June 6, 2013
By mapping the brain at rest, Damien Fair, Ph.D., is gaining important insights into pediatric neurological disorders
To Damien Fair, PA-C, Ph.D., assistant professor of behavioral neuroscience and psychiatry, one of the most vexing clinical challenges in pediatric neuroscience was captured in a mother's simple question. "How can my child have ADHD at school but not at home?"
The answer relates to the complexity of the underlying connectome. Linguistically akin to genome or biome, a connectome identifies a map of a linked network of neural pathways in the human brain. Dr. Fair's research focuses on understanding the specific connectome that will help better characterize any given child with attention deficit hyperactivity disorder (ADHD) or autism, and simultaneously, many other pediatric psychiatric conditions.
Paradoxically, a first step in mapping this – or any – connectome is to unlock the secrets of the idle brain.
Getting to the baseline
For years, scientists studying the brain have looked at how location-specific neural activity spikes when we do discrete tasks – singing, looking at the face of a loved one, choosing between shampoo or conditioner.
"But we now know that various regions of the brain are actively interacting while a person is doing nothing – sort of like a car idling at a stoplight," explained Dr. Fair. Mapping this "resting state" or intrinsic activity of the brain is also the key to unlocking the atypical brain. In short, this resting connectome provides a baseline that, by contrast, brings the abnormal neural networks into relief.
"Understanding the brain at rest helps separate typical from atypical function and therefore may help with the development of subgroups for many types of neurological disorders, such as with ADHD and autism," he said.
According to the Centers for Disease Control and Prevention, more than 5 million children three to 17 years of age have been diagnosed with ADHD. ADHD and autism are two of the most widely diagnosed neurodevelopmental disorders. However, diagnosis relies on parent and teacher interviews and clinical observation – all of which are prone to difficult-to-eliminate biases. Further, ADHD groups all symptoms into one disorder.
"Within the discipline of psychiatry, there is an overall absence of definitive biological markers for ADHD, or for most neuropsychiatric disorders for that matter," Dr. Fair said. "We want to change that."
Dr. Fair's research relies on observing the connectivity of the resting state of brains of hundreds of typically and atypically developing children of various ages with functional magnetic resonance imaging (fMRI), and integrating the resulting reams of data with computational techniques emerging from graph theory.
Using these techniques, and building on prior work with his colleagues at Washington University, Dr. Fair and his team are now able to accurately predict a young person's age just by studying their brain scan. The hope is that, eventually, this type of data will form the basis of standardized growth curves that track pediatric brain development, analogous to those already in use that track a child's weight, height or head size. From this, pediatricians might be able to identify when a child appears to be at risk for neurological disorders.
A better understanding of ADHD
How does this connectome research help answer the original question posed by the mother? That's the next step. With the normal pediatric connectome coming into view, the researchers are turning their focus to identifying the atypical aspects of these neural networks, applying the same integrated imaging techniques to large numbers of children diagnosed with ADHD.
Dr. Fair is optimistic about the potential outcome. "Our goal is to eventually subdivide the current pediatric ADHD population into more refined biological subgroups. If we can parse these kids like that, we are hopeful this will help guide future diagnostic, therapeutic and genetic studies," he said.
OHSU is among the top-funded universities in the nation for neuroscience research and supports unique resources – advanced imaging, animal models and a commitment to collaboration – that are essential for this cutting-edge research.
Dr. Fair was recruited to the School of Medicine faculty in 2011 after completing post-doctoral training at OHSU, first under the guidance of Bonnie Nagel, Ph.D., and then of Joel Nigg, Ph.D., in the Department of Psychiatry. Dr. Nigg is a leader in the realm of ADHD research with whom Dr. Fair now closely collaborates. Reflecting the cross-disciplinary aspect of his research, Dr. Fair holds a joint appointment in the Departments of Behavioral Neuroscience and Psychiatry, and the Advanced Imaging Research Center.
"OHSU was fortunate to recruit Dr. Fair here and retain him at OHSU; he represents the next generation of cutting-edge work in brain imaging methodology, and even though he's early in his career, he is already one of the most well-cited and visible investigators in this field," said Dr. Nigg.
YES to science!
Dr. Fair's dedication to children goes well beyond the lab. He founded a program called YES (Youth Engaged in Science) that mentors kids toward science careers. The program connects scientists as role models with a variety of community and educational programs, with a particular focus on groups historically underrepresented in the biomedical sciences.
"Our goal is to get as many researchers in front of these kids talking and sharing stories so they experience everyday science in ways that inspire them and open their eyes to the possibilities," said Dr. Fair.
"Building the 'pipeline' of up-and-coming scientists, researchers and health professionals is a key component of OHSU's diversity recruitment and outreach goals," said Leslie Garcia, MPA, OHSU's assistant chief diversity officer and director of OHSU's Center for Diversity & Inclusion.
Dr. Fair sees this approach as researchers – who are often funded by public sector grants – doing their part to build the next generation of scientists and health care professionals. For more information, please visit the YES program page on Facebook.
The research described in this article is supported by the National Institutes of Health.
Pictured top: Damien Fair, PA-C, Ph.D. (center), who joined the OHSU faculty in 2011, is a rising star in ADHD and autism research. Oscar Miranda-Dominguez, Ph.D., and Marguerite Matthews, Ph.D., postdoctoral researchers in Dr. Fair's lab, play key roles in the brain mapping project.(Photo credit: Michael McDermott)
Pictured bottom: Graphical representation of the connectome in typically developing children, children with autism and children with ADHD. These structural images show over-connectivity between highly connected brain regions in children with autism and under-connectivity of highly connected brain regions in children with ADHD.