Brain Makes Order From Disorder

A team of scientists from Duke, the National Institutes of Health and Johns Hopkins biomedical engineering has found that the formation and retrieval of new memories relies on disorganized brain waves, not organized ones, which is somewhat contrary to what neuroscientists have previously believed. Brain waves, or oscillations, are the brain’s way of organizing activity and are known to be important to learning, memory, and thinking.

Alex Vaz is a Duke MD/PhD student and biomedical engineering alumnus.

Although brain waves have been measured and studied for decades, neuroscientists still aren’t sure what they mean and whether or not they help cognition, said Alex Vaz, an M.D.-Ph.D. student at Duke who is the first author on the paper.

In a study appearing Jan. 6 in NeuroImage, the neuroscientists showed that brain activity became less synchronized during the formation and retrieval of new memories. This was particularly true in a brain region known as the medial temporal lobe, a structure thought to play a critical role in the formation of both short-term and long-term memories

Excessive synchronization of brain oscillations has been implicated in Parkinson’s disease, epilepsy, and even psychiatric disorders. Decreasing brain wave synchronization by electrical stimulation deep in the brain has been found to decrease the tremors of Parkinson’s. But the understanding of brain waves in movement disorders is ahead of the understanding of human memory.

The researchers had neurosurgeons at the National Institutes of Health implant recording electrodes onto the brain surface of 33 epileptic patients during seizure evaluation and then asked them to form and retrieve memories of unrelated pairs of words, such as ‘dog’ and ‘lime.’

They found that  during memory formation, brain activity became more disorganized in the frontal lobe, an area involved in

A graphical abstract from Alex’s paper.

executive control and attention, and in the temporal lobe, an area more implicated in memory and language.

“We think this study, and others like it, provide a good starting point for understanding possible treatments for memory disorders,” Vaz said. “The aging American population will be facing major neurocognitive disorders such as Alzheimer’s disease and vascular dementia and will be demanding more medical attention.”

CITATION: “Dual origins of measured phase-amplitude coupling reveal distinct neural mechanisms underlying episodic memory in the human cortex,” Alex P. Vaz, Robert B. Yaffe, John H. Wittig, Sara K. Inati, Kareem A. Zaghloul. NeuroImage, Online Jan. 6, 2017. DOI: 10.1016/j.neuroimage.2017.01.001

http://www.sciencedirect.com/science/article/pii/S1053811917300010

Post by Karl Leif Bates

Karl Leif Bates

Rooftop Observatory Tracks Hurricane Rain and Winter Snow

Jonathan Holt replaces the protective cover over the rain gauge.

Jonathan Holt replaces the protective cover over the rain gauge.

On Friday night, while most of North Carolina braced against the biting sleet and snow with hot cocoa and Netflix, a suite of research instruments stood tall above Duke’s campus, quietly gathering data on the the storm.

The instruments are part of a new miniature cloud and precipitation-monitoring laboratory installed on the roof of Fitzpatrick CIEMAS by graduate student Jonathan Holt and fellow climate researchers in Ana Barros’s lab.

The team got the instruments up and running in early October, just in time for their rain gauge to register a whooping six inches of rain in six hours at the height of Hurricane Matthew — an accumulation rate comparable to that of Hurricane Katrina when it made landfall in Mississippi. Last weekend, they collected similar data on the winter storm, their Micro Rain Radar tracking the rate of snowfall throughout the night.

The rooftop is just the latest location where the Barros group is gathering precipitation data, joining sites in the Great Smokies, the Central Andes of Peru, and Southern Africa. These three instruments, with a fourth added in early January, are designed to continuously track the precipitation rate, the size and shape of raindrops or snow flakes – which climatologists collectively dub hydrometeors — and the formation and height of clouds in the air above Duke.

