Category: Neuroscience Page 2 of 13

Keeping the Aging Brain Connected With Words and Music

On December 28, 2021

In an era of seemingly endless panaceas for age-based mental decline, navigating through the clutter can be a considerable challenge.

However, a team of Duke researchers, led by cognitive neuroscientist Edna Andrews, PhD, think they may have found a robust and long-term solution to countering this decline and preventing pathologies in an aging brain. Their approach does not require an invasive procedure or some pharmacological intervention, just a good ear, some sheet music, and maybe an instrument or two.

*Dr. Edna Andrews, pictured in 2017. (Photo by Megan Mendenhall/Duke Photography*)

In early 2021, Andrews and her team published one of the first studies to look at musicianship’s impact in building cognitive brain reserve. Cognitive brain reserve, simply put, is a way to qualify the resilience of the brain in the face of various pathologies. High levels of cognitive reserve can help stave off dementia, Parkinson’s disease or multiple sclerosis for years on end. These levels are quantified through structural measurements of gray matter and white matter in the brain. The white matter may be thought of as the insulated wiring that helps different areas of the brain communicate.

In this particular study, Andrews’ team focused on measurements of white matter integrity through an advanced MRI technique known as diffusion tensor imaging, to see what shape it is in.

Previous neuroimaging studies have revealed that normal aging leads to a decrease in white matter integrity across the brain. Over the past fifteen years, however, researchers have found that complex sensory-motor activities may be able to slow down and even reverse the loss of white matter integrity. The two most robust examples of complex sensory-motor activities are multilingualism and musicianship.

Andrews has long been fascinated by the brain and languages. In 2014, she published one of the seminal texts in the field of cognitive neurolinguistics where she laid the groundwork for a new neuroscience model of language. Around the same time, she published the first and to-date only longitudinal fMRI study of second language acquisition. Her findings, built upon decades of research in cognitive neuroscience and linguistics, served as the foundation for her popular FOCUS course: Neuroscience/Human Language.

*Dr. Andrews’ 2014 book. Published by Cambridge University Press*

In more recent years, she has shifted her research focus to understanding the impact of musicianship on cognitive brain reserve. Invigorated by her lived experience as a professional musician and composer, she wanted to see whether lifelong musicianship could increase white matter integrity as one ages. She and her team hypothesized that musicianship would increase white matter integrity in certain fiber tracts related to the act of music-making

To accomplish this goal, she and her team scanned the brains of eight different musicians ranging in age from 20 years to 67 years old. These musicians dedicated an average of three hours per day to practice and had gained years’ worth of performance experience. After participants were placed into the MRI machine, the researchers used diffusion tensor imaging to calculate fractional antisotropy (FA) values for certain white matter fiber tracts. A higher FA value meant higher integrity and, consequently, higher cognitive brain reserve. Andrews and her team chose to observe FA values in two fiber tracts, the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF), based on their relevance to musicianship in previous studies.

*Relative location of subcortical white matter fiber tracts (lateral view). Image from Wikipedia.*

Previous studies of the two fiber tracts in non-musicians found that their integrity decreased with age. In other words, the older the participants, the lower their white matter integrity in these regions. After analyzing the anisotropy values via linear regression, they observed a clear positive correlation between age and fractional anisotropy in both fiber tracts. These trends were visible in both tracts of both the left and right hemispheres of the brain. Such an observation substantiated their hypothesis, suggesting that highly proficient musicianship can increase cognitive brain reserve as one ages.

These findings expand the existing literature of lifestyle changes that can improve brain health beyond diet and exercise. Though more demanding, neurological changes resulting from the acquisition and maintenance of language and music capabilities have the potential to endure longer into the life cycle.

Andrews is one of the strongest advocates of lifelong learning, not solely for the satisfaction it brings about, but also for the tangible impact it can have on cognitive brain reserve. Picking up a new language or a new instrument should not be pursuits confined to the young child.

It appears, then, that the kindest way to treat the brain is to throw something new at it. A little bit of practice couldn’t hurt either.

Post by Vibhav Nandagiri, Class of 2025

Duke has 38 of the World’s Most Highly-Cited Scientists

By Karl Bates

On November 16, 2021

In Behavior/Psychology, Biology, Biomedical Engineering, Cardiology, Climate/Global Change, Engineering, Environment/Sustainability, Faculty, Immunology, Medicine, Neuroscience, Physics

Peak achievement in the sciences isn’t measured by stopwatches or goals scored, it goes by citations – the number of times other scientists have referenced your findings in their own academic papers. A high number of citations is an indication that a particular work was influential in moving the field forward.

Nobel laureate Bob Lefkowitz made the list in two categories this year.

