Recipe for success: Reputations start from inner circles​

A study on social network data of EDM DJs finds the relationship between social standing and identity building

Peer-Reviewed Publication

THE KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY (KAIST)

 

IMAGE: FIG 1. TOTAL CITATION NETWORK OF DJS. THE FIGURE SHOWS THE TOTAL CITATION NETWORK OF THE DJS BY ADDING UP THE TEMPORAL NETWORKS FROM EACH TIME WINDOW. THE NODE SIZE REPRESENTS THE TOTAL NUMBER OF CITATIONS BY OTHER DJS. THE EDGE WEIGHT IS PRESENTED BY THE THICKNESS OF THE EDGE. THE COLOR REPRESENTS SIX GROUPS OF MUSICAL STYLES. GROUP 1 (BLUE/PROGRESSIVE HOUSE), GROUP 2 (ORANGE/DUBSTEP, DRUM, & BASS), GROUP 3 (GREEN/ELECTRO HOUSE), GROUP 4 (PINK/TRANCE), GROUP 5 (BROWN/TECHNO, TECH HOUSE), AND GROUP 6 (YELLOW/HARDCORE, HARD DANCE). view more 

CREDIT: KAIST

If you would like to succeed in your career, carve out your own distinctiveness, then break your boundaries along with collaborators. This sounds very common. However, a study on social networks has proven that is the recipe for success.

A recent research on electric dance music DJs’ music identity and their reputation found that music DJs with a distinct genre identity as well as network positions combining brokerage and cohesion tend to place higher in terms of their social standing. 

What do Calvin Harris, the star of Electro house, Diplo, the icon of Moombahton & Trap, Sebastian Ingrosso, the master of Progressive House, and Armin Van Buuren, the leader of Trance have in common? One commonality of these star DJs in the electronic music market is that they are the leaders who build their genres with solid musical identities and are artists who constantly try experimental and innovative connections with other genres.

Professor Wonjae Lee and Dr. Hyeongseok Wi from the Graduate School of Culture and Technology analyzed the playlist data performed by electronic dance music (EDM) DJs at several EDM festivals that were popular around the world before COVID-19 and the track data that they released during that period. 

“This study investigates how social standing is attained within a professional group of artists whose members play a key role in evaluating their artistic products in the EDM market,” said Professor Lee.

Particularly, the team considered DJs' social standing as an effective means of ensuring the quality of their artwork in emerging music markets such as EDM and identified two important factors, the musical identity and the social position within the professional DJ’s group. 

They analyzed the data from 3,164 playlists of 815 DJs who performed at nine festivals held from 2013 to 2016 as a sort of citation network among DJs, and transformed it into network data to measure social positions among the DJs. They considered the DJs who received a lot of citations from other DJs as having a high social standing. In addition, the genre, beats per minute (BPM), and key scale data of the songs released during the period were quantified to analyze the association with the musical identity.

First, the results of analysis of the released track data demonstrated that focused distinct musical identity is correlated with social standing among EDM DJs. The EDM market is an emerging specialist market that is constantly developing and differentiating new styles and genres. It includes artists who establish value criteria and demarcate categorical space into separate identity positions reflecting the artistic forms of a similar type.

Second, this study focuses on the two advantages of two types of social positioning, brokerage and cohesive, which can effectively reduce uncertainty in the market. The results show that DJs with a hybrid position, combining elements of both brokerage and cohesion, have higher social standing. This hybrid position is the most advantageous position for controlling new opportunities and inflows of resources and for utilizing them. Unlike existing studies that divide the merits of the two positions into a dichotomy, this study follows the practice of recent studies that show that the two positions can generate synergy in a complementary manner. 

The remix culture prominent in EDM provides a convincing explanation for this phenomenon. Because constructing playlist sets represents a DJ’s main specialty, the ability to creatively combine a variety of tracks using one’s own artistic style is crucial. To showcase their remix skills, DJs skillfully select tracks to maximize the displays of their talent. Recognized DJs prefer to select tracks from other genres, borrowing from existing contexts and creating new reinterpretations while drawing upon their own musical backgrounds. 

“Acquiring social acknowledgement within a professional group is an effective way to ensure the quality of products they produce and a strong reputation,” explained Professor Lee.

