Prescription stimulant drugs such as Ritalin and Adderall are commonly used to treat attention deficit hyperactivity disorder (ADHD), including among children. In the United States, an estimated 3.5 million children ages 3 to 17 take medication for ADHD. That number has risen as diagnoses of the neurodevelopmental disorder have become more common.

For decades, stimulant medications have been thought to work by directly influencing brain regions responsible for attention. New research from Washington University School of Medicine in St. Louis calls that explanation into question. The study was led by Benjamin Kay, MD, PhD, an assistant professor of neurology, and Nico U. Dosenbach, MD, PhD, the David M. & Tracy S. Holtzman Professor of Neurology. Their findings suggest that these medications primarily affect brain systems involved in reward and wakefulness rather than the networks traditionally linked to attention.

Published Dec. 24 in Cell, the study indicates that stimulants may improve performance by making people with ADHD feel more alert and more interested in what they are doing. Instead of directly sharpening focus, the drugs appear to increase engagement with tasks. The researchers also observed brain activity patterns that resembled the effects of a good night's sleep, counteracting the typical brain changes associated with sleep deprivation.

"I prescribe a lot of stimulants as a child neurologist, and I've always been taught that they facilitate attention systems to give people more voluntary control over what they pay attention to," said Kay, who treats patients at St. Louis Children's Hospital. "But we've shown that's not the case. Rather, the improvement we observe in attention is a secondary effect of a child being more alert and finding a task more rewarding, which naturally helps them pay more attention to it."

Kay said the results emphasize the need to consider sleep quality alongside medication when children are being evaluated for ADHD.

Brain imaging reveals unexpected patterns

To examine how stimulants affect the brain, the researchers analyzed resting state functional MRI, or fMRI, data from 5,795 children ages 8 to 11 who took part in the Adolescent Brain Cognitive Development (ABCD) Study. Resting state fMRI measures brain activity when a person is not performing a specific task. The ABCD study is a long term, multisite project following the brain development of more than 11,000 children across the U.S., including a site at WashU Medicine.

The team compared brain connectivity in children who took prescription stimulants on the day of their scan with those who did not. Children who had taken stimulants showed stronger activity in brain regions associated with arousal and wakefulness, as well as areas involved in predicting how rewarding an activity might be. In contrast, the scans did not show notable increases in regions classically tied to attention.