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Marmoset study provides clues to link between mental health disorders and heart disease

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 08, 2017.

Changes in heart rate and blood pressure such as the ‘fight or flight’ response are a normal part of our emotional reactions. However, it is well known that people with depression or anxiety have an increased risk of heart disease along with distressing negative emotional states. The reasons why have remained unclear.

Now, in a study published in the Proceedings of National Academy of Sciences (PNAS), Dr Hannah Clarke and colleagues from the University of Cambridge and Cambridgeshire & Peterborough NHS Foundation Trust have discovered a link between two key areas of the brain and emotional responses. They also show that our brains control our cardiovascular response – changes in our heart patterns and blood pressure – to emotional situations.

To carry out the study, the researchers used marmosets with small metal tubes implanted into specific brain regions in order to administer drugs that reduce activity temporarily in that brain region. This enabled the researchers to show which regions caused particular responses. The marmosets rapidly adapt to these implants and remain housed with their partners throughout the study.

In the first task, the marmosets were presented with three auditory cues: one that was followed by a mildly aversive stimulus (a loud noise), one that was followed by a non-aversive stimulus (darkness), and one where the subsequent stimulus had a 50/50 chance of being either a loud noise or darkness. The task lasted just 30 minutes and they were exposed to this task a maximum of five days a week over a few months.

As the marmoset began to understand the cues, the researchers observed that the monkey’s heart rate and blood pressure increased in anticipation of the loud noise, and the monkey began to look around more (known as ‘vigilant scanning’). However, the team found that turning off one region (known as Area 25 – the subgenual cingulate cortex) of the prefrontal cortex in the marmosets made them less fearful: their heart rate and blood pressure did not change and they became less vigilant.

In a second task, adapted from a common rodent test of emotion, the team studied the ability of marmosets to regulate their emotional responses. In a single session of thirty minutes, an auditory cue was presented on seven occasions, and each time it was accompanied by a door opening and the marmoset being presented with a rubber snake for five seconds. As marmosets are afraid of snakes they developed similar cardiovascular and behavioural responses to the auditory cue associated with the snake as they did to the cue associated with loud noise. The next day, to break the link between the cue and snake, the researchers stopped showing the marmoset the snake when the cue was sounded.

In this task, inactivating Area 25 meant that the marmoset was quicker to adapt: once the link between the auditory cue and the snake was broken, the marmosets quickly became less fearful in response to the cue, with their cardiovascular and behavioural measurements returning to baseline faster than normal.

In both tasks, inactivating another region (Area 32 – the perigenual cingulate cortex) made normal fearful responses spread to non-threatening situations: the marmosets became less able to discriminate between fearful and non-fearful cues, showing heightened blood pressure and vigilant scanning to both. This is a characteristic of anxiety disorders.

Marmoset brain with Areas 25 and 32 highlighted

“We now see clearly that these brain regions control aspects of heart function as well as emotions,” says Dr Clarke. “This helps our understanding of emotional disorders, which involve a complicated interplay between brain and body.”

Previous studies of anxiety and depression in humans have shown altered activity in these subgenual and perigenual brain regions. However, as it is not possible to manipulate the brain regions in humans, it was not previously possible to say whether these brain regions were responsible for the alterations in behaviour and cardiovascular activity, or alternatively whether the changes in brain activity were caused by such alterations. As the structural organisation of the prefrontal cortex of non-human primates including the marmoset is very similar to that of humans, the researchers were able to directly address this issue.

Animals are only used in research where no other alternatives are available, and researchers always use the most appropriate species. In the vast majority of cases, this involves using mice, rats and zebrafish. Sometimes, however, it is necessary to use species that are closer to humans. While rodents can provide a good model for exploring and understanding many aspects of behaviour, the researchers argue that this study highlights how non-human primates in certain cases can help provide a more detailed and specific understanding of how our brains work.

“Our work highlights the importance of research using marmosets in understanding human conditions that affect many millions of people worldwide,” says Dr Clarke. “Studies using animals such as rats are important for providing insights into behaviour and disease, but for some areas of research, monkeys have greater relevance because their brains are much closer in structure to ours.”

The research was partly-funded by the Wellcome Trust.

Reference
Wallis, CU et al. Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion. PNAS; 1 May 2017; DOI: 10.1073/pnas.1620115114

A team of researchers at Cambridge has identified how two key areas of the brain govern both our emotions and our heart activity, helping explain why people with depression or anxiety have an increased risk of cardiovascular disease.

We now see clearly that these brain regions control aspects of heart function as well as emotions. This helps our understanding of emotional disorders, which involve a complicated interplay between brain and body
Hannah Clarke
Depression

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The OCD Brain: how animal research helps us understand a devastating condition

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Mar 28, 2017.

When David Adam was just 18, a teasing comment from a university friend triggered a series of thoughts that he had contracted HIV and would die of AIDS. This was around the time of peak hysteria about this new disease, but even so, his thoughts represented more than the worries of a naïve, newly-sexually active young man: the fear was unshakeable and the thoughts consumed him, dominating his life.

