̽��ֱ�� of Cambridge - Ed Bullmore

Study unpicks why childhood maltreatment continues to impact on mental and physical health into adulthood

cjb250 — Thu, 11 Apr 2024 14:31:51 +0000

Individuals who experienced maltreatment in childhood – such as emotional, physical and sexual abuse, or emotional and physical neglect – are more likely to develop mental illness throughout their entire life, but it is not yet well understood why this risk persists many decades after maltreatment first took place.

In a study published in Proceedings of the National Academy of Sciences, scientists from the ̽��ֱ�� of Cambridge and Leiden ̽��ֱ�� found that adult brains continue to be affected by childhood maltreatment in adulthood because these experiences make individuals more likely to experience obesity, inflammation and traumatic events, all of which are risk factors for poor health and wellbeing, which in turn also affect brain structure and therefore brain health.

̽��ֱ��researchers examined MRI brain scans from approximately 21,000 adult participants aged 40 to 70 years in UK Biobank, as well as information on body mass index (an indicator of metabolic health), CRP (a blood marker of inflammation) and experiences of childhood maltreatment and adult trauma.

Sofia Orellana, a PhD student at the Department of Psychiatry and Darwin College, ̽��ֱ�� of Cambridge, said: “We’ve known for some time that people who experience abuse or neglect as a child can continue to experience mental health problems long into adulthood and that their experiences can also cause long term problems for the brain, the immune system and the metabolic system, which ultimately controls the health of your heart or your propensity to diabetes for instance. What hasn’t been clear is how all these effects interact or reinforce each other.”

Using a type of statistical modelling that allowed them to determine how these interactions work, the researchers confirmed that experiencing childhood maltreatment made individuals more likely to have an increased body mass index (or obesity) and experience greater rates of trauma in adulthood. Individuals with a history of maltreatment tended to show signs of dysfunction in their immune systems, and the researchers showed that this dysfunction is the product of obesity and repeated exposure to traumatic events.

Next, the researchers expanded their models to include MRI measures of the adult’s brains and were able to show that widespread increases and decreases in brain thickness and volume associated with greater body mass index, inflammation and trauma were attributable to childhood maltreatment having made these factors more likely in the first place. These changes in brain structure likely mean that some form of physical damage is occurring to brain cells, affecting how they work and function.

Although there is more to do to understand how these effects operate at a cellular level in the brain, the researchers believe that their findings advance our understanding of how adverse events in childhood can contribute to life-long increased risk of brain and mind health disorders.

Professor Ed Bullmore from the Department of Psychiatry, Cambridge, said: “Now that we have a better understanding of why childhood maltreatment has long term effects, we can potentially look for biomarkers – biological red flags – that indicate whether an individual is at increased risk of continuing problems. This could help us target early on those who most need help, and hopefully aid them in breaking this chain of ill health.”

Professor Bullmore is a Fellow at Lucy Cavendish College and and an Honorary Fellow at Downing College.

̽��ֱ��research was supported by MQ: Transforming Mental Health, the Royal Society, Medical Research Council, National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Applied Research Collaboration East of England, Girton College and Darwin College.

Reference
Orellana, SC et al. Childhood maltreatment influences adult brain structure through its effects on immune, metabolic and psychosocial factors. PNAS; 9 Apr 2024 ; DOI: 10.1073/pnas.230470412

Childhood maltreatment can continue to have an impact long into adulthood because of how it effects an individual’s risk of poor physical health and traumatic experiences many years later, a new study has found.

We’ve known for some time that people who experience abuse or neglect as a child can continue to experience mental health problems long into adulthood

Sofia Orellana

mali desha (Unsplash)

Black and white image of boy curled up on the floor

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Charts map rapid growth and slow decline of brains

cjb250 — Wed, 06 Apr 2022 15:00:33 +0000

An international team of researchers has created a series of brain charts spanning our entire lifespan – from a 15 week old fetus to 100 year old adult – that show how our brains expand rapidly in early life and slowly shrink as we age.

