Short Circuits

Tania R.
Edghill
January 31, 2006
Kennedy Krieger Researcher Uses Innovations in MRI Technology to Study the Brain's Structure and Function in Search of the Cause of ADHD

Erin Blitz with Dr. Stewart MostofskyLaurie Blitz began to suspect that something was not quite right with her daughter as early as when she was a toddler. Erin seemed overly hyperactive, moving so much that even simple tasks like changing her diaper became lessons in patience and control. When she was old enough to walk, she would constantly run away, placing herself in danger. At bedtime, she would climb out of her crib and change into her party clothes, entertaining herself until, exhausted, she curled up into a dresser drawer or closet. "It took her a long time to wind down," recalls Mrs. Blitz.

Later, when Erin started school, her mother and teacher noticed that she was very absentminded and impulsive. She would would forget to bring assignments home and would jump from one task to another without completing any of them. To keep Erin from leaving her seat, the teacher made her sit on her knees. The signs were adding up. Mrs. Blitz always thought her daughter had attention deficit hyperactivity disorder, but it was Erin's teacher who confirmed her belief. "The teacher clued me in that Erin's behavior was different, but that was the way she learned," she says.

Over the years, Erin's inattention and hyperactivity were treated with medication and academic intervention. In 2002, at the age of 11, Erin came to Kennedy Krieger Institute to participate in a study on the brain basis of ADHD.

It is estimated that five out of every 100 children have ADHD. While the prevalence of the condition is high, its causes are still unknown. However, scientists at Kennedy Krieger are at the forefront of making discoveries about the brain's role in ADHD. Stewart Mostofsky, M.D., a research scientist in the Institute's Department of Developmental Cognitive Neurology, is among those who are leading the way.

Using a variety of research techniques, including neurobehavioral testing and innovations in magnetic resonance imaging, Dr. Mostofsky has uncovered a major clue in the puzzle: The frontal lobes of the brains of children with ADHD tend to be smaller than that of others. "While this is not an absolute across all studies, most studies, including some from our laboratory, seem to suggest that there is a decrease in frontal brain volumes in children with ADHD," he says. The theory that he is now studying is that individuals with ADHD have differences in frontal circuits that result in difficulty focusing, controlling their impulses and performing other executive functions, such as planning, reasoning, judgment, memory and concentration. With a greater understanding of the neurological basis of ADHD, scientists will be better able to define and subtype the condition and, therefore, improve diagnosis and treatment interventions.

Looking at the brain for answers

Difficulty sitting still, staying focused, remembering instructions, playing quietly and getting along with others often have a significant impact on a child's academic achievement. According to Martha Bridge Denckla, M.D., a world-renowned expert on ADHD and learning disabilities and director of the Department of Developmental Cognitive Neurology at Kennedy Krieger, children with ADHD have problems with certain cognitive components related to executive function, which involves planning, self-monitoring, managing time and organizing. "Individuals with ADHD have a brain-based cognitive circuit that is weak. This and other nearby motor and social control circuits in the brain do not function up to age or grade expectations," she explains. "As children attempt to learn new things, they find that they cannot learn on their own. In this sense, ADHD is a brain-based learning disability."

Erin Blitz with Dr. Stewart MostofskyAccording to Dr. Mostofsky, individuals with ADHD have difficulty with response inhibition, which contributes to problems with excessive impulsive, hyperactive and inattentive behavior and may also contribute to problems with executive function. "Response inhibition is the suppression of actions that are inappropriate in a given behavioral context or that are unwanted because they interfere with completion of a motor or cognitive task," he explains. For example, children with ADHD may jump from doing their homework to playing with a toy, never completing the main task. In his studies on adults, Dr. Mostofsky has linked motor response inhibition to the frontal lobe structure in the brain called the supplementary motor area, which is important for control of movement, including actions a person should make and those they should inhibit. This area neighbors the massive region in the brain committed to executive function. In his NIH-funded studies, Dr. Mostofsky is now testing his finding on response inhibition on children with ADHD. "What we're doing is extending this observation [the link between response inhibition and specific frontal lobe structures] to ADHD to see if there are differences in brain activity when children perform response inhibition tasks," Dr. Mostofsky says.

Linking performance to activity in the brain

In the functional MRI (fMRI) portion of the study, which began in 2000, Dr. Mostofsky and his colleagues have examined brain scans of 30 children, ranging in age from 8 through 12 years. Ten children with ADHD and 20 children without the condition completed two days of testing. As participants in the study, Erin and the other children received cognitive and neurological tests, which included a series of stimulus-response tasks and activities. They also were scanned in the MRI, which produced both structural images of their brains and images of their brains at work. While in the MRI, the children performed several computerized tasks, similar to a video game.

Dr. Mostofsky determined which brain regions were active during the children's performance. "We have the children perform these tasks, because it gives us ideas about the child's cognitive and behavioral function, which then gives us insight into how their brains are functioning." Differences in brain size, particularly in the frontal region, were detected with the MRI.

The study's findings provide evidence that the neurocircuitry in the brains of children with ADHD are different from that of others. "In addition, when children with ADHD perform the response inhibition task during fMRI, there appears to be differences in activation within particular frontal regions, including the supplementary motor area," Dr. Mostofsky explains. Dr. Mostofsky's findings are preliminary and need to be investigated further. He hopes to soon apply his conclusions to the diagnosis and monitoring of treatment outcomes.

"The study was very informative and beneficial. I found that we were right on target with our current plan of treatment," Mrs. Blitz says. "It's a good way to learn something about your child, as well as to give back to the community. I know we can make a difference for other people in doing a study like this. And, it gave me peace of mind."

Dr. Mostofsky is recruiting participants for his ADHD study. He is looking for children, ages 8 through 12, with or without ADHD. Parents interested in learning more about the study may contact Deana Crocetti at (443) 923-9254.