For a long time, David remained silent about his obsession, afraid to tell anyone what he was going through. It was only a couple of decades later, when the thoughts began to affect his relationship with his young daughter, to whom he was sure he would transmit his ‘infection’, that he sought help. He was subsequently diagnosed with obsessive compulsive disorder (OCD).

OCD is sometimes viewed as a personality quirk – “I’m a little bit OCD,” people will say as they carefully arrange the books on their shelf. The truth is far more devastating. People living with OCD will scrub their hands compulsively, often with bleach, till they are bleeding. Others will check that they have locked the back door thirty, forty times – otherwise, they are sure a family member will come to harm - making going out almost impossible.

David, a journalist and science writer, has written and spoken extensively about his condition. He considers himself fortunate: his condition is under control, thanks to a combination of ‘talking therapies’ and medication. Others are not so fortunate: despite intensive therapy and medication, they are still unable to hold down a job or a relationship, so dominant are their OCD behaviours.

Now, in a series of short films for the University of Cambridge, David has visited leading researchers who study OCD and asks what we know about the underlying biology that leads to the condition: just what is going on in the brain?

In the films, Professor Trevor Robbins, Head of Psychology at Cambridge, introduces David to scientists who use a combination of studies to explore the inner workings of the brain. These include studies involving rats and marmosets (small monkeys), as well as people.

One of the studies is a so-called ‘reversal learning’ test. In this test, the marmoset learns that pressing one button gives it a juice reward, while it gets no reward if it presses a second button. But then, unexpectedly, the buttons swap: how good is the marmoset at changing its thinking to adjust to this new information? A common trait in people with OCD is a tendency to have rigid, obsessive thinking that dominates their behaviour.

By manipulating localised regions of the animals’ brains, either permanently or via temporary drug infusions, scientists are able to understand better the exact pathways within the brain that malfunction in OCD and cause this rigid behaviour. As Professor Robbins explains, this would not be possible in human studies. But this knowledge will help underpin the development of new, more effective treatments – and this is crucial, as around 60% of patients with OCD do not respond to existing treatments.

The films have been produced as part of the University of Cambridge’s commitment to openness on animal research. In 2014, the University announced that it had signed the Concordat on Openness on Animal Research. The following year, it launched its first film on the subject, Fighting Cancer: Animal research at Cambridge.

We welcome comments about this article. However, as with discussions on all of our news and feature pages, comments will be moderated so please do not post contributions that are offensive or contain profanities, and please stay on topic. We do not moderate comments in real-time so there may be a delay before they appear.

OCD can be a devastating condition: therapy and medication often doesn’t work, leaving many people unable to hold down a job or a relationship – or even to leave their house. In our series of films, science writer David Adam looks at how research at Cambridge using animals helps us understand what is happening in the brain – and may lead to better treatments.

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Patients with OCD have difficulty learning when a stimulus is safe

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Mar 06, 2017.

OCD is a disorder characterised by intrusive thoughts and repetitive, irrational behaviours, for example an obsession with cleanliness leading to repetitive hand washing, or a fear that something terrible will happen if they don’t check the door dozens of times, making leaving the house extremely difficult.

A common way of helping treat OCD is to expose people to something they consider threatening – for example, if their obsession is around cleanliness, they may be made to touch a toilet seat but then prevented from washing their hands. However, so-called ‘exposure therapy’ often only has limited success and compulsions can return in times of stress. This new research, published today in the Proceedings of the National Academy of Sciences, may explain why memories about safety don’t stick.

In this study, researchers at Cambridge’s Behavioural and Clinical Neuroscience Institute tested 43 OCD patients and 35 matched healthy volunteers to see how well those people with OCD were able to reverse their thinking when a previously threatening stimulus became safe and vice versa, to examine safety versus threat learning as well as cognitive flexibility, which is thought to be significantly compromised in patients with OCD.

Volunteers lay in a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, while successively being shown one of two faces: when shown the red face, nothing happened, but when shown the green face, the volunteer would sometimes receive a mild electric shock. By measuring changes in skin conductance caused by tiny amounts of sweat, the researchers were able to see whether the volunteers learned which stimulus was safe and which threatening.

After a period of time, the researchers swapped the stimuli – now, the red face was paired with an electric shock while the green face was safe.

The researchers found that while OCD patients were able to learn initially which stimulus was threatening, they never learned that the second stimulus was safe – in fact, they seemed to pay little attention to this safe stimulus. When the stimuli were reversed, participants were unable to differentiate between the previously threatening stimulus and the newly threatening stimulus. This was also reflected in their brain activity – OCD patients showed a lack of activity in an area at the front of the brain known as the ventromedial prefrontal cortex when viewing the safe stimulus.

“Our study suggests that something is going wrong in the brains of people with OCD when they are learning what is safe, and this in turn affects how they perceive threats under updated circumstances,” explains Dr Annemieke Apergis-Schoute, the study’s first author. “This needs to be taken into consideration when we’re developing future therapies to tackle the disorder. Current exposure therapies may help the patient take control over their compulsions, but our work suggests that they might never learn that their compulsions are unnecessary and they may return in times of stress.”