Brain networks come ‘online’ during adolescence to prepare teenagers for adult life

cjb250 — Wed, 29 Jan 2020 10:18:17 +0000

Adolescence is a time of major change in life, with increasing social and cognitive skills and independence, but also increased risk of mental illness. While it is clear that these changes in the mind must reflect developmental changes in the brain, it has been unclear how exactly the function of the human brain matures as people grow up from children to young adults.

A team based in the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London has published a major new research study that helps us understand more clearly the development of the adolescent brain.

̽��ֱ��study collected functional magnetic resonance imaging (fMRI) data on brain activity from 298 healthy young people, aged 14-25 years, each scanned on one to three occasions about 6 to 12 months apart. In each scanning session, the participants lay quietly in the scanner so that the researchers could analyse the pattern of connections between different brain regions while the brain was in a resting state.

̽��ֱ��team discovered that the functional connectivity of the human brain – in other words, how different regions of the brain ‘talk’ to each other – changes in two main ways during adolescence.

̽��ֱ��brain regions that are important for vision, movement, and other basic faculties were strongly connected at the age of 14 and became even more strongly connected by the age of 25. This was called a ‘conservative’ pattern of change, as areas of the brain that were rich in connections at the start of adolescence become even richer during the transition to adulthood.

However, the brain regions that are important for more advanced social skills, such as being able to imagine how someone else is thinking or feeling (so-called theory of mind), showed a very different pattern of change. In these regions, connections were redistributed over the course of adolescence: connections that were initially weak became stronger, and connections that were initially strong became weaker. This was called a ‘disruptive’ pattern of change, as areas that were poor in their connections became richer, and areas that were rich became poorer.

By comparing the fMRI results to other data on the brain, the researchers found that the network of regions that showed the disruptive pattern of change during adolescence had high levels of metabolic activity typically associated with active re-modelling of connections between nerve cells.

Dr Petra Vértes, joint senior author of the paper and a Fellow of the mental health research charity MQ, said: “From the results of these brain scans, it appears that the acquisition of new, more adult skills during adolescence depends on the active, disruptive formation of new connections between brain regions, bringing new brain networks ‘online’ for the first time to deliver advanced social and other skills as people grow older.”

Professor Ed Bullmore, joint senior author of the paper and head of the Department of Psychiatry at Cambridge, said: “We know that depression, anxiety and other mental health disorders often occur for the first time in adolescence – but we don't know why. These results show us that active re-modelling of brain networks is ongoing during the teenage years and deeper understanding of brain development could lead to deeper understanding of the causes of mental illness in young people.”

Measuring functional connectivity in the brain presents particular challenges, as Dr František Váša, who led the study as a Gates Cambridge Trust PhD Scholar, and is now at King’s College London, explained.

“Studying brain functional connectivity with fMRI is tricky as even the slightest head movement can corrupt the data – this is especially problematic when studying adolescent development as younger people find it harder to keep still during the scan,” he said. “Here, we used three different approaches for removing signatures of head movement from the data, and obtained consistent results, which made us confident that our conclusions are not related to head movement, but to developmental changes in the adolescent brain.”

̽��ֱ��study was supported by the Wellcome Trust.

Reference
Váša, F et al. Conservative and disruptive modes of adolescent change in human brain functional connectivity. PNAS; 28 Jan 2020; DOI: 10.1073/pnas.1906144117

New brain networks come ‘online’ during adolescence, allowing teenagers to develop more complex adult social skills, but potentially putting them at increased risk of mental illness, according to new research published in the Proceedings of the National Academy of Sciences (PNAS).

" ̽��ֱ��acquisition of new, more adult skills during adolescence depends on the active, disruptive formation of new connections between brain regions, bringing new brain networks ‘online’ for the first time to deliver advanced social and other skills as people grow older"

Petra Vertes

Frantisek Vasa

Brain development during adolescence: red brain regions belong to the “conservative” pattern of adolescent development, while the blue brain regions belong to the “disruptive” pattern

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Mental health disorders: risks and resilience in adolescence

lw355 — Wed, 10 Oct 2018 08:25:17 +0000

When Charly Cox was diagnosed in her teenage years with depression and other mental health disorders, what lay ahead for her was “a long and painful ordeal of trial and error, guesswork and delay. I felt loss and frustration more times than I was ever gifted hope, knowledge or effective treatment.”

