Panel News Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF
In this issue...... Issue no.17 New facilities: MEG scanner, what does it do?
People in a vegetative Depression: state: Trying to Are they understand aware? it better
Also...... • PhD student research • A famous research participant • What’s going on at the bottom of the CBSU garden • Visiting Scientists • The Bioresource Welcome!
This edition of Panel News begins with a very big thank you to all our Volunteers for their continued support - your help with our research is essential, and we could not carry on without you.
The UK Medical Research Council (MRC) is a national organisation funded by the UK taxpayer. It promotes research into all areas of medical and related science with the aims of improving the health and quality of life of the UK public and contributing to the wealth of the nation. Here at the Cognition and Brain Sciences Unit we investigate fundamental human psychological functions in areas such as attention, memory and knowledge, emotion, speech and language, and develop experimental methods for doing this.
The Memory Group focuses on the basis and organisation of long term memory, particularly episodic memory of past events, and semantic memory of words, people and things. Experiments with volunteers and patients show how these are normally structured and which abilities are retained or lost in disorders such as Alzheimer’s, semantic dementia, and head injuries. The Emotion Group research spans a broad range from the detailed analysis of perceptual mechanisms of emotion recognition, using neuroimaging, neuropsychological, and cognitive methodologies, through investigations of attention, executive and memory mechanisms in healthy participants and in those with emotional disorders, to the development of novel therapeutic interventions and their evaluation in clinical trials. Researchers in the Attention Group are studying how the brain copes with conflicting demands for its attention and what systems are involved. Problems of selective attention, spatial cognition, consciousness and cognitive control are investigated. Both normal cognition and disorders are studied, including unilateral neglect, blindsight, Parkinson’s Disease and attention deficit hyperactivity disorder. Behavioural studies are combined with a range of physiological methods, including functional neuroimaging. The Speech and Language programme is concerned with the study of human language as a cognitive, computational, and neural system and aims to explain how normal adults understand language. Finally, the Methods Research and Infrastructure Group develops and implements methods in support of the scientific research programmes at the CBSU. The expertise of the group is in the three principal areas of Statistics and Mathematics, Physics of Magnetic Resonance, and Imaging Data Analysis.
Our on-site facilities have been greatly expanded recently, with the MRC demonstrating its confidence in our research by investing over three million pounds in the purchase of equipment. This means that we now have a functional Magnetic Resonance Imaging (fMRI) scanner housed in a new purpose-built building at the bottom of the garden, and a Magnetoencephalographic (MEG) scanner situated in our testing laboratory area. Having our own fMRI scanner means that we no longer have to conduct all of our studies at the Wolfson Brain Imaging Centre at Addenbrooke’s Hospital (although patient scanning is still carried out there). The MEG scanner provides us with a non-invasive neurophysiological technique that measures the magnetic fields generated by neuronal activity of the brain. Both these state-of-the art technologies are valuable resources made available for use by all our neuroscience partners in Cambridge (including several University departments) and will ensure that we remain at the forefront of research for many years to come.
William D Marslen-Wilson (Director of the CBSU)
02 Panel News | CBSU | 2007 Contents
Detecting awareness in the vegative state - 4 Are people in a vegative state really aware?
The MEG scanner - See how the CBSU is keeping up 6 to date with the latest brain imaging techniques.
What’s going on at the bottom of our garden - 8 Find out everything that’s been happening inside
PhD research at the unit - Looking at what the 10 CBSU Students have been up to over the past year.
The Bioresource - Find out about an exciting new 12 way you can volunteer to help medical reseach.
Depression - Taking a look at depression and trying 14 to understand the effects of it.
A famous participant in the CBSU’s research 16 programme - Find out who.
Visiting Scientists - Find out about working at the 18 CBSU from a visiting scientists point of view.
Panel News | CBSU | 2007 03 Detecting Awareness in the Vegetative State
Adrian M. Owen (Attention Group)
n 2006, scientists at the MRC Cognition and brains to the responses that we see in healthy Brain Sciences Unit, together with their volunteers undergoing the same experience in clinical colleagues at the Wolfson Brain our fMRI scanner in Chaucer Road. Last year we Imaging Centre, Addenbrooke’s Hospital, made a startling discovery. We showed that a I patient who had been diagnosed as vegetative showed that a woman who had been diagnosed as in a vegetative state was in fact consciously could not only understand speech, but she could aware and was able to make responses using only also respond in ways that allowed us to conclude her brain. The discovery, published in the journal that she was consciously aware. The woman had Science, showed for the first time that functional sustained a severe traumatic brain injury in a road magnetic resonance imaging (fMRI) could be traffic accident. She was physically unresponsive used to determine if such patients are consciously and fulfilled all the criteria for a diagnosis of aware when existing clinical techniques are vegetative state according to international unable to provide that information. The finding was reported in over 350 newspapers around the world and was widely discussed on television, radio, in print and on line.