In a second study, published recently in Biological Psychiatry, Cambridge researchers showed that this cognitive inflexibility might be in part a result of a lack of ‘chatter’ between specific brain areas.

The research, led by PhD student Matilde Vaghi, found that poor connectivity within some of the brain’s key networks as measured in an fMRI scanner while the patient was at rest may account for this inflexibility. It also may account for OCD patients’ poor goal-directed abilities (where we consciously act with a goal in mind – for example, when driving home and our route is disrupted, forcing us to take an unfamiliar route). Both are related to common symptoms of OCD.

The researchers found disrupted connectivity within discrete frontostriatal circuits – neural pathways that connect the front of the brain with the basal ganglia (responsible for important functions such as the control of movement and ‘executive functions’ such as decision-making, learning and habit formation). They believe these may underlie the repetitive behaviours seen in OCD.

Professor Trevor Robbins, Head of Psychology at Cambridge, senior author on both studies, says: “When we look at this two studies together, we can see that there is a clear imbalance between key regions at the front of the brain in people with OCD. These may underlie some of the symptoms of inflexibility that we commonly see in patients with this condition.”

The research was funded by the Wellcome Trust.

References

  1. Apergis-Schoute, AM et al.Neural basis of impaired safety signaling in Obsessive Compulsive Disorder. PNAS; 6 Mar 2017; DOI: 10.1073/pnas.1609194114
  2. Vaghi, MM et al. Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity. Biological Psychiatry; Aug 2016; DOI: 10.1016/j.biopsych.2016.08.009

People who suffer from obsessive compulsive disorder (OCD) are poorer at learning about the safety of a stimulus than healthy volunteers, which may contribute to their struggles to overcome compulsive behaviour, according to new research from the University of Cambridge.

Current exposure therapies may help the patient take control over their compulsions, but our work suggests that they might never learn that their compulsions are unnecessary
Annemieke Apergis-Schoute
OCD Letter Blocks

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Patients recovering from depression show improvements in memory from the drug modafinil

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jan 17, 2017.

Depression is one of the leading causes of disability worldwide. Symptoms such as difficulty concentrating or indecisiveness contribute to the disability associated with depression. Almost all patients with depression experience problems with concentration, memory, and attention. At least half of all patients with depression show cognitive deficits that can be measured objectively. These deficits tend to persist in the recovery phase. Patients with persistent cognitive problems have poorer outcomes such as impaired work functioning and increased risk for relapse. Depression can be relapsing and return periodically, often for several months at a time.

Depression is associated with taking time off work, but also, in some cases, with ‘presenteeism’ in the workplace, where employees may not be able to work as well as usual. People often feel distressed when they have difficulty achieving their previous level of work performance on return to work after experiencing depression.

However, currently available treatments do not specifically address cognitive deficits in depression. Recent reports have highlighted the importance of defining cognition as a target for treatment in depression.

In a study funded by the Medical Research Council (MRC) and Wellcome, researchers from the Department of Psychiatry and the Behavioural and Clinical Neuroscience Institute at the University of Cambridge investigated the potential of modafinil to treat cognitive dysfunction in depression. Modafinil has already been shown in other studies to have beneficial effects on cognitive function in psychiatric disorders such as schizophrenia.

Sixty patients aged between 18 and 65 years with remitted depression completed computerised memory, attention and planning tasks after receiving modafinil or a placebo. The results showed that patients given a dose of modafinil experienced improvements in memory functions, compared to those patients on placebo. Specifically, patients had benefits in two types of memory – episodic memory and working memory, both of which are important in our day-to-day activities.

“We use episodic memory when we are remembering where we left our keys in the house, or remembering where we parked our car,” explains Professor Barbara Sahakian, the study’s senior author. “Working memory, on the other hand, is the ability we use when we are rehearsing a new telephone number while we are trying to find a pen and paper to write it down, for example.”

The study demonstrated that patients receiving modafinil made fewer errors than those who received a placebo. For example, in one of the tasks which involved remembering the location among an increasing number of boxes of a particular pattern, patients receiving modafinil made fewer than half the number of mistakes that those receiving the placebo made, at the most difficult level.

“These results are very promising,” says lead author Dr Muzaffer Kaser from the Department of Psychiatry at the University of Cambridge. “GPs or psychiatrists often hear complaints of concentration or memory difficulties from patients with depression, but we are not good enough at treating these symptoms. Our study shows that modafinil may be a feasible option to tackle persistent cognitive problems in depression.”

It is not clear from the study whether the same effects would be seen over the long term, say the researchers. Professor Sahakian adds: “We now need a longer term study using modafinil to see if the drug, which improves cognition and motivation, can facilitate successful return to work following depression.”

