Understanding the OCD Brain part 2: Animal research at Cambridge


My name is David Adam and I have obsessive-compulsive disorder OCD. I want to find out more about my condition so I’ve come to the University of Cambridge to find out how so at the top scientists in the field are studying this disorder and why, sometimes controversially, this involves the use of animals. As our understanding of specific pathways in the brain increases, it’s our contention that there are specific pathways that go slightly wrong in OCD and those brain areas correspond to the same brain areas that we studied in experiment animals and shown the same symptoms of rigidity and thought using the same tests but the differences in the experimental animal were able to understand the mechanisms by which this rigidity occurs which we can’t in humans because we can’t use interventional techniques to test the causality of the involvement of that area in thinking or behaviour. So that’s the theory but what does research with animals actually look like well it can be a bit difficult to find out because institutions like this usually keep this work pretty secret but actually Trevor Robbins has arranged for me to see some of it for myself so we’re going to see research with humans, we’re going to look at brain scanned and we’re going to look at what’s probably among the most controversial work with marmosets but we’re going to start with a staple of research at animals we’re going to look at studied for OCD involving the laboratory rat. So these rats are part of a study looking at checking behaviour and we’re interested in the circuits of the brain that control checking behaviour. We use surgical techniques to just inactivate part of their frontal cortex and through our studies of checking behaviour we can see that this rat who has this part of his frontal cortex inactivated shows a higher level of checking behaviour than we would normally expect. Okay so you put the rat in, to do this experiment but we thought we’d leave it to do its thing and look at footage of one that you filmed earlier. So just describe what we’re looking at. So this is a picture of the inside of our test box and you can see on the right hand side there are two levers. When the rats are training on this test then we show them a light above the lever that is the correct one to press and they learn that very quickly, they learn to associate that light with a food reward. Now when we’re looking at their checking behaviour we take that light away and instead we give them a lever at the back of the box, so this lever on left hand side is a lever that they can press to give them access to the light above the correct lever to press. So it puts it on? So they press one lever to show which lever to press to get the food. Yes so they can effectively check on this lever at the back of the box for information about where to go next. But then sometimes they just return back again and again and keep checking, keep checking to see if that light is turned on or off. Right. And and do the rats with the changes in the brain then do that more? Yes, so the rats we’ve just seen with disruption to the circuits in the brain that we think are involved in OCD show much higher levels of checking behaviour than we would expect and this is an indicator that perhaps that part of the brain is somehow controlling checking behaviour. Right and in this case the checking is it’s a complete waste of their time because if they were to go to press the lever they’d get the food. It’s a waste of time it takes them away from the part of the task that’s actually useful for them which is.. Which is eating because we think the more time they spend checking the less time they get to eat. Yes. But of course rats are quite different to humans so Angela Roberts Professor of behavioral neuroscience has offered to show me what we can learn studying a closer relative of ours, the marmoset. So I’ve just been to see Dawn and we met her rats but I understand you you are working with a different animal. Can you tell me about that? Yes, so we’re working with a new world monkey called the common marmoset and we’re using the mamoset because whilst the rodent brain in some ways is very similar to that of humans, the primate brain has the much more closer resemblance to the human brain and when you’re studying these kinds of complex human behaviours then ultimately at some point you need to study a brain that’s a lot more similar to human than a rodents. So even though Dawn told me then that the mouse brain is similar enough to a human brain was was that that not enough information I mean, why do you need to do it with … We’ve gained a considerable amount of knowledge from studying the rat brain but ultimately the, if you compare a rat brain with the human brain the most important part of the brain for information processing is something called the cortex which sort of over lies the deeper structures the brain and that cortex in a rat is probably makes up about twenty eight percent of a rat brain. The human brain the cortex makes up eighty percent or besides the brain and then in monkeys it’s sort of somewhere around about 60 to 70 depending on the species so there’s far more information processing going in the cortex going on in the cortex of a monkey compared