pass the electrode through." "Rick is now ready to introduce the electrodes." "First, he uses a probe to make a path through Nanda's brain to the precise depth required." "So the sound that I hear now is a representation of the resistance of the tissue, the impedance." "Now it's in the air, it short-circuits, so we don't hear anything." "MACHINE BEEPS" "And this is it going into the cortex." "PITCH BECOMES HIGHER" "And if we go a little bit deeper, you hear it going up and this is because we leave the cortex and go into white matter." "That's it." "OK - we can turn that off, because it's an ugly noise." "Now there is a path to follow, the electrode itself goes in." "It's a bit wobbly, this electrode, but it's stiff enough to follow the trajectory that I just made." "The precise location is determined by the geometry of the head frame, but Rick uses a portable X-ray machine to double check." "So this is the electrode and you see the four different contact points that that electrode has." "Yeah..." "We seal the hole with a sort of glue...yeah." "Both electrodes are now in place." "All that's left to do is feed connecting wires to Nanda's chest, where a battery-operated power pack will eventually provide the stimulation." "So this is the stimulator." "So we put the stimulator in the pocket - it's connected." "Gosh, it really is just like a pocket, isn't it?" "Yeah." "Amazing." "It will have to be replaced when the battery is depleted, which is quite soon." "Really?" "After maybe a year and a half?" "In a few weeks, once Nanda has recovered from the surgery, the stimulator will be activated." "Only then will she know how effective the procedure might be." "I'm pleased with how this went." "Yeah, very..." "Straightforward." "Nice." "No problems along the way." "Very, very good." "So she will stay under the anaesthetic for...?" "I think they're going to wake her up just now." "NURSE SPEAKS IN DUTCH" "DBS is not a guaranteed "cure" for OCD." "It's a fairly crude technique, affecting relatively large brain areas." "But it opens up the tantalising idea that it might one day be possible to electronically manipulate individual neurons." "This is Pittsburgh, Pennsylvania, where psychiatrist and neuroscientist Susanne Ahmari is trying to do just that." "Susanne and her team are trying to understand the OCD affected-mind by understanding the neural circuitry in minute detail." "We have a scale problem." "The numbers of connections and numbers of neurons that are all communicating with each other at the same time is incredibly large." "What we need to be able to do is to look at how specific connections from one of these regions to the other region are actually talking to each other, and in order to do that, we need to be able to get down to the neural circuit level" "to specifically activate one particular connection and then see what the impact of that was on behaviour." "So, when I was in graduate school, this wasn't even on the radar." "But in 2004, a new technique was invented called optogenetics." "It works like this." "A specially engineered virus is used to carry DNA into a nerve cell which instructs the cell to make a new protein." "This protein on its own has no effect on the cell, but when it is exposed to light of a certain wave length, the protein changes shape, allowing ion flow across the cell membrane, making the neuron hyperactive" "or, depending on the wave length of the light used, stop working altogether." "In theory, neural pathways controlled at the flick of a switch." "This all sounds very impressive - and, you might think, theoretical." "But Susanne is working with mice whose connection between their frontal lobe cortex and their basal ganglia - the striatum - has been optogenetically treated." "So what we're doing now is actually taking the mice that have had the optogenetic protein implanted into their cortex and we're going to be turning the laser on to hyperstimulate those connections between the cortex and the striatum." "The mice are connected to a fibre optic cable which allows their brains to be bathed in laser light, so that, in this case, the affected neurons will be hyperactivated." "First of all, they tend to develop this increase in grooming behaviour over time." "In addition to that, though, what we're finding is that they also have changes in cognitive flexibility, and so we can do behavioural tests that actually tap into that, in a way that's very similar to what we do in people," "and so we can see how this changes over time during the optogenetic stimulation." "The ability to switch individual circuits on and off is a state-of-the-art tool in neuroscience research, but Susanne and her team are implementing a technology that takes the technique to another level." "So this is incredibly exciting technology that is really hot off the presses and it's the development of tiny little microscopes." "They're 1.9 grams, extremely light, and we can implant them into the brain in any region that we're interested in looking at." "Not only can Susanne switch neurones on and off, she can now see directly the effect this has on neural communication." "So what we're looking at here is actually a view down the