Decoding the Human Brain: How Anatomy Translates to Behavior, and the Societal Implications

Mackey Interview Episode Edited.wav
Transcript
00:00:07 Mackey
Yeah. So, I think I started with education as the thing I cared about. And so, I have been very, very focused on bringing a cognitive neuroscience lens to these educational inequalities that we see. But in my teaching, as you know, I think about how cognitive neuroscience plays a role in many other as, too. So, we see it playing a role in medicine where we can now use fMRI to map the brain and find the areas to preserve during brain surgery. We see cognitive neuroscience in law, where we think about, particularly in areas of juvenile justice. What does it mean for the brain to be adult, like to sort of achieve full criminal responsibility? At what age does that happen? Does that vary across people? There are many interesting implications there. You're starting to see kind of neuroscience and business and marketing people using neuroimaging tools as people watch ads to find the very best segments of the ad, right to make them as alluring as possible. And Penn is really a place with a lot of strength at this intersection of cognitive neuroscience and society.
00:01:24 Shannon
Hello everyone, this is Shannon. And you're listening to “ever thought about” created by undergraduates at the University of Pennsylvania. We hope to bring you exciting episodes about the diverse research undertaken around campus. Sit down with us as we chat with Penn professors about the work, they've dedicated their lives to. In this episode, we explore research on cognitive neuroscience with Professor Alison Mackey. Doctor Allison Mackey is an assistant professor of psychology here at Penn. Her research focuses on understanding the basic mechanisms underlying brain plasticity in children and how environmental factors can influence windows of peak plasticity. She is interested in studying how physical changes in the brain ultimately give rise to changes in the mind and seeks to apply such knowledge to improving educational strategies. At Penn, she teaches several courses, including Cognitive Neuroscience, Seminar and Cognitive Neuroscience, and the Psychology and neuroscience of character. Doctor Mackey is the principal investigator of her lab, the changing brain. It's a pleasure to have you here today, Professor Mackey.
00:02:32 Mackey
Thank you so much for having me.
00:02:34 Shannon
All right, to get things started off, how did you become interested in cognitive neuroscience and what made you decide to ultimately pursue your current career path?
00:02:43 Mackey
I think my first scientific interest was understanding how environments shape, behavior and as a high schooler, I was primarily interested in traveling the world, and so I was interested in environments and how they shaped lemur behavior in Madagascar. And so, I started my degree in biology at Stanford thinking I wanted to be an evolutionary biologist because I had never taken psychology or neuroscience. But when I started taking those classes, I realized that my interest in sort of how environment shapes behavior could be applied to humans. And I had always been interested in how kids learn through tutoring, through working in schools. And I realized that I had this opportunity to connect my scientific interests with what I cared about most.
00:03:24 Shannon
So, it seems like cognitive neuroscience is sort of at the intersection of psychology and neuroscience. Can you explain that intersection a little bit?
00:03:32 Mackey
Sure. So, I think the term was coined when people started having tools to study human brains. And so maybe it's more correct to call it human neuroscience. As now we don't just study cognitive processes like memory and learning, we also study processes like emotion and motivation. Sort of these more social and affective processes. But the idea was to sort of see how human brains solve problems by collecting data with FMRI or EEG, or sometimes other kinds of tools to sort of map brain activity to specific ways of thinking.
00:04:13 Shannon
Thank you for that explanation. And now the transition to talk about what your current lab research is, what led you to focus on your research on brain development in children? Can you elaborate more on the current projects going on?