to a rodent and given that highly complex behaviours in humans are ultimately being controlled by that information processing going on in cortex that’s why someone on the line you need to be able to do some of these studies in monkeys. Now using primates in science is about as controversial as it gets you know I’ve met many even fully committed scientists who don’t think we should be doing it. So why should we?l Well, I mean the answer that ultimately comes in the suffering that you see in patients with in case of what we’re studying neuropsychiatric disorders. Sixty percent of patients can’t be successfully treated very effectively with the current therapies whether that’s cognitive behavioral therapy or drugs, pharmacotherapies. And we really do need to generate a much better understanding of the kinds of brain circuits that are involved in controlling these complex behaviours in order for us to actually generate the new, new generation of drugs or therapists and in order to do that we have to turn to animals and we have to turn at some level to a primate which has got the complex brain that you see in a human. And ultimately it’s about weighing the balance and we all, we all have to make that decision about what we feel comfortable about working with but you having to balance the the studies we’re doing in primates versus the kinds of suffering that humans are under with some of these disorders which can be debilitating and for years they’ve been on one drug therapy or another one and it hasn’t worked along with all the side effects that go with taking drugs and so ultimately you’re weighing up well should we let this person continue suffering or should we do careful controlled restricted studies in animals that we think are really important and particularly in primates. Well why can’t we just do that work with humans so I have OCD why can’t you just look at my brain and and and try and work out how those treatments might be developed. Well we’ve gleaned lots of information about looking at your brain and other people’s brains with regard to some of these and disorders and we get a lot of information about what areas are brain are more active or what areas of the brain are less active compared to someone which doesn’t have that disorder but the problem with that is ultimately the informations correlation and what you don’t know is whether those changes that you’re seeing are they actually causal to some of the symptoms you’re experiencing or are they for sample compensatory? So is this bit of the brain that we’re seeing is more active is it actually more active and causing your problems or actually is it just tried to compensate not very well for the problems that you’re experiencing and you can’t address that causal question with a human that’s where you have to go to an animal because then in an animal if you’ve got those two changes in activity we can actually make those changes in an animal we can over activate one bit of the brain, we can under activate another bit and look to see which one of those potentially produces a behaviour that’s similar to a behaviour you’re experiencing. So what I want to show you here is a marmoset performing a particular tasks that we have been using which is quite useful for trying to understand some of the repetitive behaviours that you see in OCD sufferers. This particular marmoset that you can see they’re these little metal tubes just coming out of its head here and that’s because we’ve implanted what effectively what they call cannula in a one-off surgical operation we implant least annually into the brain of the momma debts allowing us to target a particular brain region this is a special surgical cement that is keep feed can you lean plate it sounds quite extreme so the monkey lives with these two tubes it’s Frank does it does it bother it no they don’t it doesn’t seem to bother them at all and their partners don’t seem to mind them takes no notice of them sometimes some of the partners will groom it so they’ll find them grooming around the area but and the map the Marmot Ector who’s got the canyon II sort of sits there enjoying his grooming from his partner so no they don’t think too bothered by it at all once it’s in place so there’s an image of a monkey with tubes coming into its brain it is is about as severe as it gets probably for people and and those are the kind of images that are used to try and counter animal research I mean would you do that sort of thing in a human well yes I mean when you do some of the surgical treatments for example Parkinson’s disease and for OCD deep brain stimulation you know you are having to insert devices into the brain and electro is all I know right now and in order to be able to perform these treatments so in that sense it’s it’s what’s being done in patients as well but of course here we’re using it to ask the experimental questions of when we temporarily activate a particular part of the brain what are the effects on that and the reason that’s a really important question to ask and sort of bills on the research we’ve done before in the past we tended to make permanent lesions so you’d make you destroy a small localized region of cell bodies and look at the effects of that in order to try and localize where some of these deficits are coming from