The vegetative state is one of the least understood and most ethically troublesome conditions in modern medicine. The term describes a unique disorder in which patients who emerge from coma appear to be awake, but show no signs of awareness. Such patients will not respond in any way to external stimulation (e.g. from their friends and family) and show no signs of understanding language. For the last 10 years, we have been conducting a collaborative series of Figure 1: Three voluteers brain responses investigations with colleagues at the Wolfson to being asked to imagine playing tennis. Brain Imaging Centre, Addenbrooke’s Hospital, to establish whether any of these patients do, in guidelines. 6 months after the accident, we fact, retain any cognitive functions, despite mapped her brain activity while we asked her appearances to the contrary. We do this by to imagine playing tennis or moving around her scanning patients under certain conditions (for home. We found that she was able to do this, example, we might play them speech sounds) activating different areas of her brain in the same and comparing the responses that we see in their way as healthy volunteers (see Figure 1). This
04 Panel News | CBSU | 2007 finding confirmed that, despite the diagnosis of vegetative state, the patient retained the ability to understand spoken commands and to respond to them through her brain activity, rather than through speech or movement. In short, the fact that she was able to imagine particular tasks when asked to do confirmed beyond any doubt that she was consciously aware of herself and her surroundings.
In September 2006, we published this startling discovery in the journal Science. The immediate response was a storm of media interest from around the world, including articles in more than Above: The brain response in the woman 350 newspapers, news reports on BBC News at who was diagnosed as vegetative (top) and Ten, ITN News, Channel 4 News and CNN and radio in a group of healthy volunteers (bottom) on more than 20 national and international radio when asked to imagine playing tennis in their stations. Over the following months, the research heads. Imaginary movements (such as was featured on a number of documentaries for playing tennis) activate the same areas of television and radio and was the subject of several the brain as actual movements. The response lengthy articles in magazines and journals. Much in the patient was indistinguishable from of this coverage (including televisions and radio that observed in the healthy volunteers reports) has been gathered together by the CBSU confirming that she was consciously aware. librarian and can be viewed on our website: http://www.mrc-cbu.cam.ac.uk/~adrian/Site/ Newslist.html
More importantly, the research has brought attention to this complex condition and has provided new impetus for our own work, and the work of other groups in this area. For example, we have subsequently begun collaborations with colleagues in Italy, Germany and the USA to establish whether this type of approach could be extended to provide a way of communicating with some patients who may be aware, but unable to move or speak. We have also seen an increase in the number of vegetative patients being scanned at Addenbrooke’s Hospital and have found similar patterns of responses in at least one other patient with a severe brain injury. But it is important to emphasise that if we don’t see a response in a vegetative patient it does not necessarily mean that they are not aware. For example, just like the healthy volunteers who help us with our research by being scanned at Chaucer Road, some patients can’t help but fall asleep while they are being scanned!
Panel News | CBSU | 2007 05 MEG magnetoencephalography Yury Shtyrov (Speech and Language Group)
n late 2006 – early 2007, the CBSU’s brain the older and more established EEG, this method imaging facilities were enriched by a new does not require attaching large numbers MEG (magnetoencephalography) laboratory. of electrodes to the person’s head, as the IThis compliments the already available fMRI magnetic fields permeate through tissues and air (functional magnetic resonance imaging) and do not need a solid conductor between the and EEG (electroencephalography) head and the measuring device. This makes units at the CBSU and makes it one MEG recordings much more convenient of the best equipped cognitive and pleasant for volunteers, as well as neuroimaging centres in the more time-efficient and hassle-free UK and worldwide. Only the for researchers. Properties of MEG technique (and the neuromagnetic fields which allow related EEG) can monitor them to spread from the brain brain activity with a high without much interaction with temporal resolution: the other tissues of our body also device installed at the allow for more direct estimates CBSU can trace neural of activity sources in the brain. activation with This enables us to see not only sub-millisecond the timing but also the spatial precision. MEG does location of neuronal this by recording activation in the brain with instantaneously higher precision. So, MEG miniscule magnetic recordings can show in real fields generated by time the complex interplay electric currents in of various brain areas as neurons, the brain’s they are processing the main working cells. information coming to our This technology is central nervous system. based on being able The potential application of to pick up tiny this technique ranges from magnetic fields using investigating how the various so-called SQUIDs complex functions (such as (super-conductive attention, memory, language or quantum interference emotions) are organised and carried devices), sophisticated out by our brains to exploring how this miniature superconductive functionality may break apart in various brain sensors distributed around a person’s deficits, leading to new insights into treating head in a helmet-shaped device. In contrast with disorders of the brain.
06 Panel News | CBSU | 2007 Even though this device is one of the first of its kind in the UK, a group of scientists at the CBSU, led by Professor F Pulvermüller, has long-standing experience in MEG research using a similar facility in Helsinki. They used MEG in a number of studies to delineate spatio-temporal patterns of brain activation in the process of language comprehension. They showed, for example, how the activation elicited by a single word spreads from left superior-temporal to inferior frontal cortex (from the back to the front of the brain) in ~15-20 milliseconds and how words of different types spark networks of activations in different brain parts reflecting the specific word’s meaning.