The research team also pointed out the unique case of Techno DJs, who are showing Galápagos syndrome by avoiding crossover between genres and sticking to their own musical identity, unlike most genres in EDM. This research was reported in Plos One on Aug. 25 and funded by KAIST and the BK21 Plus Postgraduate Organization for Content Science.

-Profile
Professor Wonjae Lee
Graduate School of Culture Technology
KAIST

-Publication
Hyeongseok Wi, Wonjae Lee “Stars inside have reached outside: The effects of electronic dance music DJ’s social standing and musical identity on track success,” Aug.25, 2021 Plos
One (https://doi.org/10.1371/journal.pone.0254618)

-About KAIST

KAIST is the first and top science and technology university in Korea. KAIST was established in 1971 by the Korean government to educate scientists and engineers committed to industrialization and economic growth in Korea.

Since then, KAIST and its 67,000 graduates have been the gateway to advanced science and technology, innovation, and entrepreneurship. KAIST has emerged as one of the most innovative universities with more than 10,000 students enrolled in five colleges and seven schools including 1,039 international students from 90 countries.

On the precipice of its semi-centennial anniversary in 2021, KAIST continues to strive to make the world better through its pursuits in education, research, entrepreneurship, and globalization.For more information about KAIST, please visit http://www.kaist.ac.kr/en/.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0254618 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Stars inside have reached outside: The effects of electronic dance music DJ’s social standing and musical identity on track success

ARTICLE PUBLICATION DATE

25-Aug-2021

COI STATEMENT

N/A

 

Moth wingtips an ‘acoustic decoy’ to thwart bat attack, scientists find

Peer-Reviewed Publication

UNIVERSITY OF BRISTOL

 

IMAGE: THE ATLAS MOTH (ATTACUS ATLAS) HAS A STRONG ANTI-BAT ACOUSTIC DECOY AT THE TIP OF ITS FOREWINGS. COMPOSITE IMAGE WITH PHOTOGRAPH ON RIGHT HALF AND ACOUSTIC TOMOGRAPHY ON THE LEFT. COLOUR INDICATES ECHO STRENGTH ON A DB SCALE AND RED INDICATES HIGHEST ECHO AMPLITUDE. NOTE THE RED HIGHLY REFLECTING STRIPE CREATED BY THE RIPPLED PART OF THE WINGTIP. view more 

CREDIT: T. NEIL AND M HOLDERIED

Wingtips of certain species of silkmoth are structured to reflect sound and throw off attackers, according to a new study.

Researchers at the University of Bristol have discovered that the tips of some saturniid moth forewings are curiously rippled and folded. They found that these unique structures strongly reflect sound, meaning that a bat hunting using echolocation is more likely to attack the wingtip region of the moth over the body, potentially saving the moth’s life.

They also discovered that the ripples and folds of the forewing tips have evolved to act as hemispheric and corner retroreflectors respectively, meaning that they reflect sound strongly back to its point of origin. Coupled together, the folds and ripples of these wingtips cover a huge range of incident sounds angles, meaning that over the entire wingbeat cycle of a flying moth and most possible positions of an attacking bat, the wingtip would consistently produce the strongest echoes. The acoustic protection of wingtips is even stronger than that of common hindwing decoys.

Prof Marc Holderied of Bristol’s School of Biological Sciences explained: “We have demonstrated that the folded and rippled wingtips on the forewings of some silkmoths act as acoustic decoys.

“Structurally, the wingtips act as acoustic retroreflectors, reflecting sound back to its source from numerous angles, meaning a bat would be more likely to strike the wingtip over the more vulnerable body of the moth.” 

The findings, published today in Current Biology, are the latest revelation in the bat-moth acoustic arms race - the battle between bats which hunt moths using echolocation, and the subsequent evolution of different defensive strategies amongst moths to increase their chances of survival.

Towed acoustic decoys are a well-established defense amongst some silkmoths. These species have evolved elongated hindwings which terminate in a coiled and twisted end. The morphology of these elongated hindwings means that they generate very strong echoes, so much so that they will often divert a bat’s acoustic gaze towards them, away from the exposed body of the moth, causing the bat to strike the expendable tail of the moth or miss the moth all together.  