For Flo Sharman, who suffered from mental illness from the age of eight: “I lost my childhood to the stigma surrounding mental health.”

James Downs recovered from disordered eating and extreme emotions, but he describes the process as being “like an experimental DIY project rather than something with clear oversight and a plan.”

One in four of us experience the debilitating, isolating and traumatic effects of mental health disorders. Around 75% of adult mental health problems begin before the age of 18, disrupting education and social interactions, affecting relationships with family and friends and future job opportunities, and in some cases, costing lives.

Charly, Flo and James are among those who have lent their support – and their stories – to the mental health charity MQ to help work towards a future in which adolescents no longer face the life-altering challenge of living with these disorders.

Dr Anne-Laura van Harmelen from Cambridge’s Department of Psychiatry leads a project funded by MQ, called HOPES, and shares this vision: “Our brains undergo complex neural development during the teenage years to prepare us to take care of ourselves. However, some of these changes may be linked to a vulnerability to mental health disorders. If we can better understand what these vulnerabilities are, we can identify those at risk and treat them early, before the disorders emerge.”

But, until recently, remarkably little has been known about what’s going on inside a teenager’s head. Unravelling some of the complexity has required the combined input of psychiatrists, neuroscientists, psychologists, social scientists, computational biologists and statisticians – and the brains of hundreds of healthy teenage volunteers. ̽��ֱ��teenagers were scanned as part of the NeuroScience in Psychiatry Network (NSPN), set up in 2012 by Professor Ian Goodyer from the Department of Psychiatry with funding from the Wellcome Trust.

So far, 2,300 healthy volunteers aged 14 to 24 years have been recruited by the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London for analysis through behavioural questionnaires, cognitive tests, and medical and socio-economic history. Some 300 adolescents have also had their brain anatomy and activity scanned millimetre by millimetre using MRI, a method that can reveal connections between brain activity centres.

̽��ֱ��result is one of the most comprehensive ‘circuit diagrams’ of the teenage brain ever attempted. “ ̽��ֱ��project has been a big step forward in looking inside the black box of the teenage brain,” explains Professor Ed Bullmore, who leads the NSPN. “We found that there were distinctive patterns of developmental change in brain structure and function during adolescence that could help to explain why mental health disorders often arise during late adolescence.”

For instance, Bullmore’s colleagues Dr Kirstie Whitaker and Dr Petra Vértes discovered that the outer region of the brain, known as cortical grey matter, shrinks, becoming thinner during adolescence. As this happens, the levels of myelin – the sheath that ‘insulates’ nerve fibres, allowing the fibres to communicate efficiently in the white matter – increase.

In a separate study, Dr František Váša designed a method to combine all of the scans of the structural changes in the brain through a ‘sliding window’ – as if viewing the changes in the brain network of an ‘average’ adolescent as they mature from 14 to 24 years of age. It sounds simple enough but this innovation was so complex that it took several years of statistical and computational analysis to perfect.

“We saw that the changes are greatest in the most connected ‘hub’ parts of the brain. Our interpretation is that when the brain develops it builds too many connections; then, during the teenage years, those that are used frequently are strengthened and others are ‘pruned’,” says Váša, whose PhD studies were funded by the Gates Cambridge Trust.

What makes this especially interesting is that Vértes and Whitaker also discovered that the brain areas undergoing the greatest structural changes during adolescence are those in which genes linked to risk of mental health disorders are most strongly expressed.

One of the disorders is schizophrenia, which affects 1% of the population and often starts in adolescence or early adult life. Vértes has recently been funded by MQ to search for unique patterns of brain connectivity among those who develop symptoms of schizophrenia, and to cross-reference them with patterns of gene expression across the brain. “Not only is this knowledge important for identifying new treatments that are more effective for a greater number of patients at an earlier stage, but it could also help in predicting those who are at risk,” she explains.

