Duke Research Blog

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

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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.”

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

Sean Carroll on the Evolution of Snake Venom

What’s in a snake bite?

According to University of Wisconsin-Madison evolutionary biologist Sean Carroll who visited Duke and Durham last week, a snake bite contains a full index of clues.

In his recent research, Carroll has been studying the adaptations of novelties in animal form, such as snake venom. Rattlesnakes, he explains, are the picture of novelty. With traits such as a limbless body, fangs, infrared pits, patterned skin, venom, and the iconic rattle, they represent an amazing incarnation of evolution at work.

Rattlesnakes: the picture of novelty (Photo from USGS)

Snake venoms contain a complex mixture of proteins. This mixture can differ in several ways, but the most interesting difference to Carroll is the presence or absence of neurotoxins. Neurotoxic venom has proven to be a very useful trait, because neurotoxins destroy the nervous tissue of prey, effectively paralyzing the animal’s respiratory system.

Some of today’s rattlesnake species have neurotoxic venom, but some don’t. So how did this happen? That’s what Carroll was wondering too.

Some genes within genomes, such as HOX genes, evolve very slowly from their original position among the chromosomes, and see very few changes in the sequence in millions of years.

But snake venom Pla2 genes are quite the opposite. In recent history, there has been a massive expansion of these genes in the snake genome, Carroll said. When animals evolve new functions or forms, the question always arises: are these changes the result of brand new genes or old genes taking on new functions?

Another important consideration is the concept of regulatory versus structural genes. Regulatory genes control the activity of other genes, such as structural genes, and because of this, duplicates of regulatory genes are generally not going to be a favorable adaptation. In contrast, structural gene activity doesn’t affect other genes, and duplicates are often a positive change. This means it is easier for a new structural gene to evolve than a regulatory one. Carroll explained.

Evolutionary Biologist Sean Carroll (Photo from seanbcarroll.com)

Carroll examined neurotoxic and non-neurotoxic snakes living in overlapping environments. His research showed that the most recent common ancestor of these species was a snake with neurotoxic venom. When comparing the genetic code of neurotoxic snakes to non-neurotoxic ones, he found that the two differed by the presence or absence of 16 genes in the metalloproteinase gene complex. He said this meant that non-neurotoxic venom could not evolve from neurotoxic venom.

So what is the mechanism behind this change? What could be the evolutionary explanation?

When Carroll’s lab compared another pair of neurotoxic and non-neurotoxic species in a different region of the US, they found that the two species differed in exactly the same way, with the same set of genes deleted as had been observed in the first discovery. With this new information, Carroll realized that the differences must have occurred through the mechanism of hybridization, or the interbreeding of neurotoxic and non-neurotoxic species.

Carroll’s lab is now doing the structural work to study if the genes that result in neurotoxic and  non-neurotoxic protein complexes are old genes carrying out new functions or entirely new genes. They are using venom gland organoids to look into the regulatory processes of these genes.

In addition to his research studying the evolution of novelties, Carroll teaches molecular biology and genetics at Madison and has devoted a large portion of his career to  storytelling and science education.

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

 

Falling Out of Love With Science and Our Civic Duties

Last Friday, I attended Falling Out of Love with Science, a lunch function during which Milan Yager,executive director of the American Institute for Medical and Biological Engineering, discussed why those of us interested in scientific research should care about the actions of prominent politicians, especially those that relate to the underfunding of scientific research.

Milan Yager of AIMBE

Milan Yager is the executive director of the American Institute for Medical and Biological Engineering.

Before attending Yager’s talk, I guess I didn’t quite realize how much of innovation was enabled by government funding. Many revolutionary discoveries are made possible through the NIH (https://www.nih.gov) that we don’t even realize we use on a daily basis.

However, as I came to realize, public support for research funding is jeopardized by the propagation of fake news defeating the need for concrete scientific research, hence propelling research under-funding. Over time, funding for the NIH and other government research funding has declined, which has slowed American innovation.

What I enjoyed most about his talk however, was the unexpected motivational turn that it took at the end. He discussed how we, as young researchers invested in finding our personal truths through science, needed to use our voices to stand up against the proliferation of myths in politics in favor of concrete facts.

NIH funding trends

Here’s a curve we definitely want to bend: NIH research funding has flattened and fallen.

Though this can be done in different ways, Yager made sure to point out how essential it is for Americans to vote, citing a statistic that points out that 20 percent of Americans don’t vote because they are “simply too lazy.” (Learn how to register to vote in North Carolina.)

He also encouraged us to send letters to our senators, rally for what we believed in, and not give up on our goals in the face of adversity — something that he called “sitting at the table.” Yager points out that if you don’t “sit at the table,” then your issue won’t get the necessary exposure needed for it to be fixed.

What can we, as Duke students, take away from what Yager had to say? Mainly this: Duke is a research institution that is partially made capable by government funding; for our capacity for research to be continued to be fully realized, we must use our voices to make sure that the propagation of ‘fake news’ does not cut funding for factual research.

This is mainly achieved by voting– those who perpetuate false “facts” in order to remain in power must be replaced with those who realize the importance of scientific research.

Perhaps, for society to fall back in love with science, we need to fall out of love with the myths propagated by tribal politics.

Post by Rebecca Williamson

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

Combatting the Opioid Epidemic

The opioid epidemic needs to be combatted in and out of the clinic.