And the peak of this peak is the annual “Highly Cited Researchers” list produced each year by the folks at Clarivate, who run the Institute for Scientific Information. The names on this list are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index – the most-cited of the cited.

Duke has 38 names on the highly cited list this year — including Bob Lefkowitz twice because he’s just that good — and two colleagues at the Duke NUS Medical School in Singapore. In all, the 2021 list includes 6,602 researchers from more than 70 countries.

The ISI says that US scientists are a little less than 40 percent of the highly cited list this year – and dropping. Chinese researchers are gaining, having nearly doubled their presence on the roster in the last four years.

“The headline story is one of sizeable gains for Mainland China and a decline for the United States, particularly when you look at the trends over the last four years,” said a statement from David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information. “(This reflects) a transformational rebalancing of scientific and scholarly contributions at the top level through the globalization of the research enterprise.”

Without further ado, let’s see who our champions are!

Biology and Biochemistry

Charles A. Gersbach

Robert J. Lefkowitz

Clinical Medicine

Pamela S. Douglas

Christopher Bull Granger

Adrian F. Hernandez

Manesh R.Patel

Eric D. Peterson

Cross-Field

Richard Becker

Antonio Bertoletti (NUS)

Yiran Chen

Stefano Curtarolo

Derek J. Hausenloy (NUS)

Ru-Rong Ji

Jie Liu

Jason W. Locasale

David B. Mitzi

Christopher B. Newgard

Ram Oren

David R. Smith

Heather M. Stapleton

Avner Vengosh

Mark R. Wiesner

Environment and Ecology

Emily S. Bernhardt

Geosciences

Drew T. Shindell

Immunology

Edward A. Miao

Microbiology

Barton F. Haynes

Neuroscience and Behavior

Quinn T. Ostrom

Pharmacology and Toxicology

Robert J. Lefkowitz

Plant and Animal Science

Xinnian Dong

Sheng Yang He

Philip N. Benfey

Psychiatry and Psychology

Avshalom Caspi

E. Jane Costello

Honalee Harrington

Renate M. Houts

Terrie E. Moffitt

Social Sciences

Michael J. Pencina

Bryce B. Reeve

John W. Williams

Post by Karl Bates

New Blogger Vibhav Nandagiri: The Curious Student Blogger

By Vibhav Nandagiri

On September 27, 2021

In Biomedical Engineering, Cardiology, Global Health, Neuroscience, Science Communication & Education, Students

Hey everyone! My name is Vibhav Nandagiri, I use he/him/his pronouns, and I’m currently a first-year student at Duke. Amidst the sea of continuous transition brought upon by college, one area of my identity that has stayed fairly constant is my geography. I’ve lived in North Carolina for sixteen of my eighteen years, and my current home lies just twenty minutes from campus in sunny, suburban Cary, NC.

The two missing years are accounted for through my adventures in my parents’ hometown–Hyderabad, India–as a toddler. Spending some of my earliest years surrounded by a large and loving family impacted my life profoundly, forever cementing a strong connection to my emotional, cultural, and linguistic roots.

The latter had a secondary impact on me, one I wouldn’t discover until my parents enrolled me in preschool after returning to the States. With hubris, I marched into my first day of class, ready to seize the day, until I soon discovered an uncomfortable fact: I couldn’t speak English. I am told through some unfortunate stories that I struggled considerably during my first month in a new, Anglicized environment; however, I soon learned the quirks of this language, and two-year-old me, perhaps realizing that he had some catching up to do, fully immersed himself in the English language.

Nowadays, I read quite a bit. Fiction and journalism, academic and satire, I firmly believe that all styles of literature play a role in educating people on the ebbs and flows of our world. In recent years, I’ve developed a thematic fascination with the future. The genre of far-future science fiction, with its rich exploration of hypothetical advanced societies, has led me to ask pressing questions about the future of the human species. How will society organize itself politically? What are the ethical implications of future medical advancements? Will we achieve a healthy symbiosis with technology? As a Duke Research Blogger, I hope to find answers to these questions while getting a front-row, multidisciplinary seat to what the future has to offer. It’s an invigorating opportunity to grow as a writer and communicator, to have my curiosity piqued on a weekly basis, to understand the futuristic visions of innovators at the top of their field.

Prior to Duke, I had the opportunity to conduct research at the Appalachian State University Pediatric Exercise and Physiology Lab, where I co-authored a published paper about adolescent fat metabolism. Not only was I introduced to the academic research process, but I also learned the importance of communicating my findings clearly through writing and presentations. I intend to bring these valuable lessons and perspectives to the Duke Research Blog.

