Research Blog

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

Category: Neuroscience Page 1 of 11

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

Inventing New Ways to Do Brain Surgery

This is the sixth and final 2019 post written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Patrick Codd is the Director of the Duke Brain Tool Laboratory and an Assistant Professor of Neurosurgery at Duke. Working as a neurosurgeon and helping with the research and development of various neurosurgical devices is “a delicate balance,” he said.

Patrick Codd

Codd currently runs a minimally invasive neurosurgery group. However, at Massachusetts General Hospital, he used to run the trauma section. When asked about which role was more stressful, he stated “they were both pretty stressful” but for different reasons. At Mass General, he was on call for most hours of the day and had to pull long shifts in the operating room. At Duke, he has to juggle surgery, teaching, and research and the development of new technology.

“I didn’t know I was going to be a neurosurgeon until I was in college,” Codd said. Despite all of the interesting specialties he learned about in medical school, he said “it was always neurosurgery that brought me back.”

Currently, he is exclusively conducting cranial surgery.

 Neurosurgeon U.S. Air Force Maj Jonathan Forbes,looks through loupes as he performs brain surgery at the Bagram Air Field in Afghanistan, Oct. 10, 2014. 

Though Dr. Codd has earned many leadership positions in his career, he said he was never focused on advancement. He simply enjoys working on topics which he loves, such as improving minimally invasive surgical techniques. But being in leadership lets him unite other people who are interested in working towards a common goal in research and development. He has been able to skillfully bring people together from various specialties and help guide them. However, it is difficult to meet everyone’s needs all of the time. What is important for him is to be a leader when he needs to be.

Dr. Codd said there are typically five to eight research papers necessary in to lay the groundwork for every device that is developed. However, some technologies are based on the development of a single paper. He has worked on devices that make surgery more efficient and less minimally invasive and those that help the surgical team work together better. When developing technologies, he tries to keep the original purpose of the devices the same. However, many revisions are made to the initial design plans as requirements from the FDA and other institutions must be met. Ironically, Dr. Codd can’t use the devices he develops in his own operating room because it would be a conflict of interest. Typically other neurosurgeons from across the country will use them instead.

Post by Andrew Bahhouth, NCSSM 2020

Does aging make our brains less efficient?

We are an aging population. Demographic projections predict the largest population growth will be in the oldest age group – one study predicted a doubling of people age 65 and over between 2012 and 2050. Understanding aging and prolonging healthy years is thus becoming increasingly important.

Michele Diaz and her team explore the effects of aging on cognition.

For Michele Diaz, PhD, of Pennsylvania State University, understanding aging is most important in the context of cognition. She’s a former Duke faculty member who visited campus recently to update us on her work.

Diaz said the relationship between aging and how we think is much more nuanced than the usual stereotype of a steady cognitive decline with age.

Research has found that change in cognition with age cannot be explained as a simple decline: while older people tend to decline with fluid intelligence, or information processing, they maintain crystallized intelligence, or knowledge.

Diaz’s work explores the relationship between aging and language. Aging in the context of language shows an interesting phenomenon: older people have more diverse vocabularies, but may take longer to produce these words. In other words, as people age, they continue to learn more words but have a more difficult time retrieving them, leading to a more frequent tip-of-the-tongue experience.

In order to understand the brain activation patterns associated with such changes, Diaz conducted a study where participants of varying ages were asked to name objects depicted in images while undergoing fMRI scanning. As expected, both groups showed less accuracy in naming of less common objects, and the older adult group showed a slightly lower naming accuracy than the younger.

Additionally, Diaz found that the approach older adults take to solving more difficult tasks may be different from younger adults: in younger adults, less common objects elicited an increase in activation, while older adults showed less activation for these more difficult tasks.

Additionally, an increase in activation was associated with a decrease in accuracy. Taken together, these results show that younger and older adults rely on different regions of the brain when presented with difficult tasks, and that the approach younger adults take is more efficient.

In another study, Diaz and her team explored picture recognition of objects of varying semantic and phonological neighborhood density. Rather than manipulation of how common the objects presented in the images are, this approach looks at networks of words based on whether they sound similar or have similar meanings. Words that have denser networks, or more similar sounding or meaning words, should be easier to recognize.

An example of a dense (left) and sparse (right) phonological neighborhood. Words with a greater number of similar sounding or meaning words should be more easily recognized. Image courtesy of Vitevitch, Ercal, and Adagarla, Frontiers in Psychology, 2011.