Lead author Dr Thomas Neil said: “There are many silkmoths that do not have these elongated hindwings, and we were interested in how they might protect themselves from bats. Through our research we discovered that there are many silkmoths that have rippled and folded structures not on the tips of their elongated hindwings but on the tips of their forewings. These resembled the twisted hindwing structures seen in other moths and so we wanted to know if they might also serve as an acoustic decoy to thwart a bat’s attack.

CAPTION

Photograph of the Atlas moth (Attacus atlas). This large silkmoth has the strongest known wingtip decoy with ripples and folds.

CREDIT

T. Neil

“To test this theory, we used innovative acoustic tomography analysis. We recorded echoes from moths from over 10,000 angles, to compare whether the echoes coming from the wingtips of these moths were stronger than the echoes from the body. If the echoes coming from the rippled and folded wingtips were stronger than that of the body, this would indicate that they were indeed acoustic decoys.    

“Conclusive support for the idea that the forewing reflector is an acoustic decoy comes from our finding that acoustic forewing decoys always evolved as an alternative to acoustic hindwing decoys, with there being no species known to possess both.” 

Now the researchers will try and collect behavioral data to corroborate their findings in the lab. They plan to monitor bats and moths with varying levels of folded wing morphologies to see how much of a survival advantage it really gives them.  

Prof Holderied added: “The results of this study introduce another exciting aspect to the story of the bat-moths acoustic arms race. We have identified a novel form of acoustic defense amongst silkmoths which may give them an advantage over hunting bats. Wider implications might include improved man-made anti radar and sonar decoy architectures.” 

CAPTION

Photograph of the Chinese tussar moth (Antheraea pernyi). This silkmoth has a strong wingtip decoy based on ripples.

CREDIT

T. Neil

Paper:

"­Wingtip folds and ripples on saturniid moths create decoy echoes against bat biosonar" in Current Biology by Thomas Neil, Ella Kennedy, Brogan Harris, and Marc Holderied.

 

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JOURNAL

Current Biology

METHOD OF RESEARCH

News article

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Wingtip folds and ripples on saturniid moths create decoy echoes against bat biosonar

ARTICLE PUBLICATION DATE

9-Sep-2021

Small, mighty robots mimic the powerful punch of mantis shrimp

Robot models the mechanics of the strongest punch in the animal kingdom

Peer-Reviewed Publication

U.S. ARMY RESEARCH LABORATORY

 

IMAGE: RESEARCHERS WITH ARMY FUNDING BUILD A ROBOT THAT MIMICS THE STRONG PUNCH OF A MANTIS SHRIMP. view more 

CREDIT: SECOND BAY STUDIOS AND ROY CALDWELL/HARVARD SEAS

RESEARCH TRIANGLE PARK, N.C. -- Modeling the mechanics of the strongest punch in the animal kingdom, researchers with U.S. Army funding built a robot that mimics the movement of the mantis shrimp. These pugnacious crustaceans could pave the way for small, but mighty robotic devices for the military.

Researchers at Harvard University and Duke University, published their work in Proceedings of the National Academy of Sciences. They shed light on the biology of mantis shrimp, whose club-like appendages accelerate faster than a bullet out of a gun. Just one strike can knock the arm off a crab or break through a snail shell. These crustaceans have even taken on an octopus and won.

“The idea of a loaded spring released by a latch is a staple in mechanical design, but the research team cleverly observed that engineers have yet to achieve the same performance out of a Latch-Mediated Spring Actuator that we find in nature,” said Dr. Dean Culver program manager, U.S. Army Combat Capabilities Development Command Army Research Laboratory. “By more closely mimicking the geometry of a mantis shrimp's physiology, the team was able to exceed accelerations produced by limbs in other robotic devices by more than tenfold.”

How mantis shrimp produce these deadly, ultra-fast movements has long fascinated biologists. Recent advancements in high-speed imaging make it possible to see and measure these strikes, but some of the mechanics have not been well understood.

Many small organisms, including frogs, chameleons, and even some kinds of plants, produce ultra-fast movements by storing elastic energy and rapidly releasing it through a latching mechanism, like a mouse trap. In mantis shrimp, two small structures embedded in the tendons of the muscles called sclerites act as the appendage’s latch. In a typical spring-loaded mechanism, once the physical latch is removed, the spring would immediately release the stored energy, but when the sclerites unlatch in a mantis shrimp appendage, there is a short but noticeable delay.