Ana Barros, a professor of civil and environmental engineering at Duke, says that her team uses these field observations, combined with atmospheric data from institutions like NOAA and NASA, to study how microscopic particles of dust, smoke, or other materials in the air called aerosols interact with water vapor to form clouds and precipitation. Understanding these interactions is a key prerequisite to building accurate weather and climate models.

“What we are trying to do here is to actually follow the lifecycle of water droplets in the air, and understand how that varies depending on weather systems, on conditions, on the climatic region and the location on the landscape,” Barros said.

A distrometer on the roof of Fitzpatrick CIEMAS.

A laser beam passing between the two heads of the distrometer detects the numbers and sizes of passing raindrops or snowflakes.

Besides tracking dramatic events like Matthew, Barros says they are also interested in gathering data on light rainfall, defined as precipitation at a rate of less than 3 mm of an hour, throughout the year. Light rainfall is a significant source of water in the region, comprising about 35 percent of the annual rainfall. Studies have shown that it is particularly prone to climate change because even modest bumps in temperature can cause these small water droplets to evaporate back to gas.

Eliminating this water source, “is not a dramatic change,” Barros said. “But it is one of those very important changes that has implications for how we manage water, how we use water, how we design infrastructure, how we have to actually plan for the future.”

Barros says she is unaware of any similar instrument suites in North Carolina, putting their rooftop site in position to provide unique insights about the region’s climate. And unlike their mountainous field sites, instruments on the roof are less prone to being co-opted by itchy bears.

“When we can gather long term rain gauge data like this, that puts our research group in a really unique position to come up with results that no one else has, and to draw conclusions about climate change that no one else can,” Holt said. “It is fun to have a truly unique perspective into the meteorology, hydrology and weather in this place.”

Micro Rain Radar data from Hurricane Matthew and the snowstorm on Jan. 6th.

The Micro Rain Radar (MRR) shoots radio waves into the sky where they reflect off water droplets or snowflakes, revealing the size and height of clouds or precipitation. The team collected continuous MRR data during Hurricane Matthew (top) and last Friday’s snow storm (bottom), creating these colorful plots that illustrate precipitation rates during the storms.

Kara J. Manke, PhD

Post by Kara Manke

Seeing Nano

Take pictures at more than 300,000 times magnification with electron microscopes at Duke

Sewer gnat head

An image of a sewer gnat’s head taken through a scanning electron microscope. Courtesy of Fred Nijhout.

The sewer gnat is a common nuisance around kitchen and bathroom drains that’s no bigger than a pea. But magnified thousands of times, its compound eyes and bushy antennae resemble a first place winner in a Movember mustache contest.

Sewer gnats’ larger cousins, horseflies are known for their painful bite. Zoom in and it’s easy to see how they hold onto their furry livestock prey:  the tiny hooked hairs on their feet look like Velcro.

Students in professor Fred Nijhout’s entomology class photograph these and other specimens at more than 300,000 times magnification at Duke’s Shared Material & Instrumentation Facility (SMIF).

There the insects are dried, coated in gold and palladium, and then bombarded with a beam of electrons from a scanning electron microscope, which can resolve structures tens of thousands of times smaller than the width of a human hair.

From a ladybug’s leg to a weevil’s suit of armor, the bristly, bumpy, pitted surfaces of insects are surprisingly beautiful when viewed up close.

“The students have come to treat travels across the surface of an insect as the exploration of a different planet,” Nijhout said.

Horsefly foot

The foot of a horsefly is equipped with menacing claws and Velcro-like hairs that help them hang onto fur. Photo by Valerie Tornini.

Weevil

The hard outer skeleton of a weevil looks smooth and shiny from afar, but up close it’s covered with scales and bristles. Courtesy of Fred Nijhout.

fruit fly wing

Magnified 500 times, the rippled edges of this fruit fly wing are the result of changes in the insect’s genetic code. Courtesy of Eric Spana.

You, too, can gaze at alien worlds too small to see with the naked eye. Students and instructors across campus can use the SMIF’s high-powered microscopes and other state of the art research equipment at no charge with support from the Class-Based Explorations Program.