Above: Distribution of magnetic sensors around the subject’s head ensured maximum coverage for registering neuromagnetic brain responses in a contact-free and comfortable fashion.
The MEG device installed at the CBSU is a masterpiece of state-of-the-art technology Above: MEG systems are designed to register produced by Elekta Neuromag (Helsinki/Stock- brain activity in real time with maximum comfort holm), an international leader in MEG for volunteers and efficiency for researchers. technology. It incorporates 306 sensors of different types making it capable of high resolution in all three dimensions; superficial, cortical surfaces are localised with highest precision. The technique is quiet and non- invasive: the recordings do not involve any currents or fields “injected” into the participant’s body (we only record what is generated by the brain itself), the operation is completely silent with the participant seated in a comfortable chair in a spacious magnetically shielded room.
What’s more, it is possible to combine MEG data with EEG and fMRI recordings to optimise algorithms used in brain activity analysis. In combination, these methods can yield an accurate spatial-temporal image of brain Above: Using MEG, we have been able to document activity. The new technology has already fine-grained spatio-temporal properties of brain generated a lot of excitement and new hopes in networks involved in perception of words of different the Cambridge neuroscience community. types (Pulvermuller, Shtyrov and Ilmoniemi, “Brain We are very much looking forward to seeing Signatures of Meaning Access Word Recognition”, these expectations turn into new exciting Journal of Cognitive Neuroscience, 2005) discoveries in the years to come.
Panel News | CBSU | 2007 07 We’reWe’re atat thethe bottombottom ofof thethe garden…butgarden…but don’tdon’t keepkeep itit aa secret!secret!
Lucille Murby (MRI Facility Administrator)
he MRI Facility at the Cognition & Brain researchers analyse the activity and are able to Sciences Unit can be glimpsed through use the information obtained to make new the trees but unless you come through discoveries into how the brain works. Tthe house or around the side of the The scan takes up to one and a half hours to main building you’d hardly know we were there. complete (depending on the study) and during It is important that people know where to find us this time the volunteer lies on the scanner bed, because we have been running fMRI studies at looking at an LCD screen that is inside the the bottom of our garden since November 2005 scanner and keeping in touch with the and continue to need the support of Cambridge radiographers and the researcher via an volunteers all year around. intercom system. The procedure is completely We are open from 8am – 8pm every week day safe and the majority of our volunteers return and carry out around thirty-five MRI scans every to assist us with subsequent studies and often week. This means that we need at least the book their next appointment on completion same number of volunteers on a weekly basis. of the scan. Often, we need more than this to cover us for Because an MRI scanner is essentially a huge those occasions when a volunteer has to cancel. magnet, all volunteers are carefully screened We are constantly looking for suitable and then scanned by a metal detector before volunteers to help us run our fMRI studies. These entering the controlled area. This is because volunteers are generally required to be between loose items such as coins, jewellery and keys 18 and 40 and need to be fluent in English. On would pose a projectile hazard in the magnet registering an interest in taking part volunteers room, and because people with metal in their are initially screened over the telephone by our body (such as pins after surgery or metal radiographers and if suitable (and still fragments in the eyes) are not able to volunteer interested) they are then booked to attend the for a scan with us. site for an appointment. All enquiries are The results obtained from our volunteer-based welcome and there is no obligation at any time studies are sometimes compared alongside to take part in our research. results from clinical patients and this helps us to Our studies generally involve up to twenty make significant developments for the future. volunteers who all carry out a simple task whilst A study last year involved volunteers imagining in the scanner. The task is fully explained prior to playing a game of tennis (involving the the scan so the volunteer knows exactly what to supplementary motor area of the brain) and the do when the program starts. During the task, findings from this study were reported in over areas of the brain are activated and our 350 newspapers around the world and were
08 Panel News | CBSU | 2007 widely discussed on national television, radio, in It’s now eighteen months since we opened our print and on line. It is thanks to the contribution new MRI facility and we would like to thank all made by our volunteers that we are able to make of the volunteers who have participated in our discoveries such as this that have a real impact research during this time. Many have been on clinical medicine. recruited by word of mouth so please do let Increasing awareness in Cambridge about other people know we are here and pass this the type of work we do is really important to us. newsletter on to friends and colleagues that We carry out numerous recruitment activities may also be interested. If you’re one of our throughout the year and have stands at both regulars then you’ll know that whatever else the Cambridge University Societies Fair and the is happening at the CBSU, we always have Anglia Ruskin University Freshers Fair. Always radiographers at the bottom of our garden… besieged by enthusiastic new students, the stands generate an influx of new panel members interested in fMRI every autumn and this is a . huge boost to our research. We also recruit more permanent residents of Cambridge and the surrounding villages into our Volunteer Panel and are continually looking to attract the interest of new participants.
