Duke Research Blog

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

Category: Neuroscience Page 1 of 10

The Importance of Moms

Emily Bray, Ph.D., might have the best job ever. Since earning her bachelor’s at Duke in 2012, she has been researching cognitive development in puppies, which basically means she’s spent the last seven years playing with dogs. If that’s not success, I don’t know what is.

Last Friday marked the 10th birthday of Duke’s Canine Cognition Center, and the 210th birthday of Charles Darwin. To celebrate, Brian Hare, Ph.D., invited former student Bray back to campus to share her latest research with a new generation of Duke undergraduates. The room was riveted — both by her compelling findings and by the darling photos of labs and golden retrievers that accompanied each slide.

Dr. Emily Bray shows photos of her study participants

During her Ph.D. program at the University of Pennsylvania, Bray worked with Robert Seyfarth, Dorothy Cheney, and James Serpell to investigate the effects of mothering on puppy development. For her dissertation, she studied a population of dog moms and their puppies at The Seeing Eye, Inc. The Seeing Eye is one of the oldest and largest guide dog schools in the U.S. They have been successfully raising and training service dogs for the blind since 1929, but like most things, it is still an imperfect science. Approximately half of the puppies bred at The Seeing Eye fail out of program. A dog that completes service training at The Seeing Eye represents two years of intensive training and care, and investing so much time and money into a dog that might eventually fail is problematic. Being able to predict the outcomes of puppies would save a lot of wasted time and energy, and Emily Bray has been doing just this.

What makes a good dog mom? (Photo from Dirk Vorderstraße, from Wikimedia Commons)

Through her work at The Seeing Eye, Bray found that, similar to humans, dogs have several types of mothering styles. She discovered that dog moms tend to fall somewhere on the spectrum from low to high maternal involvement. Some of the moms were very involved with their puppies, and seldom left their side. These hovering moms had high levels of cortisol, and became quite stressed when separated briefly from a puppy. They coddled their children, and often nursed from a laying down position, doing everything they could to make life easy for their babies. On the other side of the spectrum, Bray also observed moms that displayed much more relaxed mothering. They often took personal time, and let their puppies fend for themselves. They were more likely to nurse while sitting or standing up, which made their children work harder to feed. They were less stressed when separated from a puppy, and also just had generally lower levels of cortisol. Sound like bad parenting? Believe it or not, this tough love actually resulted in more successful puppies.

Duke’s very own assistance dogs in training!

As the puppies matured, Bray conducted a series of cognitive and temperament tests to determine if maternal style was associated with a certain way of thinking in the puppies. Turns out, dogs who experienced high maternal care actually performed much worse on the tests than dogs who were shown tough love when they were young. At The Seeing Eye graduation, it was also determined that high maternal care and ventral nursing was associated with failure. Puppies that were over-mothered were more likely to fail as service dogs.

Her theory is that tough love raises more resilient puppies. When mom is always around, the puppies don’t get the chance to experience small stressors and learn how to deal with challenge. The more relaxed moms actually did their kids a favor by not being so overbearing, and allowed for much more independent development.

Bray is now doing post-doctoral research at the University of Arizona, where she is working with Canine Companions for Independence (CCI) to determine if maternal style has similar effects on the outcomes of dogs that will be trained to assist people with a wide range of disabilities. She is also now doing cognition and temperament tests on moms pre-pregnancy to determine if maternal behavior can be predicted before the dogs have puppies. Knowing this could be a game changer, as this information could be used for selective breeding of better moms.

Me snuggling Ashton, one of the Puppy Kindergarten dogs

If you got the chance to hang out with puppies Ashton, Aiden, or Dune last semester, you have an idea of how awesome Bray’s day-to-day work is. These pups were bred at CCI, and sent to Duke to be enrolled in Duke Puppy Kindergarten, a new program on campus run through Duke’s Canine Cognition Center. Which of these three will make it to graduation? I’ve got money on Ashton, but I guess we’ll have to wait and see.

The bottom line according to Bray? “Mothering matters, but in moderation.”

Overcoming Judgment Biases in STEM

Beginning in childhood we all develop unconscious stereotypes that influence how we see ourselves and others – including what careers we choose, and who we choose to recruit, hire or promote in the workplace.

Researchers discussed the origins and effects of these judgement biases during a virtual conference titled Mitigating Implicit Bias: Tools for the Neuroscientist, which was put on by the Society for Neuroscience and screened by DIBS at Duke on Jan. 23 and 24.

