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The ENIGMA brain injury project and global data collaboration with Emily Dennis
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The ENIGMA brain injury project and global data collaboration with Emily Dennis
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https://cadmoremediastorage.blob.core.windows.net/3039ad8d-7952-453b-8e2f-678deffac51c/thumbnails/3039ad8d-7952-453b-8e2f-678deffac51c.jpg
Duration:
T00H09M51S
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https://stream.cadmore.media/player/3039ad8d-7952-453b-8e2f-678deffac51c
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https://asa1cadmoremedia.blob.core.windows.net/asset-af2ab0cf-f8fa-4964-a273-7deb3557b45d/Emily Dennis- Interview V2.mp4
Upload Date:
2020-01-21T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
EMILY DENNIS: My name is Dr. Emily Dennis. I am an Adjunct Assistant Professor at the University of Utah in the Department of Neurology (UT, USA). And my research focuses on brain imaging and traumatic brain injury.
Segment:1 What inspired you to become involved in TBI research? .
EMILY DENNIS: So my doctoral work was focused on healthy brain development and looking at metrics of connectivity in kids who are developing normally. And once I finished my PhD, as a way to build on that, I thought I wanted to look into what can go wrong in development.
EMILY DENNIS: I had studied what was normal, but there are so many ways that it could possibly go wrong. And got the opportunity to work with a pediatric traumatic brain injury dataset, and it's just-- it exploded from there into many other areas.
Segment:2 How did the ENIGMA brain injury group come about?.
EMILY DENNIS: So ENIGMA is-- as a whole, is a really large project. It was started by my PhD mentor, Paul Thompson at USC. And it was started in 2009. It has around 1,400 researchers who are involved right now.
EMILY DENNIS: And this is across many different areas. It was initially neuroimaging and genetics because they wanted to do well-powered studies linking genetic variation with brain variation, and you need tens or hundreds of thousands of individuals to do that. Of course, nobody has the money to collect that at one site. So it was a collaboration across a number of groups that had similar data to try to combine forces.
EMILY DENNIS: From there, it's branched into many other things. So the genetics was one part of it, and the disorder part came a little bit later. And there are now working groups that are focused on various psychiatric disorders like depression and schizophrenia. We have groups focused on developmental disorders like OCD and Turner syndrome, and we have newer groups focused on neurology.
EMILY DENNIS: So I started the ENIGMA Brain Injury Group about 3 years ago with Dr. Lisa Wilde and Dr. David Tate, who are both at the University of Utah (UT, USA) as well. And while it was initially one group, we quickly realized that it needed to be divided into subgroups. TBI is just a really huge area, and there's so much heterogeneity that you have to have a more targeted approach.
EMILY DENNIS: So now we have seven working groups, and I'm sure there will be more soon. We have working groups focused on military brain injury, pediatric moderate-to-severe TBI, adult moderate-to-severe TBI, acute-civilian mild TBI. Intimate partner violence is a fairly new group. Sports-related head injury and magnetic resonance spectroscopy-- that's a methods group trying to see how we can-- across lots of sites, how we can harmonize those data.
Segment:3 Could you tell us more about the pediatric moderate/severe TBI sub-group of this study?.
EMILY DENNIS: So for the pediatric moderate- to-severe TBI subgroup, this is a pretty small field in general. If you look across all of the research studies that have been published, there are really not very many groups that are focused on this, which I think is a disservice to the patients because it's a huge, huge problem around the world. So within this group, we have actually a good portion of the people who are currently doing this research involved, which is really exciting, because one, we've got all of these datasets from around the world, but two, we have all of the people who've been thinking about the problems, thinking about what needs to be done, what are the existing questions.
EMILY DENNIS: So there's a lot of intellectual contributions from these different groups.
Segment:4 What are the challenges faced when working on such a big collaborative project?.
EMILY DENNIS: Well, there are a lot of challenges when you're trying to get lots of people to work together. I think the first one that people might think of is the political issues when you're trying-- political and social issues of trying to get researchers to work together. Those have actually been very minor, happily, very minor.
EMILY DENNIS: I thought we were going to encounter a lot more resistance. You're asking people to contribute their data and their time. But they-- they've spent so much of their own time and their own research money collecting these data that it's a lot to ask someone to then share that. But the way it's been set up, I think, is really conducive to people feeling like they can be part of a collaboration but still maintain ownership and still maintain a role and still have a say over what's done with their data and what questions they want to ask.
EMILY DENNIS: So that part has been fairly easy, and I've been very happy with how collaborative everybody's been. Some of the challenges-- one of the main ones is harmonization. We have data that-- I think in the pediatric group in particular, we have some data that was collected 10 years ago versus data that was collected a couple of years ago.