but now as the approach we’ve sort of developed over the years is that you can actually inactivate these areas temporarily so if I haven’t use cannula placed firmly in the brain you can infuse drugs down them which we’ll just act for the short period of time that they are around and in which case it may be to inactivate an area or to activate an area depending on what you’re trying to mimic that seen in patients but then once the drugs worn off 20 minutes half an hour afterwards 45 minutes afterwards then the that part of the brain goes back to working normally again in this task then so what the moment that they’re doing they’re being presented with two colored Stingley on the screen and they’ve learned actually some previous day that this red and yellow one just rewarded if they respond to it where’s this other blue flower isn’t rewarded if they respond to it and so as you can see this animal knows that is in the apparatus happily pressing away the red and yellow luminous every time you responded on it there’s a little pussy sounds which comes on telling introduces available and then he’s licking redtube analogies to get into reward but the interesting part of this is that suddenly halfway through this session we’re going to change the relationship between us communal award so having been responding to the yellow and red stimulus for so long getting the board here we go everything to yell you’ve got it wrong so that’s kind of put him off a little bit and he does it again because it has always been rewarded and suddenly it isn’t so an animal normally will make few of those repetitive behaviors to the wrong stimulus getting it wrong but then he loved to start thinking oh I better do something else so then he ends up touching the other stimulus and you’ll see eventually does start to touch the other students is just under there but for us we’ve got this reward so now we can start this realizing learning oh it’s other stillness now that’s rewarded what’s interesting about this task is that firstly quite a few years ago now we showed that a particular part of the prefrontal cortex the orbitofrontal cortex which is just above the orbits hence its name if you inactivate that bit of the orbitofrontal cortex it causes animals to be more reflective in their behavior so it doesn’t stop them learning this discrimination they’re happy to learn that the yellow and red stainless is awarded but when suddenly halfway through the task whose relationship has changed they find it very difficult to change their behavior and so them stickier they just carry on responding to the stimulus that was rewarded but actually isn’t reward anymore and they no longer getting reward for it but they take much longer to switch and this task is quite interesting because it’s been used in patients with OCD and some patients with OCD you see very marked changes within the orbitofrontal cortex the very area we know oughtn’t to this task of twitching in this task we see changes in activity in the area of the brains of patients with OCD when they’re performing this task we even see it in first degree relatives and so we’re going interested in trying to understand the circuit involved in this kind of behavior because it may give us some insight into ultimately you know the development of compulsions so this is one one example of a test that we’ve been using because it does seem to have quite a lot of applicability given the effects we’ve been seeing in OCD patients and also the relationship with the drugs they’re taking in the next film I find out how this work in rats and Mama’s eps relates to what we know that further frame and what better way and to look inside my own brain you

6 thoughts on “Understanding the OCD Brain part 2: Animal research at Cambridge

  1. Thank you for your work to help people with mental illness, and thank you for showing how careful, considered, and humane animal research really is!

  2. SOME ALTERNATIVES TO THE USE OF ANIMALS IN TESTING INCLUDE

    in vitro (test tube) test methods and models based on human cell and tissue cultures

    computerized patient-drug databases and virtual drug trials

    computer models and simulations

    stem cell and genetic testing methods

    non-invasive imaging techniques such as MRIs and CT Scans

    microdosing (in which humans are given very low quantities of a drug to test the effects on the body on the cellular level, without affecting the whole body system)
    _NEAVS _

  3. I agree totally about the use of primates (specifically the rhesus macaques) in scientific experimentation as they're important in research within a number of scientific avenues, but feel that we don't need any other type of animal in the science lab though as they're generally physiologically and systematically different to us humans, and as such I therefore believe the only animals that should be, and need to be used in science is that of the aforementioned subspecies of macaque monkey, being as it's still the most commonly used/valued monkey in biomedical (and other) scientific research, favoured today over any other monkey species due to it's anatomically similar structural features to that of humans, and perhaps even somewhat a physiological resemblance to humans too.

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