Associate professor of neuroscience Anne Churchland of Cold Spring Harbor Laboratory proposed several ideas for overcoming gender bias in the workplace, especially for women in STEM or other male-dominated domains. Asking questions, speaking with authority (particularly about one’s own work), finding a way to communicate with senior colleagues, trying risky experiments, making one’s achievements known, sending one’s work to high-level journals, and applying to awards and grants are her main suggestions. Above all these strategies, she recommends finding good friends and colleagues to help. As research shows, when women are successful in arenas that are viewed as distinctly male, both women and men like them less. These negative reactions can be discouraging and even career-affecting, and any support system will help to overcome that struggle.

The ‘Brilliance Barrier ‘ is a judgement bias explored by Andrei Cimpian’s research at New York University. One study shows that for every ten parents who searched on Google, “Is my daughter talented?”, twenty-five parents looked up “Is my son talented?”

Another study describes the gendered reviews on ratemyprofessor.com. Men are two to three times more likely to be called genius than women. Women though are more likely to be portrayed as warm or caring.

Cimpian uses these studies to develop the Field-specific Ability Beliefs hypothesis (FAB). FAB attributes women’s underrepresentation to a combination of the idolized brilliance/genius and the “brilliance” equals men stereotype. The higher the FAB in a field, the greater the emphasis on brilliance in it. When graphing the percentage of women with PhDs and the FAB for a specific field such as philosophy or physics, higher FABs are associated with a lower number of PhDs. African American representation also decreases as the FAB increases. Cimpian classifies one potential mechanism of this trend as minorities having less interest in fields with high FABs. In addition, increased bias, discrimination, and imposter syndrome could explain why minorities appear to avoid getting PhDs in high FAB fields.

Cimpian also demonstrates how susceptible children are to judgement biases. At age five, the percentage of girls who pick their own gender as “really, really smart” and the percentage of boys who do the same are similar. When children reach seven though, the percentage of boys choosing men exceeds the girls picking women. He suggests de-emphasizing brilliance, genius, and gifted in favor of work ethic because minorities are more likely to be recommended when the job description asks for commitment than when it asks for intelligence. Language has the potential to change the amount of representation in high FAB fields, such as STEM.

Image result for jackie fleming cartoons
Never Give Up – Cartoon by Jackie Fleming

Lastly, psychology professor Ione Fine at the University of Washington talked about the hiring process in her lab and how she reduces bias by laying out and weighting criteria beforehand. Instead of focusing on objective criteria like GPA and GRE scores, she advocates for more interviews with set lists of questions and a paper discussion. She also recommends calling the recommendation letter writers. After selecting a diverse group of research assistants, Fine then makes sure they have the proper support and mentoring. Reinforcing that they were chosen for their potential and that she is their advocate helps them feel empowered to succeed in her lab. Through mentoring and supporting diversity, anyone can help minorities overcome the judgement biases surrounding them.   

Nature vs. Nurture and Addiction

Epigenetics involves modifications to DNA that do not change its sequence but only affect which genes are active, or expressed. Photo courtesy of whatisepigenetics.com

The progressive understanding of addiction as a disease rather than a choice has opened the door to better treatment and research, but there are aspects of addiction that make it uniquely difficult to treat.

One exceptional characteristic of addiction is its persistence even in the absence of drug use: during periods of abstinence, symptoms get worse over time, and response to the drug increases.

Researcher Elizabeth Heller, PhD, of the University of Pennsylvania Epigenetics Institute, is interested in understanding why we observe this persistence in symptoms even after drug use, the initial cause of the addiction, is stopped. Heller, who spoke at a Jan. 18 biochemistry seminar, believes the answer lies in epigenetic regulation.

Elizabeth Heller is interested in how changes in gene expression can explain the chronic nature of addiction.

Epigenetic regulation represents the nurture part of “nature vs. nurture.” Without changing the actual sequence of DNA, we have mechanisms in our body to control how and when cells express certain genes. These mechanisms are influenced by changes in our environment, and the process of influencing gene expression without altering the basic genetic code is called epigenetics.

Heller believes that we can understand the persistent nature of the symptoms of drugs of abuse even during abstinence by considering epigenetic changes caused by the drugs themselves.

To investigate the role of epigenetics in addiction, specifically cocaine addiction, Heller and her team have developed a series of tools to bind to DNA and influence expression of the molecules that play a role in epigenetic regulation, which are called transcription factors. They identified the FosB gene, which has been previously implicated as a regulator of drug addiction, as a site for these changes.