Dr Kathryn Adcock, Head of Neurosciences and Mental Health at the MRC, added: “Preventing relapse is an integral part of any ongoing treatment strategy for depression, and some people can understandably feel hampered if they find it hard to get back to their previous capacity when they go back to work after experiencing depression. These results suggest there may be a way to help these people in their recovery from depression and that’s really encouraging.”

Reference
Kaser M, et al. Modafinil Improves Episodic Memory and Working Memory Cognition in Patients with Remitted Depression: A Double-Blind, Randomized, Placebo Controlled Study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging; 17 Jan 2017; DOI: 10.1016/j.bpsc.2016.11.009.

Modafinil, a drug used to treat narcolepsy – excessive daytime sleepiness – can improve memory in patients recovering from depression, according to new research from the University of Cambridge. The findings, published today in the journal Biological Psychiatry: CNNI, result from a randomised, double-blind, placebo-controlled study and offer hope of a treatment for some of the cognitive symptoms of depression.

GPs or psychiatrists often hear complaints of concentration or memory difficulties from patients with depression, but we are not good enough at treating these symptoms
Muzaffer Kaser
P1012863

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How Cambridge Neuroscientists are tackling mental health

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 08, 2016.

Cambridge Neuroscience Seminar 2016

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 08, 2016.

Major Wellcome Trust award to UCL boosts Huntington's disease research

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 01, 2016.

Carrots and sticks fail to change behaviour in cocaine addiction

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jun 16, 2016.

“Addiction does not happen overnight but develops from behaviour that has been repeated over and over again until individuals lose control,” said Dr Karen Ersche from the Department of Psychiatry, who led the research.

In a study reported today in the journal Science, Dr Ersche and colleagues tested 125 participants, of whom 72 were addicted to cocaine and 53 had no history of drug addiction, on their inclination to develop habits. They found that people with cocaine addiction were much more likely than healthy participants to make responses in an automatic fashion, but only if they had previously been rewarded for responding in the same way. The addicted individuals simply continued repeating the same responses they had previously learned, regardless of whether their actions made sense or not.

In a different context, however, where participants had to perform an action to avoid electrical shocks, people with cocaine addiction did not develop habits. In fact, they were much less inclined than the control participants to make an effort to avoid the electric shock in the first place.

“Our experiments highlight the particular difficulties faced when it comes to changing behaviour in people with cocaine addiction: they are highly responsive if their behaviour is rewarded – for example a ‘high’ from drug use – but then quickly switch to autopilot, becoming unable to change that behaviour in light of different consequences,” said Dr Ersche. “By contrast, when cocaine users are facing adversity, they are less inclined than healthy people to do something about it.

“These findings have significant implications for the treatment of people with cocaine addiction. Clearly punitive approaches are ineffective, as the prospect of something bad happening to them won’t make cocaine users more likely to change their behaviour. Interventions that build on their particular strength in developing habits, by training the implementation of more desirable habits to replace drug-taking habits, are likely to be more effective. Our findings also suggest that cocaine users would need to be actively protected from – rather than simply warned about – adverse consequences, because they will likely fail to avoid them if left to their own devices.”

There is currently no medical treatment for cocaine addiction – most individuals are treated with talking or cognitive therapy. According to Dr Ersche, the results show that a different approach to treating cocaine addiction might be of enhanced benefit to cocaine users. The researchers are now aiming to better understand the brain systems underlying cocaine users’ proneness to habits and their lack of avoidance, and to use this knowledge to develop more effective treatments for cocaine addiction.

In the first experiment conducted by Ersche and her colleagues, participants were asked to learn the relationship between pictures, and a correct response was rewarded with points. After a long training period, participants were informed that some pictures were no longer worth any points. Participants with cocaine addiction were less likely to take on board the information about the change in reward, and were also more likely to continue responding in an automatic way, regardless of whether they were rewarded or not.

In a second experiment, the same participants were shown two different pictures on a screen, which they learned to associate with receiving an electric shock. Participants were then taught a strategy on how they could avoid the shocks by pressing a foot pedal. Those participants with cocaine addiction were less good at avoiding the electric shocks in the first place, possibly due to learning and/or motivational impairment, and subsequently did not develop avoidance habits.

The work was funded by the Medical Research Council and was conducted at the NIHR Cambridge Biomedical Research Centre and the Behavioural and Clinical Neuroscience Institute.

Reference
Ersche, KD et al. Carrots and sticks fail to change behavior in cocaine addiction. Science; 17 Jun 2016; DOI: 10.1126/science.aaf3700

People who are addicted to cocaine are particularly prone to developing habits that render their behaviour resistant to change, regardless of the potentially devastating consequences, suggests new research from the University of Cambridge. The findings may have important implications for the treatment of cocaine addiction as they help explain why such individuals take drugs even when they are aware of the negative consequences, and why they find their behaviour so difficult to change.

Sträng

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BJS & TWR: Cambridge in America event

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jan 05, 2016.

This is the script used for these fund-raising events for CAm events following receptions at Carnegie Hall, New York City and The Ferry Building, San Francisco.

