The Mason Spirit

For hundreds of years, scientists, scholars, and philosophers have tried to understand the mind and the brain. It has only been within the past few decades that any real progress has been made in this area of investigation.

It was the often-quoted James Watson, Nobel laureate and codiscoverer of the DNA structure, who called the human brain “the most complex thing we have yet discovered in our universe,” and Jim Olds, director of Mason’s Krasnow Institute for Advanced Study, would agree with him.

Jim Olds

“The brain is the seat of who we are as individuals,” says Olds. “It is also the key part of the human body for defining whether we are alive. If we want to understand how humans can create music, invent machines, and suffer from diseases like Alzheimer’s, then we must study brain function.”

Since joining Mason in 1998, Olds has been a champion for brain research. He and the institute, along with sister organization, the Santa Fe Institute, play an active role in the annual Decade of the Mind symposium. The impetus for this symposium, which brings together leading researchers from around the world, was a declaration in the 1990s by then-President George H. W. Bush that there would be a decade’s worth of research centered on neuroscience. While Bush’s decade has come and gone, the neuroscientists soldier on.

Olds divides the institute’s research into four categories:

• Healing and protecting the mind—improving public health by ameliorating or curing diseases of the brain that affect the mind, such as Alzheimer’s and Parkinson’s.
• Understanding the mind and how it emerges from brain function activity, including some key characteristics that are still not fully understood, such as consciousness, memory, and dreams.
• Enriching the mind—improving learning outcomes in education at every age level.
• Modeling the mind, either analytically or with the use of computers, is a key approach to understanding the mind. The expectation is that such models may facilitate new hypotheses that can then be tested in the laboratory or clinic.

“Mason is positioning itself to play a key role in neuroscience research,” Olds says. “We have state-of-the art facilities [which are currently being expanded] and a critical mass of highly successful faculty members from across the university who are working on the question of how cognition and consciousness fit into the mind.”

This is a look at some of the leading research being conducted at the institute.

How Does the Brain Work?

Where do character traits like creativity and humor originate? By studying nerve tissue and building a computational model, neuroscientist Giorgio Ascoli and his team of researchers are trying to answer this fundamental question.

For decades, the construction of a computational model of the brain has been a kind of holy grail in neuroscience and computing. Through his research, Ascoli wants to gain a better understanding of how mind and body connect and interact. The findings have potential biomedical implications in the study and treatment of debilitating diseases such as epilepsy, Alzheimer’s, and Parkinson’s, as well as the mental decline that comes with aging.

“We are looking at the mechanism underlying brain function,” Ascoli says. “How the nerves and their plasticity allow connectivity on a cellular level. By understanding the structure and the activity of the resulting network, we can attempt to infer answers to basic questions about how the brain works.

“When we recall an episode of our childhood, our thoughts, feelings, emotions, and imagination all correspond to or emerge from electrical waves in our brains,” he says. “How this is brought to be from a bunch of tree-shaped nerve cells is the beautiful mystery we are after.”

Why Are Some Things Addictive and Others Not?

Molecular neuroscientist Nadine Kabbani, BA Biology and Psychology ’97 is an expert on addiction, specifically nicotine addiction, and she says that things that are addictive, whether it is a narcotic or a cigarette, have something in common.

“What researchers are discovering is that these things happen to have targets within a specific pathway of the brain called the reward pathway,” says Kabbani who spent three years as a Phillip Morris Fellow at the Pasteur Institute in Paris before coming to Mason. “It is thought that anything that can perturb this pathway has addictive properties.”

Kabbani’s research focuses on the nicotinic receptors in the brain and takes place at the proteomic level, focusing on the proteins within brain cells. “Much of medicine right now works on the protein level. For example, when you take an antihistamine for allergies, you are blocking a protein called the histamine receptor.”

Proteomics remains uncharted territory in the world of research, and there is a great deal of room for discovery. “We know less than 20 percent of all the protein products of the human genome, so one obvious path for molecular biologists is to discover new proteins,” she says.

Long-range implications for her work include the possibility of discovering novel targets for drug development. “People say nicotine relaxes them and helps them to focus, so this opens up a path for thinking about nicotinic receptors as putative targets for cognitive enhancement drugs.”

Can Computers Simulate Real Life?

Kenneth De Jong

One of the computational projects of Mason computer scientist Kenneth De Jong focuses on host-pathogen interactions, using what researchers call “in silico science.”

“What we really mean by in silico science is performing experiments on computer models of the real thing you are trying to study,” says De Jong, associate director of the institute, where he oversees the Adaptive Systems Lab.

Working with the Potomac Institute for Policy Studies, De Jong and his team looked at the effects of a pathogen, inhalation anthrax, on the human body. Because a number of victims of the 2001 inhalation anthrax incident were treated at nearby Inova Fairfax Hospital, Inova has some rare data that document exactly what happened to the affected postal workers over the weeks and months following their exposure.

“We used that data, together with other information, to build what I believe is the first attempt at a computer model of the effects of inhalation anthrax on the human body,” says De Jong, who is considered a pioneer in machine learning and evolutionary computation.

While De Jong’s model is a prototype, he can see applications for this kind of computer modeling in areas such as cancer research and drug design.

“We now have the capability to build computer models with enough fidelity that they can be used in science,” he says. “This is not to replace the wet lab or field work but to add another dimension to the research.”

Do Gifted People Think Differently?

Layne Kalbfleisch oversees Krasnow Investigations of Developmental Learning and Behavior, or KIDLAB as it is more commonly known. KIDLAB’s goal is to contribute new insight into how the brain develops, learns, creates, and solves problems throughout the lifespan.