Not being part of a hospital complex, our MRI Facility is spacious and airy as well as less clinical than many other MRI sites. All the staff involved value the assistance given by our volunteers and aim to make the scan sessions a rewarding experience for everyone. Many of our fMRI volunteers come back again and again because they enjoy taking part, like the environment and Above: Though sometimes there are more get satisfaction from being involved in our work. traditional occupants! (Wear it Pink 2006) In addition, all of our volunteers get paid a minimum of £20 for their time and leave the site with a colour picture of their brain as well as a If you’d like to find out more contribution towards their travel expenses. information about what we do then please visit our website, http://www.mrc-cbu.cam.ac.uk/
You can also call me (Lucille Murby, MRI Facility Administrator) on 01223 273777 if you would like to discuss any aspects of volunteering for an MRI scan with us.
If you’d like to join our Volunteer Panel or find out about how you could assist us with our research without having an MRI scan, then please contact our Panel Manager on 01223 505610 or email [email protected] Above: CBSU Radiographers ‘Wear it Pink’ in support of Cancer Research 2006.
Panel News | CBSU | 2007 09 Student PhD research
The CBSU houses up to18 PhD students who are at varying stages of completing their PhD studies. The help given to their research by members of the Volunteer panel is invaluable. Here is just a small sample of the work that they are engaged in.
Patricia Schartau, Emotion Group However, as yet, little research has been conducted Supervisor: Tim Dalgleish with regard to the efficacy of cognitive reappraisal as an emotion regulation strategy. Furthermore, Helping people to think the possibility of training people in it systematically had, up to the time of the current study, not been positively investigated. With the assistance of several hundred panel members, our own research has shed light on Acquiring the ability to reinterpret (reappraise) these shortcomings in the literature. We have negative emotional events in more adaptive ways demonstrated that reappraisal (finding a more so as to reduce levels of associated distress is positive interpretation for an event that is initially crucial in everyday life. There are many different interpreted as highly negative) is an effective ways of how to do this and preferences depend emotion regulation strategy with regard to the on the individual. For example, whereas some reduction of negative emotions elicited by films people may find it helpful to search for the “silver when one-off reappraisal instructions were given. lining” when confronted with a tragic situation, Furthermore, it was shown that people can be others may aim at putting the distressing event trained systematically to employ cognitive into context, hence looking for the “bigger reappraisal to films and autobiographical material picture”. when they are presented with some reappraisal themes (e.g. “find the silver lining, there is The importance of positive thinking (or something good about every situation”) that reappraisal) is highlighted by the fact that it is a they can make use of. Remarkably, even a single key component of cognitive behaviour therapy training session of approximately one hour is (CBT). During therapy, for example, a highly efficient in improving people’s emotion depressive patient’s maladaptive and highly regulation skills. negative thoughts of themselves and the “outside” world is being challenged and replaced The results of our studies do not only have by more positive interpretations. These, in turn, important clinical applications, but reveal that are thought to lead to a marked decrease in cognitive reappraisal is trainable and can be a negative affect. powerful skill to improve quality of life.
10 Panel News | CBSU | 2007 Jessica Fish, Memory Group Mark Stokes, Attention Group Supervisors: Barbara Wilson and Tom Manly Supervisors: John Duncan and Adrian Owen Helping people Imaging Imagery – “remember to remember” patterns in the brain
“Prospective memory” (PM) refers to the processes underling visual involved in remembering to do something in the future. Examples of everyday PM tasks include imagination remembering to post letters, pay bills on time, make Visual imagery allows us to recreate, in our mind’s phone calls and attend appointments. These are eye, details of the visual world in the absence of generally complex tasks, involving the co-ordination direct visual input. In previous studies, of memory and attentional processes. neuroimaging methods have confirmed that brain areas typically associated with visual Most people experience PM lapses from time to perception also become active when people are time, but they probably do not interfere too much engaged in visual imagery. From this evidence of with day-to-day life. PM failures can however, co-activation, it has been argued that the brain be much more frequent and have far greater areas responsible for visual perception are also consequences for people after a brain injury or used to recreate visual experiences during imagery. other neurological illness causing memory and However, the nature of the involvement of concentration problems. As many of our daily tasks visual brain areas in visual imagery, and the involve PM, these types of problem can be very relationship to actual visual perception, remains disabling, even limiting a person’s capacity to live poorly understood. To better understand the independently. The rehabilitation of PM problems relationship between visual imagery and visual is therefore an important focus for research. perception, we conducted a neuroimaging experiment to compare patterns of activity in visual My PhD research has examined PM performance brain areas associated with imagining and actually in people with brain injury, with the aim of seeing different types of objects. While in the understanding more about how PM problems scanner, volunteers from the research panel arise. We have also evaluated the effectiveness of alternated between imagery and perceptual tasks. compensatory strategies for PM problems. In Similar to previous experiments, we found that visual areas became more active during both visual particular, we have investigated how pagers and perception and visual imagery. However, we also mobile telephones can be used as a means of discovered that the fine-scale patterns of activity prompting people to act upon intentions. This has specific to items in visual imagery differ from the included sending messages aimed at encouraging patterns associated with actually seeing the same the process of monitoring one’s behaviour items. These findings confirm previous evidence (e.g. “stop and think about what you’re doing”), that visual brain areas are involved in visual which could potentially benefit a wider range of imagery; however, our evidence further suggests tasks across a greater variety of settings than that the precise mechanisms are not identical specific prompting (e.g. “time to take your between the two mental processes. The results of medication”). We have found that use of this this study indicate important differences between strategy can lead to considerable improvements in visual imagery and actual visual perception, and PM performance. Further details of this work can we are grateful to all the volunteers from the be found in the rehabilitation section of the research panel for their participation, and their unit website (www.mrc-cbu.cam.ac.uk/rehab). active imaginations!