EMILY DENNIS: And of course, there's so many advances in imaging and image processing over that time, so there's variations in the protocols. That is something that we can't do a whole lot about, because the data has already been collected. If you're collecting it from the beginning, you can harmonize the protocols. But there is a benefit to that in that if you find a result that is robust across all of these groups with different protocols, then you can really believe it more.
EMILY DENNIS: You can know that it's not just only when you have the really high-resolution data can you collect this. It gives you more confidence in what you've been finding. So imaging data-- harmonizing that is a challenge, but not a huge one. Some of what we're trying to deal with now is figure out how to harmonize all of the clinical and the cognitive data.
EMILY DENNIS: There are just thousands of clinical variables that you could potentially bring into this, and everyone's collected slightly different ones. So trying to see where the overlap is, what-- maybe groups use different scales, but there are some common questions, and how we can-- how we can glean the common information across all of those so that we can know that we're looking at the correct domains.
Segment:5 What are your hopes for the future of this field?.
EMILY DENNIS: Well, I'm really excited about where we're going, and I'm really optimistic given how many people have been involved. We've only just started. The military group is farthest along because there are a number of studies in the US, multi-site studies on military brain injury. So we were able to benefit from all of the work that's been done in that area so far.
EMILY DENNIS: But as I said, we've got so many other groups that have recently started and are learning how to combine all of their data. So some of the things that I'm really hoping that this is going to lead to are understanding some of the larger questions in terms of what factors impact outcome. Gender is a major topic, and there have been a number of studies looking at how gender might differ-- might impact outcome.
EMILY DENNIS: But in some groups, particularly in pediatric studies, those are usually very small studies, and so it's hard to actually find significant differences. So I'm hoping that when we combine all of these datasets, that we'll be able to have a better idea of how things like gender impact outcome, age. We also-- I think another area that people are starting to realize that they would want to look at-- but it's hard to have enough data-- is patient subtypes.
EMILY DENNIS: So there are so many different factors that can influence outcome, as we're hearing today-- clinical, demographic variables. And in one study, you couldn't possibly take a machine-- ideally you'd be able to take a machine-learning approach to try to see how these things might cluster. But if you only have 30 subjects in your study, you can't do that. Once you have several hundred or several thousand, you can start to think about some of these big-data approaches.
EMILY DENNIS: I think we are-- I think we are going to find that there are patient subtypes that have-- that are influenced by these demographic and clinical variables that have some bearing on outcome. If we can find that, it potentially opens the door for more targeted treatment. If we can know that someone who has this constellation of factors is more likely to have issues with sleep, or this person is more representative of a different profile, that maybe they're more likely to have cognitive deficits-- if we can get a better idea of what the possible subtypes are, what the pattern of disruption is, then it could be-- and this is all very much in the future, of course, but it could be that there are different treatment approaches that might help individuals come to have a healthier trajectory after injury.
EMILY DENNIS: [MUSIC PLAYING]
Segment:0 .
[MUSIC PLAYING]
EMILY DENNIS: My name is Dr. Emily Dennis. I am an Adjunct Assistant Professor at the University of Utah in the Department of Neurology (UT, USA). And my research focuses on brain imaging and traumatic brain injury.
Segment:1 What inspired you to become involved in TBI research? .
EMILY DENNIS: So my doctoral work was focused on healthy brain development and looking at metrics of connectivity in kids who are developing normally. And once I finished my PhD, as a way to build on that, I thought I wanted to look into what can go wrong in development.
EMILY DENNIS: I had studied what was normal, but there are so many ways that it could possibly go wrong. And got the opportunity to work with a pediatric traumatic brain injury dataset, and it's just-- it exploded from there into many other areas.
Segment:2 How did the ENIGMA brain injury group come about?.
EMILY DENNIS: So ENIGMA is-- as a whole, is a really large project. It was started by my PhD mentor, Paul Thompson at USC. And it was started in 2009. It has around 1,400 researchers who are involved right now.
EMILY DENNIS: And this is across many different areas. It was initially neuroimaging and genetics because they wanted to do well-powered studies linking genetic variation with brain variation, and you need tens or hundreds of thousands of individuals to do that. Of course, nobody has the money to collect that at one site. So it was a collaboration across a number of groups that had similar data to try to combine forces.
EMILY DENNIS: From there, it's branched into many other things. So the genetics was one part of it, and the disorder part came a little bit later. And there are now working groups that are focused on various psychiatric disorders like depression and schizophrenia. We have groups focused on developmental disorders like OCD and Turner syndrome, and we have newer groups focused on neurology.
EMILY DENNIS: So I started the ENIGMA Brain Injury Group about 3 years ago with Dr. Lisa Wilde and Dr. David Tate, who are both at the University of Utah (UT, USA) as well. And while it was initially one group, we quickly realized that it needed to be divided into subgroups. TBI is just a really huge area, and there's so much heterogeneity that you have to have a more targeted approach.