Biologist Eric Spana’s experimental genetics class uses the microscopes to study fruit flies that carry genetic mutations that alter the shape of their wings.

Students in professor Hadley Cocks’ mechanical engineering 415L class take lessons from objects that break. A scanning electron micrograph of a cracked cymbal once used by the Duke pep band reveals grooves and ridges consistent with the wear and tear from repeated banging.

cracked cymbal

Magnified 3000 times, the surface of this broken cymbal once used by the Duke Pep Band reveals signs of fatigue cracking. Courtesy of Hadley Cocks.

These students are among more than 200 undergraduates in eight classes who benefitted from the program last year, thanks to a grant from the Donald Alstadt Foundation.

You don’t have to be a scientist, either. Historians and art conservators have used scanning electron microscopes to study the surfaces of Bronze Age pottery, the composition of ancient paints and even dust from Egyptian mummies and the Shroud of Turin.

Instructors and undergraduates are invited to find out how they could use the microscopes and other nanotech equipement in the SMIF in their teaching and research. Queries should be directed to Dr. Mark Walters, Director of SMIF, via email at mark.walters@duke.edu.

Located on Duke’s West Campus in the Fitzpatrick Building, the SMIF is a shared use facility available to Duke researchers and educators as well as external users from other universities, government laboratories or industry through a partnership called the Research Triangle Nanotechnology Network. For more info visit http://smif.pratt.duke.edu/.

Scanning electron microscope

This scanning electron microscope could easily be mistaken for equipment from a dentist’s office.

s200_robin.smith

Post by Robin Smith

Totally Tubular! Fluid forces that affect the development of biological tubes

Have you ever wondered how something as simple as fluid can impact the development of a large organism? How about the way tubes form in relation to each other? Or maybe you’ve wondered how it is possible for something as rigid as a spine to be formed from fluid?

Zebrafish embryos are relatively transparent, making them easier to study.

Zebrafish embryos are relatively transparent, making them easier to study.

Dr. Michel Bagnat and his lab work to analyze each of these questions and more in their research about how biological tubes are formed and how pressure exerted by these fluids affects the formation of these tubes.

Dr. Bagnat, an associate professor of cell biology, uses ‘forward genetics,’ a process by which genes are modified in order to see the effect and function of each gene in the organism. The technique enables them to identify and analyze the role of fluid secretion in zebrafish. Fluid secretion also plays a role in many human diseases, including cystic fibrosis and polycystic kidney disease.

The void in a blood vessel is called the lumen. Bagnat studies the cells lining the lumen.

The void in a blood vessel is called the lumen. Bagnat studies the cells lining the lumen.

One of the most interesting aspects of tubal formation is that biological tubes often form in relation to each other. Dr. Bagnat and his lab study this type of tubal formation through studying the lumen, or the thin membrane lining the intestinal tubes of zebrafish. There are many cellular mechanisms that can affect the formation of the lumen, and extensive research is conducted in order to better understand these mechanisms.

These same sorts of forces can even help build a structure as complex as the spine. Dr. Bagnat’s research covers this specific field. The notochord of zebrafish, or the scaffold which will develop into a spine, is heavily affected by the growth of vacuoles, or fluid-filled sacs in the cell. Dr. Bagnat’s research explores the deeper mechanisms behind the filling of these fluid vacuoles in cells and how each cell’s vacuole stops and starts filling with fluid.

This image of fluid-filled sacs forming a fish notochord was on the cover of a journal.

This image of fluid-filled sacs forming a fish notochord was on the cover of a journal.

Overall, Dr. Bagnat’s research holds strong implications for how we understand the development and formation of biological tubes not just in zebrafish but in our own human bodies.