Beyond exercise science, I am intrigued by a diverse range of research areas, from Public Health to Climate Change to Business to Neuroscience, the latter of which I hope to explore further through the Cognitive Neuroscience and Law FOCUS. I was drawn to the program for the opportunity to build strong relationships with professors and investigators; I intend to approach my work at the Duke Research Blog with a similar keenness to listen and connect with researchers and readers alike. When I’m not reading or typing away furiously at my computer, you can find me hitting on the tennis courts, singing Choral or Indian Classical music, or convincing my friends that my music taste is better than theirs.

Post By Vibhav Nandagiri, Class of 2025

Learning Something Surprising About “SuperLearners”

By Karl Bates

On May 4, 2021

In Behavior/Psychology, Biology, Neuroscience

The discovery of a signaling pathway in the brain that could make mice into ‘superlearners’ understandably touched off a lot of excitement a few years back.

But new work led by Duke neurologist and neuroscientist Nicole Calakos MD PhD suggests there’s more to the story of the superlearner chemical pathway than anybody realized.

A genetically-enhanced ‘smart mouse’ doing some important work. (Boston University)

In a study led by postdoctoral researchers Ashley Helseth and Ricardo Hernandez-Martinez, the Calakos lab developed a new tool to visualize activity of this Integrated Stress Response (ISR) signaling pathway because it contributes to synaptic plasticity – the brain’s ability to rewire circuits – as well as to learning and memory.

What they didn’t expect to see is that a population of cells called cholinergic interneurons, which comprise only 1 or 2 percent of the whole basal ganglia structure, seem to have the ISR pathway working all the time. The basal ganglia, which is the focus of much of Calakos’ work, plays a role in Parkinson’s and Huntington’s diseases, Tourette’s syndrome, obsessive compulsive disorder and more.

Nicole Calakos, the Lincoln Financial Group distinguished professor of Neurobiology and Neurology. (Alex Boerner)

“This totally changes how you think about the pathway,” Calakos said. “Everybody thought this pathway used an on-demand response type of mechanism, but what if some cells needed it for their everyday activities?”

To answer this, they blocked the ISR in just those rare interneurons in mice and it actually reproduced the enhanced performance on learned tasks that the earlier studies had shown when the pathway was blocked universally throughout the brain. This finding focuses attention on this select subset of brain cells, the cholinergic interneurons that release the chemical signal acetylcholine, as being responsible for at least some of the ‘superlearner’ behavior.

Since the integrated stress response pathway and its potential to enhance learning and memory was identified, drugs for dementia and traumatic brain injury are being designed to manipulate it and help the brain recover. But there may be more to the story than anyone realized, Calakos said.

“Our results show that the ISR plays a major role in acetylcholine-releasing cells, and our current best dementia drugs boost acetylcholine,” she said.

With their new tool, SPOTlight, the team were able to highlight the presence of cholinergic interneurons (red) which are only 1 to 2 percent of the cell population in the ganglia. (Helseth et al)

Acetylcholine, the chemical that these rare cholinergic interneurons use to signal in the brain, is well known for its powerful effects on influencing brain states for attention and learning. This finding suggests that at least some of the ‘superlearner’ properties of inhibiting the ISR occur by influencing brain state, rather than acting directly in the cells that are being rewired during learning.

In addition to the full research article, Science published on April 23 an article summary by Helseth and Calakos and a perspective piece by a pair of University of Minnesota neuroscientists highlighting the finding’s importance.

More work is required to sort out what ISR is and is not doing, but it’s possible that these new findings can help to develop “more precise, more nuanced Alzheimer’s drugs,” Calakos said.

Post by Karl Leif Bates

A Virtual Stroll through the 2021 Bass Connections Showcase

By Meghna Datta

On April 23, 2021

In Art, Behavior/Psychology, Climate/Global Change, Field Research, Neuroscience, Science Communication & Education, Students

Posters, presentations, and formalwear: despite the challenge of a virtual environment, this year’s annual Fortin Foundation Bass Connections Showcase still represented the same exciting scholarship and collegiality as it has in years past.

While individuals could no longer walk around to see each of this year’s 70+ teams present in person, they were instead able to navigate a virtual hall with “floors” designated for certain teams. With labels on each virtual table, it almost mimicked the freedom of leisurely strolls down a hall lined with posters, stopping at what catches your eye. Three sessions were held over Thursday, April 15 and Friday, April 16.

The beginning of each session featured five-minute “lightning” presentations by a diverse set of teams, representing the range of research that students and faculty participated in. One such presentation was lead by Juhi Dattani ’22 (NCSU) and Annie Roberts ’21, who covered research generated by their team, “Regenerative Grazing to Mitigate Climate Change.” The team was an inter-institutional project bringing together UNC, NCCU, NCSU, and Duke. And as they aptly summarized, “It’s not the cow, but how.” Cows can help fight instead of contribute to the climate crisis, through utilizing regenerative grazing – which is an indigenous practice that has been around for hundreds of years – to improve soil health and boost plant growth.