Another area where there has been little improvement in predicting behaviours is that of suicide – the second leading cause of death among the young.

“Around 16% of teens think about suicide and 8% report making an attempt, yet there has been little improvement in our ability to predict suicidal behaviours in 50 years,” says van Harmelen, who is a Royal Society Dorothy Hodgkin fellow. ̽��ֱ��HOPES project she leads aims to develop a model to predict who is at risk of suicide by analysing brain scans and data on suicidal behaviour of young people from across the world to identify specific, universal risk factors.

“These risk factors may be connected with traumatic and stressful events early in their lives,” she adds. “In fact, we know that about a third of all mental health problems are attributable to events such as bullying, abuse and neglect. Much of my work has been to understand the impact of these factors on the developing brain.”

She discovered that childhood adversity is related to an altering of the structure and function of parts of the brain, and that this increases vulnerability to mental health problems. Intriguingly, some adolescents with traumatic early life experiences fared a lot better than would be predicted. This ‘resilience’ was enhanced by receiving the right kind of support at the right time. She calls this ‘social buffering’ and finds that for 14-year-olds it most often comes from family members, and for 19-year-olds from friendships.

With funding from the Royal Society, she is now starting to look for biological factors that underpin resilient functioning – for instance, how does the immune system interact with the brain during periods of psychosocial stress in resilient adolescents? Are there biomarkers that can be used to predict resilience after childhood adversity?

“We are diving deeper into the factors and mechanisms that might help,” says van Harmelen. “We know there are lots of social, emotional and behavioural factors that help to build resilience, and that these factors are amenable to intervention by therapists – but which are the most important, or is it a specific combination of these factors?

“If you speak to anyone who has had a mental health problem, you will know the effect it’s had on them and their families,” she adds. “Even a minor contribution to lowering this effect through early diagnosis and treatment is worth a lot of effort.”

Video: In this video you can see the regions of the brain coloured by how much they change between 14 and 24 years of age. ̽��ֱ��darker the colour the more the myelin changes. ̽��ֱ��size of the 'nodes' of the network represents how well connected they are and halfway through the movie the smallest nodes are removed and only the hubs remain. ̽��ֱ��edges that are added in are the strongest connections between these hub regions and represent the brain's 'rich club'. Data taken from 'Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome' by Whitaker, Vertes et al. published in PNAS in July 2016. DOI: 10.1073/pnas.1601745113 Link: http://dx.doi.org/10.1073/pnas.160174.

Read a profile of Dr František Váša on the Gates Cambridge website.

Deeper understanding of the wiring and rewiring of the adolescent brain is helping scientists pinpoint why young people are especially vulnerable to mental health problems – and why some are resilient.

If you speak to anyone who has had a mental health problem, you will know the effect it’s had on them and their families. Even a minor contribution to lowering this effect through early diagnosis and treatment is worth a lot of effort

Anne-Laura van Harmelen

Photo by Jon Tyson on Unsplash

Yes

New brain mapping technique highlights relationship between connectivity and IQ

cjb250 — Tue, 02 Jan 2018 14:21:01 +0000

In recent years, there has been a concerted effort among scientists to map the connections in the brain – the so-called ‘connectome’ – and to understand how this relates to human behaviours, such as intelligence and mental health disorders.

Now, in research published in the journal Neuron, an international team led by scientists at the ̽��ֱ�� of Cambridge and the National Institutes of Health (NIH), USA, has shown that it is possible to build up a map of the connectome by analysing conventional brain scans taken using a magnetic resonance imaging (MRI) scanner.

̽��ֱ��team compared the brains of 296 typically-developing adolescent volunteers. Their results were then validated in a cohort of a further 124 volunteers. ̽��ֱ��team used a conventional 3T MRI scanner, where 3T represents the strength of the magnetic field; however, Cambridge has recently installed a much more powerful Siemens 7T Terra MRI scanner, which should allow this technique to give an even more precise mapping of the human brain.