Panel News | CBSU | 2007 11 TheThe CambridgeCambridge BioResourceBioResource
Jill Keane (Emotion Group)
he identification and sequencing of the genes Brain imaging studies in that make up the entire human genome is one Parkinson’s disease Tof the greatest scientific developments in modern science and will enable scientists in medical research to identify the genetic basis of Parkinson’s disease is a common disorder which inheritable medical conditions. For the Cognition and principally affects the production of a chemical in Brain Sciences Unit, it will offer the opportunity to the brain known as dopamine and manifests with study the genetic basis of psychiatric disorders, movement difficulties. Although all patients with personality traits, and basic psychological functions Parkinson’s disease have the same underlying such as language, memory, motivation and emotion. pathological process going on in their brains, only a proportion of them seem to develop difficulties with thinking and problem solving which have Many of you will have received information about important implications for quality of life and the Cambridge BioResource, a new Bioresource care needs. Volunteer Panel comprising a bank of genetic information from a large cross-section of individuals One of the exciting new ways in which the throughout the Cambridge area who have agreed underlying causes of some of these thinking to take part in genetic research. The new panel is a problems in Parkinson’s disease can be explored is collaborative study among MRC Epidemiology Unit, by using functional magnetic resonance imaging MRC Cognition and Brain Sciences Unit and the (fMRI). This involves performing brain scans at University of Cambridge. It provides a highly valuable the same time as an individual is performing a resource of individuals with different genetic particular task. The areas of the brain which are make-ups who can be contacted to participate in most active during the task can then be identified, studies which look at links between genes, and these areas of brain activation can be psychological functions, the environment and compared between groups of individuals. common diseases. Our colleagues at Epidemiology and the University of Cambridge are currently This technique was used to investigate whether working to identify the genetic basis of conditions the difference in performance on thinking and such as obesity and diabetes. problem solving can be explained, at least in part, by genetic variation. Specifically, MRI brain scans The following recent study by Dr Caroline were carried out on 31 patients with Parkinson’s Williams-Gray of the Brain Repair Centre and disease whilst they performed two types of Dr Adrian Owen of the MRC Cognition and Brain computerised task: a problem-solving task Sciences Unit is an example of the sort of (Figure 1 and 2), and a task requiring them to experiments that may be carried out : shift their attention between different stimuli.
12 Panel News | CBSU | 2007 The genetic variant known as catechol-O-meth- Similar experiments using individuals without yltransferase (COMT) affects concentration in the Parkinson’s disease will now be performed so brain of dopamine, the chemical that is deficient in that it can be determined whether this genetic Parkinson’s disease. Although COMT is not effect on brain function also occurs in healthy diagnostic of Parkinson’s disease, the study individuals.
These sorts of experiments are very important in terms of furthering the understanding of the neurobiological basis of memory and thinking problems in Parkinson’s disease, and may ultimately help in the planning of the best treatment strategies for patients.
This study has been published in the Journal of Neuroscience. Williams-Gray, C.H., Hampshire, A., Robbins, T.W., Barker, R. A. Owen, A.M. “COMT val158met genotype influences frontoparietal activity during planning in patients with Parkin- Figure 1: This is the ‘Tower of London’ test, an son’s disease.” Journal of Neuroscience, May 2007. example of one of the computerised tests performed by patients with Parkinson’s disease A big thank you to those of you who have already in the fMRI scanner. Can you rearrange the expressed interest and decided to join the snooker balls in the bottom table to match the Cambridge BioResource. arrangement in the top table? What is the minimum number of moves requires to do this? If you are interested but have not yet participated, all that is required is to provide a saliva sample for genetic analysis and basic information such as your name, address, date of birth, sex and ethnic group. Your saliva sample will be identified by a study number only and stored for 5 years. All information gathered about you during the course of the research will be kept strictly confidential.
