Improving how we visualize brain changes from youth to adulthood
or technically,
Adam Pines was the lead author on this study. Adam is a PhD candidate in Ted Satterthwaite's Lab. He is interested in understanding how psychopathology emerges from neurocognitive development
Leveraging multi-shell diffusion for studies of brain development in youth and young adulthood
[See Original Abstract on Pubmed]
Authors of the study: Adam R. Pines, Matthew Cieslak, Bart Larsen, Graham L. Baum, Philip A. Cook, Azeez Adebimpe, Diego G. Dávila, Mark A. Elliott, Robert Jirsaraie, Kristin Murtha, Desmond J. Oathes, Kayla Piiwaa, Adon F.G. Rosen, Sage Rush, Russell T. Shinohara, Danielle S. Bassett, David R. Roalf, Theodore D. Satterthwaite
As people grow from childhood to adolescence, most changes are pretty clear: you might see a niece or nephew again after a couple years and find they have changed quite a bit, whether they are several inches taller or sporting new favorite phrases and hobbies. During this time of growing up, there are many complex changes happening in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. that are less visible.
One of the things that changes across development is the strength of connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions. Why does this matter? Well, different parts of your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. communicate with each other to produce the thoughts and actions that guide our daily life. When a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region communicates more with a particular brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region than another, that connection gets stronger. The changes in these connections usually follow a reliable pattern across development, with some individual differences based on our unique experiences. It is important to know what changes to expect in the connections between different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions during development, so that we can learn to spot when things go awry. Adam Pines of the UPenn Neuroscience Graduate Group and member of the Satterthwaite lab was interested in finding the best ways to measure changes in these connections across development by comparing several methods for analysis.
To visualize the connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions, scientists look at a type of tissue called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions. To understand what white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and why it is important, we need to zoom in and start with the basic building block of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.: the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles. NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are a specialized kind of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cell. The communication between neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles is what drives most everything we see, think, and do. The part of the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that makes up white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is often covered in an insulating coating called myelin. Myelin helps signals travel faster from one end of a neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to the other. Collectively, these connections are called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions because the coating makes them appear white.
Techniques have been developed to image white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions using an odd-sounding but effective principle: “follow the water.” You may not think of water when you think of the inner-workings of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., but 73% of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is actually water.1 In areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. without this myelin coating, water is going in all directions. However, myelin is resistant to water, so it essentially forms little water slides in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Only where there is white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is the water moving in one direction more than all others. Researchers take advantage of this and “follow the water” to measure 1) the direction of the water and 2) how fast it is going. This tells them the direction of the connection between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions and the strength of those connections. This technique is called diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging.. With these basic principles, diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. is able to map out where white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and measure its properties.
Although it is a powerful tool, interpreting the results of diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. requires a lot of complex modelling. Not all models are best suited for studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. The best model would be the one that showed changes in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. with age and that was not affected too much by people moving while they were in the scanner (called in-scanner motion). Imaging of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. has the same problem you do when taking a picture of anything moving - things get blurry. Lots of people can get fidgety in the scanner but especially kids, making finding a metric that isn’t affected by in-scanner motion extra important when studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. Adam wanted to figure out which diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. measures researchers should be using to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.
Adam tested different methods by seeing how the output of each related to age and to in-scanner motion. Each method had a slightly different set of outputs or metrics that he looked at. He found that the metrics of each related to age and in-scanner motion differently. Some metrics were more affected by the age of the participant than others whereas other metrics were more affected by in-scanner motion. Remember, in order to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development, the best metrics would be the ones that were most affected by age and least affected by in-scanner motion. Adam found that each metric varied quite a bit in how well it was associated with age. However, he found that one particular method, the Laplacian-regularized Mean Apparent Propagator (MAPL), was less affected by in-scanner motion than the other methods he tested. MAPL is a relatively new method and, before Adam’s study, no one was sure how well it would work for measuring brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.
