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.
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.
“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.
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.
Chances are, you’ve heard about survival of the fittest. But what about survival of the friendliest? While we often think that the strongest, meanest, and most powerful organisms often prevail as the most fit, it seems that friendship bears the real evolutionary winners.
In the history of evolution, friendliness often proceeds unusual evolutionary success, meaning that friendly species prevail over time. Hare and Woods are uncovering critical factors for why this pattern emerges in their research. For the context of their work, Woods defined friendliness as anything that is mutually beneficial between organisms. Their questions and investigation were first centered around dogs.
“Where did dogs come from?” Hare said. This poses a really “fascinating evolutionary problem.” Prior research shows that dogs first originated 15,000-25,000 years ago, delineated from wolves. But why? Dogs have become one of the “top two or three most successful animals,” while wolves have nearly gone extinct.
The answer to their evolution and their success is found in friendliness. “Dogs have remarkable social genius,” Hare said, they are able to understand communicative gestures and in return communicate with humans in a way that not even one of our closet genetic relatives, the Bonobo, can. This evolutionary selection for friendliness drove the stark contrasts seen between dogs and wolves today, fundamentally changing dogs’ physical shapes and forms along with their psychology. The same pattern of genetic inheritance encoding for inclination to cooperate also changes much of a species morphology in signature ways.
Hare and Woods ventured to Siberia to analyze the findings of an experiment pertaining to fox behavior that has been ongoing since it was first set up by a Russian geneticist in 1959. One group of foxes has experienced randomly selected mating, while the other group of foxes has been artificially shaped by manmade selection for the friendliest foxes.
When they compared the long-term results of decades separate population changes, Hare and Woods found the friendlier foxes had shorter faces, different colorations, curlier tails, and smaller canines. These are the same factors used by archaeologists to distinguish dogs from wolves. The morphological and physiological changes for niceness are synonymous across the two species.
They have also found a similar pattern in humans. Our species as not alone on the planet when it first evolved, said Hare: We shared the planet with approximately four other Hominids who also had big brains, cultural artifacts, and linguistic abilities like we do. “There had to be something in addition to those traits that allowed our species to survive while others went extinct.” He proposes survival of the friendliness and the development of different physical characteristics.
In a study comparing modern humans to archaic ones, Hare and Woods found that modern humans have traits like much smaller brow ridges and narrower, shorter faces – what you would expect to see, based on the fox model from their work in Siberia that also helped explain the evolution of dogs. Our white sclera – the white part of your eye – acts as our “curly tail.” The white tissue likely has been selected for with the development of our other friendly features, as we are the only primate whose sclera is light, which makes communication by glance easier.
If we are the friendliest, Woods asked, then why are we capable of such cruelty and malice? Even though we are extremely friendly to in-group strangers, when our in-group is threatened, we are prepared to defend them against out-group strangers.
“We are all capable of dehumanization when we feel that the group that we love … is threatened,” Woods said. This is a model they are referring to as the mother bear hypothesis: A mother bear is most patient when she is dealing with her cubs, but most angry when another organism threatens her offspring.
The number one predictor of dehumanization is the feeling that your own group or identity is being dehumanized, and in those moments, the same part of the brain that enables cooperative communication shuts down and is dampened.
The duo cited cross-group friendships, democracy, and our perception of other animals as important factors for offsetting dehumanization in the human species. Cross-group friendships provide a bridge of empathy, democracy contributes to collective group identity and decisions, and our perceptions of other animals limit dehumanization when we have an ecological view of our relation to other species rather than a top-down, human-centric approach.
“You have to understand what was wrong about the past but not blind yourself to what you do find,” Woods said when asked about the dark history of morphology-based pseudo-sciences that prompted racial persecutions. This is something that the pair reckons with for a whole chapter in their book.
“You can see in our faces the faces of friendliness,” Hare said.
May we all lean into this niceness after encountering Hare and Woods work. It’s gotten us this far, and it seems particularly vital for our collective future.
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.
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.
Creighton, who has an MS in exercise physiology and has spent her career involved in clinical research and community health at both UNC-Chapel Hill and Duke, has spinocerebellar ataxia, a hereditary neurodegenerative condition characterized by a lack of muscle coordination. The illness is commonly visible through slurred speech, stumbling, falling, and incoordination due to damage to the cerebellum – the part of the brain that controls muscle coordination.