Increased expression of the FosB gene has been shown to increase sensitivity to cocaine, meaning individuals expressing this gene respond more than those not expressing it. Heller found that cocaine users show decreased levels of the protein responsible for inhibiting expression of FosB. This suggests cocaine use itself is depleting the protein that could help regulate and attenuate response to cocaine, making it more addictive.

Another gene, Nr4a1, is important in dopamine signaling, the reward pathway that is “hijacked” by drugs of abuse.  This gene has been shown to attenuate reward response to cocaine in mice. Mice who underwent epigenetic changes to suppress Nr4a1 showed increased reward response to cocaine. A drug that is currently used in cancer treatment has been shown to suppress Nr4a1 and, consequently, Heller has shown it can reduce cocaine reward behavior in mice.

The identification of genes like FosB and Nr4a1 and evidence that changes in gene expression are even greater in periods of abstinence than during drug use. These may be exciting leaps in our understanding of addiction, and ultimately finding treatments best-suited to such a unique and devastating disease.   

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

Pursuing Smell as a Path Into the Brain

Although the mystery of how the brain works and grows is a massive puzzle to figure out, the hope is that piece by piece, we can start to work towards a better understanding.

A person’s (or fly’s) sense of smell, or their olfactory system, is one of these pieces.

Though olfaction may not be the first part of the nervous system to cross someone’s mind when it comes to how we understand the brain, it is actually one of the most complex and diverse systems of an organism, and there’s a lot to understand within it, says Pelin Volkan, an assistant professor of biology and neurobiology and investigator in the Duke Institute for Brain Sciences.

Pelin Volkan in her lab.

Volkan and her lab have been working with fruit flies to try to unfold the many layers of the olfactory system, or the, “giant hairball,” as Volkan calls it.

Though she has been doing this work for years, she didn’t begin with an interest in neuroscience. Volkan was more interested in genetics in college and didn’t really start exploring neurobiology and development until her master’s degree at a Turkish university, when she worked with rats.

Not keen on working with rodents as model organisms but sticking with them anyway, she moved from Turkey to UNC to get her PhD, where she strayed away from neuroscience into molecular biology and development. Eventually, she realized she had a stronger passion for neuroscience, and ended up doing a postdoc at a Howard Hughes Medical Institute lab at UCLA for six years.

There, she became interested in receptors and neuronal wiring in the brain, propelling her to come to Duke and continue research on the brain’s connections and development.

One of the main reasons she loves working with the olfactory system is the many different scientific approaches that can be used to study it. Bouncing between using genetics, evolution, development, molecular biology,and other areas of study to understand the brain, her work is never static and she can take a more interdisciplinary approach to neuroscience where she is able to explore all the topics that interest her.

 Volkan says she has never had to settle on just one topic, and new questions are always arising that take her in directions she didn’t expect, which is what makes her current work particularly enjoyable for her.

“You have your stories, you close your stories, but then new questions come into play,” Volkan says. “And you have no choice but to follow those questions, so you just keep on going.”

And isn’t that what science is all about?

Guest Post by Angelina Katsanis, NCSSM 2019

Drug Homing Method Helps Rethink Parkinson’s

The brain is the body’s most complex organ, and consequently the least understood. In fact, researchers like Michael Tadross, MD, PhD, wonder if the current research methods employed by neuroscientists are telling us as much as we think.

Michael Tadross is using novel approaches to tease out the causes of neuropsychiatric diseases at a cellular level.

Current methods such as gene editing and pharmacology can reveal how certain genes and drugs affect the cells in a given area of the brain, but they’re limited in that they don’t account for differences among different cell types. With his research, Tadross has tried to target specific cell types to better understand mechanisms that cause neuropsychiatric disorders.

To do this, Tadross developed a method to ensure a drug injected into a region of the brain will only affect specific cell types. Tadross genetically engineered the cell type of interest so that a special receptor protein, called HaloTag, is expressed at the cell membrane. Additionally, the drug of interest is altered so that it is tethered to the molecule that binds with the HaloTag receptor. By connecting the drug to the Halo-Tag ligand, and engineering only the cell type of interest to express the specific Halo-Tag receptor, Tadross effectively limited the cells affected by the drug to just one type. He calls this method “Drugs Acutely Restricted by Tethering,” or DART.