With this framework, Diaz found no age effect on recognition ability for differences in semantic or phonological neighborhood density. These results suggest that adults may experience stability in their ability to process phonological and semantic characteristics as they age.

Teasing out these patterns of decline and stability in cognitive function is just one part of understanding aging. Research like Diaz’s will only prove to be more important to improve care of such a growing demographic group as our population ages.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

Predicting sleep quality with the brain

Modeling functional connectivity allows researchers to compare brain activation to behavioral outcomes. Image: Chu, Parhi, & Lenglet, Nature, 2018.

For undergraduates, sleep can be as elusive as it is important. For undergraduate researcher Katie Freedy, Trinity ’20, understanding sleep is even more important because she works in Ahmad Hariri’s Lab of Neurogenetics.

After taking a psychopharmacology class while studying abroad in Copenhagen, Freedy became interested in the default mode network, a brain network implicated in autobiographical thought, self-representation and depression. Upon returning to her lab at Duke, Freedy wanted to explore the interaction between brain regions like the default mode network with sleep and depression.

Freedy’s project uses data from the Duke Neurogenetics Study, a study that collected data on brain scans, anxiety, depression, and sleep in 1,300 Duke undergraduates. While previous research has found connections between brain connectivity, sleep, and depression, Freedy was interested in a novel approach.

Connectome predictive modeling (CPM) is a statistical technique that uses fMRI data to create models for connections within the brain. In the case of Freedy’s project, the model takes in data on resting state and task-based scans to model intrinsic functional connectivity. Functional connectivity is mapped as a relationship between the activation of two different parts of the brain during a specific task. By looking at both resting state and task-based scans, Freedy’s models can create a broader picture of connectivity.

To build the best model, a procedure is repeated for each subject where a single subject’s data is left out of the model. Once the model is constructed, its validity is tested by taking the brain scan data of the left-out subject and assessing how well the model predicts that subject’s other data. Repeating this for every subject trains the model to make the most generally applicable but accurate predictions of behavioral data based on brain connectivity.

Freedy presented the preliminary results from her model this past summer at the BioCORE Symposium as a Summer Neuroscience Program fellow. The preliminary results showed that patterns of brain connectivity were able to predict overall sleep quality. With additional analyses, Freedy is eager to explore which specific patterns of connectivity can predict sleep quality, and how this is mediated by depression.

Freedy presented the preliminary results of her project at Duke’s BioCORE Symposium.

Understanding the links between brain connectivity, sleep, and depression is of specific importance to the often sleep-deprived undergraduates.

“Using data from Duke students makes it directly related to our lives and important to those around me,” Freedy says. “With the field of neuroscience, there is so much we still don’t know, so any effort in neuroscience to directly tease out what is happening is important.”

Post by undergraduate blogger Sarah Haurin
Post by undergraduate blogger Sarah Haurin

Beyond Classroom Walls: Research as an Undergrad

“Science is slow,” says Duke undergraduate Jaan Nandwani. That’s one of the takeaways from her first experience with scientific research. For Nandwani, being part of a supportive lab makes it all worthwhile. But we’re getting ahead of ourselves. This statement needs context.

Nandwani, a prehealth sophomore, currently conducts research in the lab of neurologist Nicole Calakos, MD, PhD. The Calakos lab is focused on synaptic plasticity: changes that occur at the communication junctions between nerve cells in the brain. The lab researches how the brain responds to changes in experience. They also investigate the mechanistic mishaps that can occur with certain neurological conditions.

A neuron from a mouse brain. From Wikimedia Commons.

As a continuation of an 8-week summer research program she participated in earlier this year, Nandwani has been studying dystonia, a brain disorder that causes uncontrollable muscle contractions. She’s using western blot analysis to determine if the activity of a protein called eIF2α is dysregulated in the brain tissue of mice with dystonia-like symptoms, compared with their normal littermates. It is currently unclear if and when targeting the eIF2 signaling pathway can improve dystonia, as well as where in the brain “selective vulnerability” to the signaling occurs. If Nandwani is able to identify a specific region or time point “in which the pathway’s dysregulation is most predominant,” more effective drug therapy and pharmacological interventions can be used to treat the disorder. 

Outside of her particular project, Nandwani attends lab meetings, learning from and contributing to the greater Calakos lab community. Scientific work is highly collaborative and Nandwani’s experience is testament to that. Along with providing feedback to her own presentations in meetings and answering any questions she may have, Nandwani’s fellow labmates are always eager to discuss their projects with her, give her advice on her own work, and have helped her “develop a passion for what [she is] studying.” They’ve also helped her learn new and improved ways to conduct the western blot process that is so integral to her work. Though she admits it is tedious, Nandwani said that she enjoys being able to implement better techniques each time she conducts the procedure. She also says she is thankful to be surrounded by such a supportive lab environment.

