Building a Strong Foundation: CAR’s Roots in Brain Imaging Research
Looking back over the last decade, much of the research on autism spectrum disorder (ASD) has been centered on one goal: to find the cause or causes of this neurodevelopmental diagnosis that affects so many. Ten years ago, CAR’s co-founder and scientific director, Bob Schultz, PhD, was a researcher at Yale; he was among a small but growing group of scientists using advances in brain imaging to hone in on how autism develops in the brain. In 2008, he relocated from Yale to join Susan Levy, MD, MPH, in establishing one of the first multidisciplinary autism research centers in the country, at CHOP.
Reflecting on the progress in brain research since CAR was founded, Dr. Schultz recalls, “Just as I was moving to CHOP, my research also began to shift to study the earliest stages of child development, which are a key to understanding and preventing ASD. Now, ten years later, we’ve made remarkable progress as part of an NIH-funded collaborative science network that studies brain development in the first two years of life in babies at high risk for autism. Most recently, we were able to detect brain differences in infants younger than one year old, that could predict with 90 percent or greater accuracy which infants would develop autism by age 2. This is an extremely important finding, because studies have shown that early intervention leads to better long-term outcomes for children with ASD.”
Of course, this progress didn’t occur overnight. So, how did we get here?
John Herrington, PhD, one of the first scientists to join CAR after it was founded, explains, “Back then, the field was focused on discovering a brain signature for autism spectrum disorder. The research was geared toward comparing brain scans of individuals with and without autism, to create a one-to-one mapping of the brain that would show us, ‘this is what causes ASD’.”
Elaborating on how scientists’ understanding of the brain’s role in ASD has evolved, Benjamin Yerys, PhD, a child psychologist and neuroimaging researcher at CAR, explains, “When researchers first began to use neuroimaging to study autism twenty or so years ago, we were looking for one brain region that causes ASD. About ten years ago, when CAR began, we were beginning to move on from looking for specific brain regions to looking for one brain network that caused ASD”. As the science of autism progressed, researchers like Drs. Schultz, Herrington and Yerys began to grasp the complexity of ASD, as well as the complexity of the brain - and understood that ASD could not be narrowly ascribed to one brain region or even one network. Instead, they began to pursue research that explored how distinct networks in the brain interact to influence the constellation of symptoms that comprise autism.
CAR’s initial brain imaging research lead to several foundational discoveries. In studying specific brain regions and networks, researchers were able to establish that parts of the brain involved in ASD are also involved with other disorders. For example, ASD and anxiety show a great deal of overlap in the brain. In particular both disorders are known to affect the amygdala – a key brain region in processing emotions. Dr. Herrington, who specializes in co-occurring ASD and anxiety, explains “The reasons many individuals with autism are so anxious may have something fundamental to do with the parts of the brain that were affected by autism in the first place”. Similar research also connected the dots in the complicated history between the ASD and the amygdala, showing that when co-occurring anxiety is taken into consideration, this once complicated story of the amygdala comes into focus.
For the last decade, with leadership from Bob Schultz, PhD and Juhi Pandey, PhD, a pediatric neuropsychologist, CAR has participated in the multi-site NIH Infant Brain Imaging Study (IBIS), enrolling infant siblings of children diagnosed with ASD to look for the earliest developmental signs of ASD. “At the time it began, it was an incredibly novel and unique idea to scan the brains of younger siblings and follow them prospectively,” says Dr. Pandey of the IBIS initiative. With nearly 1,200 participating families, IBIS has now revealed differences in the brains of siblings who have gone on to be diagnosed with ASD, when compared to those who do not receive an ASD diagnosis. Over the course of several years, IBIS is laying the groundwork to understand the developmental trajectory of ASD, and the study recently expanded to follow the same sibling pairs through elementary and middle school. “We’ve had the pleasure of staying in contact with these families over the last decade, and now we’re beginning to understand how brain differences in infancy may predict who develops autism or language problems and who develops typically”, Dr. Pandey says, alluding to the current focus of IBIS.
While IBIS relies on magnetic resonance imaging (MRI), Timothy Roberts, PhD, vice-chair of research for the Department of Radiology and the Oberkircher Family Endowed Chair in Pediatric Radiology at CHOP, and his team capitalized on the use of magneto-encephalography (MEG), a new imaging technology that looks like a salon hair dryer and scans the magnetic fields given off during brain activity, to understand how ASD affects auditory processing. Even though MEG was the new kid on the imaging block at the time, Dr. Roberts insisted CHOP invest in a “baby MEG” scanner to allow his team to look for differences in brain processing as language develops in infants and toddlers. Containing 123 detectors into a smaller helmet, the baby MEG scanner was and still is “North America’s first and, one could argue, the world’s first dedicated infant MEG scanner,” said Dr. Roberts. With both MEG scanners, Dr. Roberts and his team discovered that children with ASD process simple sounds, like a beep, with a delay of fractions of a second compared to children with neurotypical brains. The delay in processing grows as the sounds become more complicated. “For example, in a word like elephant, when everyone else in the room has finished making the image of an elephant, the child with ASD is still processing the sound ‘el’,” explains Dr. Roberts. As this processing delay compounds, it’s easy to see how understanding words, and ultimately social communication, becomes increasingly difficult for an individual with ASD.
CAR has also been a trailblazer in shifting toward a focus on ecologically valid research, moving studies from unrealistic lab environments with a single-task approach to incorporating an environment and research tools and approaches aimed at replicating a child’s day-to day home or school environment, and whenever possible- having the research take place within that day-to-day environment. Dr. David Mandell’s Philly AIMS study remains the largest school-based study of autism interventions in the classroom. Other improvements to research methods include replacing outdated still-photos of adults’ facial expressions to using peer-actors or current video to provide a more true-to-life experience for research participants.
When combined with the work of our colleagues across the world, these advances over the past decade have changed the way we understand the roots of autism in the brain. Current and future research at CAR is paving the way to understanding the individual complexities inherent in ASD and tailoring personalized treatments- both behavioral and medical- that target brain mechanisms responsible for the core symptoms of ASD and comorbid conditions like anxiety and ADHD throughout an individual’s lifetime.