Feature | Leaving Fear Behind

 



GSU's Elliott Albers heads the Center for Behavioral Neuroscience, a research and education consortium of eight Atlanta institutions, including Emory, where scientists are studying the neurobiology of fear, aggression, affiliation, and reproduction.



A cross-section of the brain shows striking differences in activation (red areas) in the amygdala between a male brain (left) and a female brain while the subjects were watching sexually arousing images.



Emory School of Medicine's Xiaoping Hu (above) and GSU's Don Edwards developed an innovative MRI technique to identify anatomical structures and neural pathways in animals as small as crayfish, a widely used animal model for the study of aggression.



A member of the aggression collaboratory, Morehouse College psychologist Duane Jackson and students study the neurobiology of organized warfare in termites.



CBN scientists at Emory who study the amygdala will move under one roof when Yerkes opens its new $27 million neuroscience building next fall. It will also house state-of-the-art brain imaging equipment, and an entire floor will be devoted to CBN researchers at Emory -- one of the highest densities of scientists in the world studying a single region of the brain.

We've created an exceptional and diverse community of scientists who are uniquely suited to answer the complex questions behavioral neuroscience poses.


Changing the face of neuroscience

Ebony Glover first became interested in neuroscience as an undergraduate at Spelman College. Although she had previously planned on a career in medicine, a Center for Behavioral Neuroscience (CBN) faculty member encouraged her to consider studying neuroscience. Through a CBN mentoring program called BRAIN (Behavioral Research Advancements in Neuroscience), Glover had the opportunity to work side-by-side with the CBN's Mike Davis (see previous article) and gain valuable research experience that ultimately led to her admission to Emory's graduate psychology program.

The CBN graduate scholar, who now studies fear conditioning in Davis' lab, wants to be a role model for African-American women considering careers in neuroscience. "I want to go into academia," said Glover, "and hopefully start a neuroscience program geared specifically toward African-American women."



Ebony Glover wants to be a role model for African-American women considering careers in neuroscience.

Minority recruitment has historically been a problem for all science disciplines. Less than 1% of all doctorates awarded annually in neuroscience go to African-Americans. This lack of diversity stymies discovery, especially in neuroscience where complex problems require a range of analytical perspectives.

As part of its mandate from the National Science Foundation (NSF), the CBN is working to improve those statistics through an array of educational programs designed to attract minority students at many points during their education and retain them in the neurosciences.

"These programs will make Atlanta an international center to study behavioral neuroscience," says Paul Lennard, CBN co-director and director of Emory's neuroscience and behavioral biology program. "They focus on getting students excited about neuroscience early in their education and attract them to careers in the field."

CBN education programs focus on recruiting and retaining minority students.


The CBN's undergraduate education programs have been especially successful in recruiting African-Americans to study neuroscience. Headed by Emory's Danielle Gray, CBN deputy director for education, BRAIN has attracted more than 200 undergraduates, mostly African-Americans from institutions throughout the consortium, for 13-week immersions in a CBN "collaboratory."

"We have the potential to make a great contribution at the undergraduate level," says Peter MacLeish, director of the Morehouse School of Medicine Neuroscience Institute and a member of the CBN management team. "This is the time when students are deciding what they will be doing later in life."

MacLeish believes the CBN has hastened the acceptance of neuroscience in the undergraduate curriculum. The CBN recently developed a catalog of neuroscience-related courses to encourage more undergraduates to study neuroscience and facilitate cross-institutional course registration.

The CBN also helped inaugurate a new program called PROMISE (Postbaccalaureate Research Opportunities for Minorities in the Biomedical Sciences) with a $2.45 million grant from the National Institutes of Health. More than a dozen minority students who graduated last spring are currently participating in intensive biomedical research experiences in preparation for graduate school. The program also includes graduate-level courses and a GRE preparatory course.

Like BRAIN, PROMISE establishes a comprehensive support system designed to nurture minority students through the education pipeline. "When our students embark on a career in behavioral neuroscience, they are going to be afforded many mentors in the CBN," says Gray. "They're going to be part of a living, breathing learning center."


In this issue

From the CEO / Letters
No fear
Consummate chemistry
Moving forward
Noteworthy
On Point:
  The toughest decision
Last Word:
  Your voice counts in tort reform

 

 



 

By Poul Olson    

 

Beth Cox glows today with the image of a transformed woman. Until last year, the 50-year-old had spent most of her adult life avoiding elevators, bridges, even vacations. "My family and I drove to the top of Pike's Peak one summer," recalls Cox, "and I missed the whole experience because I was cowering in the back seat with my head down."

The elementary reading and math teacher had no hope of overcoming her abnormal fear of heights until she saw a television commercial seeking volunteers for a fear of heights study led by researchers at the Center for Behavioral Neuroscience (CBN). "I must have been the first one to call," she says.