00:04:25 Mackey
Sure. I think sort of going back to early experiences in schools that were underfunded. I had this sort of early interest in social justice and helping kids learn, especially kids who are coming from high poverty backgrounds or other kinds of disadvantage and. And so, my first project as a PhD student was trying to help kids build up cognitive skills. And I designed an intervention based on having worked in a toy store in high school where I sort of knew which games popular, which games were used the brain in the ways that we were most interested in. So particularly supporting fluid reasoning, the ability to solve novel problems. And so, we created this intervention. We set up an after-school program in West Oakland, and we found that kids in general get much better at reasoning when they practice for just eight weeks. So about 10 points in IQ, just with this very targeted practice. But of course, there's a lot of variability, right? So given the same kind of intervention, some people change a lot and other people don't change as much. And you see this not just in cognitive interventions, but in mental health interventions and school changes. Some people's minds change, and other people don't. And so, I got interested in trying to understand where these individual differences were coming from. I got interested in the idea of plasticity not just as a process, so not just thinking about plasticity as how cells that fire together wire together, or how your brains change as a function of practice. But really this idea of plasticity as potential right everyone's brain will change in some circumstances and not others. And we know a lot about what gates. Plasticity from research and animal models, and so we know that maturation will decrease plasticity. This is why kids can be better at learning new languages or new musical instruments or new motor skills like new sports. And we also know that motivation can enhance brain plasticity sort of throughout life, right? So, we have this very adaptive process of gluing our brains into place as we craft perfect systems to match our environment. But sort of always keeping the door open to change as adults. When we really need to learn something new. And so that's what my lab works on now is understanding maturation and motivation. How these things shape learning and how experiences of stress of poverty and of positive experiences to shape brain plasticity.
00:07:03 Shannon
Yeah. So, you talk a bit about how there's a lot of variation across different people's brains. How do you establish a baseline to go about studying these general trends? People's brains are so complex and so specific to the individual person.
00:07:18 Mackey
Yeah. So, the question is how do we develop proxy measures of brain plasticity in humans and sort of going back to that animal work on maturation? One of the key processes that seems to matter is myelination. And so, as Cortex gets myelinated, it becomes less and less likely to change. There are tools in MRI that allow you to have a sense of what myelination might look like. It's not a direct measure, right? Because we can't sort of take brains out and look at them closely. But we know sort of how myelin should influence signal properties in our scans. And then for each person we can get a map of T1T2. And look at how that map changes as kids develop. What we see is first, sensory parts of cortex sort of closed off and then motor areas and then cognitive areas last and not until adulthood and then understand how variability then maps to experiences like stress.
00:08:18 Shannon
So far, based on the data and the research that you've done, what have been some like potential applications of this research?
00:08:25 Mackey
So, I think you can split applications into policy and practice, and I'll start with practice. So, from our sort of game-based work early in my career, we know that cognitive skills can change, right? Kids don't walk into kindergarten as smart as they're ever going to be, yet there is sort of little conscious efforts to make kids smarter, and it's almost something that has become taboo to talk about, but I think this idea that particular kinds of activities which a lot of kids from advantage homes have access to already really does like these activities really do build up intelligence. That we should create classrooms that allow for kids to engage with novel challenges, to engage with the fun activities and games that are social and challenging. So, a way to think about how to structure the classroom in terms of policy, we see that brain differences, both in maturation and in motivation systems, seem to grow as kids get older and sort of another piece in this argument for early intervention, right? So, if you want to construct policies that reduce disparities in income, reduce disparities in stress exposure that some of those policies need to think about what kids are going through in the first few years of life and what families are going through. In the first few years of life that makes a lot of sense. Yeah, so you talk a lot about how findings and cognitive neuroscience can actually make a big difference in like other sectors of society, and I think that's really fascinating because a lot of times people think that, like research in one area will only, like benefit the future of research down that one lane. But in reality, it seems like everything is more connected than we may believe. Yeah. So, I think I started with education as the thing I cared about. And so, I have been very, very focused on bringing a cognitive neuroscience lens to these educational inequalities that we see. But in my teaching, as you know, I think about how cognitive neuroscience plays a role in many other areas too. So, we see it playing a role in medicine where we can now use fMRI to map the brain and find the areas to preserve during brain surgery. We see cognitive neuroscience in law, where we think about, particularly in areas of juvenile justice. What does it mean for the brain to be adult, like to sort of achieve full criminal responsibility? At what age does that happen? Does that vary across people? There are lots of interesting implications there. We're starting to see cognitive neuroscience in business and marketing. People using neuroimaging tools as people watch ads to find the very best segments of the ad right to make them as alluring as possible. And Penn is really a place with a lot of strength at this intersection of cognitive neuroscience and society. So, we have a Center for neuroscience and society that's directed by Professor Martha Farah that is just growing and growing to try to tackle some of the new challenges that we'll see in the future.
00:11:33 Shannon
Yeah. And how do neuroscientists approach the study of an organ as complex as the brain? I feel like that's a really common question that is getting asked these days.
