The task for the teenaged volunteer in the fMRI brain scanner sounds simple.
When the word “green” spelled in red letters pops up on a computer screen, all he has to do is report what color the letters appear in. It’s a question that trips up many people (the answer is red), but the urge to blurt out “green” is even harder to suppress for children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD).
When the brain needs to focus, the "idling" center (blue) shuts down while an attention circuit (red) activates. The brains of youth with untreated ADHD do neither.
Studies like this, using new sophisticated techniques in brain imaging, have now allowed Brad Peterson, MD, one of the country’s leading ADHD researchers, to pinpoint the circuits in the brain that cause ADHD and the circuits that are targeted by ADHD medications. The findings appear in a series of papers published in the last year.
“The point of identifying the circuits is to find the precise molecular changes that alter them, which may lead to better and more predictably helpful medications,” says Peterson, the chief of child and adolescent psychiatry at Columbia University College of Physicians & Surgeons. “Stimulant medications like Adderall and Ritalin are the most effective treatments for ADHD by far, but they don’t work for everyone and they can have substantial side effects.”
As the teenager makes his choice during the colored word test, two circuits affected by ADHD become apparent.
“In healthy controls, the colored word test activates a circuit in the prefrontal cortex [seen in red to the right] that turns on for tasks demanding close attention,” he says. “At the same time, there’s a decrease in activity in the brain’s “idling” center [shown in blue]. This center lets your mind wander and daydream, but it has to be shut off before you can complete the colored word test.”
In scans from ADHD subjects, the pattern is different. The attention circuit doesn’t turn on, and the idling center doesn’t turn off.
“We know the attention circuit helps people turn off the idling center, and one reason we think ADHD kids have trouble focusing is that they can’t activate the attention circuit,” Peterson adds.
ADHD medications increase brain volume (red and yellow) in the same regions that shrink (purple and blue) in ADHD youth. The images above show changes in three regions of the brain's basal ganglia.
Other imaging studies from Peterson’s lab have identified additional ADHD circuits in the cortex, thalamus, and basal ganglia (right).
These anatomical studies, which can identify millimeter-sized differences in brain volume, represent the strongest evidence to date that the circuits, know to control attention, impulse control, and physical activity, also help trigger the disorder’s behavioral and attention problems.
Both types of imaging studies also reveal that when ADHD medications work, the return these circuits to normal, making brain scans of treated ADHD patients indistinguishable from unaffected youth.
Peterson says, “What all this research allows us to do now is look for the precise changes at the molecular and cellular level that are producing the macroscopic changes we see in the brain scans,” adding that it’s those microscopic changes that could be targets for new therapies. “Identifying the microscopic changes has been difficult, but we think the clues we’ve gotten from imaging will now lead us to them.”