Cox is among some 19 million Americans who suffer from acrophobia and other anxiety-related disorders that stem from a malfunction in the brain's fear response, regulated by the amygdala. In a normal brain, these physiologic and emotional responses are rational and controllable. In acrophobics, however, the amygdala short-circuits; heights and other fear stimuli elicit a neural cascade that can result in shortness of breath, profuse sweating, muscle cramps, and often paralyzing terror.

Emory School of Medicine researchers Michael Davis, Kerry Ressler, and Barbara Rothbaum have developed a way to inhibit the malfunctioning fear mechanism in an acrophobic's brain. The therapy uses d-cycloserine (DCS), a drug originally developed for treating tuberculosis. Davis' laboratory discovered that low doses of DCS activate specialized receptors within the amygdala involved in a process called fear extinction.

In a pilot clinical study, Cox and 26 other people were pretreated with DCS tablets or a placebo and then exposed to a fearful simulation, a virtual reality simulation of standing in a rising glass elevator. Preliminary evidence indicates that acrophobics who received two treatments of DCS in combination with virtual-reality exposure experienced a greater reduction in their fear of heights compared with those who received the sugar pill. This improvement has been maintained months after concluding treatment.

The therapy gave Cox her life back. "I am phenomenally better," says Cox, who can now traverse Atlanta's infamous highway interchange, Spaghetti Junction, with little apprehension. "This treatment is going to free people. I didn't realize how much I was missing out on life."

Years of basic research into the neurobiology of fear culminated in the DCS therapy, which promotes fear extinction. It represents a potentially radical breakthrough in treating anxiety-related disorders by correcting the underlying neurologic dysfunction. "It's the first time to our knowledge that anyone has used this strategy," says Davis. "There are many studies that combine cognitive behavioral therapy with medications like antidepressants or anti-anxiety compounds. But nobody else has taken this tack of using cognitive enhancers to improve the learning that happens during psychotherapy."

The CBN team is planning a larger clinical trial of its DCS therapy for people who have an abnormal fear of public speaking, a disorder that affects an estimated 15% of the population.


Defining who we are

Trying to understand the neurobiology of fear and other behaviors is what links the 90 scientists from a variety of disciplines and schools at the CBN, founded in 1999 and now a leading international center for the study of behavioral neuroscience. One of the most rapidly growing scientific fields, behavioral neuroscience seeks to explain the biological essence of humanity by puzzling out the underpinnings of complex behaviors and their interplay with the environment. Behavioral neuroscience underwent a significant growth spurt in the 1990s with technological advances in brain imaging. More recently, new interdisciplinary programs such as the CBN have yielded significant findings about how the brain works.

The CBN was conceived in 1997 by Tom Insel, then director of the Yerkes National Primate Research Center, and by Pat Marsteller, director of Emory's Center for Science Education. With an initial $200,000 planning grant from the Robert W. Woodruff Foundation, faculty from the member institutions developed a proposal to create the CBN as both a research and education consortium. By pooling the intellectual and physical resources of multiple institutions, the group believed that their research and educational accomplishments could be more significant.

"We already had well-developed behavioral neuroscience programs at Georgia State (GSU) and Emory, and an engineering component at Georgia Tech," recalls Insel, the CBN's first director. "But the most important selling point was the diversity of the consortium that we proposed. Our combination seemed to work for what the National Science Foundation (NSF) wanted."

The psychiatrist's long-standing relationship with GSU's Elliott Albers, who was appointed CBN director in 2002 when Insel was named director of the National Institute of Mental Health, provided an additional advantage to launching the center in Atlanta. Equally important to the CBN's founding was its potential to improve neuroscience education and minority representation in the neurosciences by having access to large African-American student populations at the Atlanta University Center (AUC) and GSU.

With the departure of Insel, GSU became the lead institution in late 2002. The consortium also draws from Georgia Tech and the AUC, which includes Morehouse, Spelman, and Morris Brown colleges; Morehouse School of Medicine; and Clark Atlanta University. Entering its fifth year, the CBN recently received the "unanimous and enthusiastic support" from the NSF for funding through 2009, bringing total NSF support to $37 million.

Through its collaborative approach to conducting behavioral neuroscience, the CBN has created a community of scientists and resources focused on common scientific problems. CBN scientists, who include biologists, psychologists, anthropologists, psychiatrists, and neurologists, are organized into teams called collaboratories, focusing on one of four principal research areas: fear, aggression, affiliation, and reproduction. Individual research projects are funded through a venture grant system that requires investigators within the consortium to work together. Five cores support the collaboratories with specialized personnel and equipment, such as magnetic resonance imaging (MRI), so that scientists have the tools they need to conduct their research.