Guest Post by Vaishnavi Siripurapu, North Carolina School of Math and Science, Class of 2018

bagnatselfie

 

 

 

Treating Traumatic Brain Injury

After a traumatic brain injury (TBI), the brain produces an inflammatory response. This prolonged swelling is known as cerebral edema and can be fatal. Unfortunately, the only medications available just address symptoms and cannot directly treat the inflammation.

Daniel Laskowitz

Daniel Laskowitz, M.D. M.H.S, is a professor of neurology.

Some people can walk out okay after suffering from this injury, yet others can become comatose or may even die. This raises the intriguing question: why do people with similar injuries end up with vastly different outcomes? TBI affects nearly 2 million Americans every year and nearly 52,000 of these injuries are fatal.

“To a certain extent, the way the body responds to injury is probably genetically hardwired,” said Dr. Daniel Laskowitz, a neurologist at Duke who has been working on the mysteries of traumatic brain injuries for two decades. He said in medical school, he preferred the approach of treating the whole body and not super specializing. He chose to work specifically with brain injury because he could treat patients with other conditions along with brain injury.

One of Dr. Laskowitz’s first publications was about brain injury. As a fellow training in neurology in the mid-1990s, he looked at genetic factors that could make a difference in the outcome of a brain injury and found that genetic variation in a protein called apolipoprotein E (apoE) played a role.  ApoE comes in three slightly different flavors, and one of the common forms of apoE (apoE4) was associated with bad outcomes after brain injury. This raised the question of what apoE was doing in the brain to affect outcome after injury.

In 1997, he published an article about the effect of apoE on mice suffering a stroke and found that mice with the apoE allele had a better recovery than mice with an apoE deficiency. These findings were later repeated in an article in 2001,which found that following traumatic brain injury, animals with apoE had better outcomes than animals without this protein.

Since it was found that apoE could improve an injured patient’s neurologic outcomes, it became a model for medication to treat brain injuries. However, apoE does not easily cross the blood-brain-barrier, making it a challenging molecule to dispense as a drug.

Dr. Laskowitz’s lab has spent almost a decade looking at how apoE works. They have recently developed a peptide made of 5 amino acids, CN-105, that is based off of this protein and is able to cross the blood-brain-barrier, giving it the potential to be distributed as a treatment. This has been tested in mice and shown to improve outcomes.

In July, CN-105  completed a first phase clinical trial and found that  drug administration was safe and well tolerated. In the coming year, a phase 2 study will look at whether  CN-105 improves outcomes in patients with brain hemorrhages.

The plan is to give the peptide through an IV every six hours for three days, the time period when most of the swelling happens after injury.

Dr. Laskowitz’s research has already had a significant impact on the treatment of brain injury, and hopefully, this new medication could be another great contribution to this field.

Ryan SheltonGuest Post by Ryan Shelton, North Carolina School of Math and Science, Class of 2017

Acoustic Metamaterials: Designing Plastic to Bend Sound

I recently toured Dr. Steven Cummer’s lab in Duke Engineering to learn about metamaterials, synthetic materials used to manipulate sound and light waves.

Acoustic metamaterials recently bent an incoming sound into the shape of an A, which the researchers called an acoustic hologram.

Acoustic metamaterials recently bent an incoming sound into the shape of an A, which the researchers called an acoustic hologram.

Cummer’s graduate student Abel Xie first showed me the Sound Propagator. It was made of small pieces that looked similar to legos stacked in a wall. These acoustic metamaterials were made of plastic and contained many winding pathways that delay and propagate, or change the direction, of sound waves. The pieces were configured in certain ways so they could design a sound field, a sort of acoustic hologram.

These metamaterials can be configured to direct a 4 kHz sound wave into the shape of a letter ‘A’. The researchers measured the outgoing sound wave using a 2D sweeping microphone that passed back and forth over the A-shaped sound like a lawnmower, moving to the right, then up, then left, etc. The arrangement of metamaterials that reconfigures sound waves is called a lens, because it can focus sound waves to one or more points like a light-bending lens.