As Creighton described, prior to writing her book in her late forties, she hadn’t successfully communicated to anyone the impact of ataxia on her life. And so, her memoir was organically born, but as Creighton says, “it was hard for me to type as fast as I was thinking, and that lasted for several months.”
It took Creighton a couple of years just to write the foundation of the book, which draws on neuroplasticity research, personal memories, and medical records to highlight the importance of storytelling in deriving meaning from illness. She spent the next two years after that re-shaping the arc, drawing on a wealth of her own experiences as well as decades of journaling that had left her with a meticulous set of notes.
As both Creighton and Dr. Mantri emphasized, writing is a deeply cathartic exercise as well as a way to share significant personal narratives. This is especially true in a field such as medicine, where people are so often treated as an illness or statistic rather than a human being.
While the recognition of patient and doctor narratives has been around for many years, it was not until fairly recently that narrative medicine emerged as a field of knowledge that doctors could educate themselves in.
Dr. Mantri is familiar with the benefits of narrative medicine from a clinical perspective, holding an M.S in Narrative Medicine from Columbia University and being a leader of various narrative medicine initiatives at Duke, both with doctors and medical students.
According to Dr. Mantri, elucidating these narratives is crucial to understanding that at the end of the day, doctors and patients work to navigate challenges of illnesses with different perspectives. It’s necessary to hear the story of a patient as well as understand the story of a clinician. Only then can doctors work to find moments of alignment between these two perspectives, resulting in care that is more patient-centered.
From the patient perspective, Creighton remarks that a chapter in her book delves into narrative medicine, even though at the time she had no idea what it was. As she learned more about the field, though, it became clear just how integral narrative medicine was to her experience processing and coming to terms with her ataxia. Prior to taking a class on narrative medicine, she assumed that it wouldn’t be a positive experience. But years later, she credits the process of writing her memoir with allowing her to move on, in many ways, from the hold her illness had on her.
Creighton also pointed out that as humans, “we want the same things – to feel heard and to make meaningful connections with others who can potentially help us navigate whatever condition we’re going through.”
To that end, Dr. Mantri and Creighton both referred to several resources that can help people with illnesses find communities of other individuals with the same illness, in order to find the type of solidarity and understanding promoted by sharing experiences. One such resource is PatientsLikeMe, where individuals can ask questions and exchange tips on their specific illness with others going through similar struggles.
Finally, Creighton was asked about the things she’d like clinicians to know from her perspective as a patient. She described the disconnect that she had often felt, not only with doctors but with therapists and counselors, stemming from a feeling that the help she was offered often did not meet her where she was. In brainstorming ways to mitigate this gap, both Dr. Mantri and Creighton pointed to a need for doctors to focus on a patients’ needs and desires, and a need for patients to advocate for themselves.
As the conversation concluded, Creighton emphasized the importance of being seen as a human rather than a victim of a disease. Spinocerebellar ataxia is neurodegenerative, meaning that symptoms progressively get worse. But as Creighton remarked: “Losing my abilities is going to happen. Losing my abilities doesn’t change the human that I am.”
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.
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.
“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.
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.
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.
We are still in the midst of an opioid epidemic. In 2019, an average of six North Carolinians died each day from unintentional medication or drug overdose. A striking 79% of drug overdose deaths in NC in 2018 involved opioids. This has garnered attention from many organizations and institutions in the state and prompted new concerns relating to patient-centered care.
A Duke Global Health discussion on March 17 concluded that the social response can be aided by a refined focus on mental health, as well as the use of telehealth – the delivery of health care and education remotely through various technologies.
Moderated by Brandon Knettel (Ph.D.), the Duke Global Health Institute panel considered treatment, community engagement, and public policy in addressing the opioid epidemic with panelists Nidhi Sachdeva (MPH), Padma Gulur (M.D.) Hilary Campbell (PharmD, J.D.), and Theresa Coles (Ph.D.)