Based on Adam’s work, other researchers now know what metrics are best to study white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions to determine what is happening in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. during development. This work is important because it allows future research on brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development to be more reliable by leading researchers away from model metrics that would miss the effects they are most interested in. By looking at white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions during development using previous methods, researchers have already discovered different pathways that are related to normal development, anxiety and depression, and more. Adam’s work will allow for many more future discoveries like these that help us better understand problems that occur during development!
One of the things that changes across development is the strength of connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions. Why does this matter? Well, different parts of your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. communicate with each other to produce the thoughts and actions that guide our daily life. When a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region communicates more with a particular brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region than another, that connection gets stronger. The changes in these connections usually follow a reliable pattern across development, with some individual differences based on our unique experiences. It is important to know what changes to expect in the connections between different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions during development, so that we can learn to spot when things go awry. Adam Pines of the UPenn Neuroscience Graduate Group and member of the Satterthwaite lab was interested in finding the best ways to measure changes in these connections across development by comparing several methods for analysis.
To visualize the connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions, scientists look at a type of tissue called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions. To understand what white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and why it is important, we need to zoom in and start with the basic building block of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.: the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles. NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are a specialized kind of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cell. The communication between neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles is what drives most everything we see, think, and do. The part of the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that makes up white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is often covered in an insulating coating called myelin. Myelin helps signals travel faster from one end of a neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to the other. Collectively, these connections are called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions because the coating makes them appear white.
Techniques have been developed to image white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions using an odd-sounding but effective principle: “follow the water.” You may not think of water when you think of the inner-workings of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., but 73% of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is actually water.1 In areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. without this myelin coating, water is going in all directions. However, myelin is resistant to water, so it essentially forms little water slides in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Only where there is white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is the water moving in one direction more than all others. Researchers take advantage of this and “follow the water” to measure 1) the direction of the water and 2) how fast it is going. This tells them the direction of the connection between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions and the strength of those connections. This technique is called diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging.. With these basic principles, diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. is able to map out where white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and measure its properties.
Although it is a powerful tool, interpreting the results of diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. requires a lot of complex modelling. Not all models are best suited for studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. The best model would be the one that showed changes in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. with age and that was not affected too much by people moving while they were in the scanner (called in-scanner motion). Imaging of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. has the same problem you do when taking a picture of anything moving - things get blurry. Lots of people can get fidgety in the scanner but especially kids, making finding a metric that isn’t affected by in-scanner motion extra important when studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. Adam wanted to figure out which diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. measures researchers should be using to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.
Adam tested different methods by seeing how the output of each related to age and to in-scanner motion. Each method had a slightly different set of outputs or metrics that he looked at. He found that the metrics of each related to age and in-scanner motion differently. Some metrics were more affected by the age of the participant than others whereas other metrics were more affected by in-scanner motion. Remember, in order to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development, the best metrics would be the ones that were most affected by age and least affected by in-scanner motion. Adam found that each metric varied quite a bit in how well it was associated with age. However, he found that one particular method, the Laplacian-regularized Mean Apparent Propagator (MAPL), was less affected by in-scanner motion than the other methods he tested. MAPL is a relatively new method and, before Adam’s study, no one was sure how well it would work for measuring brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.
Based on Adam’s work, other researchers now know what metrics are best to study white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions to determine what is happening in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. during development. This work is important because it allows future research on brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development to be more reliable by leading researchers away from model metrics that would miss the effects they are most interested in. By looking at white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions during development using previous methods, researchers have already discovered different pathways that are related to normal development, anxiety and depression, and more. Adam’s work will allow for many more future discoveries like these that help us better understand problems that occur during development!
About the brief writer: Sara Taylor
Sara Taylor is a PhD Candidate in Ted Brodkin’s lab. She is interested in understanding how behaviors associated with Autism Spectrum are related to each other as well as their genetic basis.
Citations:
Mitchell, H. H., Hamilton, T. S., Steggerda, F. R., & Bean, H. W. (1945). The chemical composition of the adult human body and its bearing on the biochemistry of growth. Journal of Biological Chemistry, 158(3), 625-637.
You can find the paper here.