Xie then showed me a version of the acoustic metamaterials 10 times smaller that propagated ultrasonic (40 KHz) sound waves. He told me that since 40 kHz was well out of the human range of hearing, it could be a viable option for the wireless non-contact charging of devices like phones. The smaller wave propagator could direct inaudible sound waves to your device, and then another piece of technology called a transfuser would convert acoustic energy into electrical energy.

This structure, with a microphone in the middle, can perform the "cocktail party" trick that humans can -- figuring out where in the room a sound is coming from.

This structure with a microphone in the middle can perform the “cocktail party” trick that humans can — picking out once voice among many.

Now that the waves have been directed, how do we read them? Xie directed me to what looked like a plastic cheesecake in the middle of the table. It was deep and beige and was split into many ‘slices.’ Each slice was further divided into a unique honeycomb of varying depth. The slices were separated from each by glass panes. This directed the soundwaves across the unique honeycomb of each slice towards the lone microphone in the middle. A microphone would be able to recognize where the sound was coming from based on how the wave had changed while it passed over the different honeycomb pattern of each slice.

Xie described the microphone’s ability to distinguish where a sound is coming from and comprehend that specific sound as the “cocktail party effect,” or the human ability to pick out one person speaking in a noisy room. This dense plastic sound sensor is able to distinguish up to three different people speaking and determine where they are in relation to the microphone. He explained how this technology could be miniaturized and implemented in devices like the Amazon Echo to make them more efficient.

Dr. Cummer and Abel Xie’s research is changing the way we think about microphones and sound, and may one day improve all kinds of technology ranging from digital assistants to wirelessly charging your phone.

Frank diLustro

Frank diLustro is a senior at the North Carolina School for Science and Math.

 

Using the Statistics of Disorder to Unravel Real-World Chaos

What do election polls, hospital records, and the Syrian conflict have in common? How can a hospital use a patient’s vital signs to calculate their risk of cardiac arrest in real time?

Duke statistical science professor Rebecca Steorts

Duke statistical science professor Rebecca Steorts

Statistician Rebecca Steorts is developing advanced data analysis methods to answer these questions and other pressing real-world problems. Her research has taken her from computer science to biostatistics and hospital care to human rights.

One major focus of Steorts’ research has been estimating death counts in the Syrian civil war. She is working with her research group at Duke and the Human Rights Data Analysis Group (https://hrdag.org/) on combining databases of death records into a single master list of deaths in the conflict, a task known as record linkage.

“The key problem of record linkage is this: you have this duplicated information, how do you remove it?” explained Steorts. For example, journalists from different organizations might independently record the same death in their databases. Those duplicates have to be removed before an accurate death toll can be determined.

At first glance, this might seem like an easy task. But typographic errors, missing information, and inconsistent record-keeping make hunting for duplicates a complex and time consuming problem; a simple algorithm would require days to sort through all the records. So Steorts and her collaborators designed software to sift through the different databases using powerful machine learning techniques. In 2015, she was named one of MIT Technology Review’s 35 Innovators Under 35 for her work on the Syrian conflict. She credits a number of colleagues and students for their contributions to the project, including Anshumali Shrivastava (Rice University), Megan Price (HRDAG), Brenda Betancourt and Abbas Zaid (Duke University), Jeff Miller (Harvard Biostatistics, formerly Duke University), Hanna Wallach (Microsoft Research), and Giacomo Zanella (University of Bocconi and Visitor of Duke University in 2016).

Steorts’ work towards estimating death counts in the Syrian conflict is still ongoing, but human rights isn’t the only field that she plans to study. “I think of my work as very interdisciplinary,” she said. “For me, it’s all about the applications.”

Recently, Steorts, colleague Ben Goldstein, and students Reuben McCreanor and Angie Shen have been applying statistical methods to medical data from the Duke healthcare system. Her ultimate goal is to find techniques that can be used for many different applications and data sets.