My amygdala made me do it

In both research and education, the CBN has already made significant contributions. In several areas of behavioral neuroscience, including its basic research on the amygdala and the mechanisms of fear learning and extinction, the CBN is becoming a world leader.

Compared with other brain regions, the neurophysiology of the amygdala in humans closely resembles that found in rats and other animals. For that reason, it can be much more easily studied than other brain regions. Most CBN research programs model biological processes and behaviors in animals that share many of the same genes with humans. (Those animals include nematodes, crustaceans, birds, amphibians, mice, rats, birds, and nonhuman primates.) A number of CBN researchers are using these animal models to study the amygdala from molecular, cellular, behavioral, and electrophysiologic perspectives.

"I predict within a decade, we will have its neurobiology almost completely understood," says Ressler, a psychiatrist and co-director of the post-traumatic stress disorder (PTSD) clinic at Grady Memorial Hospital. Understanding the amygdala and the neurobiology of fear has a wealth of implications for the development of new treatments for many psychiatric disorders, including PTSD and even addictions.

While CBN's fear research promises the most immediate clinical relevance, the affiliation collaboratory has captured equal attention for its findings. Around Valentine's Day, media outlets regularly interview Yerkes scientist Larry Young to explain the brain processes involved in love. Among his many findings, Young has determined that a single brain chemical, vasopressin, plays a key role in the formation of social attachments between animals by acting on the reward circuitry in the brain to facilitate pair bonding. The finding could have implications for research on autism, a dysfunction of the ability to form social relationships.

In one human study on the amygdala, Emory researchers Kim Wallen and Stephan Hamann of the reproduction collaboratory examined how men and women process visual sexual stimuli differently. Using MRI technology, the scientists discovered much higher levels of amygdala activation in the male brain than the female brain. The finding demonstrates that men and women process visual sexual stimuli differently and may explain gender variations in reproductive behaviors.

In addition to encouraging innovative research projects that otherwise might not attract traditional sources of funding, the NSF charges its science and technology centers (STCs) such as the CBN with devising new technologies for studying behavioral neuroscience. In a collaboration between GSU's Don Edwards and Emory School of Medicine's Xiaoping Hu, the CBN developed an innovative MRI technique that has yielded images never before seen. The scientists use manganese to identify anatomical structures and neural pathways in animals as small as crayfish, one of the most widely used animal models for the study of aggression. Other CBN imaging innovations have yielded a three-dimensional view of the brain of a termite, one of the few nonhuman species that engage in organized warfare.


Emerging biotech player

The NSF established its STC program in the late 1980s to enhance the nation's economic competitiveness. The foundation currently funds 11 centers across the country, but most of them focus on engineering or specialized fields, such as hydrology, that have defined industrial applications. The CBN is the only center with a life sciences focus. Although the CBN's principal mission is basic research, the NSF hopes that the center's findings will result in commercial and clinical applications.

From its inception, the CBN attracted the attention of the Georgia Research Alliance, a state-funded agency designed to increase economic development in biotechnology through partnerships among universities, government, and industry. As an emerging player in the South's biotech industry, the CBN originally received $7.5 million from the GRA to renovate labs and purchase equipment at consortium institutions. With the recent NSF grant renewal, the GRA has committed an additional $8.5 million for more infrastructure improvements, which are essential to the CBN's ongoing efforts to recruit and retain top scientific talent.

GRA Director Mike Cassidy is confident the CBN will soon achieve a critical mass of leading neuroscience researchers, who will give Georgia a competitive edge in developing biotechnology companies around the neurosciences. The CBN's reputation is already drawing many of the best behavioral neuroscientists to Atlanta.

"Another critically important factor for us is the CBN's educational emphasis on developing the next generation of neuroscientists," Cassidy says. "We have to develop a work force that is familiar with the field if we are going to fuel the formation of new companies."

Research and education are inextricably intertwined within the CBN. The center has developed comprehensive graduate and postdoctoral neuroscience training programs and currently supports more than 50 graduate students and 20 postdoctoral students, who conduct research with CBN faculty in all the collaboratories. The number of CBN graduate students and postdocs has nearly doubled every year since the CBN's founding. Undergraduates also have the opportunity to participate in CBN research. The CBN's signature educational program BRAIN (Behavioral Research Advancements in Neuroscience) includes research internships in collaboratories for undergraduates from under-represented minority groups.

Because the NSF supports its STCs for a maximum of 10 years, the CBN is expected to develop alternate revenue streams to sustain its programs after NSF funding ends. Cassidy and Albers project the center will have to develop a mix of funding sources, including federal grants and industry support. The CBN's research, such as its findings about the fear mechanisms involved in anxiety-related disorders, will ultimately determine the market relevance for potential industry partners. Among the possibilities are collaborative projects with pharmaceutical companies to identify new chemical targets for the treatment of autism and neurodegenerative diseases such as Alzheimer's.