Please note that the Cambridge BioResource is a separate panel to the Cognition and Brain Figure 2: Areas shaded red on this picture Sciences volunteer panel. If you would like indicate regions of the brain which are activated to take part in the Cambridge BioResource, during the ‘Tower of London’ planning task. please use one of the following methods: investigated whether it might account for the 1.Call freephone number 0800 085 6183 differences in thinking and problem solving in the 2.Email: [email protected] patient group. Half of the patients carried a ‘high (including your name, address and telephone activity’ variant of the COMT gene, whereas the number) other half carried a ‘low activity’ variant. Comparison of these two genetic groups revealed If you would like further information before not only a significant between-group difference in deciding, or have any queries about anything terms of ability to perform the tasks but also a clear concerning the study, please contact the difference in levels of brain activation during the study team on freephone number tasks. These results suggest that an individual’s 0800 085 6183 or email: genotype directly influences brain function. [email protected]
Panel News | CBSU | 2007 13 Understanding Barney Dunn (Emotion Group)
The experience of short periods of unhappiness, often in response to unpleasant or upsetting events happening, is a normal part of everyday life. Clinical depression is when these feelings become intense, long lasting, and severely disrupt an individual’s ability to cope. Symptoms of depression can include feeling sad all of the time, losing the ability to experience pleasure or motivation, becoming very self-critical and guilty, finding it hard to make decisions, feeling tired or restless, having disturbed sleep and eating patterns, wanting to withdraw socially, and sometimes feeling suicidal. As well as the personal cost for the individual, it makes it hard to having been depressed in the past). function at work and can damage relationships. To improve this situation, science needs to develop more sophisticated understandings of The World Health Organisation recently reported what triggers and maintains depression, so that that depression (after back pain) is the second treatments really ‘get to the root of the problem’. biggest cause of working days lost in the Western This is the focus of some of the research carried World. Depression affects individuals from all out by the Emotion Group at the CBSU. We walks of life at all parts of the life span. For examine how depressed individuals (either those example, World War II Prime Minister Winston reporting high levels of depression symptoms or Churchill suffered from recurrent depression those who have received a formal diagnosis of throughout his life, which he described as his depression) think and feel, contrasting this ‘black dog’. It is estimated that one in ten of us to ‘control’ participants with no history of will suffer a clinically significant depression at depression. By identifying differences between some point in our lives and the disorder has depressed and healthy individuals we can begin been called the ‘common cold’ of psychiatry. to refine our theoretical models of depression. For around two percent of people treated for Below we summarise some findings from recent severe depression, their symptoms will be so experiments investigating depression run by bad that they successfully commit suicide. members of the Emotion Group. Over the past fifty years a range of treatments has been developed for depression, including A key under-pinning of many existing talking anti-depressant medication (for example, treatments for depression is that the disorder is ‘Prozac’) and talking therapies (for example, maintained by negative thinking patterns, where attempting to modify negative thinking patterns individuals emphasise the significance of with Cognitive Behavioural Therapy). While these negative events that happen. For example, approaches are known to be helpful, there is still when evaluating how a job interview has gone a way to go to effectively manage depression. In a a depressed individual might become number of cases symptoms only partially improve preoccupied with the one question they or do not improve at all following treatment and struggled with. This is typically used as strong depression frequently recurs (indeed, the most supporting evidence for the depressed reliable predictor of becoming depressed is individual’s underlying belief that they are not
14 Panel News | CBSU | 2007 Depression
and never will be a successful, likeable person. ing about personal upsetting memories from the Thinking in this way makes depressed past) we would also have found evidence for individuals feel sad and self-critical. Therefore, exaggerated negativity in depression. treatments like Cognitive Behavioural Therapy (CBT) focus on identifying this ‘negative bias’ In another study we measured how accurately in how information is processed and depressed individuals make judgments about how developing a more even-handed view of the well they are doing. CBT theories would predict that world, in an attempt to reduce the experience depressed individuals are negatively biased in how of negative emotions. But what if this tendency they evaluate themselves, for example thinking to experience high levels of negative emotions they are doing worse than they actually are. An and think negatively is only one side of the coin alternative idea (called the depressive realism in depression? The other dominant feature of hypothesis) is that healthy individuals are overly depression is the inability to experience any positive when evaluating themselves whereas positive emotions or feel motivated. It might depressed individuals are more realistic. In other be the case that to improve existing treatments words, depressed people cease to ‘wear rose for depression we need to find ways to increase coloured glasses’ and see the world as it really is. positivity as well as decrease negativity. For To test these competing models we asked example, rather than challenging the negative depressed and non-depressed individuals to thinking accompanying the ‘difficult’ question judge how well they were performing on a at the job interview, we should strengthen and difficult memory task. We found that everybody elaborate the positive thinking surrounding all over-estimated how well they were doing, but the questions that were answered successfully. the extent of this positive bias was reduced in In a series of experiments we have begun to depressed individuals. Again, this suggests that investigate whether depression is best a reduced positive reaction, rather than an characterised by elevated negativity, blunted exaggerated negative reaction, might best positivity, or a combination of the two. characterize depression. The challenge in treating depression might be to encourage depressed In one study we showed depressed individuals a individuals to ‘wear rose coloured glasses’ more range of happy, sad, and fearful emotional often. Sometimes we need to hold ‘positive images and asked them to rate how they felt illusions’ to keep us motivated and enthusiastic in reaction to each of them. We compared their in life. ratings to people with no current or past history of depression. Depressed individuals reported What these findings indicate is that existing experiencing significantly less happiness and a treatments for depression might be improved by bit more sadness when viewing positive having a greater emphasis on reconnecting people images, compared to non-depressed to positive emotions and developing a more individuals. Surprisingly, depression was not optimistic way of evaluating themselves and the associated with elevated experience of future. The next stage of our research will be to sadness and fear when viewing negative attempt to better understand exactly what leads emotional images. At face value these results to this reduction in positivity in depression and to suggest that a blunted reaction to positive develop therapeutic approaches that can repair it. material, rather than an exaggerated response We would not be able to carry out these experiments to negative material, is central to depression. without the volunteers from the subject panel However, we suspect that had we used more and we are very grateful for people’s time and personally relevant material (for example, think- enthusiasm in taking part.