A typical MRI scan will provide a single image of the brain, from which it is possible to calculate multiple structural features of the brain. This means that every region of the brain can be described using as many as ten different characteristics. ̽��ֱ��researchers showed that if two regions have similar profiles, then they are described as having ‘morphometric similarity’ and it can be assumed that they are a connected network. They verified this assumption using publically-available MRI data on a cohort of 31 juvenile rhesus macaque monkeys to compare to ‘gold-standard’ connectivity estimates in that species.

Using these morphometric similarity networks (MSNs), the researchers were able to build up a map showing how well connected the ‘hubs’ – the major connection points between different regions of the brain network – were. They found a link between the connectivity in the MSNs in brain regions linked to higher order functions – such as problem solving and language – and intelligence.

“We saw a clear link between the ‘hubbiness’ of higher-order brain regions – in other words, how densely connected they were to the rest of the network – and an individual’s IQ,” explains PhD candidate Jakob Seidlitz at the ̽��ֱ�� of Cambridge and NIH. “This makes sense if you think of the hubs as enabling the flow of information around the brain – the stronger the connections, the better the brain is at processing information.”

While IQ varied across the participants, the MSNs accounted for around 40% of this variation – it is possible that higher-resolution multi-modal data provided by a 7T scanner may be able to account for an even greater proportion of the individual variation, says the researchers.

“What this doesn’t tell us, though, is where exactly this variation comes from,” adds Seidlitz. “What makes some brains more connected than others – is it down to their genetics or their educational upbringing, for example? And how do these connections strengthen or weaken across development?”

“This could take us closer to being able to get an idea of intelligence from brain scans, rather than having to rely on IQ tests,” says Professor Ed Bullmore, Head of Psychiatry at Cambridge. “Our new mapping technique could also help us understand how the symptoms of mental health disorders such as anxiety and depression or even schizophrenia arise from differences in connectivity within the brain.”

̽��ֱ��research was funded by the Wellcome Trust and the National Institutes of Health.

Reference
Seidlitz, J et al. Morphometric Similarity Networks Detect Microscale Cortical Organisation and Predict Inter-Individual Cognitive Variation. Neuron; 21 Dec 2017; DOI: 10.1016/j.neuron.2017.11.039

A new and relatively simple technique for mapping the wiring of the brain has shown a correlation between how well connected an individual’s brain regions are and their intelligence, say researchers at the ̽��ֱ�� of Cambridge.

This could take us closer to being able to get an idea of intelligence from brain scans, rather than having to rely on IQ tests

Ed Bullmore

Alan Stark

"Mini Stack" Interchange of Interstate 10, Loop 202, and State Route 51 at Night (2)

Researcher profile: Jakob Seidlitz

Jakob Seidlitz is at PhD student on the NIH Oxford-Cambridge Scholars Programme. A graduate of the ̽��ֱ�� of Rochester, USA, he spends half of his time in Cambridge and half at the National Institutes of Health in the USA.

Jakob’s research aims to better understand the origins of psychiatric disease, using techniques such as MRI to study child and adolescent brain development and map patterns of brain connectivity.

“A typical day consists of performing MRI data analysis, statistical testing, reading scientific literature, and preparing and editing manuscripts. “It’s great being able to work on such amazing large-scale neuroimaging datasets that allow for answering longstanding questions in psychiatry,” he says.

“Cambridge is a great place for my work. Ed [Bullmore], my supervisor, is extremely inclusive and collaborative, which meant developing relationships within and outside the department. Socially, the college post-grad community is amazingly diverse and welcoming, and the collegiate atmosphere of Cambridge can be truly inspiring.”

Jakob is a member of Wolfson College. Outside of his research, he plays football for the ‘Blues’ (the Cambridge ̽��ֱ�� Association Football Club).

̽��ֱ��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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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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Changes in brain structure during teenage years provide clues to onset of mental health problems

cjb250 — Mon, 25 Jul 2016 19:00:37 +0000

In a study published today in the Proceedings of the National Academy of Sciences, researchers from the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London (UCL) used magnetic resonance imaging (MRI) to study the brain structure of almost 300 individuals aged 14-24 years old.