Tadross has been using the DART method to better understand the mechanisms underlying Parkinson’s disease. Parkinson’s is a neurological disease that affects a region of the brain called the striatum, causing tremors, slow movement, and rigid muscles, among other motor deficits.

Only cells expressing the HaloTag receptor can bind to the AMPA-repressing drug, ensuring virtually perfect cell-type specificity.

Patients with Parkinson’s show decreased levels of the neurotransmitter dopamine in the striatum. Consequently, treatments that involve restoring dopamine levels improve symptoms. For these reasons, Parkinson’s has long been regarded as a disease caused by a deficit in dopamine.

With his technique, Tadross is challenging this assumption. In addition to death of dopaminergic neurons, Parkinson’s is associated with an increase of the strength of synapses, or connections, between neurons that express AMPA receptors, which are the most common excitatory receptors in the brain.

In order to simulate the effects of Parkinson’s, Tadross and his team induced the death of dopaminergic neurons in the striatum of mice. As expected, the mice displayed significant motor impairments consistent with Parkinson’s. However, in addition to inducing the death of these neurons, Tadross engineered the AMPA-expressing cells to produce the Halo-Tag protein.

Tadross then treated the mice striatum with a common AMPA receptor blocker tethered to the Halo-Tag ligand. Amazingly, blocking the activity of these AMPA-expressing neurons, even in the absence of the dopaminergic neurons, reversed the effects of Parkinson’s so that the previously affected mice moved normally.

Tadross’s findings with the Parkinson’s mice exemplifies how little we know about cause and effect in the brain. The key to designing effective treatments for neuropsychiatric diseases, and possibly other diseases outside the nervous system, may be in teasing out the relationship of specific types of cells to symptoms and targeting the disease that way.

The ingenious work of researchers like Tadross will undoubtedly help bring us closer to understanding how the brain truly works.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

 

Aging and Decision-Making

Who makes riskier decisions, the young or the old? And what matters more in our decisions as we age — friends, health or money? The answers might surprise you.

Kendra Seaman works at the Center for the Study of Aging and Human Development and is interested in decision-making across the lifespan.

Duke postdoctoral fellow Kendra Seaman, Ph.D. uses mathematical models and brain imaging to understand how decision-making changes as we age. In a talk to a group of cognitive neuroscientists at Duke, Seamen explained that we have good reason to be concerned with how older people make decisions.

Statistically, older people in the U.S. have more money, and additionally more expenditures, specifically in healthcare. And by 2030, 20 percent of the US population will be over the age of 65.

One key component to decision-making is subjective value, which is a measure of the importance a reward or outcome has to a specific person at a specific point in time. Seaman used a reward of $20 as an example: it would have a much higher subjective value for a broke college student than for a wealthy retiree. Seaman discussed three factors that influence subjective value: reward, cost, and discount rate, or the determination of the value of future rewards.

Brain imaging research has found that subjective value is represented similarly in the medial prefrontal cortex (MPFC) across all ages. Despite this common network, Seaman and her colleagues have found significant differences in decision-making in older individuals.

The first difference comes in the form of reward. Older individuals are likely to be more invested in the outcome of a task if the reward is social or health-related rather than monetary. Consequently, they are more likely to want these health and social rewards  sooner and with higher certainty than younger individuals are. Understanding the salience of these rewards is crucial to designing future experiments to identify decision-making differences in older adults.

A preference for positive skew becomes more pronounced with age.

Older individuals also differ in their preferences for something called “skewed risks.” In these tasks, positive skew means a high probability of a small loss and a low probability of a large gain, such as buying a lottery ticket. Negative skew means a low probability of a large loss and a high probability of a small gain, such as undergoing a common medical procedure that has a low chance of harmful complications.

Older people tend to prefer positive skew to a greater degree than younger people, and this bias toward positive skew becomes more pronounced with age.

Understanding these tendencies could be vital in understanding why older people fall victim to fraud and decide to undergo risky medical procedures, and additionally be better equipped to motivate an aging population to remain involved in physical and mental activities.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

Quantifying Sleepiness and How It Relates to Depression

Sleep disturbance is a significant issue for many individuals with depressive illnesses. While most individuals deal with an inability to sleep, or insomnia, about 20-30% of depressed patients report the opposite problem – hypersomnia, or excessive sleep duration.