Sachdeva is a Senior Research Program Leader with the Department of Population Health Sciences at Duke Medical School. Dr. Gulur is a Professor of Anesthesiology and Population Health with Duke Medical School and Executive Vice Chair of the Pain Management and Opioid Surveillance with Duke University Health System. Campbell is director of Sheps Health Workforce Health Professions Data System at UNC-Chapel Hill. Coles is Assistant Professor in Population Health Sciences with Duke Medical School.
Sachdeva opened the panel with a discussion of the Duke Opioid Collaboratory. The Collaboratory currently houses 25 different projects relating to improving data surveillance, health system quality, and public health in the realm of research on opioids.
“We’re losing more and more folks every day,” said Sachdeva. Duke’s projects represent a systems approach to the opioid epidemic, meaning there is lots of valuable overlap and connectivity between projects, and external partnerships that have provided a unique opportunity for academic and community collaboration.
Dr. Gulur stated that Duke Health has seen improvements in opioid use and prescription over the last five to six years: the ambulatory prescribing rate has gone down, fewer patients are requiring high-dose opioids overall, and there has been significant increase in availability to offer medication-assisted treatment for opioid use disorder. Like Sachdeva, Gulur’s work with Duke’s Pain Management and Opioid Surveillance exists within a larger network of organizations dedicated to the opioid issue.
“We have a very committed and collaborative infrastructure with [other] initiatives in the state,” said Gulur, who added that she is dedicated to making “sure we have all the voices at the table.”
Simply decreasing opioid prescriptions “doesn’t necessarily work” and solving this issue will not be a quick fix. Campbell said that her own research found that at the same time the “supply side” of opioids was shrinking, the state was “seeing the crisis getting worse.”
Enter telehealth and the need for expanded support to mental health resources. Coles explained their pertinence through discussion of her work with Granville-Vance Public Health. Coles has been working on an expanding project that assesses training, operational challenges, patient centered goals, and success from the patient’s perspective within Granville-Vance’s opioid program.
Coles found that inconsistent funding lead to lapses in access to mental health support and the “dropout of someone there to help [with behavioral health] was challenging for patients.” Telehealth bridges the gaps of inconsistent access. Further, in the case of Coles’ study, it also played a large role in increased access for patients who experienced transportation issues since the investigation took place in conjunction to Covid-19, which lowered patients’ abilities to physically attend the program in-person.
Because “no one person experiences opioid abuse … in a vacuum,” as Sachdeva said, it is important to get a comprehensive “assessment of what a person’s life looks like and their priorities for treatment” before jumping into treatment.
Though the last year living under the Covid-19 pandemic has been difficult for the entire globe, the increased need for access to resources through the internet and various technologies has been positively reinforced. With new understandings of relationships to others and limited physical access to in-person healthcare, telehealth has emerged as a means to resolve decreased access. It can also serve as a way to expand access for populations who have historically suffered from inadequate access to healthcare resources, like rural populations.
Opioids “have and will continue to play a role in pain management,” Dr. Gulur said. However, better efforts to involve patients and their families in decision making around opioids, as well as more fully informed understandings of the potential risks and side effects, is necessary for centering patient priorities in care management.
Sachdeva emphasized a “nothing about us without us” philosophy for approaching the opioid epidemic. This means that the systems of care being changed to address opioid crises must depend directly on people who use opioids. It is important to center “lived experience through the whole thing.” Because each community is different, it is inadequate to make assumptions about “what a community is, what it might need, or what its story is.”
Underlying this work is a question from Dr. Gulur, “What are you trying to treat?”
To treat the opioid epidemic, we need to treat people as complex, multi-dimensional people living complicated lives. Opioid use is only one facet of this narrative, making it pertinent to understand the rest of the story to adequately tackle this problem our nation faces. Mental health and access to care are central to this collective narrative more largely.
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.
“Research is a slow iterative process and it rarely ever works how you expect it to.”
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.”
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.”
Two Covid vaccines have been approved via Emergency Use Authorizations. But, many scientists, health professionals, and regulatory members alike are left wondering how to best ensure the American and global public opt-in to getting vaccinated.
Dr. Fauci has become a household name this year as a member of the White House Coronavirus Task Force but is more widely regarded as one of the most trusted U.S. medical figures and has been director of the National Institute of Allergy and Infectious Disease since 1984.
