Scientists are updating their view of how drugs like Adderall and Ritalin help children with attention deficit hyperactivity disorder stay on task.

The latest evidence is a study of thousands of brain scans of adolescents that confirms earlier hints that stimulant drugs have little direct impact on brain networks that control attention.

Instead, the drugs appear to activate networks involved in alertness and the anticipation of pleasure, scientists report in the journal Cell.

"We think it's a combination of both arousal and reward, that kind of one-two punch, that really helps kids with ADHD when they take this medication," says Dr. Benjamin Kay, a pediatric neurologist at Washington University School of Medicine in St. Louis and the study's lead author.

The results, along with those of smaller studies, support a "mindset shift about what stimulants are doing for people," says Peter Manza, a neuroscientist at the University of Maryland who was not involved in the research.

The new research analyzed data from the Adolescent Brain Cognitive Development Study, a federally funded effort that includes brain scans of nearly 12,000 children. About 4% of these kids had ADHD when they entered the study, and nearly half of those were on a prescription stimulant.

About 3.5 million children in the U.S. take an ADHD medication, and the number is rising.

Medication and brain networks

The brain scan data included a type of MRI that measures brain activity when a person is at rest. That allowed Kay and a team of scientists to see which brain areas were becoming more active in response to the drugs.

Kay expected to find lots of activity in areas that let a person control what they pay attention to.

"What I actually found was that those were the parts of the brain that were least affected," he says.

Instead, the drugs were stimulating areas that help people stay awake and alert, and areas that anticipate a pleasurable reward.

This double effect seems to occur because stimulants like Ritalin and Adderall boost levels of two different brain chemicals, says Dr. Nico Dosenbach, the paper's senior author and a professor at Washington University.

The first chemical is norepinephrine, which prepares the body and brain for action.

The study found that this "fight or flight" response counteracts the usual cognitive declines associated with sleep deprivation on cognitive performance. Lack of sleep is a problem for many adolescents, but especially those with ADHD.

The second brain chemical is dopamine, which plays an important role in the brain's reward system. And a boost in dopamine levels may help children with ADHD feel more positive about mundane tasks like homework.

Usually, the brain's expectation is, "this is going to be terrible, this is going to be boring," Dosenbach says. "Dopamine can make you more tolerant because you are feeling a slight, low-level reward."

It's still too soon to know whether that's what's going on, Manza says. But he agrees that stimulants are doing something in the brain that helps kids with ADHD do things like homework.

"They don't find math problems very interesting, but after a dose of Ritalin it might seem more interesting to them," he says, "and so they're willing to persist and finish the task."

Brain scans before drugs?

The new study's findings shouldn't undermine clinicians' confidence in the effectiveness of stimulants for ADHD, Kay says. But they do suggest that it's important to rule out factors like sleep deprivation before turning to medication.

"This was a really personal paper for me because I prescribe these drugs all the time," Kay says.

The results also suggest that brain scans might eventually offer a way to know whether a child is likely to benefit from drug treatment, Manza says.

"Stimulants don't work for everyone," he says, "so we need to better target the individuals who need them."

MRI scans could even offer a better way to diagnose ADHD someday, Manza says. That's badly needed, he says, in an era where more and more children and young adults are being told they have the disorder and should be on medication.

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