Duke Research Blog

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

Category: Neuroscience (Page 2 of 13)

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

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

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

Depression Screening Questions Seem to Miss Men

Women may be more likely to be diagnosed and treated for anxiety and depression not because they are, but because they’re more willing than men to honestly answer the questions used to diagnose mental health problems, a new Duke study finds.

man drinking - Wellcome Images

Asking men about their drinking might identify more cases of the blues like this guy. (Blauwe Week 1936 advertisement against alcohol. From Wellcome Images via Wikimedia Commons)

Jen’nan Read, a Duke sociologist and lead-author of the study, said men seem to adhere to a societal stigma to remain “macho” and are less likely to open up about their feelings. Her findings appear in Sociological Forum available online now and will appear in print in December.

Read’s study examines connections between mental and physical health in both men and women and suggests that the criteria used to examine mental health should be expanded beyond depression to include questions on substance abuse, which is another form of expressing mental distress, and more common among men.

The study finds that while depression is often how women express problems with mental health, men do so by drinking alcohol. The Duke study found that questioning men about alcohol use is a better way to diagnose both mental and physical health problems.

“Depression gives a lopsided picture,” Read said. “It makes mental health look like a women’s issue.”

A common set of questions include asking how often people have trouble getting to sleep or staying asleep, felt sad, lonely or like ‘you couldn’t shake the blues.’

Jen'nan Read is a Duke sociologist

Jen’nan Read is a Duke sociologist

“It’s more acceptable for women to answer affirmatively to these questions,” Read said. “Men are less likely to say they have feelings of anxiety. Issues of masculinity lead many to mask their problems.”

The result is often missed diagnoses of mental health problems in men.

The study crunches data from the Aging Status and Sense of Control Survey, in which people answer questions about their mental and physical health, diet, family situation, access and use of health care and other life factors. The average of women surveyed is about 54, and the average age of men was about 51.

Read’s study found that both men and women suffering from poor mental health are likely to suffer physical problems as well, like high blood pressure, diabetes and other issues.

The study was conducted by Read, Jeremy R. Porter, a sociologist with the City University of New York – Brooklyn College, and Bridget K. Gorman, a sociologist at Rice University.

Eric FerreriGuest Post by Eric Ferreri, Duke News and Communications

Mapping the Brain With Stories

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Dr. Alex Huth. Image courtesy of The Gallant Lab.

On October 15, I attended a presentation on “Using Stories to Understand How The Brain Represents Words,” sponsored by the Franklin Humanities Institute and Neurohumanities Research Group and presented by Dr. Alex Huth. Dr. Huth is a neuroscience postdoc who works in the Gallant Lab at UC Berkeley and was here on behalf of Dr. Jack Gallant.

Dr. Huth started off the lecture by discussing how semantic tasks activate huge swaths of the cortex. The semantic system places importance on stories. The issue was in understanding “how the brain represents words.”

To investigate this, the Gallant Lab designed a natural language experiment. Subjects lay in an fMRI scanner and listened to 72 hours’ worth of ten naturally spoken narratives, or stories. They heard many different words and concepts. Using an imaging technique called GE-EPI fMRI, the researchers were able to record BOLD responses from the whole brain.

Dr. Huth explaining the process of obtaining the new colored models that revealed semantic "maps are consistent across subjects."

Dr. Huth explaining the process of obtaining the new colored models that revealed semantic “maps are consistent across subjects.”

Dr. Huth showed a scan and said, “So looking…at this volume of 3D space, which is what you get from an fMRI scan…is actually not that useful to understanding how things are related across the surface of the cortex.” This limitation led the researchers to improve upon their methods by reconstructing the cortical surface and manipulating it to create a 2D image that reveals what is going on throughout the brain.  This approach would allow them to see where in the brain the relationship between what the subject was hearing and what was happening was occurring.