Cassidy points out that Georgia Tech's and Emory's successful experiences in drug discovery are an asset for the CBN in its potential applied research efforts. In its first public demonstration of its intent to become a player in the region's biotech industry, the CBN recently participated in the annual Georgia Life Sciences Summit, a gathering of companies and academic and government organizations involved in the life sciences industry.

"We have become a leader within the field of behavioral science," says Albers. "Today we're looking at the center as an incubator to get projects started that we hope will be self-sustaining after 2009 by attracting new funds from the National Institutes of Health, the NSF, and private funding sources. The NSF has given us the means to develop the proof of concept. Now we have to use this traction to generate alternate sources of funding."


Growing pains

Key to the long-term success of the CBN will be strengthening research collaborations within the consortium through more efficient exchange of information and ideas. Despite the proximity of the eight consortium members, physical collaboration among scientists has proven challenging. Among its initiatives, the CBN is working to enhance a video conferencing system that will allow scientists at multiple institutions to interact and transmit data simultaneously.

An intrinsic hurdle to the development of the CBN was developing a research culture that integrated scientists from disparate academic disciplines, cultures, and institutions. For Emory and Georgia State, the CBN provided an opportunity to grow behavioral neuroscience research programs already in place. However, for teaching institutions, specifically several of the Atlanta University Center schools, behavioral neuroscience didn't fit at first with their priorities and goals.

"We made some missteps initially in terms of thinking each institution would be more or less the same and would interact with the center in the same fashion," says Albers. "That clearly wasn't the case, and we recognized that early on. We asked every institution how they wanted to be involved in the center and how the CBN could help them. We had to define how we interacted. Then we moved ahead rapidly."

Duane Jackson, a psychologist at Morehouse College, is among the CBN faculty at the AUC schools who have benefited from the effort to provide release time to develop research programs. A member of the aggression collaboratory, Jackson studies the neurobiology of organized warfare in termites. "Before the CBN, I was working in isolation for the most part in a lab one-third the size of my current one," he recalls. "The CBN provided me the funds to buy data analysis equipment and more important, take on five students." Jackson credits the CBN for opening doors to AUC students who otherwise might not have considered studying behavioral neuroscience or pursuing a career in the discipline. "My research would not be accelerating the way it is today without the CBN," Jackson adds. "Ironically, with the research I'm doing now, I need even more students."

Besides its training programs for graduate and post-doctoral students, the CBN has developed an array of educational programs to capture students, especially under-represented minorities, at all levels of their educational careers, beginning as early as elementary school. In addition to regular school visits, CBN educators work with metro Atlanta schools to develop neuroscience education programs, including a summer workshop on animal behavior and the brain at Zoo Atlanta for 17 middle and high school teachers.


Inspiring wonder

Another key component of the CBN's effort to improve neuroscience education and draw more under-represented minority and female students into the field is its community partnerships. In addition to the zoo, the CBN has forged relationships with SciTrek, Fernbank Science Center, and the new aquarium. Center scientists have developed a permanent crayfish exhibit at the zoo and are helping organize a genomics exhibit at Fernbank that will open next spring.

Stuart Zola, who replaced Insel as Yerkes director, plays a major role in administration of the CBN at Emory. As co-director for knowledge transfer, he leads the center's community efforts to educate the public about the importance and excitement of scientific discovery. Through its community partners, the CBN has a wealth of opportunity to inspire interest in neuroscience, Zola says.

"Our alliances are a great venue through which we can interest children and make them aware of the wonders of science," says Zola. "If a child who never had any knowledge about genes, the brain, or neuroscience comes out of Fernbank Museum saying, 'Mom, I want to study the brain,' then I think we've achieved something really amazing."

In many respects, Albers believes the CBN has changed the model system for how science research and education are conducted. "We've created an exceptional and diverse community of scientists who are uniquely suited to answer the complex questions that behavioral neuroscience poses," says Albers. "The center is beginning to blossom. So far, we have recruited 23 new faculty members in behavioral neuroscience in our member institutions, and we will be recruiting more. These scientists will bring new energy and perspectives to all aspects of the center." As the center continues to build more synergies among its scientists and institutions, more discoveries like the DCS therapy for acrophobia are certain to emerge. In the meantime, Beth Cox is reminded every day of the payoff of the CBN's novel approach to science as she traverses Spaghetti Junction, rides elevators, and, most important, no longer lives in constant fear.


Poul Olson is education and knowledge transfer partnership coordinator for the Center for Behavioral Neuroscience.


Copyright © Emory University, 2004. All Rights Reserved.
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Web version by Jaime Henriquez.