The team during the 2019-2020 year, pre-COVID, on the Triangle Land Conservancy’s Williamson Preserve.

Research is not just relegated to the physical sciences. Brittany Forniotis, a PhD candidate ’26, and Emma Rand ’22 represented the team “Mapping History: Seeing Premodern Cartography through GIS and Gaming.” Their team was as interdisciplinary as it gets, drawing from the skills of individuals in everything from art history to geography to computer science. They posited that mapmakers use features of map to argue how people should see the world, not necessarily how they saw the world. To defend this hypothesis, they annotated maps to record and categorize data and even converted maps to 3D to make them virtual, explorable worlds. The work of this team enabled the launch of Sandcastle, which aims to “enable researchers to visualize non-cartesian, premodern images of places in a comparative environment that resembles the gestural, malleable one used by medieval and early modern cartographers and artists.”

The work of the team added to a project launch of Sandcastle.

Sophie Hurewitz (T ’22) and Elizabeth Jones (MPP ’22) presented on behalf of the “North Carolina Early Childhood Action Plan: Evidence-based Policy Solutions”, Their recommendations for alleviating childhood food insecurity in North Carolina as outlined by the North Carolina Early Childhood Action Plan will provide a roadmap for NC Integrated Care for Kids (NC InCK) to consider certain policy changes.

One of the most remarkable parts of Bass Connections is how it opens doors for students to pursue avenues and opportunities that they may have never been exposed to otherwise. Hurewitz said that “Being a part of this team led me and a team member to apply for the 2021 Bass Connections Student Research Award, which we were ultimately awarded to study the barriers and facilitators to early childhood diagnosis of Autism Spectrum Disorder (ASD) among Black and Latinx children in North Carolina.” In addition to the award, Hurewitz and fellow team member Ainsley Buck were able to present their team’s research at the APA Region IV Annual Meeting.

From gene therapy for Alzheimer’s disease to power grids on the African continent, this year’s teams represented a wide range of research and collaboration. Erica Langan ’22, a member of the team “REGAIN: Roadmap for Evaluating Goals in Advanced Illness Navigation”, said that “For me, Bass Connections has been an extraordinary way to dive into interdisciplinary research. It’s an environment where I can bring my existing skills and knowledge to the table and also learn and grow in new ways.” This interdisciplinary thinking is a hallmark of not just Bass Connections, but Duke as a research institution, and it’s clear that this spirit is alive and well, even virtually.

Post by Meghna Datta

Using Data Science for Early Detection of Autism

By Anna Gotskind

On March 31, 2021

In Behavior/Psychology, Computers/Technology, Data, Faculty, Medicine, Neuroscience

Autism Spectrum Disorder can be detected as early as six to twelve months old and the American Academy of Pediatrics recommends all children be screened between twelve and eighteen months of age.

But most diagnoses happen after the age of 4, and later detection makes it more difficult and expensive to treat.

One in 40 children is diagnosed with Autism Spectrum Disorder and Duke currently serves about 3,000 ASD patients per year. To improve care for patients with ASD, Duke researchers have been working to develop a data science approach to early detection.

Geraldine Dawson, the William Cleland Distinguished Professor in the Department of Psychiatry & Behavioral Sciences and Director of the Duke Center for Autism and Brain Development, and Dr. Matthew Engelhard, a Conners Fellow in Digital Health in Psychiatry & Behavioral Sciences, recently presented on the advances being made to improve ASD detection and better understand symptoms.

The earlier ASD is detected, the easier and less expensive it is to treat. Children with ASD face challenges in learning and social environments.

ASD differs widely from case to case, however. For most people, ASD makes it difficult to navigate the social world, and those with the diagnosis often struggle to understand facial expressions, maintain eye contact, and develop strong peer relations.

However, ASD also has many positive traits associated with it and autistic children often show unique skills and talents. Receiving a diagnosis is important for those with ASD so that they can receive learning accommodations and ensure that their environment helps promote growth.

Because early detection is so helpful researchers began to ask:

“Can digital behavioral assessments improve our ability to screen for neurodevelopmental disorders and monitor treatment outcomes?”
Dr. geraldine DawsoN

The current approach for ASD detection is questionnaires given to parents. However, there are many issues in this method of detection such as literacy and language barriers as well as requiring caregivers to have some knowledge of child development. Recent studies have demonstrated that digital assessments could potentially address these challenges by allowing for direct observation of the child’s behavior as well as the ability to capture the dynamic nature of behavior, and collect more data surrounding autism.