Mr. Alda, though popularized through his acting career, has been a life-long advocate for science. He hosted PBS show “Scientific American Frontiers,” founded the Alan Alda Center for Communicating Science at SUNY Stony Brook, and recently released a podcast titled “Soldiers of Science.” At Stanford, Mr. Greely is director for the Center for Law and Biosciences and the Program in Neuroscience and Society, as well as a Professor of Law.
Greely asked about the public’s current level of trust for science and what must be done to get it “where it should be.” Alda said that there “seems to be this awful fall off of trust in science … at the worst possible time.” But Dr. Fauci pointed out that we have seen the evolution of lack of trust in science over the previous couple of years. The pandemic fell in the middle of extreme American divisiveness, he said, leading to individuals “developing their own set of facts instead of interpreting [actual] data that exists.”
Alda and Fauci both emphasized the need for transparent and clear scientific communication as a main tactic for increasing public faith in science. This includes use of the words “I don’t know,” particularly in response to the question of vaccine longevity, a question Dr. Fauci said will be answered “in due time.”
Alda said scientific communicators should “communicate with audience[s] with respect … with personal contact where trust builds up more quickly.” He pointed out that this means communicators must become more familiar with their audiences, what terms would be best to use, and what their audiences are “ready to hear.” Dr. Fauci added that when someone is “speaking science” to any group, the objective should not be to “impress the [audience] as to how smart [they] are.” The two major objectives laid out by Fauci: 1) Know the audience and 2) know your message, avoiding granularity and inaccessible language.
Greely interjected that the though all three panelists agree on trust in science, they were three white guys “of mature years.” He continued to say that, “One of the saddest ironies [is that] people getting hammered hardest by [Covid] tend to be people from racial and ethnic minorities … those are also [the same] groups of people that have understandable historic reasons to have less trust [in scientific agencies].” How do we reach these groups?
To do this, Dr. Fauci proposed that we need to get messengers for vaccination to “to look like and understand to whom [we] we are delivering the message.” Leaning into an idea by Alda – that we should get celebrities and widely-respected and admired individuals to get vaccinated on television – Fauci described how Surgeon General Jerome Adams got publicly vaccinated Friday morning.
Adams also delivered a message to his “Black and Brown sisters and brothers” in support of vaccination. Dr. Fauci believes more positive messaging like this will be effective. Alda reinforced that “we can’t guess about the people we’re trying to talk to.” We have to know about their biases and cause for hesitancy in order to meet them where they are, as well as address their concerns in genuine, non-condescending ways.
Alda also proposed that individuals snap a quick shot of themselves getting vaccinated and post it to social media as a #vaccie – a play on the #selfie sensation – which Greely said was “brilliant.”
Alda and Fauci concurred that the most powerful proponents of restoring faith in science may lie in the impact of individual civilians who share their trust in and compliance with vaccination amongst family and friends. Fauci said individuals should not “underestimate the impact that they have in their own immediate environment.”
This impact could be either positive or negative, though, as Alda pointed out the problem with social media algorithms. While working on “Soldiers of Science,” he learned that social media sites are designed to “keep your eyeballs on the screen” as long as possible. This means that social media sites keep “showing you what you want to see,” which is your own bias and affirmation that your ideas are correct. If #vaccie starts trending, this might provide necessary momentum for widescale vaccine uptake.
However, because we have become “addicted to [our] bias” and convinced “over and over again that only our view is right,” according to Alda, we must work intentionally to see commonalities across seemingly alienating lines. Reflecting on his work with AIDS, Dr. Fauci suggested that we take what scientific communicators and regulatory bodies learned during that time. “What do we all want?” Fauci said, ”And how do we get there in a way that is synergistic [instead of] opposing?”
In his parting thoughts, Alda stated simply that “science will save us.” It has and will continue to allow us to “counterattack the attacks we get from our mother nature.” Dr. Fauci said that in dealing with the current pandemic, “biomedical research and science has given us something that just a decade ago would have seemed unimaginable.”
“When this is over, and it’s going to be over,” Fauci said, “We’re [going to] look back and say, ‘It was science that got us out of this, pure science.’”
Greely said we have learned a lot about science communication this year – invaluable information that we must carry forward with us.
I, like so many others around the world, can’t wait for my turn to get the Covid vaccine and to kiss 2020 and the pandemic goodbye.
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.”