All of this has contributed to the understanding of the biological basis of A.D.H.D., and the complexity of it. “There are structural differences in brain volumes, there are connections between brain regions reflected in white matter changes in people with A.D.H.D., there are chemical changes in some of the major transmitter systems in the brain,” Dr. Mahone said. “When the brain is asked to do something, the brains of children with A.D.H.D. do the same task but the brain is less efficient.”

None of the children in the study had ever taken any kind of medication for A.D.H.D., which is important, Dr. Mahone said, because questions have been raised in the past about whether having taken stimulant medications might have contributed to some of the brain differences seen in older children with A.D.H.D.

But what matters most is not so much what the brain looks like at any particular moment, Dr. Mahone said, but how the brain grows and changes; it’s the trajectory that needs to be understood, and which will help project future function and target help and interventions. By starting early and following these children, there will be a lot to learn about typical and atypical development.

“We’re betting some of them are going to grow out of it,” he said, and will not eventually have the diagnosis. The matched controls will also be followed. “And some who don’t have symptoms at 4, may later on.”

This is a descriptive study, Dr. Griffin said, which looks at patterns in brain development, but cannot establish cause and effect. But with longitudinal studies, looking at these children’s brains as they change over time will be very important. Eventually, he said, we may be able to look at questions like, “if we had started a behavioral intervention at age 2, would we still see these changes?”

“This is very much a biological disorder,” Dr. Mahone said, and it’s clearly possible to distinguish A.D.H.D. from normal 4-year-old behavior. “Very clear evidence of things happening differently in the brain helps us reinforce that this is a very real condition with onset very early in life.” Trying to identify it earlier and start behavioral interventions as early as possible, he said, may improve outcomes.

“These children and their families are providing invaluable data that allow us to learn more about children with A.D.H.D. symptomology and atypical development as well as typical development,” Dr. Griffin said. “You have children with A.D.H.D. symptomology who have to be still in a scanner; this is not an insignificant undertaking and commitment on their part.”