“Our goal is to reduce disparities in access to screening and enable earlier detection of ASD by developing digital behavioral screening tools that are scalable, feasible, and more accurate than current paper-and-pencil questionnaires that are standard of care.”
Dr. Geraldine Dawson

Guillermo Sapiro, a James B. Duke Distinguished Professor of Electrical and Computer Engineering, and his team have developed an app to do just this.

On the app, videos are shown to the child on an iPad or iPhone that prompt the child’s reaction through various stimuli. These are the same games and stimuli typically used in ASD diagnostic evaluations in the clinic. As they watch and interact, the child’s behavior is measured with the iPhone/iPad’s selfie camera. Some behavioral symptoms can be detected as early as six months of age are, such as: not paying as much attention to people, reduced affective expression, early motor differences, and failure to orient to name.

In the proof-of-concept study, computers were programmed to detect a child’s response to hearing their name called. The child’s name was called out by the examiner three times while movies were shown. Toddlers with ASD demonstrated about a second of latency in their responses.

Another study used gaze monitoring on an iPhone. Nearly a thousand toddlers were presented with a split screen where a person was on one side of the screen and toys were on the other. Typical toddlers shifted their gaze between the person and toy, whereas the autistic toddlers focused more on the toys. Forty of the toddlers involved in the study received an ASD diagnosis. Using eye gaze, researchers were also able to look at how toddlers responded to speech sounds as well as to observe early motor differences because toddlers with ASD frequently show postural sway (a type of head movement).

“The idea behind the app is to begin to combine all of these behaviors to develop a much more robust ASD algorithm. We do believe no one feature will allow us to detect ASD in developing children because there is so much variation”
DR. GERALDINE DAWSON

The app has multiple features and will allow ASD detection to be done in the home. Duke researchers are now one step away from launching an at-home study. Other benefits of this method include the ability to observe over time with parents collecting data once a month. In the future, this could be used in a treatment study to see if symptoms are improving.

Duke’s ASD researchers are also working to integrate information from the app with electronic health records (EHR) to see if information collected from routine medical care before age 1 can help with detection.

Duke Senior Mixes Memory Research with Criminal Justice Reform

By Cydney Livingston

On March 26, 2021

In Behavior/Psychology, Neuroscience, Policy, Students

What do you get when you mix double majors in Philosophy and Psychology with a certificate in Philosophy, Politics, and Economics? You get someone like Kelis Johnson, a junior from Lithonia, Georgia in suburban Atlanta, who works in not one research lab at Duke, but two.

Kelis is a member of The Marsh Lab studying learning and memory in Psychology and Neuroscience, and The Wilson Center for Science and Justice at Duke Law, using legal and scientific research to advance criminal justice reform.

Kelis Johnson, member of the Marsh Lab and the Wilson Center for Science and Justice

“Managing two research assistant positions while working as an embedded writing consultant with the Thompson Writing Studio, on top of my academics, can definitely be a challenge,” Kelis says. But, she said, “The way that I have been able to manage these positions along with the rest of my busy schedule is cohesion: Although working in a lab provides a different context than the material from my classes, I think my lab work and classwork supplement one another in a profound way.”

After taking a class with Elizabeth Marsh, the lab’s Principal Investigator, Kelis found herself “interested in deepening [her] knowledge of and experience with memory research,” so she reached out to get involved in the summer of 2020. The lab has provided her a means to explore her interests in the “intersections between memory and personal identity, education and the law.”

Simultaneously, in the midst of the (first) Covid-19 summer, Kelis worked with the Microworlds Lab. She conducted historical research that profiled Black female activists. “I felt like my interests and passions began to converge on activism and bringing about change while also exploring empirical research,” she said, “This passion aligned with the work being done at the Wilson Center who use research to advance civil rights.” She joined her second lab in the fall of 2020.

Dr. Elizabeth Marsh surrounded by research assistants of the Marsh Lab

In both positions, Kelis meets weekly with her fellow colleagues to discuss an overview of the labs work or the current research in the field. She finds this fulfilling, knowing that the work she and fellow research assistants have contributed to is providing “concrete advancements … in the labs and the world more broadly.” Kelis’ work consists mostly of coding or scoring data. This means reading study participants’ responses and using a codebook (like a grading rubric) to determine how each response compares to the standard established in the experimental protocol. Kelis also participates in literature reviews and stimuli creation, where she generates relevant material such as questions, statements, or images that will be used in experiments to test research questions.