A model was then created that would require voxel interpretation, which “is hard and lots of work,” said Dr. Huth, “There’s a lot of subjectivity that goes into this.” In order to simplify voxel interpretation, the researchers simplified the dimensional subspace to find the classes of voxels using principal components analysis. This meant that they took data, found the important factors that were similar across the subjects, and interpreted the meaning of the components. To visualize these components, researchers sorted words into twelve different categories.

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The Four Categories of Words Sorted in an X,Y-like Axis

These categories were then further simplified into four “areas” on what might resemble an x , y axis. On the top right was where violent words were located. The top left held social perceptual words. The lower left held words relating to “social.” The lower right held emotional words. Instead of x , y axis labels, there were PC labels. The words from the study were then colored based on where they appeared in the PC space.

By using this model, the Gallant could identify which patches of the brain were doing different things. Small patches of color showed which “things” the brain was “doing” or “relating.” The researchers found that the complex cortical maps showing semantic information among the subjects was consistent.

These responses were then used to create models that could predict BOLD responses from the semantic content in stories. The result of the study was that the parietal cortex, temporal cortex, and prefrontal cortex represent the semantics of narratives.

meg_shieh_100hedPost by Meg Shieh

Nature vs. Nurture: Predicting Our Futures

Sitting in The Connection at the Social Science Research Institute in Gross Hall was intimidating. I was surrounded by distinguished people: professors, visiting professors from distinguished universities, researchers, and postdocs, all of whom had gathered together to view a showing of the documentary, Predict My Future: The Science of Us.

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Dr. Terrie Moffitt, a Duke professor. Image courtesy of Moffitt and Caspi.

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Dr. Avshalom Caspi, a Duke professor. Image Courtesy of Moffitt and Caspi.

Predict My Future documents the work of Terrie Moffitt and Avshalom Caspi, two Duke professors who study people in Dunedin, New Zealand. They have followed the lives of all the children born within a year in Dunedin for the last 40 years to measure genetics, personal habits, environment, jobs, physical attributes, and etc.  The Dunedin Longitudinal Study is the largest study of its kind and offers deep insights into how children become adults.

The episode, “The Early Years,” first posed the questions, “Why do some people become successful and others become outcasts? Why are we the way that we are?” By tracking all of these personal factors and some  behaviors, including risky sexual activities, criminal activities, and drinking and smoking habits, the Dunedin Longitudinal Study can answer these questions. The researchers can tell which children are likely to become “problem children,” “geniuses,” and so on, based on the child’s personality type.

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Q&A Session After the Viewing of the Documentary. Image Courtesy of Duke SSRI and Taken By Shelbi Fanning.

The study first identified five different personality types in young children, and researchers discovered that the children’s’ personality types did not change in adulthood. The three personality types that are typically associated with doing well in life, having better health, having friends, and being more successful are: “well-adjusted,” “reserved,” and “confident.” The two personality types associated with having poorer quality of life in adulthood are “inhibited” and “undercontrolled.”

Then, the study identified other factors that lead to serious consequences later in life or simply predict futures. Children who experienced delays in walking and in talking were likely to have issues with brain development. Boys with these traits typically disliked school, did poorly in school, and were more likely to be involved in criminal activity.

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The full house watching the documentary. Image Courtesy of Duke SSRI and Taken by Shelbi Fanning.

The amount of sleep children received between the ages of five and eleven would determine obesity in adulthood. Adults who received the least amount of sleep as children tended to be obese by age 32.

Schizophrenia, researchers discovered, starts developing in young children, not just adults as had previously been thought. About half of the 11-year-olds in the study who said they had seen or heard things that weren’t there had developed schizophrenia two decades later.

Watching more TV was associated with a higher likelihood of smoking and having anxiety. Regardless of IQ or environment, children who watched more TV were more likely to leave school without qualifications.

The important lesson the documentary emphasized was that having a good childhood is important. Warm, sensitive, stimulating, family-feeling invoking environments are great protective factors to risk factors.

Overall, this was a brilliant, stimulating, easy-to-understand documentary.

meg_shieh_100hedPost by Meg Shieh

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