00:11:44 Mackey
It's a really good question, and there are so many approaches and so at the meeting for the Society, for Neuroscience, there are usually about 35,000 scientists working on the brain studying sort of the brain at every level, from single channels to cells to how cells interact in circuits. All the way up to sort of what we work on in humans and so. Right now I think we're starting to see themes across systems, so themes around how networks interact at various scales, how temporal dynamics emerge at various scales, and in some areas that is getting applied to modeling brains, so like artificial intelligence approaches and changing brain. So, there are old quotes about how you don't understand something until you can change it, or until you can create. And I think that's sort of where neuroscience is heading, but we're still a long way off and there's been huge investment in particular towards clinical applications, finding new medications, finding new treatments for mental illness, for neurological disorders, for developmental disorders. And for that investment, I don't know if we've found any really game changing treatments yet, but I'm hopeful that that will change in the future.
00:13:21 Shannon
Yeah. And a line that I know that you used to introduce our class back last fall. You said cognitive neuroscientists are interested in seeing how physical changes in the brain lead to changes in the mind. And I was just wondering if you could elaborate more on how societies understanding of how the mind is organized has sort of changed and evolved over time?
00:13:42 Mackey
It's a really good question. I think one of the earliest cases of this is Phineas Gage, as you know, where he was working in the railroads and a tamping iron blew through the front of his time. And it fundamentally changed his personality. And this was a problem for people who thought that our personalities emerge not from the brain, right, that we have some ineffable soul that drives the way we think, and how we make decisions and who we are. And this was evidence that our brains are really responsible for these things. And if we change our brain then our personalities are dramatically altered, and we saw that two with a patient when he had surgery to remove his hippocampus and couldn't make any memories anymore. So again, this physical that changed the deep core part of him. And I wish I had been around at the time to sort of watch how popular opinion changed. And it's because I'm a neuroscientist. It's hard to fully imagine what the beliefs were like before, and it would be fun to briefly time travel to see that social change as it unfolded.
00:14:51 Shannon
So, you talked about like some cases that have led to shifts in thinking in cognitive neuroscience. What do you believe are some notable milestones like whether or not like they're sort of innovations in this field or other more notable case studies that have contributed to rapid progress and overwhelming interests in cognitive neuroscience today?
00:15:15 Mackey
Oh, that's a very good question. Then I guess there are lots of ways of looking at this. I think one fairly recent notable milestone was the development of optogenetics to sort of selectively turn on and off neurons at a very precise level. And because so much of neuroscience is correlational, right, you see sort of this change in brain. And it causes this change in the mind, but back to the Phineas Gage example or the HMM example. These parts that were knocked out are interconnected with many other parts. And so, it's hard to know if it was really that part of the brain or some connection with some other part. And so being able to selectively turn off and turn on neurons has given us much better evidence for specifically which circuits control specific behaviors. In my field, there's also been a huge increase in understanding of how environments shape the brain, both in animal models and in humans and in humans. We've just been scaling up our approaches, so it used to be that labs would collect data on 20 people, and that was a good sample size, and we learned a lot from that. But there is more and more evidence that we might need something like 1000 people to look at individual differences. And so, there's been a push towards more team science, more big data approaches, including software engineers and computer scientists in our study of the brain.
00:16:47 Shannon
Yeah. Would you mind elaborating more on that in terms of what team science looks like here at Penn, a lot of the most successful studies bring in experts from various different fields on tackling a research question. And so, can you talk a bit about how your lab has used team science?