This work has enabled Kelis to meet fellow undergraduates, along with graduate students and faculty mentors, who have similar interests to her own. She has learned more about grant writing, research ethics, and statistical tools. Along with providing her invaluable research experience, strengthening her passions for criminal justice reform, and reinforcing her plans to go to law school following graduation from Duke, through her work with the Wilson Center, Kelis has been able to learn more about Durham and North Carolina. This prompted her to think deeper about her role in the larger communities around her.

Image of Duke Law School, where the Wilson Center is located.

Kelis’ research is valuable outside of the lab. “Memory research is essential to how we learn, how we structure our life and personal identity, and how we form relationships with others,” Kelis said. She also stated that, “Learning about and reforming our criminal justice system is something we must all care about. In order to attack the systematic oppression of marginalized groups, we have to understand it.”

Unfortunately, due to Covid-19, Kelis has been unable to participate in person with either of her labs. This is something she is emphatically looking forward to. However, the virtual realm has enabled other forms of meaningful interactions and experiences through digital platforms. Kelis says she really appreciates “the events hosted by the [Wilson Center] Lab that often feature exonerated individuals who speak about their experience within the criminal justice system.”

Kelis’ contributions to projects from memory difference in older and younger adults to autobiographical memory are surely only the first steps in a planned lifetime of standing at the intersection between memory, identity, and the structures of our society.

Post by Cydney Livingston

Meet a Duke Senior at the Intersection Of Computation, Neuroscience and T-Pain

By Anna Gotskind

On March 15, 2021

In Behavior/Psychology, Computers/Technology, Neuroscience, Students

As Daniel Sprague ‘21 prepares to graduate from Duke this Spring with a double major in Computer Science and Neuroscience, I had the opportunity to interview him on his undergraduate research experience. In his final semester, Sprague reflects on what he accomplished and learned in the three research labs he was a part of over his four years at Duke.

Outside of the lab, Sprague is also active in the arts community at Duke. He has been a member of Hoof ‘n’ Horn since his freshman year and has performed in four student-run musical theater productions. He is also a part of Speak of the Devil, one of Duke’s acapella groups that he was the president of during his Junior year. Recently, a video they uploaded more than two years ago has picked up speed and acquired over 150,000 views on YouTube. I think it’s fair to say Sprague is even more than a triple threat.

Sprague was interested in neuroscience and biology before he came to Duke and knew he wanted to participate in undergraduate research when he arrived. His first year, planning on pursuing pre-med, he joined Rima Fathi Kaddurah-Daouk’s lab where he worked with metabolomics, the large-scale study of small molecules within cells, biofluids, tissues, or organisms as it relates to neuropsychiatric disorders. While he learned a lot and enjoyed working in this lab, Sprague was eager to explore more.

The summer after his first year, Sprague was accepted to the Huang Fellows Program run by Duke’s Science & Society initiative.

Sprague described their focus as, “The way that research, science, communication, and medicine interact with social issues and ethics.”

As a part of the program, Sprague was matched and placed in Ornit Chiba-Falek’s lab. There he conducted work in genomics and neuroscience, centered around neurodegenerative diseases, specifically, Parkinson’s and Alzheimer’s. His job involved processing mouse brains to extract neurons for genomic sequencing. From there, the lab would conduct genome-wide association studies to correlate specific human or animal genotypes with genetic markers.

“We were trying to identify SNPs (Single-nucleotide polymorphism) which are single base pair variations in a genome that correlated with Alzheimer’s” Sprague explained

Along with working in a lab, Sprague also attended research seminars, learned about how science publishing works, and participated in a science symposium at the culmination of the summer experience.

Daniel Sprague presents his research at Duke Science and Society’s Huang Fellows Program Poster Session

“Research is a slow iterative process and it rarely ever works how you expect it to.”
Daniel sprague

Sprague continued working in the Chiba-Falek lab through his sophomore year and contributed to the publication of two research papers: Shared genetic etiology underlying Alzheimer’s disease and major depressive disorder and Bioinformatics strategy to advance the interpretation of Alzheimer’s disease GWAS discoveries: The roads from association to causation. However, partway through the year, he realized he missed math and computational thinking. He began taking more math and computer science classes. After learning more, he realized he really wanted to find a lab doing research at the intersection of computation, math, and neuroscience.

Junior year brought Sprague to the John Pearson’s Lab where they build modeling and analysis tools for brain data.

He also began taking courses in machine learning which he brought into his lab work. His role involved working on the lab’s code base and aiding in the development of a software system for analyzing the brain. He was specifically looking at calcium imaging data. Sprague explained that there are a lot of different ways to do neuroimaging and visualize brain cell function. His work involved using fluorescent calcium.