In the U.S. 115 people die from opioids every day. The number of opioid overdoses increased fivefold from 1999 to 2016. While increased funding for resources like Narcan has helped — the opioid overdose-reversing drug now carried by emergency responders in cities throughout the country — changes to standard healthcare practices are still sorely needed.

Ashwin A Patkar, MD, medical director of the Duke Addictions Program, spoke to the Duke Center on Addiction and Behavior Change about how opioid addiction is treated.

The weaknesses of the current treatment standards first appear in diagnosis. Heroin and cocaine are currently being contaminated by distributors with fentanyl, an opioid that is 25 to 50 times more potent than heroin and cheaper than either of these drugs. Despite fentanyl’s prevalence in these street drugs, the standard form and interview for addiction patients does not include asking about or testing for the substance.

Patkar has found that 30 percent of opioid addiction patients have fentanyl in their urine and do not disclose it to the doctor. Rather than resulting from the patients’ dishonesty, Patkar believes, in most cases, patients are taking fentanyl without knowing that the drugs they are taking are contaminated.

Because of its potency, fentanyl causes overdoses that may require more Narcan than a standard heroin overdose. Understanding the prevalence of Narcan in patients is vital both for public health and educating patients so they can be adequately prepared.

Patkar also pointed out that, despite a lot of research supporting medication-assisted therapy, only 21 percent of addiction treatment facilities in the U.S. offer this type of treatment. Instead, most facilities rely on detoxification, which has high rates of relapse (greater than 85 percent within a year after detox) and comes with its own drawbacks. Detox lowers the patient’s tolerance to the drug, but care providers often neglect to tell the patients this, resulting in a rate of overdose that is three times higher than before detox.

Another common treatment for opioid addiction involves using methadone, a controlled substance that helps alleviate symptoms from opioid withdrawal. Because retention rate is high and cost of production is low, methadone poses a strong financial incentive. However, methadone itself is addictive, and overdose is possible.

Patkar points to a resource developed by Julie Bruneau as a reference for the Canadian standard of care for opioid abuse disorder. Rather than recommending detox or methadone as a first line of treatment, Bruneau and her team recommend buprenorphine , and naltrexone as a medication to support abstinence after treatment with buprenorphine.

Buprenorphine is a drug with a similar function as methadone, but with better and safer clinical outcomes. Buprenorphine does not create the same euphoric effect as methadone, and rates of overdose are six times less than in those prescribed methadone.

In addition to prescribing the right medicine, clinicians need to encourage patients to stick with treatment longer. Despite buprenorphine having good outcomes, patients who stop taking it after only 4 to 12 weeks, even with tapering directed by a doctor, exhibit only an 18 percent rate of successful abstinence.

Patkar closed his talk by reminding the audience that opioid addiction is a brain disease. In order to see a real change in the number of people dying from opioids, we need to focus on treating addiction as a disease; no one would question extended medication-based treatment of diseases like diabetes or heart disease, and the same should be said about addiction. Healthcare providers have a responsibility to treat addiction based on available research and best practices, and patients with opioid addiction deserve a standard of care the same as anyone else.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger 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

Better Butterfly Learners Take Longer to Grow Up

Emilie Snell-Rood studies butterflies to understand the factors that influence plasticity.

The ability of animals to vary their phenotypes, or physical expression of their genes, in different environments is a key element to survival in an ever-changing world.

Emilie Snell-Rood, PhD, of the University of Minnesota, is interested in why this phenomena of plasticity varies. Some animals’ phenotypes are relatively stable despite varying environmental pressures, while others display a wide range of behaviors.

Researchers have looked into how the costs of plasticity limit its variability. While many biologists expected that energetic costs should be adequate explanations for the limits to plasticity, only about 30 percent of studies that have looked for plasticity-related costs have found them.

Butterflies’ learning has provided insight into developmental plasticity.

With her model of butterflies, Snell-Rood has worked to understand why these researchers have come up with little results.

Snell-Rood hypothesized that the life history of an animal, or the timing of major developmental events like weaning, should be of vital importance in the constraints on plasticity, specifically on the type of plasticity involved in learning. Much of learning involves trial and error, which is costly – it requires time, energy, and exposure to potential predators while exploring the environment.

Additionally, behavioral flexibility requires an investment in developing brain tissue to accommodate this learning.

Because of these costs, animals that engage in this kind of learning must forgo reproduction until later in life.

To test the costs of learning, Snell-Rood used butterflies as a subject. Butterflies require developmental plasticity to explore their environments and optimize their food finding strategies. Over time, butterflies get more efficient at landing on the best host plants, using color and other visual cues to find the best food sources.

Studying butterfly families shows that families that are better learners have increased volume in the part of the brain associated with sensory integration. Furthermore, experimentally speeding up an organism’s life history leads to a decline in learning ability.

These results support a tradeoff between an organism’s developmental plasticity and life history. While this strategy is more costly in terms of investment in neural development and energy investment, it provides greater efficacy in adaptation to environment. However, further pressures from resource availability can also influence plasticity.

Looking to the butterfly model, Snell-Rood found that quality nutrition increases egg production as well as areas of the brain associated with plasticity.

Understanding factors that influence an animal’s plasticity is becoming increasingly important. Not only does it allow us to understand the role of plasticity in evolution up to this point, but it allows us to predict how organisms will adapt to novel and changing environments, especially those that are changing because of human influence. For the purposes of conservation, these predictions are vital.

By Sarah Haurin

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 

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