Hallucinations linked to differences in brain structure

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Nov 17, 2015.

The study, led by the University of Cambridge in collaboration with Durham University, Macquarie University, and Trinity College Dublin, found that reductions in the length of the paracingulate sulcus (PCS), a fold towards the front of the brain, were associated with increased risk of hallucinations in people diagnosed with schizophrenia.


The PCS is one of the last structural folds to develop in the brain before birth, and varies in size between individuals. In a previous study, a team of researchers led by Dr Jon Simons from the Department of Psychology at the University of Cambridge, found that variation in the length of the PCS in healthy individuals was linked to the ability to distinguish real from imagined information, a process known as ‘reality monitoring’.

In this new study, published today in the journal Nature Communications, Dr Simons and his colleagues analysed 153 structural MRI scans of people diagnosed with schizophrenia and matched control participants, measuring the length of the PCS in each participant’s brain. As difficulty distinguishing self-generated information from that perceived in the outside world may be responsible for many kinds of hallucinations, the researchers wanted to assess whether there was a link between length of the PCS and propensity to hallucinate.

The researchers found that in people diagnosed with schizophrenia, a 1 cm reduction in the fold’s length increased the likelihood of hallucinations by nearly 20%. The effect was observed regardless of whether hallucinations were auditory or visual in nature, consistent with a reality monitoring explanation.

“Schizophrenia is a complex spectrum of conditions that is associated with many differences throughout the brain, so it can be difficult to make specific links between brain areas and the symptoms that are often observed,” says Dr Simons. “By comparing brain structure in a large number of people diagnosed with schizophrenia with and without the experience of hallucinations, we have been able to identify a particular brain region that seems to be associated with a key symptom of the disorder.”

The researchers believe that changes in other areas of the brain are likely also important in generating the complex phenomena of hallucinations, possibly including regions that process visual and auditory perceptual information. In people who experience hallucinations, these areas may produce altered perceptions which, due to differences in reality monitoring processes supported by regions around the PCS, may be misattributed as being real. For example, a person may vividly imagine a voice but judge that it arises from the outside world, experiencing the voice as a hallucination.

“We think that the PCS is involved in brain networks that help us recognise information that has been generated ourselves,” adds Dr Jane Garrison, first author of the study, “People with a shorter PCS seem less able to distinguish the origin of such information, and appear more likely to experience it as having been generated externally.

“Hallucinations are very complex phenomena that are a hallmark of mental illness and, in different forms, are also quite common across the general population. There is likely to be more than one explanation for why they arise, but this finding seems to help explain why some people experience things that are not actually real.”

The research was primarily supported by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the UK Medical Research Council and the Wellcome Trust.

Reference
Garrison, J.R., Fernyhough, C., McCarthy-Jones, S., Haggard, M., The Australian Schizophrenia Research Bank, & Simons, J.S. (2015). Paracingulate sulcus morphology is associated with hallucinations in the human brain. Nature Communications, 6, 8956.

People diagnosed with schizophrenia who are prone to hallucinations are likely to have structural differences in a key region of the brain compared to both healthy individuals and people diagnosed with schizophrenia who do not hallucinate, according to research published today.

Hallucinations are very complex phenomena that are a hallmark of mental illness and, in different forms, are also quite common across the general population. There is likely to be more than one explanation for why they arise
Jane Garrison
HALLUZINATION

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Professor Trevor Robbins reveals his Ten (?) Secrets of Success in Science

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 28, 2015.

Differences in brain structure and memory suggest adolescents may not ‘grow out of’ ADHD

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 27, 2015.

The findings, published today in the journal European Child Adolescent Psychiatry, suggest that aspects of ADHD may persist into adulthood, even when current diagnostic criteria fail to identify the disorder.

ADHD is a disorder characterised by short attention span, restlessness and impulsivity, and is usually diagnosed in childhood or adolescence. Estimates suggest that more than three in every 100 boys and just under one in every 100 girls has ADHD. Less is known about the extent to which the disorder persists into adulthood, with estimates suggesting that between 10-50% of children still have ADHD in adulthood. Diagnosis in adulthood is currently reliant on meeting symptom checklists (such as the American Psychiatric Association’s Diagnostic and Statistical Manual).

Some have speculated that as the brain develops in adulthood, children may grow out of ADHD, but until now there has been little rigorous evidence to support this. So far, most of the research that has followed up children and adolescents with ADHD into adulthood has focused on interview-based assessments, leaving questions of brain structure and function unanswered.

Now, researchers at Cambridge and Oulu have followed up 49 adolescents diagnosed with ADHD at age 16, to examine their brain structure and memory function in young adulthood, aged between 20-24 years old, compared to a control group of 34 young adults. The research was based within the Northern Finland Birth Cohort 1986, which has followed up thousands of children born in 1986 from gestation and birth into adulthood. The results showed that the group diagnosed in adolescence still had problems in terms of reduced brain volume and poorer memory function, irrespective of whether or not they still met diagnostic checklist criteria for ADHD.