“When brain cells spike, they release a fluorescent calcium trace that we can visualize with a camera to detect brian cell function with a high degree of temporal and spatial specificity,” Sprague said. “This allows us to accurately detect brain cell function on a millisecond and single cell scale.”

In many neuroscience studies, a stimulus is presented to an organism and the response is observed. The Pearson lab wants to be able to dynamically adjust which stimulus they present based on the intermediary results during the experiment.

“A big limitation in neuroscience research is it just has an absurd amount of data, even for a very small organism,” Sprague said. “Even a couple thousand brain cells will provide so much data that it can’t be visualized or analyzed quick enough to adjust the experiment in ways that would improve it.”

As a result of this limitation, they are trying to adapt conventional computational neuroscience methods to be used in an “online fashion,” which means working with the data as it comes in. Ultimately, they are developing methods to analyze data that traditionally would take hours due to computational time and trying to condense it to a millisecond.

“There are a lot of similar problems that computer scientists work on, but they focus on theoretical analyses of types of functions and how mathematical functions work. What’s cool about this is that it’s very applied with the constraints of a biological system and also requires knowledge of multiple disciplines.”
daniel sprague

Sprague will continue to apply these skills as he begins working next year as an associate consultant at Bain & Company in San Francisco. He is very interested in the connection between science, tech, and society.

Additionally, he is hoping to learn more about how artificial intelligence and machine learning are used in industry as well as their future directions, ethical dilemmas, and legal considerations. Consulting is becoming an increasingly data-driven industry and Sprague hopes to continue developing his domain knowledge and work with these ideas in an applied setting.

As Sprague prepares to leave Duke he reflects on his time here and the research he has had the opportunity to participate in.

“One thing I’m grateful for is having the chance to have different experiences but still settle into one lab for two years. Don’t be afraid to get involved early, and don’t feel like you have to stay in the same lab for four years.”
daniel Sprague

Post by Anna Gotskind

Brain Structure May Not Influence Personality After All

By Niba Audrey Nirmal

On December 7, 2020

In Behavior/Psychology, Biology, Computers/Technology, Neuroscience

New study casts doubt on links between personality and brain structure. MRI scan courtesy of Annchen Knodt, Duke University

We know personality comes from the brain, but does that mean the brain’s shape and composition affect personality as well?

Previous studies have attempted to find links between brain structure and personality types, but new data indicates otherwise. A new study, the largest of its kind, suggests these links may not be so strong after all. In fact, they may not even exist.

Recently Duke researchers, led by Reut Avinun Ph.D., a postdoctoral associate at Professor Ahmad Hariri’s lab, analyzed the MRI scans of over a thousand people to determine potential links between personality and brain shape.

Although there are many personality neuroscience studies, consistent and reliable findings have not been established. While most previous studies used less than 300 individuals, this study has a large sample of 1,107 individuals. Additionally, this research comprehensively measures personality with 240 items.

“When I got into the field, people were collecting data sets with only 10 people and doing analysis with only 20 participants,” said Avram Holmes, an asssociate professor of psychology at Yale who was not involved in the study.

Personality studies such as this typically use the “Big Five” personality traits: neuroticism, extraversion, agreeableness, conscientiousness, and openness-to-experience. Extraverted people tend to be outgoing and social and those with high openness-to-experience are imaginative, curious, and enjoy trying new things. High neuroticism and low conscientiousness have been associated with negative health behaviors such as smoking. These were even connected to negative life outcomes, such as depression, anxiety, and poor sleep. By understanding what underlies these behaviors, scientists may be able to better treat them.

For brain shape, Avinun and her colleagues examined brain morphometry, cortical thickness, cortical surface area, subcortical volume, and white matter microstructural integrity. She used a univariate approach, looking at the relationship between one phenotype and one behavior. Statistical analysis also accounted for the factors of race/ethnicity, sex, and age.

Last year, researchers published a paper finding 15 correlations between specific personality traits and neuroanatomical structures. However, Avinun’s new research found that none of these connections held true in the large Duke Neurogenetics Study sample.

When scientists analyze an MRI dataset, there is a lot of freedom in the phenotypes collected and the types of analyses. “With so many degrees of investigative freedom and the expectation that you should see something there, researchers may accidentally find false positives. It’s easy to fall into the trap of making a story about why the effect has this particular brain pattern and see an association that doesn’t exist,” Holmes explained.

Ultimately, Avinun found no links between the Big Five personality traits and multiple features of brain structure.

While this may seem anticlimactic, even null findings are incredibly useful and could lead to recommendations to future research in this area. By showing that links between brain morphometry and personality tend to be small, this research may push the field toward studies with larger samples and guidelines for higher replication rates.