It might seem hard to believe granted the scope and potential impacts of her work, but this is Nandwani’s first experience with research in a lab. She knew when coming to Duke that she wanted to get involved with research, but she says that her experience has surpassed any expectations she had – by far. Though she doesn’t necessarily foresee continuation of research in the form of a career and is more fascinated by clinical applications of scientific research, the experience cannot be replicated within a classroom setting. Beyond the technical skills that Nandwani has developed, she says that the important and valuable mentoring relationships she has gained simply couldn’t be obtained otherwise.

Duke undergraduate Jaan Nandwani doing research in the Calakos lab.

Nandwani hopes to continue in the Calakos lab for the remainder of her time at Duke – that’s two and a half more years. Though she will work on different projects, the quest to pose and answer scientific questions is endless – and as Nandwani said, science is slow. The scientific process of research takes dedication, curiosity, collaboration, failure, and a continued urge to grow. The scientific process of research takes time, and lots of it. Of course the results are “super exciting,” Nandwani says, but it is the experience of being part of such an amazing group of scholars and scientists that she values the most.

By Cydney Livingston

Researchers Urge a Broader Look at Alzheimer’s Causes

Just about every day, there’s a new headline about this or that factor possibly contributing to Alzheimer’s Disease. Is it genetics, lifestyle, diet, chemical exposures, something else?

The sophisticated answer is that it’s probably ALL of those things working together in a very complicated formula, says Alexander Kulminski, an associate research professor in the Social Science Research Institute. And it’s time to study it that way, he and his colleague, Caleb Finch at the Andrus Gerontology Center at the University of Southern California, argue in a recent paper that appears in the journal Alzheimer’s and Dementia, published by the Alzheimer’s Association.

Positron Emission Tomography scan of a brain affected by cognitive declines . (NIH)

“Life is not simple,” Kulminski says. “We need to combine different factors.”

“We propose the ‘AD Exposome’ to address major gaps in understanding environmental contributions to the genetic and non-genetic risk of AD and related dementias,” they write in their paper. “A systems approach is needed to understand the multiple brain-body interactions during neurodegenerative aging.”

The analysis would focus on three domains, Kulminski says: macro-level external factors like rural v. urban, pollutant exposures, socio-economcs; individual external factors like diet and infections; and internal factors like individual microbiomes, fat deposits, and hormones.

That’s a lot of data, often in disparate, broadly scattered studies. But Kulminski, who came to Duke as a physicist and mathematician, is confident modern statistics and computers could start to pull it together to make a more coherent picture. “Twenty years ago, we couldn’t share. Now the way forward is consortia,” Kulminski said.

The vision they outline in their paper would bring together longitudinal population data with genome-wide association studies, environment-wide association studies and anything else that would help the Alzheimer’s research community flesh out this picture. And then, ideally, the insights of such research would lead to ways to “prevent, rather than cure” the cognitive declines of the disease, Kulminsky says.  Which just happens to be the NIH’s goal for 2025.

An Undergraduate Student Grapples with Morality

Existential speculations are normal part of college, and parents shouldn’t worry too much if their child calls home freshman year to speculate on the writings of Immanuel Kant or Sigmund Freud with them. It’s all part of growing up.

But for Shenyang Huang (C’20), these existential questions aren’t just pastimes: They’re work.

As a neuroscience major and a participant in Duke’s Summer Neuroscience Program, Huang has spent eight weeks of his summer in the Imagination and Modal Cognition laboratory researching under Dr. Felipe De Brigard, a three-in-one professor of philosophy, psychology, and neuroscience. Huang has been working at the intersection of those fields with PhD student Matt Stanley to explore some hefty questions about morality and memory.

Shenyang Huang is a rising senior Neuroscience student at Duke. (Image provided by Huang)

The team is grappling with our past mistakes, and how they’ve impacted who we are today. Specifically, how do we remember moments when we behaved immorally? And how do those moments shape the way we think of ourselves?

These questions have been approached from various angles in different studies. One such study, published in 2016 by Maryam Kouchaki and Frencesca Gino, claims that “Memories of unethical actions become obfuscated over time.” Or rather, we forget the bad things we’ve done in the past. According to their study, it’s a self-preservation method for our current concepts of self-worth and moral uprightness.