Educational psychologist and cognitive neuroscientist Layne Kalbfleisch plans to find out. In her research, she is trying see how the brains of intellectually gifted children, especially those who have attention deficit hyperactivity disorder and high-functioning autism, operate differently than the typical brain.

To do this, she is using neuroimaging technology known as fMRI, functional magnetic resonance imaging. A safe, noninvasive technology, fMRI measures the rapid changes that occur in certain parts of the brain. When a subject is working to solve some intellectual task in the fMRI, researchers can see parts of the brain begin to glow and fade like lights switched on and off in different rooms of a house. Although fMRI labs are normally affiliated with medical centers, Mason is one of only three nonmedical schools in the country with its own scanner.

To help her examine children’s brain activity, Kalbfleisch has devised a series of nonverbal behavioral exercises that look like puzzles. Some are based on the Naglieri Nonverbal Ability Test, developed by Mason psychology professor Jack A. Naglieri. Because these tests are based on patterns, they are not language-based, which allows her to test young children as well as subjects who speak different languages, a boon for her planned collaboration with Dutch researchers to study environmental influences on brain development and function.

“We’ll be able to see the trade-off in brain real estate—certain areas people will and won’t use to solve problems,” says Kalbfleisch, the Pomata Term Professor of Cognitive Neuroscience.

She indicates the long-term results of her research have implications for educational intervention and the construction of educational environments, in both school classrooms and adult education venues, as well as health care, possibly allowing doctors to identify brain disorders earlier and pharmaceutical companies to develop drugs to “block” disease.

Can the Onset of Alzheimer’s Be Predicted?

Raja Parasuraman

Mason cognitive neuroscientist Raja Parasuraman is midway through a five-year longitudinal study that he hopes will answer that question. “The incidence of Alzheimer’s disease (AD) is undergoing explosive growth,” he says. Studies indicate that approximately 360,000 new cases of AD are reported each year.

Supported by a $2.6 million grant from the National Institutes of Health, Parasuraman and his colleagues are testing more than 500 middle-age and older adults to identify precursors of AD. “One or two genes are shown to predict [AD], but not with 100 percent reliability,” he says.

In this study, the team is primarily looking at the gene apolipoprotein E (APOE) and its effects on attention and memory. To do this, the team is using genetic testing, which involves a simple swab to the inside of one’s cheek, and cognitive testing. For the cognitive testing, they are looking at brain activity or what Parasuraman calls event-related potentials with the help of electroencephalogram (EEG) and magnetic resonance imaging. Parasuraman is the chair of the NeuroImaging Core of the Krasnow Institute, which oversees use of the institute’s Siemens Magnetom Allegra 3 Tesla scanner.

Parasuraman, who has devoted more than two decades to this kind of research, hopes to make advancements in detecting the onset of AD by identifying markers sensitive to APOE. Early detection would allow individuals at greater risk to receive prevention therapies that could delay the onset of AD for several years.

Are There Other Ways to Treat Parkinson’s Disease?

As the principal investigator at the Computational and Experimental Neuroplasticity Lab, Kim Avrama Blackwell is focusing her research on the biophysical and biochemical mechanisms of long-term memory storage.

About 50,000 people are diagnosed with Parkinson’s disease each year, and at present there is no cure. For those affected by Parkinson’s, the dopamine-producing neurons in the brain are destroyed. Current treatments involve replacing dopamine, a chemical in the brain that helps relay signals between the neuron and other cells, but this technique only provides relief for a while. Mason neuroscientist Kim Avrama Blackwell believes the answer to Parkinson’s may lie farther down the neural pathway.

“When dopamine binds with its receptors, many other molecules get activated,” says Blackwell, who is the principal investigator of the institute’s Computational and Experimental Neuroplasticity Laboratory. “A whole cascade of biochemical reactions takes place.”

This “cascade,” or signaling pathway, is what she is focusing on in her research that uses computer modeling and experiments. “I want to find out which of those molecules are critical and how things change when you block those molecules.”

An expert in neuroplasticity, an area of science that focuses on learning or the brain’s ability to make connections, Blackwell believes that when those molecules are identified they could be targets for drug design, and medicine could bypass the dopamine altogether.

“Some of the molecules ‘downstream’ from dopamine are critical to dopamine’s function,” she says. “We have to understand what those molecules are and how they change the activity of the neuron.”

Jim Greif, Dave Andrews, and Robin Herron contributed to this article.

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About the Institute

Shelley Krasnow, a long-time resident of Fairfax, Virginia, was trained as an electrical engineer and lived life with a very broad outlook. A man of many interests, he was committed to supporting basic biomedical research.

When Krasnow died in 1989, he bequeathed a substantial portion of his extensive estate to George Mason University to establish an institute whose purpose was the general advancement of human knowledge for the betterment of mankind. From this bequest, the Krasnow Institute for Advanced Study was created.

The work of the institute began with a major scientific conference, cosponsored with the Santa Fe Institute and hosted at George Mason University. This conference titled “The Mind, the Brain, and Complex Adaptive Systems” brought together an extraordinary group of scientists, including two Nobel laureates, and produced exciting new approaches to this frontier.

These collaborative efforts set the institute on the path of seeking to understand the human mind. A second strand of inquiry also emerged: how can understanding the human mind be applied to education, decision making, and the countless activities that define individuality? These areas of interest come together under the general heading of cognition, the essence of the institute’s mission, and the legacy of Krasnow’s vision.