“When you look at the striking process on an ultra-high-speed camera, there is a time delay between when the sclerites release and the appendage fires,” said Nak-seung Hyun, a postdoctoral fellow at Harvard John A. Paulson School of Engineering and Applied Sciences and co-first author of the paper. “It is as if a mouse triggered a mouse trap, but instead of it snapping right away, there was a noticeable delay before it snapped. There is obviously another mechanism holding the appendage in place, but no one has been able to analytically understand how the other mechanism works.”

Biologists have hypothesized that while the sclerites initiate unlatching, the geometry of the appendage itself acts as a secondary latch, controlling the movement of the arm while it continues to store energy. But this theory had not yet been tested.

The research team tested this hypothesis first by studying the linkage mechanics of the system, then building a physical, robotic model. Once they had the robot, the team was able to develop a mathematical model of the movement. The researchers mapped four distinct phases of the mantis strike, starting with the latched sclerites and ending with the actual strike of the appendage. They found that, indeed, after the sclerites unlatch, geometry of the mechanism takes over, holding the appendage in place until it reaches an over-centering point and then the latch releases.

“This process controls the release of stored elastic energy and actually enhances the mechanical output of the system,” said Emma Steinhardt, a graduate student at Harvard John A. Paulson School of Engineering and Applied Sciences and first author of the paper. “The geometric latching process reveals how organisms generate extremely high acceleration in these short duration movements, like punches.”

The device is faster than any similar devices at the same scale to date.

“This study exemplifies how interdisciplinary collaborations can yield discoveries for multiple fields,” said co-author Dr. Sheila Patek, professor of biology at Duke University. “The process of building a physical model and developing the mathematical model led us to revisit our understanding of mantis shrimp strike mechanics and, more broadly, to discover how organisms and synthetic systems can use geometry to control extreme energy flow during ultra-fast, repeated-use, movements.”

This approach of combining physical and analytical models could help biologists understand and roboticists mimic some of nature’s other extraordinary feats, such as how trap jaw ants snap their jaws so quickly or how frogs propel themselves so high.

“Actuator architecture like this offers impressive capabilities to small and lightweight mechanisms that need to deliver impulsive forces for the Army,” Culver said. “But I think there's a broader takeaway here - something the engineering community and defense research can keep in mind. We're not done learning about mechanical performance from nature and biological systems. Things we take for granted, like a simple sprung actuator, are still ripe for further investigation at many scales."

Visit the laboratory's Media Center to discover more Army science and technology stories

# # # 

As the Army’s foundational research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command’s core technical competencies, DEVCOM leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation’s wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2026833118 

ARTICLE TITLE

A physical model of mantis shrimp for exploring the dynamics of ultrafast systems

ARTICLE PUBLICATION DATE

17-Aug-2021

 

Regular exercise may lower risk of developing anxiety by almost 60%

The findings of a study published with Frontiers suggests that those who engage in regular exercise may lower their risk of developing anxiety by almost 60%.

Peer-Reviewed Publication

FRONTIERS

A quick online search for ways to improve our mental health will often come up with a myriad of different results. However, one of the most common suggestions put forward as a step to achieving wellness – and preventing future issues – is doing some physical exercise, whether it be a walk or playing a team sport.

Anxiety disorders – which typically develop early in a person’s life – are estimated to affect approximately 10% of the world’s population and has been found to be twice as common in women compared to men. And while exercise is put forward as a promising strategy for the treatment of anxiety, little is known about the impact of exercise dose, intensity or physical fitness level on the risk of developing anxiety disorders.

To help answer this question, researchers in Sweden have published a study in Frontiers in Psychiatry to show that those who took part in the world’s largest long-distance cross-country ski race (Vasaloppet) between 1989 and 2010 had a “significantly lower risk” of developing anxiety compared to non-skiers during the same period.

The study is based on data from almost 400,000 people in one of the largest ever population-wide epidemiology studies across both sexes.