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Guest post by Angela Deng, North Carolina School of Science and Math, Class of 2017

Life Lessons from a Neuroscientist

I recently had the privilege of sitting down with Dr. Anne Buckley, a professor and  neuropathologist working in Dr. Chay Kuo’s cell biology lab at Duke. I got a first-hand account of her research on neuron development and function in mice. But just as fascinating to me were the life lessons she had learned during her time as a researcher.

Anne Buckley, M.D. Ph.D., is an assistant professor of pathology

Anne Buckley, M.D. Ph.D., is an assistant professor of pathology

Buckley’s research looks at brain tumors in mice. She recently found that some of the mice developed the tumors in an area full of neurons, the roof of the fourth ventricle, which is of particular interest because humans have developed tumors in the same location. This discovery could show how neurological pathways affect tumor formation and progression.

Buckley also gave me some critical words of advice, cautioning me that research isn’t for everyone.

“Research is not glamorous, and not always rewarding,” she warned me. When she first started research, Buckley learned a hard lesson: work doesn’t necessarily lead to results. “For every question I went after, I found ten more unresolved,” she said. “To be a researcher, it takes a lot of perseverance and resilience. A lot of long nights.”

But that’s also the beauty of research. Buckley says that she’s learned to find happiness in the small successes, and that she “enjoys the process, enjoys the challenge.”

And when discoveries happen?

“When I look at data, and I see something unexpected, I get really excited,” she says. “I know something that no one else knows. Tomorrow, everyone will know. But tonight, I’m the only person in the world who knows.”

kendra_zhong_headshotGuest Post by Kendra Zhong, North Carolina School of Science and Math, Class of 2017

Evolutionary Genetics Shaping Health and Behavior

Dr. Jenny Tung is interested in the connections between genes and behavior: How does behavior influence genetic variation and regulation and how do genetic differences influence behavior?

A young Amboseli baboon hitches a ride with its mother. (Photo by Noah Snyder-Mackler)

A young Amboseli baboon hitches a ride with its mother. (Photo by Noah Snyder-Mackler)

An assistant professor in the Departments of Evolutionary Anthropology and Biology at Duke, Tung is interested in evolution because it gives us a window into why the living world is the way it is. It explains how organisms relate to one another and their environment. Genetics explains the actual molecular foundation for evolutionary change, and it gives part of the answer for trait variation. Tung was drawn as an undergrad towards the combination of evolution and genetics to explain every living thing we see around us; she loves the explanatory power and elegance to it.

Tung’s longest collaborative project is the Amboseli Baboon Research Project (ABRP), located in the Amboseli ecosystem of East Africa. She co-leads it with Susan Alberts, chair of evolutionary anthropology at Duke, Jeanne Altmann at Princeton, and Beth Archie at Notre Dame.

Tung has spent months at a time on the savannah next to Mount Kilimanjaro for this project. The ABRP monitors hundreds of baboons in several social groups and studies social processes at several levels. Recently the project has begun to include genetics and other aspects of baboon biology, including the social behaviors within the social groups and populations, and how these behaviors have changed along with the changing Amboseli ecosystem. Tung enjoys different aspects of all of her projects, but is incredibly grateful to be a part of the long-term Amboseli study.

Jenny Tung

Jenny Tung is an assistant professor in evolutionary anthropology and biology.

The process of discovery excites Tung. It is hard for her to pin down a single thing that makes research worth it, but “new analyses, discussions with students who teach me something new, seeing a great talk that makes you think in a different way or gives you new research directions to pursue” are all very exciting, she said.

Depending on the project, the fun part varies for her; watching a student develop as a scientist through their own project is rewarding, and she loves collaborating with extraordinary scientists. Specific sets of collaborators make the research worth it. “When collaborations work, you really push each other to be better scientists and researchers,” Tung said.

Raechel ZellerGuest post by Raechel Zeller, North Carolina School of Science and Math, Class of 2017