David Plante’s work investigates the relationship between depressive disorders and hypersomnolence. Photo courtesy of sleepfoundation.org

Patients who experience hypersomnolence report excessive daytime sleepiness (EDS) and often seem to be sleep-deprived, making the condition difficult to identify and poorly researched.

David Plante’s research focuses on a neglected type of sleep disturbance: hypersomnolence.

David T. Plante, MD, of the University of Wisconsin School of Medicine and Public Health, studies the significance of hypersomnolence in depression. He said the condition is resistant to treatment, often persisting even after depression has been treated, and its role in increasing risk of depression in previously healthy individuals needs to be examined.

One problem in studying daytime sleepiness is quantifying it. Subjective measures include the Epworth sleepiness scale, a quick self-report of how likely you are to fall asleep in a variety of situations. Objective scales are often involved processes, such as the Multiple Sleep Latency Test (MSLT), which requires an individual to attempt to take 4-5 naps, each 2 hours apart, in a lab while EEG records brain activity.

The MSLT measures how long it takes a person to fall asleep. Individuals with hypersomnolence will fall asleep faster than other patients, but determining a cutoff for what constitutes healthy and what qualifies as hypersomnolence has made the test an inexact measure. Typical cutoffs of 5-8 minutes provide a decent measure, but further research has cast doubt on this test’s value in studying depression.

The Wisconsin Sleep Cohort Study is an ongoing project begun in 1988 that follows state employees and includes a sleep study every four years. From this study, Plante has found an interesting and seemingly paradoxical relationship: while an increase in subjective measures of sleepiness is associated with increased likelihood of depression, objective measures like the MSLT associate depression with less sleepiness. Plante argues that this paradoxical relationship does not represent an inability for individuals to report their own sleepiness, but rather reflects the limitations of the MSLT.

Plante proposed several promising candidates for quantitative measures of excessive daytime sleepiness. One candidate, which is already a tool for studying sleep deprivation, is a ‘psychomotor vigilance task,’ where lapses in reaction time correlate with daytime sleepiness. Another method involves infrared measurements of the dilation of the pupil. Pupils dilate when a person is sleepy, so this somatic reaction could be useful.

High density EEG allowed Plante to identify the role of disturbed slow wave sleep in hypersomnolence.

Another area of interest for Plante is the signs of depressive sleepiness in the brain. Using high density EEG, which covers the whole head of the subject, Plante found that individuals with hypersomnolence experience less of the sleep cycle most associated with restoration, known as slow wave sleep. He identified a potential brain circuitry associated with sleepiness, but emphasized a need for methods like transcranial magnetic stimulation to get a better picture of the relationship between this circuitry and observed sleepiness.

By Sarah Haurin

Detangling Stigma and Mental Illness

Can you imagine a world without stigma? Where a diagnosis of autism or schizophrenia didn’t inevitably stick people with permanent labels of “handicap,” “abnormal,” “disturbed,” or “dependent”?

Roy Richard Grinker can. In fact, he thinks we’re on the way to one.

It’s a subject he’s studied and lectured on extensively—stigmas surrounding mental health conditions, that is. His expertise, influence, and unique insight in the field led him to April 12, where he was the distinguished speaker of an annual lecture commemorating Autism Awareness Month. The event was co-sponsored by the Duke Center for Autism and Brain Development, the Duke Institute for Brain Sciences, and the Department of Cultural Anthropology.

Roy Richard Grinker was the invited speaker to this year’s annual Autism Awareness Month commemorative lecture. Photo credit: Duke Institute for Brain Sciences

Grinker’s credentials speak to his expertise. He is a professor of Anthropology, International Affairs, and Human Sciences at George Washington University; he has authored five books, several New York Times op-eds, and a soon-to-be-published 600-page volume on the anthropology of Africa; he studied in the Democratic Republic of the Congo as a Fulbright scholar in his early career; and, in the words of Geraldine Dawson, director of the Center for Autism and Brain Development, “he fundamentally changed the way we think about autism.”

Grinker began with an anecdote about his daughter, who is 26 years old and “uses the word ‘autism’ to describe herself—not just her identity, but her skills.”

She likes to do jigsaw puzzles, he said, but in a particular fashion: with the pieces face-down so their shape is the only feature she can use to assemble them, always inexplicably leaving one piece out at the end. He described this as one way she embraces her difference, and a metaphor for her understanding that “there’s always a piece missing for all of us.”

