Following the people and events that make up the research community at Duke

Category: Neuroscience Page 1 of 12

Learning Something Surprising About “SuperLearners”

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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

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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.

The 2019-2020 team, pre-COVID.

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

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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.

Post by Anna Gotskind

Duke Junior Mixes Memory Research with Criminal Justice Reform

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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

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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

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

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.

Aaron Reuben

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

Predictive maps in the brain

How do we represent space in the brain? Neuroscientists have been working to understand this question since the mid-20th century, when researchers like EC Tolman started experimenting with rats in mazes. When placed in a maze with a food reward that the rats had been trained to retrieve, the rats consistently chose the shortest path to the reward, even if they hadn’t practiced that path before.

Sam Gershman is interested in how we encode information about our environments.

Over 50 years later, researchers like Sam Gershman, PhD, of Harvard’s Gershman Lab are still working to understand how our brains encode information about space.

Gershman’s research questions center around the concept of a cognitive map, which allows the brain to represent landmarks in space and the distance between them. He spoke at a Center for Cognitive Neuroscience colloquium at Duke on Feb. 7.

Maps are formed via reinforcement learning, which involves predicting and maximizing future reward. When an individual is faced with problems that have multiple steps, they can do this by relying on previously learned predictions about the future, a method called successor representation (SR), which would suggest that the maps we hold in our brain are predictive rather than retroactive.

One specific region implicated in representations of physical space is the hippocampus, with hippocampal place cell activity corresponding to positions in physical space. In one study, Gershman found, as rats move through space, that place field activity corresponding to physical location in space skews opposite of the direction of travel; in other words, activity reflects both where the rodent currently is and where it just was. This pattern suggests encoding of information that will be useful for future travel through the same terrain: in Gershman’s words, “As you repeatedly traverse the linear track, the locations behind you now become predictive of where you are going to be in the future.”

Activation patterns in place cells correspond to both where the animal is and where the animal just was, pointing to the construction of a predictive map during learning. Graphic courtesy of Stachenfield et al., 2017.

This idea that cognitive activity during learning reflects construction of a predictive map is further supported by studies where the rodents encounter novel barriers. After being trained to retrieve a reward from a particular location, introducing a barrier along this known path leads to increased place cell activity as they get closer to the barrier; the animal is updating its predictive map to account for the novel obstacle.

This model also explains a concept called context preexposure facilitation effect, seen when animals are introduced to a new environment and subsequently exposed to a mild electrical shock. Animals who spend more time in the new environment before receiving the shock show a stronger fear response upon subsequent exposures to the box than those that receive a shock immediately in the new environment. Gershman attributes this observation to the time it takes the animal to construct its predictive map of the new environment; if the animal is shocked before it can construct its predictive map, it may be less able to generalize the fear response to the new environment.

With this understanding of cognitive maps, Gershman presents a compelling and far-reaching model to explain how we encode information about our environments to aid us in future tasks and decision making.

Brain networks change with age

Graph theory allows researchers to model the structural and functional connection between regions of the brain. Image courtesy of Shu-Hsien Chu et al.

As we age, our bodies change, and these changes extend into our brains and cognition. Although research has identified many changes to the brain with age, like decreases in gray matter volume or delayed recall from memory, researchers like Shivangi Jain, PhD, are interested in a deeper look at how the brain changes with age.

Shivangi Jain uses graph theory to study how the brain changes with age.

As a post-doctoral associate in the David Madden Lab at Duke, Jain is interested in how structural and functional connectivity in the brain change with age. Jain relies on the increasingly popular method of graph theory, which is a way of modeling the brain as a set of nodes or brain regions that are interconnected. Studying the brain in this way allows researchers to make connections between the physical layout of the brain and how these regions interact when they are active. Structural connectivity represents actual anatomical connections between regions in the brain, while functional connectivity refers to correlated activity between brain regions.

Jain’s studies use a series of tasks that test speed, executive function, and memory, each of which decline with age. Using fMRI data, Jain observed a decline in functional connectivity, where functional modules become less segregated with age.  In terms of structural connectivity, aging was associated with a decline in the strength of white matter connections and global efficiency, which represents the length between modules with shorter paths being more efficient. Thus, the aging brain shows changes at the anatomical, activational, and behavioral levels.

Jain then examined how these network-level changes played a role in the observed behavioral changes. Using statistical modeling, she found that the decline in performance in tasks for executive control could be explained by the observed changes in functional connectivity. Furthermore, Jain found that the changes in structural connectivity caused the change in functional connectivity. Taken together, these results indicate that the physical connections between areas in the brain deteriorate with age, which in turn causes a decrease in functional connectedness and a decline in cognitive ability.

Research like Jain’s can help explain the complicated relationships between brain structure and function, and how these relationships affect behavioral output.

Post by undergraduate blogger Sarah Haurin
Post by Sarah Haurin

Visual Perception in Congenitally Blind Adults

Vision provides a rich source of information that most people’s lives revolve around. Yet, for blind people, how do they conceive of visual intake and what happens to regions of the brain dedicated to vision if a person doesn’t have typical visual input? These are questions that drive Marina Bedny PhD, an Assistant Professor of Psychological and Brain Sciences and principal investigator of a neuroplasticity and development lab at John Hopkins University.

Bedny spoke at Duke’s Institute for Brain Sciences on Friday, January 17th, about her work with congenitally blind adults. Her lab explores similarities and distinctions of visual perceptions between blind and seeing people and seeks to understand how nuanced, natural variation in experience shapes the human mind and brain.

Many of the studies Bedny discussed have very important linguistic components. In one trial, she investigated the meaning of verbs pertaining to light events and visual perception as compared to touch, amodal, auditory, and motion verbs.

Both blind and sighted people displayed nearly identical results when comparing the different types of verbs used in the study. This showed that there were no differences in what blind people knew about the terms. Analysis of the verbs revealed that linguistic dimensions of intensity and instability were used to evaluate the words’ comparative meanings. Blind people agreed more on the comparison of sound emission and touch perception words. This shows that blind participants have more aligned comprehension of the meanings of other sensory terms compared to sighted people.

In other cases, Bedny’s lab assessed what blind individuals know about color. One study used three object types – natural kinds, functional artifacts, and non-functional artifacts. These categories were used to evaluate agreeance not only on color, but the relevancy of color to certain objects’ functions as well.

Another crucial question of Bedny’s work looks at how the innate structure of the brain constrains cortical function. The findings show that the visual system in blind participants has been repurposed for higher cognitive functions and that portions of the visual system connected to high cognitive abilities are invaded by the visual systems. Along with repurposing visual regions for linguistic use, Bedny’s lab found that visual regions of the brain are active during numerical processing tasks too.

Blind people display additional activity in the visual centers of their brain in numerous studies beyond having the same regional brain responsiveness as sighted people. Though further research is necessary, Bedny proposes that there is a sensitive period during development that is critical to the specialization of the brain. Study participants who have adult-onset blindness do not show the same sensitivity and patterned responses in visual cortices repurposed for different functions as congenitally blind subjects.

At birth, the human cortex is pluripotent – providing the best of both worlds, Bedny said. The brain is prepared but highly flexible. Her studies have repeatedly shown that the brain is built for and transformed by language, and they underscore the importance of nature and nurture in human development.

Post by Cydney Livingston

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