̽��ֱ�� of Cambridge - Kirstie Whitaker

Inside the mind of a young person

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

Opinion: How mapping teenagers’ brains has helped us understand more about schizophrenia

ljm67 — Wed, 15 Mar 2017 10:47:28 +0000

When I was studying for my PhD at the ̽��ֱ�� of California at Berkeley, I spent an awful lot of my weekends asking teenagers to lie still in a magnetic resonance imaging (MRI) scanner. While they were lying as still as they could they also had to answer questions they saw on the screen.

We were interested in which parts of the brain these young people were using when they completed an analogical reasoning task. They saw three pictures and were asked to choose the fourth picture to complete the relationships, for example dress is to wardrobe, as milk is to fridge.

We found that association cortex – the parts of the brain that bring together information from many other regions – was used to answer these questions and, importantly, that these regions are activated more and more as you get older. ̽��ֱ��study was recently published in Developmental Science.

A question teenagers answered during a functional MRI scan. Association cortex was activated during this task (top right, orange) and regions in prefrontal cortex were more active as participants got older (bottom right, red). Kirstie Whitaker

Fast forward a few years and I’m now a member of the Neuroscience in Psychiatry Network (NSPN), a collaboration between the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London, funded by the Wellcome Trust.

NSPN aims to better understand the biological mechanisms that lead to young people developing a variety of mental health disorders. ̽��ֱ��network includes experts in epidemiology, adolescent psychopathology, cognition and brain development who are investigating the question of adolescent mental health from multiple angles.

Beautiful brains

I’m in the MRI team, which has collected brain scans from 300 young people between the ages of 14 and 24. This time, instead of asking them to complete questions while they were lying in the scanner, we took structural MRI scans. These are different to the brain scans we use to assess what the brain is doing (“functional MRI”) and they look really beautiful.

A vertical slice through the author’s head using a structural MRI. Cortical thickness (the distance between the red and yellow lines) decreases during the teenage years as adolescents refine their brain networks. Kirstie Whitaker

One of the measures we extract is “cortical thickness” – the depth of the outside layer of the brain (the cortex) that contains synapses. A synapse is where two brain cells (neurons) join together and transmit messages. We have around 100 billion neurons but 100 trillion synapses in our brains. It is the complexity of these connections that allows humans to generate and understand complex thoughts and feelings, including being able to solve analogies in the real world.

Changing minds

In work published in the Proceedings of the National Academy of Science in 2016 the NSPN consortium showed that the cortex got thinner between the ages of 14 and 24. In particular, association cortex – the same regions that are used for complex thought and reasoning – showed the greatest amount of change.

This finding may seem counter-intuitive – at first glance you’d imagine that getting better at something would mean having more brain cells working on the project. In fact, you are born with more neurons than you’ll ever have again, and one of the most important developmental processes is “synaptic refinement” – pruning away some of the connections to ensure your brain is working efficiently.

We also looked at the brain as a network. You can imagine an airline network with connections going around the world between different airports. ̽��ֱ��really important locations are network “hubs” – they have lots of flights in and out every day. In the brain, we found that these hubs are located in association cortex. It makes sense that the brain regions that are important for complex thought need information to liaise with many other different parts of the brain.

̽��ֱ��brain as a network: different brain regions (nodes) are connected by edges. These regions show prolonged development during adolescence and are important for complex thought.

We found that the hubs of the brain’s structural network change most during adolescence. This is likely to reflect prolonged development for these regions – the other parts of the brain are closer to their adult structure and have slowed down by the age of 14. If you think back to my descriptions of synapses being pruned away, it makes sense to keep as many as you need for a long time, until you’re sure of which connections are going to allow you to best reason in the complex world around you.

I made a big deal earlier about the fact that we can not see the actual cells and connections in the brain using MRI. However, innovative work by Petra Vértes and data shared by the Allen Institute for Brain Science gives us some clues as to what is going on at the cellular level in these brain regions.

̽��ֱ��Allen Institute has measured the expression of 20,000 genes at 500 locations around the brains of six brains donated to research after their owner died. Vértes showed that the brain regions in association cortex – the same ones that change structurally the most during the teenage years – have greater expression of genes related to synaptic plasticity. This means that genes controlling how our brain cells adapt their connections based on our experiences are more active in these regions.

These regions are also related to genes associated with schizophrenia – a psychiatric disorder that is most likely to emerge during the late teenage years. Our work provides evidence for a mechanism as to why people with a genetic risk for schizophrenia may not experience symptoms until they are around 20-years-old. ̽��ֱ��affected brain regions are still developing and it may take these many years before the differences in brain structure are big enough to cause the hallucinations and delusions associated with this mental health disorder.

There is still a long way to go in our search to understand the biological underpinnings of mental health disorders. We will continue to work together, both within the Neuroscience in Psychiatry Network and with other researchers around the world, to find treatments for mental health disorders, and, if possible, to find ways to prevent the symptoms from emerging all together.

̽��ֱ��author is appearing on March 21 as part of the Cambridge Science Festival.

Kirstie Whitaker, Research Associate, Department of Psychiatry, ̽��ֱ�� of Cambridge

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

Teenage years can be difficult enough, but for people affected by schizophrenia, this is when symptoms first tend to arise. Dr Kirstie Whitaker (Department of Psychiatry), who is speaking at this year's Cambridge Science Festival, explains in ̽��ֱ��Conversation how her work may shed light on why this is the case.

Kirstie Whitaker

̽��ֱ��brain’s structural network. ̽��ֱ��hubs of this network continue to develop during adolescence.

̽��ֱ��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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