̽��ֱ�� of Cambridge - Wolfson Brain Imaging Centre

Powerful new MRI scans enable life-changing surgery in first for adults with epilepsy

cjb250 — Fri, 21 Mar 2025 00:01:25 +0000

Scientists have developed a new technique that has enabled ultra-powerful MRI scanners to identify tiny differences in patients’ brains that cause treatment-resistant epilepsy. It has allowed doctors at Addenbrooke’s Hospital, Cambridge, to offer the patients surgery to cure their condition.

Ultra-powerful brain scanners offer hope for Parkinson’s disease patients

cjb250 — Tue, 17 May 2022 08:00:09 +0000

7T MRI scanners could be used to help identify those patients with Parkinson’s disease and similar conditions most likely to benefit from new treatments for previously-untreatable symptoms, say scientists.

Marmoset study gives insights into loss of pleasure in depression

cjb250 — Tue, 04 Dec 2018 16:00:03 +0000

Now, in a study involving marmosets, scientists at the ̽��ֱ�� of Cambridge have identified the region of the brain that contributes to this phenomenon, and shown that the experimental antidepressant ketamine acts on this region, helping explain why this drug may prove effective at treating anhedonia.

Depression is a common and debilitating condition which is recognised as a leading cause of disability worldwide. A survey published in 2016 found that 3.3 out of every 100 UK adults had experienced depression in the week before being interviewed.

A key symptom of depression is anhedonia, typically defined as the loss of ability to experience pleasure. However, anhedonia also involves a lack of motivation and lack of excitement in anticipation of events. All these aspects have proven difficult to treat. One major issue slowing down progress in developing new treatments is that the brain mechanisms that give rise to anhedonia remain largely unknown.

“Imaging studies of depressed patients have given us a clue about some of the brain regions that may be involved in anhedonia, but we still don't know which of these regions is causally responsible,” says Professor Angela Roberts from the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge.

“A second important issue is that anhedonia is multi-faceted – it goes beyond a loss of pleasure and can involve a lack of anticipation and motivation, and it’s possible that these different aspects may have distinct underlying causes.”

In fact, even when existing therapies do work, the reasons why they are effective are not always clear, making it difficult to target these therapies to individuals.

Using marmosets, a type of non-human primate, Professor Roberts and MBPhD student Laith Alexander, along with other colleagues, including those at the Wolfson Brain Imaging Centre and Translational Neuroimaging Laboratory, have shown how over-activity in a specific area of the brain’s frontal lobe blunts the excitement seen when anticipating a reward and the motivation to work for that reward. Their results are published today in the journal Neuron.

In the present study marmosets were trained to respond to two sounds: if they heard sound A, they would receive a treat of marshmallows; if they heard sound B, they would not receive a treat. Once they had learned the association, they would become aroused at sound A, reflected in an increase in blood pressure and excited movements of the head. They would not show the same response to B.

̽��ֱ��researchers then infused either a drug or a saline solution into a region of the brain known as ‘area 25’ through thin cannulae (metal tubes) in the marmosets’ head. Cannulae are inserted during a single surgical procedure, and once the anaesthetic has worn off they do not trouble the animals.

̽��ֱ��effect of the drug was to temporarily make this particular brain region over-active, and this resulted in the marmosets showing less excitement and anticipation at the prospect of a marshmallow treat. They were however as quick to eat the marshmallow treat as before. ̽��ֱ��saline infusion made no difference to the activity in area 25 or to the marmosets’ excitement and anticipation.

In a second task, the marmosets had to make more and more responses to get their reward – while initially they would receive a marshmallow treat after pressing a coloured shape on a touch sensitive computer screen just once, as the task proceeded, they would be required to press the coloured shape an increasing number of times. Eventually, the marmoset would reach a point where it gave up, considering the treat to be no longer worth the effort required.

When the marmosets’ area 25 was over-activated, the researchers observed that the marmosets gave up much faster. This lack of motivation is another key symptom associated with anhedonia.

By using PET scanning techniques to observe activity across the marmoset’s brain the researchers found that over-activity in area 25 had a knock-on effect to other brain regions, which also became more active, indicating that these were all part of brain circuity controlling anticipatory excitement.

Finally, the researchers investigated the effect of the experimental antidepressant, ketamine. Marmosets were given the antidepressant 24 hours ahead of the experiment. This time, even when marmosets were administered the treatment to make area 25 over-active, they still showed excitement and anticipation at the marshmallow reward. PET scanning revealed that the brain circuits were functioning normally. In other words, ketamine had blocked the effects of over-activating area 25, which would otherwise blunt anticipation.

“Understanding the brain circuits that underlie specific aspects of anhedonia is of major importance, not only because anhedonia is a core feature of depression but also because it is one of the most treatment-resistant symptoms,” says Laith Alexander, the study’s first author.