By analysing the structural magnetic resonance imaging (MRI) brain scans and comparing them to the controls, the researchers found that the adolescents with ADHD had reduced grey matter in a region deep within the brain known as the caudate nucleus, a key brain region that integrates information across different parts of the brain, and supports important cognitive functions, including memory.

To investigate whether or not these grey matter deficits were of any importance, the researchers conducted a functional MRI experiment (fMRI), which measured brain activity whilst 21 of the individuals previously diagnosed with ADHD and 23 of the controls undertook a test of working memory inside the scanner.

One third of the adolescents with ADHD failed the memory test compared to less than one in twenty of the control group (an accuracy of less than 75% was classed as a fail). Even amongst the adolescent ADHD sample who passed the memory test, the scores were on average 6 percentage points less than controls. The poor memory scores seemed to relate to a lack of responsiveness in the activity of the caudate nucleus: in the controls, when the memory questions became more difficult, the caudate nucleus became more active, and this appeared to help the control group perform well; in the adolescent ADHD group, the caudate nucleus kept the same level of activity throughout the test.

There were no differences in brain structure or memory test scores between those young adults previously diagnosed with ADHD who still met the diagnostic criteria and those who no longer met them.

Dr Graham Murray from the Department of Psychiatry, University of Cambridge, who led the study, says: “In the controls, when the test got harder, the caudate nucleus went up a gear in its activity, and this is likely to have helped solve the memory problems. But in the group with adolescent ADHD, this region of the brain is smaller and doesn’t seem to be able to respond to increasing memory demands, with the result that memory performance suffers.

“We know that good memory function supports a variety of other mental processes, and memory problems can certainly hold people back in terms of success in education and the workplace. The next step in our research will be to examine whether these differences in brain structure and memory function are linked to difficulties in everyday life, and, crucially, see if they respond to treatment.”

The fact that the study was set in Finland, where medication is rarely used to treat ADHD, meant that only one of the 49 ADHD adolescents had been treated with medication. This meant the researchers could confidently rule out medication as a confounding factor.

To date, ‘recovery’ in ADHD has focused on whether people do or do not continue to meet symptom checklist criteria for diagnosis. However, this research indicates that objective measures of brain structure and function may continue to be abnormal even if diagnostic criteria are no longer met. The results therefore emphasize the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

The research was funded in part by the Medical Research Council, with additional support from the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre.

Reference
Roman-Urrestarazu, A et al. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence. European Child Adolescent Psychiatry; 27 Aug 2015

Young adults diagnosed with attention deficit/hyperactivity disorder (ADHD) in adolescence show differences in brain structure and perform poorly in memory tests compared to their peers, according to new research from the University of Cambridge, UK, and the University of Oulu, Finland.

Good memory function supports a variety of other mental processes, and memory problems can certainly hold people back in terms of success in education and the workplace
Graham Murray
ADHD

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BBC Newsnight on smart pills

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 24, 2015.

Professor Barbara Sahakian will be appearing on BBC Newsnight this evening (21.8.15 at 10.30pm on BBC2) as part of an item discussing the use of modafinil by healthy people.

‘Brain training’ app may improve memory and daily functioning in schizophrenia

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Aug 03, 2015.

Schizophrenia is a long-term mental health condition that causes a range of psychological symptoms, ranging from changes in behaviour through to hallucinations and delusions. Psychotic symptoms are reasonably well treated by current medications; however, patients are still left with debilitating cognitive impairments, including in their memory, and so are frequently unable to return to university or work.

There are as yet no licensed pharmaceutical treatments to improve cognitive functions for people with schizophrenia. However, there is increasing evidence that computer-assisted training and rehabilitation can help people with schizophrenia overcome some of their symptoms, with better outcomes in daily functioning and their lives.

Schizophrenia is estimated to cost £13.1 billion per year in total in the UK, so even small improvements in cognitive functions could help patients make the transition to independent living and working and could therefore substantially reduce direct and indirect costs, besides improving the wellbeing and health of patients.

In a study published today in the Philosophical Transactions of the Royal Society B, a team of researchers led by Professor Barbara Sahakian from the Department of Psychiatry at Cambridge describe how they developed and tested Wizard, an iPad game aimed at improving an individual’s episodic memory. Episodic memory is the type of memory required when you have to remember where you parked your car in a multi-storey car park after going shopping for several hours or where you left your keys in home several hours ago, for example. It is one of the facets of cognitive functioning to be affected in patients with schizophrenia.

The game, Wizard, was the result of a nine-month collaboration between psychologists, neuroscientists, a professional game-developer and people with schizophrenia. It was intended to be fun, attention-grabbing, motivating and easy to understand, whilst at the same time improving the player’s episodic memory. The memory task was woven into a narrative in which the player was allowed to choose their own character and name; the game rewarded progress with additional in-game activities to provide the user with a sense of progression independent of the cognitive training process.