By comparing the brain structure of teenagers of different ages, they found that during this important period of development, the outer regions of the brain, known as the cortex, shrink in size, becoming thinner. However, as this happens, levels of myelin – the sheath that ‘insulates’ nerve fibres, allowing them to communicate efficiently – increase within the cortex.

Previously, myelin was thought mainly to reside in the so-called ‘white matter’, the brain tissue that connects areas of the brain and allows for information to be communicated between brain regions. However, in this new study, the researchers show that it can also be found within the cortex, the ‘grey matter’ of the brain, and that levels increase during teenage years. In particular, the myelin increase occurs in the ‘association cortical areas’, regions of the brain that act as hubs, the major connection points between different regions of the brain network.

Dr Kirstie Whitaker from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, the study’s joint first author, says: “During our teenage years, our brains continue to develop. When we’re still children, these changes may be more dramatic, but in adolescence we see that the changes refine the detail. ̽��ֱ��hubs that connect different regions are becoming set in place as the most important connections strengthen. We believe this is where we are seeing myelin increasing in adolescence.”

̽��ֱ��researchers compared these MRI measures to the Allen Brain Atlas, which maps regions of the brain by gene expression – the genes that are ‘switched on’ in particular regions. They found that those brain regions that exhibited the greatest MRI changes during the teenage years were those in which genes linked to schizophrenia risk were most strongly expressed.

Dr Petra Vértes, the other first author, also from the Department of Psychiatry explains: "A lot of information already exists on the function of various genes: which parts of the cell they are important for, what biological processes they are involved in and which diseases they are associated with. Matching up MRI brain maps with the Allen Brain Atlas allows us to make connections between large-scale brain changes observed through MRI – such as thinning of the cortex – and the microscopic biological processes that are likely to underpin these changes and which may be compromised in certain disorders."

“Adolescence can be a difficult transitional period and it’s when we typically see the first signs of mental health disorders such as schizophrenia and depression,” explains Professor Ed Bullmore, Head of Psychiatry at Cambridge. “This study gives us a clue why this is the case: it’s during these teenage years that those brain regions that have the strongest link to the schizophrenia risk genes are developing most rapidly.

“As these regions are important hubs that control how regions of our brain communicate with each other, it shouldn’t be too surprising that when something goes wrong there, it will affect how smoothly our brains work. If one imagines these major hubs of the brain network to be like international airports in the airline network, then we can see that disrupting the development of brain hubs could have as big an impact on communication of information across the brain network as disruption of a major airport, like Heathrow, will have on flow of passenger traffic across the airline network.”

̽��ֱ��researchers are confident about the robustness of their findings as they divided their participants into a ‘discovery cohort’ of 100 young people and a ‘validation cohort’ of almost 200 young people to ensure the results could be replicated.

̽��ֱ��study was funded by a Strategic Award from the Wellcome Trust to the Neuroscience in Psychiatry Network (NSPN) Consortium.

Dr Raliza Stoyanova in the Neuroscience and Mental Health team at Wellcome, which funded the study, comments: “A number of mental health conditions first manifest during adolescence. Although we know that the adolescent brain undergoes dramatic structural changes, the precise nature of those changes and how they may be linked to disease is not understood.

“This study sheds much needed light on brain development in this crucial time period, and will hopefully spark further research in this area, and tell us more about the origins of serious mental health conditions such as schizophrenia.”

Video
Nodes of the adolescent brain's structural network coloured by how much they change between 14 and 24 years of age. ̽��ֱ��size of the nodes represent how well connected they are and halfway through the movie the smallest nodes are removed and only the hubs remain. ̽��ֱ��edges that are added in are the strongest connections between these hub regions and represent the brain's rich club. Credit: Kirstie Whitaker

Reference
Whitaker, KJ, Vertes, PE et al. Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. PNAS; 25 July 2016; DOI: 10.1073/pnas.1601745113

Scientists have mapped the structural changes that occur in teenagers’ brains as they develop, showing how these changes may help explain why the first signs of mental health problems often arise during late adolescence.