“By revealing the specific symptoms and brain circuits that are sensitive to antidepressants like ketamine, this study moves us one step closer to understanding how and why patients may benefit from different treatments.”

Marmosets are used to study brain disorders such as depression because of the similarity of the frontal lobes to those of humans. Rats, which are often used in psychology studies, have frontal lobes quite different to those of humans, making it less easy to translate studies of frontal lobe circuitry directly into the clinic.

“Depression affects many millions of people worldwide, so it’s important we get to the problems within the brain that underlie the various symptoms,” says Professor Roberts. “Studying these symptoms in non-human primates, such as marmosets can help bridge the gap between findings from rodent studies and the clinic.

“Using marmosets, we are able to manipulate the activity in specific brain regions, helping us see which regions are causally involved. These effects are temporary, and wear off after a short time.”

̽��ֱ��research was funded by Wellcome.

Reference
Alexander, L, et al. Fractionating blunted reward processing characteristic of anhedonia by over-activating primate subgenual anterior cingulate cortex. Neuron; 4 Dec 2018; DOI: 10.1016/j.neuron.2018.11.021

‘Anhedonia’ (the loss of pleasure) is one of the key symptoms of depression. An important component of this symptom is an inability to feel excitement in anticipation of events; however the brain mechanisms underlying this phenomenon are poorly understood.

Understanding the brain circuits that underlie specific aspects of anhedonia is of major importance, not only because anhedonia is a core feature of depression but also because it is one of the most treatment-resistant symptoms

Laith Alexander

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Cambridge extends world leading role for medical imaging with powerful new brain and body scanners

cjb250 — Mon, 24 Oct 2016 07:22:25 +0000

̽��ֱ��equipment, funded by the Medical Research Council (MRC), Wellcome Trust and Cancer Research UK, sits within the newly-refurbished Wolfson Brain Imaging Centre (WBIC), which today celebrates two decades at the forefront of medical imaging.

At the heart of the refurbishment are three cutting-edge scanners, of which only a very small handful exist at institutions outside Cambridge – and no institution other than the ̽��ֱ�� of Cambridge has all three. These are:

a Siemens 7T Terra Magnetic Resonance Imaging (MRI) scanner, which will allow researchers to see detail in the brain as tiny as a grain of sand
a GE Healthcare PET/MR scanner that will enable researchers to collect critical data to help understand how cancers grow, spread and respond to treatment, and how dementia progresses
a GE Healthcare hyperpolarizer that enables researchers to study real-time metabolism of cancers and other body tissues, including whether a cancer therapy is effective or not

These scanners, together with refurbished PRISMA and Skyra 3T MRI scanners at the WBIC and at the Medical Research Council Cognition and Brain Sciences Unit, will make the Cambridge Biomedical Campus the best-equipped medical imaging centre in Europe.

Professor Ed Bullmore, Co-Chair of Cambridge Neuroscience and Scientific Director of the WBIC, says: “This is an exciting day for us as these new scanners will hopefully provide answers to questions that we have been asking for some time, as well as opening up new areas for us to explore in neuroscience, mental health research and cancer medicine.

“By bringing together these scanners, the research expertise in Cambridge, and the latest in ‘big data’ informatics, we will be able to do sophisticated analyses that could revolutionise our understanding of the brain – and how mental health disorders and dementias arise – as well of cancers and how we treat them. This will be a powerful research tool and represents a big step in the direction of personalised treatments.”

Dr Rob Buckle, Director of Science Programmes at the MRC, adds: “ ̽��ֱ��MRC is proud to sponsor this exciting suite of new technologies at the ̽��ֱ�� of Cambridge. They will play an important role in advancing our strategy in stratified medicine, ultimately ensuring that the right patient gets the right treatment at the right time.”

Slide show: Click on images to expand

7T Medical Resonance Imaging (MRI) scanner

̽��ֱ��Siemens 7T Terra scanner – which refers to the ultrahigh strength of its magnetic field at 7 Tesla – will allow researchers to study at unprecedented levels of detail the workings of the brain and how it encodes information such as individual memories. Current 3T MRI scanners can image structures 2-3mm in size, whereas the new scanner has a resolution of just 0.5mm, the size of a coarse grain of sand.

“Often, the early stages of diseases of the brain, such as Alzheimer’s and Parkinson’s, occur in very small structures – until now too small for us to see,” explains Professor James Rowe, who will be leading research using the new 7T scanner. “ ̽��ֱ��early seeds of dementia for example, which are often sown in middle age, have until now been hidden to less powerful MRI scanners.”

̽��ֱ��scanner will also be able to pick up unique signatures of neurotransmitters in the brain, the chemicals that allow its cells to communicate with each other. Changes in the amount of these neurotransmitters affect how the brain functions and can underpin mental health disorders such as depression and schizophrenia.