The researchers assigned twenty-two participants, who had been given a diagnosis of schizophrenia, to either the cognitive training group or a control group at random. Participants in the training group played the memory game for a total of eight hours over a four-week period; participants in the control group continued their treatment as usual. At the end of the four weeks, the researchers tested all participants’ episodic memory using the Cambridge Neuropsychological Test Automated Battery (CANTAB) PAL, as well as their level of enjoyment and motivation, and their score on the Global Assessment of Functioning (GAF) scale, which doctors use to rate the social, occupational, and psychological functioning of adults.

Professor Sahakian and colleagues found that the patients who had played the memory game made significantly fewer errors and needed significantly fewer attempts to remember the location of different patterns in the CANTAB PAL test relative to the control group. In addition, patients in the cognitive training group saw an increase in their score on the GAF scale.

Participants in the cognitive training group indicated that they enjoyed the game and were motivated to continue playing across the eight hours of cognitive training. In fact, the researchers found that those who were most motivated also performed best at the game. This is important, as lack of motivation is another common facet of schizophrenia.

Professor Sahakian says: “We need a way of treating the cognitive symptoms of schizophrenia, such as problems with episodic memory, but slow progress is being made towards developing a drug treatment. So this proof-of-concept study is important because it demonstrates that the memory game can help where drugs have so far failed. Because the game is interesting, even those patients with a general lack of motivation are spurred on to continue the training.”

Professor Peter Jones adds: “These are promising results and suggest that there may be the potential to use game apps to not only improve a patient’s episodic memory, but also their functioning in activities of daily living. We will need to carry out further studies with larger sample sizes to confirm the current findings, but we hope that, used in conjunction with medication and current psychological therapies, this could help people with schizophrenia minimise the impact of their illness on everyday life.”

It is not clear exactly how the apps also improved the patients’ daily functioning, but the researchers suggest it may be because improvements in memory had a direct impact on global functions or that the cognitive training may have had an indirect impact on functionality by improving general motivation and restoring self-esteem. Or indeed, both these explanations may have played a role in terms of the impact of training on functional outcome.

In April 2015, Professor Sahakian and colleagues began a collaboration with the team behind the popular brain training app Peak to produce scientifically-tested cognitive training modules. The collaboration has resulted in the launch today of the Cambridge University & Peak Advanced Training Plan a memory game, available within Peak’s iOS app, designed to train visual and episodic memory while promoting learning.

The training module is based on the Wizard memory game, developed by Professor Sahakian and colleague Tom Piercy at the Department of Psychiatry at the University of Cambridge. Rights to the Wizard game were licensed to Peak by Cambridge Enterprise, the University’s commercialisation company.

“This new app will allow the Wizard memory game to become widely available, inexpensively. State-of-the-art neuroscience at the University of Cambridge, combined with the innovative approach at Peak, will help bring the games industry to a new level and promote the benefits of cognitive enhancement,” says Professor Sahakian.

Reference
Sahakian, BJ et al. The impact of neuroscience on society: Cognitive enhancement in neuropsychiatric disorders and in healthy people. Phil. Trans. R. Soc. B; 3 Aug 2015

Home page image: Brain Power by Allan Ajifo

A ‘brain training’ iPad game developed and tested by researchers at the University of Cambridge may improve the memory of patients with schizophrenia, helping them in their daily lives at work and living independently, according to research published today.

This proof-of-concept study is important because it demonstrates that the memory game can help where drugs have so far failed
Barbara Sahakian
Cambridge Advanced Training Programme

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Professor Trevor Robbins receives Lifetime Achievement Award from BAP

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jul 28, 2015.

Novel Thoughts #8: Amy Milton on Hubert Selby’s Requiem for a Dream

By lw355 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jul 03, 2015.

Amy Milton

Dr Amy Milton from Cambridge’s Department of Psychology relates how Requiem for a Dream, Hubert Selby’s bleak portrayal of drug addiction, motivated her to dedicate her academic career to finding treatments for addiction.

Here she talks about this favourite book as part of ‘Novel Thoughts’, a series exploring the literary reading habits of eight Cambridge scientists. From illustrated children’s books to Thomas Hardy, from Star Wars to Middlemarch, we find out what fiction has meant to each of the scientists and peak inside the covers of the books that have played a major role in their lives.

‘Novel Thoughts’ was inspired by research at the University of St Andrews by Dr Sarah Dillon (now a lecturer in the Faculty of English at Cambridge) who interviewed 20 scientists for the ‘What Scientists Read’ project. She found that reading fiction can help scientists to see the bigger picture and be reminded of the complex richness of human experience. Novels can show the real stories behind the science, or trigger a desire in a young reader to change lives through scientific discovery. They can open up new worlds, or encourage a different approach to familiar tasks.

View the whole series: Novel Thoughts: What Cambridge scientists read.

Read about Novel Thoughts.

Is there a novel that has inspired you? Let us know! #novelthoughts

New film series Novel Thoughts reveals the reading habits of eight Cambridge scientists and peeks inside the covers of the books that have played a major role in their lives. In the final film, Dr Amy Milton talks about how Hubert Selby's Requiem for a Dream has inspired her pursuit of treatments for addiction.