00:17:05 Mackey
Sure. Yeah. Yeah. I mean, I think a lot of the big progress in science is at the boundaries between fields, and it's impossible to be an expert in everything. And so you know, truly novel science will come out of a team of, say, a biologist and a chemist and engineer. Now, neuroscience is becoming more of a profession, but there are different kinds of expertise that need to interact. I'll give you one concrete example from our lab, which is that we've been interested in. Trying to understand maturation at scale. Right. So, we see in our brain data that kids from higher stress backgrounds tend to show faster maturation of the brain. But if you wanted to tackle questions like where are socioeconomic disparities, the biggest across the country or historically right? When were there the biggest differences in the pace of maturation? Or did cash transfers during the pandemic change the pace of maturation?  Or did the pandemic itself change the pace of maturation? We can't actually collect. Brain scans on all of these people? They're too expensive. There aren't that many scanners, and the data isn't really something you can compare easily across time and space. And so, we've been thinking about looking at molars instead. And that idea comes from evolutionary biology, because they've had this problem of how to map the duration of childhood across species in the fossil record. And so, they can see that humans have the longest childhood, right? Our first permanent molar doesn't erupt until about age 6. And so, we wondered. OK, do kids who experience more stress, do their teeth grow up faster, too, right? Could this possibly be a more scalable biomarker and to ask that we needed to work with pediatric dental radiologists to go back through our MRI scans and look at the teeth as they grow in? We knew nothing about teeth going into this, right? So, they had to teach us about the follicular SAC that was around the molar. Very young kids and how that changes as the roots grow down and the tooth gets pushed up and we've learned a lot about teeth, but we really needed this partnership as a first step. So, we did find that kids from lower income and higher stress backgrounds get their molars earlier, and we were able to then replicate that in an epidemiological data set, and yet another disciplinary lens. And then we were able to show that kids who get their molars earlier have weaker cognitive skills above and beyond other stressors, right? So, we're actually seeing that molars can capture. How much stress has been embedded in the Organism. So that sort of brings in the psychology lens. And actually, the educational lens as well.
00:20:03 Shannon
Thank you. In terms of the future of this field, what do you think are the biggest challenges facing cognitive neuroscience today?
00:20:13 Mackey
I think skill is one of them. How to collect enough data and? Also, how to collect high quality data and so a lot of these really big studies will try to measure a cognitive skill with 5 minutes of data right here. Do this computer rise task for 5 minutes and that will give us your intelligence or your memory or other kinds of cognitive. Those, and that's just not how humans operate, and I've been very interested in sort of better approaches to behavioral measurement to map back to the brain of understanding variability. So, getting the same measure whether it's self-control or persistence or memory or learning multiple times over several weeks. So, you can ask questions about how the brain relates to average behavior, how the brain relates to variability and behavior, and how the brain relates insensitivity of behavior to other environmental factors. And so, this is going to sort of bring in yet another set of approaches from ecological momentary assessment to get a better handle on how kids behavior varies day-to-day to help kids sort of be the best versions of themselves. And so we're kind of coming down to these.
00:21:26 Shannon
Just few questions here. I was wondering if you could elaborate on what you think is sort of in store for the future of this field.
00:21:36 Mackey
So, I think there are many paths forward. I think in our lab we are interested in moving beyond just correlational approaches. So, this experience is correlated with this brain or cognitive outcome to thinking more about causality. And that is very, very hard. So, one example is can we change kids environments for the better and see differences in rate of maturation or motivational circuitry? And so that's something that we've been working with community partners for years to develop. I mean, it's their intervention from age 2 to age 4, and that includes parent coaching and new books and new toys for over a year. And so that we'll see whether that change in the environment changes the brain and I think but, but that's hard work to do and that's hard work to sort of get enough kids in to be able to draw conclusions. For our molar eruption work, we're trying to think about causality by moving backwards into animal models and developing collaborations where we can change an animal's experience and then look at the pace of molar eruption and other kinds of somatic development that historically people weren't interested in, right, didn't know, could become interesting in humans. So that's another way. To get at causality, Penn is a site of the HBCD project that will enroll 7500 pregnant mothers nationwide and follow those babies from in utero through age 8, and there it will still be correlational, but we'll get probably temporal precedence, right? So, when particular kinds of experiences happen, what are the sort of longitudinal implications for brain development and development of cognitive skills? So that's one set of paths I see for the field. I think better integration with education or law would be really exciting. I think better integration with big data and data science kinds of methods we'll see almost for sure. But it's hard to know exactly. I'm excited to see what's next.
00:23:48 Shannon
A last question to end on here. How do you think Penn students who are interested in this area can get involved on campus?
00:23:57 Mackey
So, they can reach out so they can go to thechangingbrain.com and just read about our projects and see what's exciting to them. Typically, students work for work study or pay through their first three years. And they're involved in lots of different parts of research so they can see which part is most exciting for them. So, they'll help us scan kids, they'll help us administer neuropsychological assessments. We really try to tailor their roles to what they're excited about after Penn. And then we have many students who will complete an honors thesis or independent research in their 4th year.
00:24:34 Shannon
Very cool. Well, that and our list of questions. Thank you so much, Professor Mackey, for taking time to be with us.
00:24:42 Mackey
Today, thank you for having me.