Panel News | CBSU | 2007 15 An unusually famous participant in the CBSU’s research programme Karalyn Patterson & John Hodges (Memory Group)
Normally, we work pre-illness level of competence from her published quite hard to preserve novels (26 of them, not to mention 6 books on the anonymity of philosophy which was her academic discipline). the people who Extensive research on the course of Alzheimer’s
participate in our Judges Photo: Rob disease has established that the insidious disease research. This is process begins years before the symptoms become true whether the obvious. When we started to assess Dame Iris in 1996, participant is a her symptoms were already moderately severe: for person with a Above: Pictured Dame Iris Murdoch example, she could not identify – from a list of the titles normal, healthy and husband Professor John Bayley of her novels – which of her books had won the coveted brain or someone who is being tested from a Booker Prize; in fact, she did not remember winning ‘neuropsychological’ perspective, that is, in an the prize at all, and we were not even sure that she still attempt to learn how brain disease affects cognitive knew what it signified. From this evidence of fairly function. In the research project briefly summarised advanced symptoms, we can be confident that, when here, however, we intentionally revealed the identity she was writing her last novel (Jackson’s Dilemma, of the participant – Dame Iris Murdoch, one of the written in 1993-1994), there was already substantial most celebrated British writers of the 20th century. Alzheimer’s pathology in her brain. The question in our This deliberate ‘breach’ of anonymity occurred minds then was: would there be sub-clinical evidence because Dame Iris’s husband, Professor John Bayley, of diminished competence in Jackson’s Dilemma? hoped that publicity about her illness would increase It should be noted, by the way, that Iris Murdoch always public awareness of the distressing consequences of refused even the tiniest editorial revision to the Alzheimer’s disease, and hence of the need for manuscripts that she produced (and by virtue of her research on the topic. great success as a novelist, her demand was respected by her publishers). We therefore know that Jackson’s Iris Murdoch’s fame certainly increased people’s Dilemma was entirely her own work. interest in how she performed on the tests that we did with her. From our point of view, however, her We tackled this question through a systematic status as a writer served another, more directly comparison of extracts from three of Iris Murdoch’s useful function. One of the problems in novels: her first (Under the Net, written when she neuropsychological research is having a baseline was in her early 30’s); one from the middle of her against which to measure a patient’s successes writing career (The Sea, The Sea, which is in fact and failures on various tests. Of course we always the novel that won the Booker Prize); and of course collect what we refer to as ‘control data’ on the tests her final novel, Jackson’s Dilemma. This analysis that we use with neurological patients, so that we demonstrated that, relative to both earlier books, have some measure of the range of normal scores; the final novel contained significantly fewer different many members of the CBSU participant panel have content words (that is, specific nouns, verbs, contributed to our research by serving as such adjectives etc – not so-called function words like the, ‘control subjects’. Ordinarily, however – apart from and, of, with) relative to the total number of words. rather general factors like age and amount of In other words, her use of varied and sophisticated education – there is no precise way in which to vocabulary – for which she was especially famous – estimate where in the range of normal scores a had deteriorated and become more simple and given patient would have belonged before he or she repetitive, even before her disease was diagnosed. became a patient. In Iris Murdoch’s case, however, at least with regard to tests of ability like vocabulary, An article on this research was published in the we had an astonishingly rich public record of her neurological journal Brain in 2005.
16 Panel News | CBSU | 2007 Cambridge Science Festival
ach year, the University of Cambridge holds a two-week Science Festival with informative talks and fun events for adults and children. We at theCBSU participate in this, and put on an afternoon of short talks and practical experimentsE geared towards helping adults (16+yrs) understand our research and its practical implications.