“I was surprised when I read the Kouchaki and Gino study,” Huang explains. “They claim that people try to forget the bad things they’d done, but that doesn’t feel right. In my life, it’s not right.”

In their two-part study, Stanley and Huang surveyed nearly 300 online participants about these moments of moral failure. They reported memories ranging from slightly immoral events, like petty thievery and cheating on small assignments, to highly immoral incidences, like abusing animals or cheating on significant others. Through questionnaires, the team measured the severity of each incident, how vividly the person recollected the experience, how often the memory would bubble to consciousness on its own, how they emotionally responded to remembering, and how central each event was to the subject’s life.

Their preliminary results resonate more with Huang: Highly immoral actions were recalled more vividly than milder transgressions, and they were generally considered more central in subjects’ life narratives.

“Moral memories are central to one’s sense of self,” Huang says, “and the other paper didn’t discuss centrality in one’s life at all.”

Felipe DeBrigard is an assistant professor of philosophy and a member of the Duke Institute for Brain Sciences. (Les Todd, Duke Photo)

Though contradictory to what Kouchaki and Gino found, the findings have a firm foundation in current psychology literature, De Brigard says. “There are a lot of studies backing the contrary [to Kouchaki and Gino], including research on criminal offenses. People who have committed crimes of passion are known to suffer from a kind of moral PTSD — they constantly relive the event.”

Huang’s study is only one branch of research in a comprehensive analysis of morality and memory De Brigard is exploring now, with the help from the six graduate and eight undergraduate students operating out of his lab.

“Working in a lab with philosophers, psychologists, and neuroscientists, you see different approaches to the same overarching problem,” Huang says. And as he begins to consider PhD programs in neuroscience, this interdisciplinary exposure is a huge asset.

“It’s helpful and inspiring — I can’t take every class, but I can sit and overhear conversations in the lab about philosophy or psychology and learn from it. It widens my perspective.”


by Vanessa Moss

How Many Neuroscientists Does it Take to Unlock a Door?

Duke’s Summer Neuroscience Program kicked off their first week of research on June 4 with a standard morning meeting: schedules outlined, expectations reiterated, students introduced. But that afternoon, psychology and neuroscience professor Thomas Newpher and undergraduate student services coordinator Tyler Lee made the students play a very unconventional get-to-know-you game — locking them in a room with only one hour to escape.

Not the usual team building activity: Students in Duke’s 8-week Summer Neuroscience Program got to know each other while locked in a room.

Bull City Escape is one of a few escape rooms in the Triangle, but the only one to let private groups from schools or companies or families to come and rent out the space exclusively. Like a live-in video game, you’re given a dramatic plot with an inevitably disastrous end: The crown jewels have been stolen! The space ship is set to self-destruct! Someone has murdered Mr. Montgomery, the eccentric millionaire! With minutes to go, your rag-tag bunch scrambles to uncover clues to unlock locks that yield more clues to yet more locks and so on, until finally you discover the key code that releases you back to the real world.

This summer’s program dips into many subfields, in hopes of pushing the the 16 students (most of them seniors) toward an honors thesis. According to Newpher, three quarters of the senior neuroscience students who participated in the 2018 SNP program graduated with distinction last May.

From “cognitive neuro” that addresses how behavior and psychology interacts with your neural network, to “translational neuro” which puts neurology in a medical context, to “molecular and cellular neuro” that looks at neurons’ complex functions, these students are handling subjects that are not for the faint of heart or dim of mind.

But do lab smarts carry over when you’re locked in a room with people you hardly know, a monitor bearing a big, red timer, blinking its way steadily toward zero?

Apparently so. The “intrepid team of astronauts” that voyaged into space were faced with codes and locks and hidden messages, all deciphered with seven minutes left on the clock, while the “crack-team of detectives” facing the death of Mr. Montgomery narrowly escaped, with less than a minute to spare. At one point, exasperated and staring at a muddled bunch of seemingly meaningless files, a student looked at Dr. Newpher and asked, “Is this a lesson in writing a methods section?”

The Bull City Escape website lists creative problem-solving, focus, attention to detail, and performance under pressure as a few of the skills a group hones by playing their game — all of which are relevant to this group of students, many of whom are pre-med. But hidden morals about clarity and strength-building aside, Newpher picked the activity because it allows different sides of people’s personalities to come out: “When you’re put in that stressful environment and the clock is ticking, it’s a great way to really get to know each other fast.”

By Vanessa Moss
By Vanessa Moss

Page 1 of 11

Powered by WordPress & Theme by Anders Norén