lens of the microscope into the orbital-frontal cortex of the mouse, which allows us to see many different neurons all firing in concert at the same time," "so that we have this real symphony of neuronal communication happening here." "And each of these white spots lighting up is an individual neuron that's firing and communicating with its neighbours." "This is really, um...a huge leap from our current abilities to intervene in the brain through things like drug therapy." "Even with the electrical stimulation techniques we have right now, they're a little bit more precise, but they stimulate a broad variety of neurons that are in their local area." "With optogenetics, you get one set of neurons." "And it does provide this proof of concept that we may be able to find other technologies that will allow us to turn neurons on and off in very precise ways in very specific groups of neurons, with time control as well as spatial control" "in order to develop new treatments." "Back in Holland, it's now two weeks since Nanda's operation." "Today, she's come back to the hospital to have her stimulator switched on." "DAMIAAN:" "Hi, hello." "Hi, welcome." "THEY SPEAK IN DUTCH" "Nanda's stimulator will be programmed using a simple hand-held computer." "So what we will do is we'll start with, like, a low voltage, and then gradually go up." "OK." "Yeah?" "Yeah." "OK." "Once communication is established between Nanda and the computer, the stimulation can begin." "It feels like you're a little bit tipsy." "Yeah?" "Yeah - like you drank two glasses of wine, something like that." "OK." "Yeah." "Yeah." "But no side effects, no other things that are...?" "OK." "Yeah." "So..." "I suggest we go up a voltage." "Yeah, to the next stage?" "Feel more anxious?" "Yeah, I feel more nervous." "A little bit more nervous and anxious now." "OK." "Yeah." "The obsessions are coming back, I know this." "Yeah?" "Yeah." "Obsessions coming back?" "Yeah." "During the waiting..." "Yeah?" "Is it possible to compare them and see which is the best for you?" "Yeah - the previous one." "The previous one?" "Yeah." "OK." "Yeah." "Shall we go back to the 3, then, the 3V, and see...?" "Yeah." "THEY SPEAK IN DUTCH" "OK." "Yeah." "Mm, yeah." "But this feels better." "This feels better?" "Yeah." "OK." "I feel..." "You feel the difference?" "Yeah, I feel...very strange." "Yes, you have to adjust to it - it's strange for the first time, and people..." "Yeah." "Yeah." "Why are you crying?" "Ah - it's such a good feeling." "I almost forgot how it felt like." "Yeah." "I gave up hope of feeling like this." "Ja." "Ja." "So...it's actually wonderful." "And that...yeah." "I feel my obsessions are still there, but they're more..." "In the background?" "In the background, yeah." "OK." "Yeah, great." "Yeah." "Yeah." "That's why we did it." "Yeah." "And that's a good sign." "Yeah." "It's a very good sign." "Congratulations." "Thanks." "The last 50 years have seen a phenomenal increase in understanding how our minds work and therefore, we've been able to make huge advances in treatments of disorders like OCD." "But OCD presents us with a paradox." "It does confirm that mind and brain are one and the same thing, but it also suggests that they can be at odds with one another." "Now, most of us, most of the time, just forget that it's our brain that produces all our thoughts, and therefore, we can easily dismiss the unwanted ones." "OCD removes that option." "Patients with OCD feel utterly responsible for their thoughts, however repugnant they may be." "I find this a most surprising insight not just into OCD, but in what it means to be human." "I'd like to be free of the compulsive behaviour and the behaviour that limits my life and stops me being good at things." "Yeah, I think everybody who has it would welcome...welcome a little bit of respite, especially when it's very strong." "I would want to be free of OCD completely, but I wouldn't take away my experiences from having OCD." "On the other hand, I kind of want to keep the person who is meticulous for the reason that he wants to be a good person and I want to be the person people like for it, but I don't want to be the unhappy person that it's made me." "I would initially say, "Yes, I'd love to be cured."" "You know, I'd love to return to the carefree young person I was." "But it's shaped who I am today." "It's made me more empathetic." "If somebody could wave a magic wand and say, "Clive, it's going to go away forever tomorrow,"" "I'd say, "Yes, please."" "Only if in its place, you could give me a more positive, effective coping mechanism, cos what's going to come in OCD's place?" "That's the fear for me." "If there was no OCD in my life any more," "I would have so much time and I would have confidence that I've completely lost and..." "TEARFULLY:" "It would be the most amazing thing in the world, but I don't think it's ever going to go." "Since we finished this programme," "Richard has decided to try CBT treatment for the very first time." "Sophie has now successfully finished therapy and is looking forward to starting A-levels." "Nanda still struggles with OCD, but hopes that it will diminish with fine-tuning of the stimulator and CBT."