Surprising finding among female skiers

“We found that the group with a more physically active lifestyle had an almost 60% lower risk of developing anxiety disorders over a follow-up period of up to 21 years,” said first author of the paper, Martine Svensson, and her colleague and principal investigator, Tomas Deierborg, of the Department of Experimental Medical Science at Lund University, Sweden.

“This association between a physically active lifestyle and a lower risk of anxiety was seen in both men and women.”

However, the authors found a noticeable difference in exercise performance level and the risk of developing anxiety between male and female skiers.

While a male skier’s physical performance did not appear to affect the risk of developing anxiety, the highest performing group of female skiers had almost the double risk of developing anxiety disorders compared to the group which was physically active at a lower performance level.

“Importantly,” they said, “the total risk of getting anxiety among high-performing women was still lower compared to the more physically inactive women in the general population”.

These findings cover relatively uncharted territory for scientific research, according to the researchers, as most previous studies focused on depression or mental illness as opposed to specifically diagnosed anxiety disorders. Furthermore, some of the largest studies looking at this topic only included men, were much smaller in sample size, and had either limited or no follow-up data to track the long-term effects of physical activity on mental health.

Next steps for research

The surprising discovery of an association between physical performance and the risk for anxiety disorders in women also emphasized the scientific importance of these findings for follow-up research.

“Our results suggest that the relation between symptoms of anxiety and exercise behavior may not be linear,” Svensson said.

“Exercise behaviors and anxiety symptoms are likely to be affected by genetics, psychological factors, and personality traits, confounders that were not possible to investigate in our cohort. Studies investigating the driving factors behind these differences between men and women when it comes to extreme exercise behaviors and how it affects the development of anxiety are needed.”

They added that randomized intervention trials, as well as long-term objective measurements of physical activity in prospective studies, are also needed to assess the validity and causality of the association they reported. But does this mean that skiing in particular can play an important role in keeping anxiety at bay, as opposed to any other form of exercise? Not so, Svensson and Deierborg said, given that previous studies have also shown the benefits of keeping fit on our mental health.

“We think this cohort of cross-country skiers is a good proxy for an active lifestyle, but there could also be a component of being more outdoors among skiers,” they said.

“Studies focusing on specific sports may find slightly different results and magnitudes of the associations, but this is most likely due to other important factors that affect mental health and which you cannot easily control in research analysis.”

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JOURNAL

Frontiers in Psychiatry

DOI

10.3389/fpsyt.2021.714014 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Physical activity is associated with lower long-term incidence of anxiety in a population-based, large-scale study

ARTICLE PUBLICATION DATE

10-Sep-2021

COI STATEMENT

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 

Smart dental implants

Geelsu Hwang of the University of Pennsylvania and colleagues are developing a smart dental implant that resists bacterial growth and generates its own electricity through chewing and brushing to power a tissue-rejuvenating light.

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA

More than 3 million people in America have dental implants, used to replace a tooth lost to decay, gum disease, or injury. Implants represent a leap of progress over dentures or bridges, fitting much more securely and designed to last 20 years or more.

But often implants fall short of that expectation, instead needing replacement in five to 10 years due to local inflammation or gum disease, necessitating a repeat of a costly and invasive procedure for patients.

“We wanted to address this issue, and so we came up with an innovative new implant,” says Geelsu Hwang, an assistant professor in the University of Pennsylvania School of Dental Medicine, who has a background in engineering that he brings to his research on oral health issues.

The novel implant would implement two key technologies, Hwang says. One is a nanoparticle-infused material that resists bacterial colonization. And the second is an embedded light source to conduct phototherapy, powered by the natural motions of the mouth, such as chewing or toothbrushing. In a paper in the journal ACS Applied Materials & Interfaces and a 2020 paper in the journal Advanced Healthcare Materials, Hwang and colleagues lay out their platform, which could one day be integrated not only into dental implants but other technologies, such as joint replacements, as well.

“Phototherapy can address a diverse set of health issues,” says Hwang. “But once a biomaterial is implanted, it’s not practical to replace or recharge a battery. We are using a piezoelectric material, which can generate electrical power from natural oral motions to supply a light that can conduct phototherapy, and we find that it can successfully protect gingival tissue from bacterial challenge.”