Some past talks have investigated the notion that feedback from the body can influence how we make ‘intuitive’ decisions, looked at memory and its disorders, examined how we can detect awareness in the Vegetative State, considered how the brain makes sense of spoken language, explored rhythm processing in the brain, and explained how cochlear implants can partially restore severely damaged hearing.
Those attending this “Exploring Mind and Brain” event enjoy trying out some practical experiments which help demonstrate how we carry out our research to discover the answers to important questions. These experiments are the same ones that we ask our Volunteers to do. Above: Karalyn Patterson gives one of the many talks at the CBSU on Science day.
If you would like information about the next event please contact: [email protected]
You can find out about all the Cambridge Science Festival events at: http://www.cambridgescience.org/
Panel News | CBU | 2007 03 New research into brain damage has scientists in two minds about amnesia
Morgan Barense (Research Fellow, Peterhouse College)
ur understanding of how memory breaks memory-impaired individual is asked to learn, own after brain damage may have to therefore, influences the likely success of their be revised according to new research learning. Ocarried out by Morgan Barense and colleagues at the MRC Cognition and Brain Sciences As damage to the medial temporal lobe (MTL) is Unit in Cambridge, published in in the Journal of associated with many types of disease, including Neuroscience, November 2005. The research may Alzheimer’s disease, this research shows that have implications for the early diagnosis of brain memory may not be as globally affected as damage and our approach to rehabilitation. previously believed. This has implications Until now, scientists believed that structures in the for development brain’s medial temporal lobe (MTL) made up a of more accurate single functional system, or module, that supports tests for early learning of new memories and was independent diagnosis and of other cognitive functions, such as language and differentiation perception. The MRC scientists have now shown, of dementia, however, that there is a division of labour within as well as for the MTL - not all parts support the same type of the way we memory - and also that these parts may play a role think about in perception as well as memory. rehabilitation of memory loss. The research was carried out in individuals who had suffered damage to different parts of the MTL, the perirhinal cortex and/or the hippocampus. People with damage to the perirhinal cortex had extreme difficulty in memorising objects when they About visting Scientists had several features in common (e.g., comparing pictures of a zebra and a tiger or comparing We are host to a number of visiting Scientists barcodes) but showed normal learning when at the Unit. The time they spend here varies the objects looked distinct. As the amount of from a few weeks to a few years. Some come information to be remembered was identical for from the UK, but others come from more similar and dissimilar objects, this result implies an distant corners of the world – Cuba, South underlying difficulty with perception of objects. America, Canada, the USA, Europe, Iran to In contrast, amnesic individuals with damage limited name but a few – to collaborate with MRC to another part of the MTL, the hippocampus, scientists. We are also privileged from time performed normally on these tests. This suggests to time to have with us Cambridge College that the hippocampus, long thought to be the Fellows. These people are funded by Colleges neural basis for memory, is not critical for memory in Cambridge, but carry out their research for objects, but may, as other experiments have here. All of our visitors make full use of our shown, play an important role in spatial memory facilities, including the Volunteer Panel. and perception, for example in remembering a route home from work. The type of material a
18 Panel News | CBSU | 2007 WANT TO HELP MEDICAL RESEARCH? WANT TO GET PAID? VOLUNTEER YOUR BRAIN TODAY!
What do I get?
You will receive approximately £20 and a photograph of your brain, as well as the chance to take part in research that will help understand normal brain function, and have important implications for clinical patients. Volunteers will be given a contribution towards the cost of their travel expenses.
Who can volunteer?
You have to be over 18, in good health, with no history of neurological injury, or currently on any psychiatric medication - and you cannot have any pieces of metal in your body, such as metal supports for bones or non-removable body piercings, although fillings are fine.
What does it involve?
We measure brain function using an instrument called a magnetic resonance imaging (MRI) scanner. The procedure is completely non-invasive and there are no known risks associated with it. You will lie in our scanner for about 1 hour, while you perform simple cognitive tasks (involving, for example, memory or language). In addition, 10 minutes of anatomical scans will be taken and you will just need to lie still for these. Your whole time at the imaging centre should be around one and a half hours.
Where does it take place?
The scanning occurs at the MRC Cognition and Brain Sciences Unit, located at 15 Chaucer road, Cambridge, CB2 7EF. This is a five minute cycle ride from the city centre.
How can I find out more?
If you think you would like to take part in brain scanning research, have questions you would like to ask, or would just like more information before making a decision, then please visit our website at http://www.mrc-cbu.cam.ac.uk/volunteer or, alternatively, contact our Panel Manager at the MRC Cognition and Brain Sciences Unit on 01223 505610 (direct line).
Email: [email protected] Website: http://www.mrc-cbu.cam.ac.uk
Panel News | CBU | 2007 03 Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF Website: www.mrc-cbu.cam.ac.uk Phone: 01223 355294