“The brain is plastic and it is affected every day by our experiences, so expecting to find straightforward associations between brain morphometry and personality traits may be too naïve,” Avinun said. “We are beginning to realize that large samples and multivariate methods are needed in neuroscience. Trying to understand what makes us who we are is exciting. Research is really challenging as the field is constantly changing, but it is constantly improving as well.”

Niba Nirmal is a multimedia science communicator based in San Francisco, CA. She graduated in the Duke class of 2020, with a Master’s degree in Genetics. Find samples of her work at www.notesbyniba.com

Dealing With Lead for Life

By Cydney Livingston

On September 21, 2020

In Behavior/Psychology, Biology, Genetics/Genomics, Global Health, Neuroscience, Science Communication & Education

Though lead has been widely eliminated from use in products due to proven health risks, the lifelong consequences of childhood lead exposure for children born in the era of lead use in gasoline are still unknown.

Aaron Reuben, fifth-year Ph.D. candidate in clinical psychology at Duke, spoke about the long-term implications of childhood lead exposure Friday, September 18th through the Nicholas School’s Environmental Health and Toxicology Seminar series. He conducts research as a member of the Moffitt and Caspi Lab, studying genes, environment, health, and behavior.

Reuben started with a brief history of lead exposure. After the United States’ initial use of lead in gasoline in 1923, the practice became widespread with the U.S. Public Health Services approval for expansion. Five decades later, in the mid-1970s, the Environmental Protection Agency issued the first restrictions on lead use in gasoline products. Simultaneously, surveillance of population-level blood-lead levels indicated cause for concern. Though lead was phased of out of gas completely by 1995, the peak led exposures in the 70s were on average three to four times higher than current levels that demand clinical attention. Despite lead regulations, the impacts of exposure did not miraculously cease as well.

Lead use in gasoline quickly increased after its initial introduction.

The research Reuben covered in his talk centers on the Dunedin Study. This study of 1,037 people born between April 1972 and March 1973 in Dunedin, New Zealand is an ongoing longitudinal research project comprised of over 30 years of data. The cohort of participants provide a unique chance for research in which social and economic factors do not have to be detangled from findings as they represent the full range of socioeconomic statuses in their city.

Reuben’s first question was about the impact of lead exposure on psychiatric and personality differences in adulthood. Study members were asked about symptoms such as substance dependence, depression, fears and phobias, or mania. These reports were transformed into a continuous measure of general psychopathology, which indicated that children with high lead levels experienced more psychiatric problems across adulthood. Though the developmental differences were modest, the associations between lead and psychopathological issues are of a similar magnitude to other known risk factors like childhood maltreatment and family history of mental illness. Yet, unlike the latter two risk factors, Reuben said, “Lead exposure is not preordained – it’s modifiable.”

The research team also measured participant personality using the Big Five Inventory and found that individuals with high-blood level levels as children exhibited more difficult personality styles as adults. The biggest difference between groups with high and low childhood blood-lead level was the trait of conscientiousness, which has impacts on goal obtainment within one’s education and occupation, as well as overall satisfaction with relationships.

Findings from the Big Five Inventory of Dunedin participants.

The next question of the presentation centered on differences in adulthood cognitive ability. At midlife, defined as age 38 for this question, children with higher blood-lead levels had lower cognitive ability, experiencing a deficit of two IQ points per five microgram per deciliter increase of blood-lead level. Once again, though these findings were relatively modest, the loss of IQ points was accompanied by downward social mobility compared to participants’ parents. Further, when evaluations that took place at age 45 were included in the data, researchers saw even larger declines in IQ points between exposure-level groups, which Reuben predicts may even represent a trend of acceleration. He believes that as the study continues with the participants, they will find rapid decline around age 65, with higher levels of dementia symptoms among participants compared to same-aged peers.

The last question evaluated the structural integrity of the brain at midlife. The team found that children with higher lead exposure had lower gray-matter integrity, lower white-matter integrity, and older estimated brain age at age 45. Estimated brain age was predicted by an algorithm based on MRI scans, as brains look physically different as they age and gray- and white-matter integrity refers to the conditions of physical structures in the brain. These findings suggest that childhood led exposure may result in an overall lowered brain integrity at midlife, as well as accelerated brain aging.

Reuben’s take-away findings from his presentation.

Reuben’s work is important for understanding how childhood exposure to this neurotoxin has the ability to influence continued development, behavior, emotion, and life outcomes decades later. It is crucial to evaluate long-term ramifications of childhood lead exposure – a phenomena experience by hundreds of millions of people across the globe during the era of lead in gasoline who are likely unknowingly dealing with impacts now.

Post by Cydney Livingston