Grinker and Geraldine Dawson, director of the Center for Autism and Brain Development, pose outside Love Auditorium in the minutes before his talk. Source: Duke Institute for Brain Sciences

“What historical and cultural conditions made it possible for people like Isabel to celebrate forms of difference that were a mark of shame only a few decades ago?” Grinker asked.  “To embrace the idea that mental illnesses are an essential feature of what it means to be human?”

He identified three processes as drivers of what he described as the “pivotal historical moment” of the decoupling of stigma and mental illness: high-profile figures, from celebrity talk-show hosts to the Pope, speaking up about their mental illnesses instead of hiding them; a shift from boxing identities into racial, spiritual, gender, and other categories to placing them on a spectrum; and economies learning to appreciate the unique skills of people with mental illness.

This development in the de-stigmatization of mental illness is recent, but so is stigma itself. Grinker explained how the words “normal” and “abnormal” didn’t enter the English vocabulary until the mid-19th century—the idea of “mental illness” had yet to make its debut.

“There have always been people who suffer from chronic sadness or had wildly swinging moods, who stopped eating to the point of starvation, who were addicted to alcohol, or only spoke to themselves.” Grinker said. “But only recently have such behaviors defined a person entirely. Only recently did a person addicted to alcohol become an alcoholic.”

Grinker then traced the development of mental illness as an idea through modern European and American history. He touched on how American slaveowners ascribed mental illness to African Americans as justification for slavery, how hysteria evolved into a feminized disease whose diagnoses became a classist tool after World War I, and how homosexuality was gradually removed from the Diagnostic and Statistical Manual of Mental Disorders (DSM) by secretly gay psychiatrists who worked their way up the rankings of the American Psychiatric Association in the 1960s and 70s.

Source: Duke Institute for Brain Sciences

Next, Grinker described his anthropological research around the world on perceptions of mental illness, from urban South Korea to American Indian tribes to rural villages in the Kalahari Desert. His findings were wide-ranging and eye-opening: while, at the time of Grinker’s research, Koreans viewed mental illness of any kind as a disgrace to one’s heritage, members of Kalahari Desert communities showed no shame in openly discussing their afflictions. Grinker told of one man who spoke unabashedly of his monthly 24-mile walk to the main village for antipsychotic drugs, without which, as was common knowledge among the other villagers, he would hear voices in his head urging him to kill them. Yet, by Grinker’s account, they didn’t see him as ill — “a man who never hallucinates because he takes his medicine is not crazy.”

I could never do justice to Grinker’s presentation without surpassing an already-strained word limit on this post. Suffice it to say, the talk was full of interesting social commentary, colorful insights into the history of mental illness, and words of encouragement for the future of society’s place for diversity in mental health. Grinker concluded on such a note:

“Stigma decreases when a condition affects us all, when we all exist on a spectrum,” Grinker said. “We see this in the shift away from the categorical to the spectral dimension. Regardless, we might need the differences of neurodiversity to make us, humans, interesting, vital, and innovative.”

Post by Maya Iskandarani

ECT: Shockingly Safe and Effective

Husain is interested in putting to rest misconceptions about the safety and efficacy of ECT.

Few treatments have proven as controversial and effective as electroconvulsive therapy (ECT), or ‘shock therapy’ in common parlance.

Hippocrates himself saw the therapeutic benefits of inducing seizures in patients with mental illness, observing that convulsions caused by malaria helped attenuate symptoms of mental illness. However, depictions of ECT as a form of medical abuse, as in the infamous scene from One Flew Over the Cuckoo’s Nest, have prevented ECT from becoming a first-line psychiatric treatment.

The Duke Hospital Psychiatry program recently welcomed back Duke Medical School alumnus Mustafa Husain to deliver the 2018 Ewald “Bud” Busse Memorial Lecture, which is held to commemorate a Duke doctor who pioneered the field of geriatric psychiatry.

Husain, from the University of Texas Southwestern, delivered a comprehensive lecture on neuromodulation, a term for the emerging subspecialty of psychiatric medicine that focuses on physiological treatments that are not medication.

The image most people have of ECT is probably the gruesome depiction seen in “One Flew Over the Cuckoo’s Nest.”

Husain began his lecture by stating that ECT is one of the most effective treatments for psychiatric illness. While medication and therapy are helpful for many people with depression, a considerable proportion of patients’ depression can be categorized as “treatment resistant depression” (TRD). In one of the largest controlled experiments of ECT, Husain and colleagues showed that 82 percent of TRD patients treated with ECT were remitted. While this remission rate is impressive, the rate at which remitted individuals experience a relapse into symptoms is also substantial – over 50% of remitted individuals will experience relapse.

