̽��ֱ�� of Cambridge - Petra Vertes

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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Inside the mind of a young person

cjb250 — Thu, 15 Nov 2018 17:18:17 +0000

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

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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