“How a patient responds to a particular drug may depend on how much of a particular neurotransmitter present is currently present,” says Professor Rowe. “We will be looking at whether this new scanner can help provide this information and so help us tailor treatments to individual patients.”

̽��ֱ��scanner will begin operating at the start of December, with research projects lined up to look at dementias caused by changes to the brain almost undetectable by conventional scanners, and to look at how visual and sound information is converted to mental representations in the brain.

PET/MR scanner

̽��ֱ��new GE Healthcare PET/MR scanner brings together two existing technologies: positron emission tomography (PET), which enables researchers to visualise cellular activity and metabolism, and magnetic resonance (MR), which is used to image soft tissue for structural and functional details.

Purchased as part of the Dementias Platform UK, a network of imaging centres across the UK, the scanner will enable researchers to simultaneously collect information on physiological and disease-related processes in the body, reducing the need for patients to return for multiple scans. This will be particularly important for dementia patients.

Professor Fiona Gilbert, who will lead research on the PET/MR scanner, explains: “Dementia patients are often frail, which can present challenges when they need separate PET and MR scanners. So, not only will this new scanner provide us with valuable information to help improve understanding and diagnosis of dementia, it will also be much more patient-friendly.”

PET/MR will allow researchers to see early molecular changes in the brain, accurately map them onto structural brain images and follow their progression as disease develops or worsens. This could enable researchers to diagnose dementia before any symptoms have arisen and to understand which treatments may best halt or slow the disease.

As well as being used for dementia research, the scanner will also be applied to cancer research, says Professor Gilbert.

“At the moment, we have to make lots of assumptions about what’s going on in tumour cells. We can take biopsies and look at the different cell types, how aggressive they are, their genetic structure and so on, but we can only guess what’s happening to a tumour at a functional level. Functional information is important for helping us determine how best to treat the cancer – and hence how we can personalise treatment for a particular patient. Using PET/MR, we can get real-time information for that patient’s specific tumour and not have to assume it is behaving in the same way as the last hundred tumours we’ve seen.”

̽��ֱ��PET/MR scanner will begin operation at the start of November, when it will initially be used to study oxygen levels and blood flow in the tumours of breast cancer patients and in studies of brain inflammation in patients with Alzheimer’s disease and depression.

Hyperpolarizer

̽��ֱ��third new piece of imaging equipment to be installed is a GE Healthcare hyperpolarizer, which is already up and running at the facility.

MRI relies on the interaction of strong magnetic fields with a property of atomic nuclei known as ‘spin’. By looking at how these spins differ in the presence of magnetic field gradients applied across the body, scientists are able to build up three-dimensional images of tissues. ̽��ֱ��hyperpolarizer boosts the ‘spin’ signal from tracers injected into the tissue, making the MRI measurement much more sensitive and allowing imaging of the biochemistry of the tissue as well as its anatomy.

“Because of underlying genetic changes in a tumour, not all patients respond in the same way to the same treatment,” explains Professor Kevin Brindle, who leads research using the hyperpolarizer. “Using hyperpolarisation and MRI, we can potentially tell whether a drug is working, from changes in the tumour’s biochemistry, within a few hours of starting treatment. If it’s working you continue, if not you change the treatment.”

̽��ֱ��next generation of imaging technology, newly installed at the ̽��ֱ�� of Cambridge, will give researchers an unprecedented view of the human body – in particular of the myriad connections within our brains and of tumours as they grow and respond to treatment – and could pave the way for development of treatments personalised for individual patients.

By bringing together these scanners, the research expertise in Cambridge, and the latest in ‘big data’ informatics, we will be able to do sophisticated analyses that could revolutionise our understanding of the brain – and how mental health disorders and dementias arise – as well of cancers and how we treat them

Ed Bullmore

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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̽��ֱ��psychology of gambling

tdk25 — Sun, 01 Apr 2007 00:00:00 +0000

Gambling is a thriving form of entertainment in the UK, but may also become a form of addiction for some individuals. Just why do people gamble when ‘the house always wins’? Advances in brain imaging techniques are helping Cambridge scientists find out.

Gambling has been a popular source of entertainment for many centuries and across many cultures. With current changes in gambling legislation in the UK, its popularity looks set to continue. New casinos are to be established, including a large ‘super-casino’, and novel forms of gambling like internet gambling and electronic gaming machines are flourishing. Some argue these changes are a good thing: gambling is a recreational activity enjoyed by around 70% of the British public at least annually, and the gambling industry is a useful source of taxable revenue.

But all this comes at a cost – for a minority of individuals, gambling is a spiralling habit that they become unable to control. Problem (or ‘pathological’) gambling is a recognised psychiatric diagnosis present in around 1% of the population. These prevalence rates are higher in local communities around gambling facilities, and clinicians are concerned that the relaxation of British legislation will increase the incidence of problem gambling in years to come.