̽��ֱ��hubs that connect different regions are becoming set in place as the most important connections strengthen. We believe this is where we are seeing myelin increasing in adolescence

Kirstie Whitaker

Nodes and Edges: NSPN_WhitakerVertes_PNAS2016

Bob Bradburn

Teenager

̽��ֱ��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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Opinion: How LSD helped us probe what the ‘sense of self’ looks like in the brain

Anonymous — Thu, 14 Apr 2016 13:47:38 +0000

Every single person is different. We all have different backgrounds, views, values and interests. And yet there is one universal feeling that we all experience at every single moment. Call it an “ego”, a “self” or just an “I” – it’s the idea that our thoughts and feelings are our own, and no one else has access to them in the same way. This may sound a bit like post-war French existentialism or psycho-analysis, but it’s actually a topic that’s being increasingly addressed by neuroscientists.

We were part of a team interested in finding out how this sense of self is expressed in the brain – and what happens when it dissolves. To do that, we used brain imaging and the psychedelic drug LSD.

Our sense of self is something so natural that we are not always fully aware of it. In fact, it is when it is disturbed that it becomes the most noticeable. This could be due to mental illnesses such as psychosis, when people might experience the delusional belief that their thoughts are no longer private, but can be accessed and even modified by other people. Or it could be due to the influence of psychedelic drugs such as LSD, when the user can feel that their ego is “dissolving” and they are becoming at one with the world. From a scientific point of view, these experiences of “ego death” or ego dissolution are also opportunities to search for this sense of self in the brain.

Our study, led by Enzo Tagliazucchi and published in Current Biology, set out to probe what is happening in the brain when our sense of self becomes altered by psychedelic drugs (link to Enzo’s paper). We studied 15 healthy volunteers before and after taking LSD, which altered their normal feelings of their selves and their relationship with the environment. These subjects were scanned while intoxicated and while receiving placebo using functional MRI, a technique which allows us to study the brain’s activity by measuring changes in blood flow. By contrasting the activity of the brain when receiving a placebo with its activity after taking LSD, we could start exploring the brain mechanisms involved in the normal experience of the self.

A holistic understanding

Results of this study showed that the experience of ego-dissolution induced by LSD was not related to changes in only one region of the brain. Instead, the drug affected the way that several brain regions were communicating with the rest of the brain, increasing their level of connectivity. These included the fronto-parietal region, an area that has previously been linked to self awareness, and the temporal region, an area involved in language comprehension and creating visual memories. ̽��ֱ��brain on LSD would therefore be similar to an orchestra in which musicians are no longer playing together in time, rather than an orchestra in which some are missing or malfunctioning.

Brain anatomy. Primalchaos/wikimedia

In a previous paper, we showed that the brain tends to organise itself into groups or modules of regions working closely together and specialising in a specific activity, a property called modularity. For example, the brain regions specialised for vision are normally organised as a module of the human brain network. LSD disrupted this modular organisation of the brain – and the level of modular disorganisation was linked with the severity of ego-dissolution that volunteers experienced after taking the drug. It seems the modular organisation of the healthy brain works as the scaffolding that allows us to maintain a sense of self.

But on a more fundamental note, these results highlight that a full understanding of the brain will never be complete unless we focus on the connectivity between regions as part of a complex network. This is irrespective of the level of microscopic detail we might have about what a single region does. Just as a symphony is fully appreciated only when one listens to all members of the orchestra playing it together, and not by studying each individual instrument separately.

By investigating the psychedelic effects of LSD with brain scanning, we can open the doors of perception to discover how the familiar, egotistical sense of self depends on a particular pattern of brain network organisation. Our sense of individuality may be down to the overall configuration that emerges from the interactions of multiple brain regions. When this organisation is disrupted by LSD, and particularly when the modular organisation falls apart, our sense of self, and the distinct boundaries between us, the environment and others might be lost.

Nicolas Crossley, Honorary Research Fellow at the Department of Psychosis Studies, King's College London and Ed Bullmore, Professor of Behavioural and Clinical Neuroscience , ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Ed Bullmore (Department of Psychiatry) and Nicolas Crossley (King's College London) discuss their work trying to find out how sense of self is expressed in the brain.

̽��ֱ��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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