Amy Milton

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Study suggests new treatment for impulsivity in some dementia patients

By cjb250 from University of Cambridge - Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jun 25, 2015.

Around 16,000 people in the UK are estimated to be affected by frontotemporal dementia (also known as Pick’s disease). Patients are often affected at a young age, 50-65 years old. The disease affects the frontal and temporal lobes of the brain, at the front with both shrinkage and loss of important brain chemicals like serotonin. As a result, symptoms of frontotemporal dementia include changes in personality and behaviour, and difficulties with language.

One of the key symptoms is disinhibition – impulsivity and impetuous behaviour. This is partly a result of a deficiency in serotonin, an important chemical within the brain which is responsible for maintaining normal behaviour as well as mood.

A team led by Dr James Rowe from the University of Cambridge and the Medical Research Council (MRC) Cognition and Brain Sciences Unit at Cambridge looked at whether citalopram, a commonly-prescribed antidepressant, might restore the brain function – and potentially alleviate the symptoms of disinhibition. Citalopram is known to restore levels of serotonin, even in patients who do not have depression; this increase in serotonin helps the brain activity needed make decisions about what to do, and what not to do.

The researchers examined the brain activity associated with disinhibition in patients and healthy volunteers. The patients received either a dose of citalopram or a placebo, in a double-blinded placebo-controlled trial. Participants took part in a ‘Go-NoGo’ task whilst their brain activity was monitored using a combination of magnetoencephalography (MEG) and electroencephalography (EEG). In the task, the volunteers needed to intermittently hold back from a habitual action, choosing to press or not to press buttons.

As expected, patients with frontotemporal dementia made many errors on the task, with difficulty holding back from actions. The performance on the task was closely related to their everyday impulsive and disinhibited behaviours.  Compared to the placebo, citalopram boosted activity in the dementia patients in their right inferior frontal gyrus, a critical region of the brain for controlling our behaviour, even though this part of the brain was shrunken by the disease.

Dr Laura Hughes from the University of Cambridge and the MRC Cognition and Brain Sciences Unit, first author on the study, says: “This is a very promising result, which builds on a lot of basic laboratory science here in Cambridge. It suggests that it may be possible to treat patients safely and effectively for high risk and challenging impulsive behaviours, although more work is needed to identify those who are most likely to benefit from this type of drug.”

The research was primarily funded by the Wellcome Trust with additional support from the Medical Research Council and the NIHR Cambridge Biomedical Research Centre.

Reference
Hughes, LE et al. Improving response inhibition systems in frontotemporal dementia with citalopram. Brain; e-pub 22 May 2015

Restoring the low levels of the chemical serotonin may help improve brain function and reduce impulsivity in some dementia patients, according to Cambridge researchers. A study published in the July edition of the journal Brain suggests a potential new treatment for people affected by frontotemporal dementia.

This is a very promising result, which suggests that it may be possible to treat patients safely and effectively for high risk and challenging impulsive behaviours
Laura Hughes
Brain coral

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Professor Trevor Robbins gives Plenary Lecture at UCLA Integrative Center for Addictions Symposium

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Apr 23, 2015.

Unique risk taking in different disorders of natural and drug reward.

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Oct 13, 2014.

Children with autism have elevated levels of steroid hormones in the womb

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jul 15, 2014.

Brain activity in sex addiction mirrors that of drug addiction

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Jul 11, 2014.

Creatures of habit: disorders of compulsivity share common pattern and brain structure

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 29, 2014.

Explicit feedback alters risk-seeking attitudes and brain activity in binge drinkers

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Cannabis gender and schizophrenia: which factors affect early onset psychosis

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Professor Barbara Sahakian and Dr Annette Bruhl speak about stress and anxiety at Cambridge Science Festival

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Out of mind, out of sight: suppressing unwanted memories reduces their unconscious influence on behaviour

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Dr Luke Clark to present opening lecture at international symposium on problem gambling

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Modafinil reduces depressions severity when taken with anti-depressants

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Head first: reshaping how traumatic brain injury is treated

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Males and females differ in specific brain structures

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Biomarker for depression could improve diagnosis and treatment

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Dr Jennifer Murray took part in a Stemettes outreach day

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

New study reveals scale of problem gambling among homeless population

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Scientists identify part of brain linked to gambling addiction

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Dr Gonzalo Urcelay gave Extinction Learning Symposium Lecture in November 2013

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Dr Luke Clark to Head a new Gambling Research Centre in Canada this summer.

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Dr Mike Aitken to be awarded Pilkington Prize this summer.

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Professor Trevor Robbins is awarded the Brain Prize for his pioneering research on higher brain mechanisms

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on May 15, 2014.

Biomarker for Clinical Depression in Teenage Boys Identified

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Feb 19, 2014.

Brain imaging study demonstrates that dopamine dysregulation is not the cause of ADHD

From Behavioural and Clinical Neuroscience Institute (BCNI). Published on Nov 01, 2013.