Against the odds

At its heart, gambling is a rather paradoxical behaviour because it is widely known that ‘the house always wins’. Whether you are gambling on fruit machines, horseracing, blackjack or roulette, the odds will have been meticulously arranged to ensure a steady profit for the casino or bookmaker. ̽��ֱ��only way to achieve this is for the gambler to make a steady loss. So why do gamblers, and particularly problem gamblers, continue to play when the overwhelming likelihood is that they will lose money?

Dr Luke Clark, in the Department of Experimental Psychology, is interested in the different ways in which gamblers over-estimate their chances of winning, including the effects of near-misses and personal choice. These features of gambling games promote an ‘illusion of control’: the belief that the gambler can exert skill over an outcome that is actually defined by chance.

Imaging the gambling brain

Recent advances in brain imaging technology are helping scientists to understand how these features of gambling games are so effective in maintaining continued play. At the Wolfson Brain Imaging Centre at Addenbrooke’s Hospital in Cambridge, Dr Clark is using functional magnetic resonance imaging (fMRI) to measure patterns of brain activity while volunteers perform a gambling game.

Previous research has shown a reliable pattern of brain activity when humans receive monetary wins. In particular, a region called the striatum, near the centre of the brain, is a crucial component in a reward circuit that also responds to natural reinforcers like food and sexual stimuli, as well as drugs of abuse like cocaine. In ongoing research, Dr Clark is measuring activity in this reward circuit as volunteers experience near-misses and choice effects during a gambling task.

Hallmarks of addiction

Both near-misses and personal choice cause gamblers to play for longer and to place larger bets. Over time, these distorted perceptions of one’s chances of winning may precipitate ‘loss chasing’, where gamblers continue to play in an effort to recoup accumulating debts. Loss chasing is one of the hallmarks of problem gambling, which actually bears much resemblance to drug addiction. Problem gamblers also experience cravings and symptoms of withdrawal when denied the opportunity to gamble.

In addition to an array of psychological factors, problem gambling may also have some important biological determinants. ̽��ֱ��brain chemical dopamine is known to play a key role in drug addiction and may also be abnormally regulated in problem gambling. Patients with Parkinson’s disease, who show degeneration of dopamine cells, can sometimes show a sudden interest in gambling, linked to their use of medications that increase dopamine transmission. Other systems in the brain are also critical, particularly the part of the frontal lobes immediately above the eye sockets, known as the orbitofrontal cortex.

Following damage to the orbitofrontal region, neurosurgical patients often show changes in their judgment and risk-taking. One patient, examined at the ̽��ֱ�� of Iowa, made a series of disastrous decisions involving extravagant business ventures and dubious personal relationships after having a tumour removed from his orbitofrontal cortex. In a collaborative study with Dr Antoine Bechara at the ̽��ֱ�� of Southern California, Dr Clark is measuring betting behaviour in a group of similar patients with damage in this region, using a simple gambling task. More subtle chemical imbalances in this brain region may accompany the transition from regular gambling to problem gambling.

Help for problem gamblers?

By further understanding the breakdown of self-control in gamblers, this programme of research carries important implications for the treatment of problem gambling, using both pharmacological and psychological therapies. Moreover, the development of objective tasks of gambling will provide more valid outcome measures for assessing the effectiveness of new treatments. By understanding how subtle features of gambling games, like near-misses and personal choice, are linked to the addictiveness of these games, future changes in gambling legislation may be in a better position to protect vulnerable individuals.

Promoting an illusion of control

Near-missesoccur when the outcome is close to the jackpot, but there is no actual win. Near-misses are common in many forms of gambling, such as when your chosen horse finishes in second place in a horserace. A moderate frequency of near-misses encourages prolonged gambling, even in student volunteers who do not gamble on a regular basis. Problem gamblers often interpret near-misses as evidence that they are mastering the game and that a win is on the way.

Personal choiceis a further determinant of illusory control, referring to situations where the gambler has some responsibility in arranging their gamble. As an example, roulette players will place higher bets if they can throw the ball onto the roulette wheel themselves, compared with if the croupier throws the ball for them. Lottery players often prefer a number sequence they have selected themselves, and may refuse to exchange their ticket for several tickets of random numbers. Choice appears to encourage a belief that the game involves skill when in fact the outcome is entirely random.

For more information, please go towww.psychol.cam.ac.uk/BCNIor contact the author Dr Luke Clarklc260@cam.ac.uk

Gambling is a thriving form of entertainment in the UK, but may also become a form of addiction for some individuals. Just why do people gamble when &lsquo;the house always wins&rsquo;? Advances in brain imaging techniques are helping Cambridge scientists find out.

Gambling games promote an ‘illusion of control’: the belief that the gambler can exert skill over an outcome that is actually defined by chance.

Dr Luke Clark

Erna from Flickr

Changing Luck for the Better

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