Husain’s study continued to test whether a continuation of ECT would be a potentially successful therapy to prevent relapse in the first six months after acute ECT. He found that continuation of ECT worked as well as the current best combination of drugs used.

From this study, Husain made an interesting observation – the people who were doing best in the 6 months after ECT were elderly patients. He then set out to study the best form of treatment for these depressed elderly patients.

Typically, ECT involves stimulation of both sides of the brain (bilateral), but this treatment is associated with adverse cognitive effects like memory loss. Using right unilateral ECT effectively decreased cognitive side effects while maintaining an appreciable remission rate.

After the initial treatment, patients were again assigned to either receive continued drug treatment or continued ECT. In contrast to the previous study, however, the treatment for continued ECT was designed based on the individual patients’ ratings from a commonly used depression scaling system.

The results of this study show the potential that ECT has in becoming a more common treatment for major depressive disorder: maintenance ECT showed a lower relapse rate than drug treatment following initial ECT. If psychiatrists become more flexible in their prescription of ECT, adjusting the treatment plan to accommodate the changing needs of the patients, a disorder that is exceedingly difficult to treat could become more manageable.

In addition to discussing ECT, Husain shared his research into other methods of neuromodulation, including Magnetic Seizure Therapy (MST). MST uses magnetic fields to induce seizures in a more localized region of the brain than available via ECT.

Importantly, MST does not cause the cognitive deficits observed in patients who receive ECT. Husain’s preliminary investigation found that a treatment course relying on MST was comparable in efficacy to ECT. While further research is needed, Husain is hopeful in the possibilities that interventional psychiatry can provide for severely depressed patients.

By Sarah Haurin 

How a Museum Became a Lab

Encountering and creating art may be some of mankind’s most complex experiences. Art, not just visual but also dancing and singing, requires the brain to understand an object or performance presented to it and then to associate it with memories, facts, and emotions.

A piece in Dario Robleto’s exhibit titled “The Heart’s Knowledge Will Decay” (2014)

In an ongoing experiment, Jose “Pepe” Contreras-Vidal and his team set up in artist Dario Robleto’s exhibit “The Boundary of Life Is Quietly Crossed” at the Menil Collection near downtown Houston. They then asked visitors if they were willing to have their trips through the museum and their brain activities recorded. Robleto’s work was displayed from August 16, 2014 to January 4, 2015. By engaging museum visitors, Contreras-Vidal and Robleto gathered brain activity data while also educating the public, combining research and outreach.

“We need to collect data in a more natural way, beyond the lab” explained Contreras-Vidal, an engineering professor at the University of Houston, during a talk with Robleto sponsored by the Nasher Museum.

More than 3,000 people have participated in this experiment, and the number is growing.

To measure brain activity, the volunteers wear EEG caps which record the electrical impulses that the brain uses for communication. EEG caps are noninvasive because they are just pulled onto the head like swim caps. The caps allow the museum goers to move around freely so Contreras-Vidal can record their natural movements and interactions.

By watching individuals interact with art, Contreras-Vidal and his team can find patterns between their experiences and their brain activity. They also asked the volunteers to reflect on their visit, adding a first person perspective to the experiment. These three sources of data showed them what a young girl’s favorite painting was, how she moved and expressed her reaction to this painting, and how her brain activity reflected this opinion and reaction.

The volunteers can also watch the recordings of their brain signals, giving them an opportunity to ask questions and engage with the science community. For most participants, this is the first time they’ve seen recordings of their brain’s electrical signals. In one trip, these individuals learned about art, science, and how the two can interact. Throughout this entire process, every member of the audience forms a unique opinion and learns something about both the world and themselves as they interact with and make art.

Children with EEG caps explore art.

Contreras-Vidal is especially interested in the gestures people make when exposed to the various stimuli in a museum and hopes to apply this information to robotics. In the future, he wants someone with a robotic arm to not only be able to grab a cup but also to be able to caress it, grip it, or snatch it. For example, you probably can tell if your mom or your best friend is approaching you by their footsteps. Contreras-Vidal wants to restore this level of individuality to people who have prosthetics.

Contreras-Vidal thinks science can benefit art just as much as art can benefit science. Both he and Robleto hope that their research can reduce many artists’ distrust of science and help advance both fields through collaboration.

Post by Lydia Goff

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