In the paper, the material the researchers explored was barium titanate (BTO), which has piezoelectric properties that are leveraged in applications such as capacitators and transistors, but has not yet been explored as a foundation for anti-infectious implantable biomaterials. To test its potential as the foundation for a dental implant, the team first used discs embedded with nanoparticles of BTO and exposed them to Streptococcus mutans, a primary component of the bacterial biofilm responsible for tooth decay commonly known as dental plaque. They found that the discs resisted biofilm formation in a dose-dependent manner. Discs with higher concentrations of BTO were better at preventing biofilms from binding.

While earlier studies had suggested that BTO might kill bacteria outright using reactive oxygen species generated by light-catalyzed or electric polarization reactions, Hwang and colleagues did not find this to be the case due to the short-lived efficacy and off-target effects of these approaches. Instead, the material generates enhanced negative surface charge that repels the negatively charged cell walls of bacteria. It’s likely that this repulsion effect would be long-lasting, the researchers say.

“We wanted an implant material that could resist bacterial growth for a long time because bacterial challenges are not a one-time threat,” Hwang says.

The power-generating property of the material was sustained and in tests over time the material did not leach. It also demonstrated a level of mechanical strength comparable to other materials used in dental applications.

Finally, the material did not harm normal gingival tissue in the researchers’ experiments, supporting the idea that this could be used without ill effect in the mouth.

The technology is a finalist in the Science Center’s research accelerator program, the QED Proof-of-Concept program. As one of 12 finalists, Hwang and colleagues will receive guidance from experts in commercialization. If the project advances to be one of three finalists, the group has the potential to receive up to $200,000 in funding.

In future work, the team hopes to continue to refine the “smart” dental implant system, testing new material types and perhaps even using assymetric properties on each side of the implant components, one that encourages tissue integration on the side facing the gums and one that resists bacterial formation on the side facing the rest of the mouth.

“We hope to further develop the implant system and eventually see it commercialized so it can be used in the dental field,” Hwang says.

Geelsu Hwang is an assistant professor in the Division of Restorative Dentistry and Department of Preventive and Restorative Sciences in the University of Pennsylvania’s School of Dental Medicine.

Hwang’s coauthors on the paper were Penn Dental Medicine’s Atul Dhall and Yu Zhang and Temple University’s Sayemul Islam, Moonchul Park, and Albert Kim.

The research was supported by the National Institutes for Dental and Craniofacial Research(Grant DE027970) and the National Science Foundation (Grant 2029077). It was carried out in part at Penn’s Singh Center for Nanotechnology, which is supported by the NSF National Nanotechnology Coordinated Infrastructure Program under Grant NNCI-1542153.

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DOI

10.1021/acsami.1c11791 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications

ARTICLE PUBLICATION DATE

18-Aug-2021

Preventing the long-term effects of traumatic brain injury

New study points to a potential new treatment that could prevent chronic complications

Peer-Reviewed Publication

GLADSTONE INSTITUTES

 

IMAGE: A TEAM OF RESEARCHERS LED BY JEANNE PAZ (LEFT) AND STEPHANIE HOLDEN (RIGHT) POINTS TO A POTENTIAL NEW TREATMENT THAT COULD PREVENT THE LONG-TERM EFFECTS OF TRAUMATIC BRAIN INJURY. view more 

CREDIT: PHOTO: MICHAEL SHORT/GLADSTONE INSTITUTES

SAN FRANCISCO, CA—September 9, 2021—You’ve been in a car accident and sustained a head injury. You recovered, but years later you begin having difficulty sleeping. You also become very sensitive to noise and bright lights, and find it hard to carry out your daily activities, or perform well at your job.

This is a common situation after a traumatic brain injury—many people experience bad side effects months or years later. These long-term effects can last a few days or the rest of a person’s life.

“No therapies currently exist to prevent the disabilities that can develop after a brain trauma,” says Jeanne Paz, PhD, associate investigator at Gladstone Institutes. “So, understanding how the traumatic brain injury affects the brain, especially in the long term, is a really important gap in research that could help develop new and better treatment options.”