EMILY DENNIS: So now we have seven working groups, and I'm sure there will be more soon. We have working groups focused on military brain injury, pediatric moderate-to-severe TBI, adult moderate-to-severe TBI, acute-civilian mild TBI. Intimate partner violence is a fairly new group. Sports-related head injury and magnetic resonance spectroscopy-- that's a methods group trying to see how we can-- across lots of sites, how we can harmonize those data.
Segment:3 Could you tell us more about the pediatric moderate/severe TBI sub-group of this study?.
EMILY DENNIS: So for the pediatric moderate- to-severe TBI subgroup, this is a pretty small field in general. If you look across all of the research studies that have been published, there are really not very many groups that are focused on this, which I think is a disservice to the patients because it's a huge, huge problem around the world. So within this group, we have actually a good portion of the people who are currently doing this research involved, which is really exciting, because one, we've got all of these datasets from around the world, but two, we have all of the people who've been thinking about the problems, thinking about what needs to be done, what are the existing questions.
EMILY DENNIS: So there's a lot of intellectual contributions from these different groups.
Segment:4 What are the challenges faced when working on such a big collaborative project?.
EMILY DENNIS: Well, there are a lot of challenges when you're trying to get lots of people to work together. I think the first one that people might think of is the political issues when you're trying-- political and social issues of trying to get researchers to work together. Those have actually been very minor, happily, very minor.
EMILY DENNIS: I thought we were going to encounter a lot more resistance. You're asking people to contribute their data and their time. But they-- they've spent so much of their own time and their own research money collecting these data that it's a lot to ask someone to then share that. But the way it's been set up, I think, is really conducive to people feeling like they can be part of a collaboration but still maintain ownership and still maintain a role and still have a say over what's done with their data and what questions they want to ask.
EMILY DENNIS: So that part has been fairly easy, and I've been very happy with how collaborative everybody's been. Some of the challenges-- one of the main ones is harmonization. We have data that-- I think in the pediatric group in particular, we have some data that was collected 10 years ago versus data that was collected a couple of years ago.
EMILY DENNIS: And of course, there's so many advances in imaging and image processing over that time, so there's variations in the protocols. That is something that we can't do a whole lot about, because the data has already been collected. If you're collecting it from the beginning, you can harmonize the protocols. But there is a benefit to that in that if you find a result that is robust across all of these groups with different protocols, then you can really believe it more.
EMILY DENNIS: You can know that it's not just only when you have the really high-resolution data can you collect this. It gives you more confidence in what you've been finding. So imaging data-- harmonizing that is a challenge, but not a huge one. Some of what we're trying to deal with now is figure out how to harmonize all of the clinical and the cognitive data.
EMILY DENNIS: There are just thousands of clinical variables that you could potentially bring into this, and everyone's collected slightly different ones. So trying to see where the overlap is, what-- maybe groups use different scales, but there are some common questions, and how we can-- how we can glean the common information across all of those so that we can know that we're looking at the correct domains.
Segment:5 What are your hopes for the future of this field?.
EMILY DENNIS: Well, I'm really excited about where we're going, and I'm really optimistic given how many people have been involved. We've only just started. The military group is farthest along because there are a number of studies in the US, multi-site studies on military brain injury. So we were able to benefit from all of the work that's been done in that area so far.
EMILY DENNIS: But as I said, we've got so many other groups that have recently started and are learning how to combine all of their data. So some of the things that I'm really hoping that this is going to lead to are understanding some of the larger questions in terms of what factors impact outcome. Gender is a major topic, and there have been a number of studies looking at how gender might differ-- might impact outcome.
EMILY DENNIS: But in some groups, particularly in pediatric studies, those are usually very small studies, and so it's hard to actually find significant differences. So I'm hoping that when we combine all of these datasets, that we'll be able to have a better idea of how things like gender impact outcome, age. We also-- I think another area that people are starting to realize that they would want to look at-- but it's hard to have enough data-- is patient subtypes.
EMILY DENNIS: So there are so many different factors that can influence outcome, as we're hearing today-- clinical, demographic variables. And in one study, you couldn't possibly take a machine-- ideally you'd be able to take a machine-learning approach to try to see how these things might cluster. But if you only have 30 subjects in your study, you can't do that. Once you have several hundred or several thousand, you can start to think about some of these big-data approaches.
EMILY DENNIS: I think we are-- I think we are going to find that there are patient subtypes that have-- that are influenced by these demographic and clinical variables that have some bearing on outcome. If we can find that, it potentially opens the door for more targeted treatment. If we can know that someone who has this constellation of factors is more likely to have issues with sleep, or this person is more representative of a different profile, that maybe they're more likely to have cognitive deficits-- if we can get a better idea of what the possible subtypes are, what the pattern of disruption is, then it could be-- and this is all very much in the future, of course, but it could be that there are different treatment approaches that might help individuals come to have a healthier trajectory after injury.
EMILY DENNIS: [MUSIC PLAYING]
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