In a new study published in the journal Science, Paz and her team helped close that gap. They identified a specific molecule in a part of the brain called the thalamus that plays a key role in secondary effects of brain injury, such as sleep disruption, epileptic activity, and inflammation. In collaboration with scientists at Annexon Biosciences, a clinical-stage biopharmaceutical company, they also showed that an antibody treatment could prevent the development of these negative outcomes.

A Vulnerable Brain Region

Traumatic brain injuries, which range from a mild concussion to a severe injury, can be the result of a fall, sports injury, gunshot injury, blow to the head, explosion, or domestic violence. Often, soldiers returning from war also suffer head injuries, which commonly lead to the development of epilepsy. Traumatic brain injury affects 69 million people around the world annually, and is the leading cause of death in children and a major source of disability in adults.

“These injuries are frequent and can happen to anyone,” says Paz, who is also an associate professor of neurology at UC San Francisco (UCSF) and a member of the Kavli Institute for Fundamental Neuroscience. “The goal of our study was to understand how the brain changes after traumatic brain injuries and how those changes can lead to chronic problems, such as the development of epilepsy, sleep disruption, and difficulty with sensory processing.”

To do so, Paz and her team recorded the activity of different cells and circuits in the brain of mice after brain injury. The researchers monitored the mice continually and wirelessly, meaning the mice could go about their normal activities without being disrupted.

“We collected so much data, from the time of injury and over the next several months, that it actually crashed our computers,” says Paz. “But it was important to capture all the different stages of sleep and wakefulness to get the whole picture.”

During a trauma to the head, the region of the brain called the cerebral cortex is often the primary site of injury, because it sits directly beneath the skull.

But at later time points, the researchers discovered that another region—the thalamus—was even more disrupted than the cortex. In particular, they found that a molecule called C1q was present at abnormally high levels in the thalamus for months after the initial injury, and these high levels were associated with inflammation, dysfunctional brain circuits, and the death of neurons.

“The thalamus seems particularly vulnerable, even after a mild traumatic brain injury,” says Stephanie Holden, PhD, first author of the study and former graduate student in Paz’s lab at Gladstone. “This doesn’t mean the cortex isn’t affected, but simply that it might have the necessary tools to recover over time. Our findings suggest that the higher levels of C1q in the thalamus could contribute to several long-term effects of brain injury.”

The Paz Lab collaborated with Eleonora Aronica, MD, PhD, a neuropathologist at the University of Amsterdam, to validate their findings in human brain tissues obtained from autopsies, in which they found high levels of the C1q molecule in the thalamus 8 days after people had sustained a traumatic brain injury. In addition, by working with fellow Gladstone Assistant Investigator Ryan Corces, PhD, they determined that C1q in the thalamus likely came from microglia, the immune cells in the brain.

“Our study answered some very big questions in the field about where and how changes are happening in the brain after a trauma, and which ones are actually important for causing deficits,” says Paz.

The Right Window to Treat Chronic Effects After Traumatic Brain Injury

The C1q molecule, which is part of an immune pathway, has well-documented roles in brain development and normal brain functions. For instance, it protects the central nervous system from infection and helps the brain forget memories—a process needed to store new memories. The accumulation of C1q in the brain has also been studied in various neurological and psychiatric disorders and is associated, for example, with Alzheimer’s disease and schizophrenia.

“C1q can be both good and bad,” says Paz. “We wanted to find a way to prevent this molecule’s detrimental effect, but without impacting its beneficial role. This is an example of what makes neuroscience a really hard field these days, but it’s also what makes it exciting.”

She and her group decided to leverage the “latent phase” after a traumatic brain injury, during which changes are occurring in the brain but before long-term symptoms appear.

“My cousin, for example, was hit in the head when he was 10 years old, and the impact broke his skull and damaged his brain,” says Paz. “But it wasn’t until he was 20 that he developed epilepsy. This latent phase presents a window of opportunity for us to intervene in hopes of modifying the disease and preventing any complications.”

Paz reached out to her collaborators at Annexon Biosciences, who produce a clinical antibody that can block the activity of the C1q molecule. Then, her team treated the mice who sustained brain injury with this antibody to see if it might have beneficial effects.

When the researchers studied mice genetically engineered to lack C1q at the time of the trauma, the brain injury appeared much worse. However, when they selectively blocked C1q with the antibody during the latent phase, they prevented chronic inflammation and the loss of neurons in the thalamus.

“This indicates that the C1q molecule shouldn’t be blocked at the time of injury, because it’s likely very important at this stage for protecting the brain and helping prevent cell death,” says Holden. “But at later time points, blocking C1q can actually reduce harmful inflammatory responses. It’s a way of telling the brain, ‘It’s okay, you’ve done the protective part and you can now turn off the inflammation.’”

“There is a paucity of treatments for patients who have suffered from an acute brain injury,” says Ted Yednock, PhD, executive vice president and chief scientific officer at Annexon Biosciences, and an author of the study. “This result is exciting because it suggests that we could treat patients in the hours to days after an acute injury like traumatic brain injury to protect against secondary neuronal damage and provide significant functional benefit.”

Path to a Potential Treatment

In addition to chronic inflammation, Paz and her team also uncovered abnormal brain activity in the mice with traumatic brain injury.

First, the researchers noticed disruptions in sleep spindles, which are normal brain rhythms that occur during sleep. These are important for memory consolidation, among other things. The scientists also found epileptic spikes, or abnormal fluctuations in brain activity. These spikes can be disruptive to cognition and normal behavior, and are also indicative of a greater susceptibility to seizures.

The scientists observed that the anti-C1q antibody treatment not only helped restore the sleep spindles, but also prevented the development of epileptic activities.

“Overall, our study indicates that targeting the C1q molecule after injury could avoid some of the most devastating, long-term consequences of traumatic brain injury,” says Holden. “We hope this could eventually lead to the development of treatments for traumatic brain injury.”

Annexon’s anti-C1q inhibitors are designed to treat multiple autoimmune and neurological disorders, and are already being examined in clinical trials, including for an autoimmune disorder known as Guillain-Barré syndrome, where the drug has been shown to be safe in humans.

“The fact that the drug is already in clinical trials may speed the pace at which a treatment could eventually be made available to patients,” says Yednock. “We already understand doses of drug that are safe and effective in patients for blocking C1q in the brain, and could move directly into studies that ameliorate the chronic effects after traumatic brain injury.”

For Holden, who previously worked with individuals who experienced brain injury and heard many of their personal stories, the impact of this study is particularly meaningful.

“Brain injury is a hidden disability for many of the people I met,” she says. “The side effects they experience can be difficult to diagnose and their physicians often can’t provide any medical treatment. Being able to contribute to finding ways to treat the detrimental consequences of the injury after it happens is really inspiring.”

Paz and her lab are continuing to expand their understanding of what happens in the brain after injury. Next, they will focus on studying whether they can help prevent convulsive seizures, which are often reported by people with severe traumatic brain injuries.

“The holy grail would be to have a treatment that could be offered to a patient after a trauma and that would prevent chronic inflammation in the brain, sleep disruption, and seizures,” she adds. “Wouldn’t it be wonderful if our study helped make that a reality?”

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About the Study

The paper “Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury" was published by the journal Science on September 10, 2021.

Other authors include Fiorella C. Grandi, Oumaima Aboubakr, Bryan Higashikubo, Frances S. Cho, Andrew H. Chang, and Allison R. Morningstar from Gladstone; Alejandro Osorio Forero and Anita Luthi from the University of Lausanne; Vidhu Mathur, Logan J. Kuhn, Poojan Suri, Sethu Sankaranarayanan, and Yaisa Andrews-Zwilling from Annexon Biosciences; Andrea J. Tenner from the University of California, Irvine; and Eleonora Aronica from the University of Amsterdam.

The work at Gladstone was funded by the Department of Defense (grant EP150038), as well as the National Institutes of Health (grants R01 NS078118, T32-GM007449, and F31 NS111819-01A1), the National Science Foundation (grants 1608236 and 1144247), Gladstone Institutes, the Michael Foundation, the Vilcek Foundation, the ARCS Foundation, the Kavli Institute for Fundamental Neuroscience at UCSF, the Ford Foundation Dissertation Fellowship, the Weill Foundation, the American Epilepsy Society, and the Graduate Division at UCSF.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.

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JOURNAL

Science

DOI

10.1126/science.abj2685 

ARTICLE TITLE

Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury

ARTICLE PUBLICATION DATE

10-Sep-2021