ADHD Research Spreads Throughout the Brain

Brain-imaging studies of people with attention-deficit/hyperactivity disorder (ADHD) are moving beyond historic concentration on the frontal lobe to examine activity in other regions of the brain as well as considering the medication status of the subjects.

Originally, brain researchers studying ADHD looked at that area because people with ADHD exhibited behavior like those with frontal-lobe lesions. Later, they began to look at the frontal subcortical regions and related areas, and now research has expanded its scope further still.

For instance, when subjects were given tests of attention, functional MRI images of persons with ADHD showed less activation than controls in the posterior parietal attention system, noted Leanne Tamm, Ph.D., Vinod Menon, Ph.D., and Allan Reiss, M.D., of the Department of Psychiatry and Behavioral Sciences at the Stanford University School of Medicine, in the June American Journal of Psychiatry.

The researchers administered a visual oddball task, a test of directed attention, to 14 right-handed adolescent boys. The oddball task requires pressing one button when the subject sees a circle (the standard stimulus, presented more frequently) on the test screen or a second button when a triangle (the “oddball” stimulus, presented less often) appears. Twelve healthy boys were tested as controls. The two groups were closely matched in cognitive and academic functioning. Reaction times and errors committed were recorded.

The ADHD group pressed the wrong button more often than the control group, but reaction times did not differ. However, the ADHD subjects showed less activation in the bilateral association cortex, the right precuneus, and the thalamus. Pressing the wrong button—an error of commission— indicates impulsivity, while the differentially activated brain regions reveal their difficulty in shifting attention and making alternative responses.

“These findings suggest a critical role for these brain regions in accurate target detection and task performance, which may underlie known deficits in directed attention in individuals with ADHD,” wrote Tamm and her colleagues. “[I]t is important to reconsider the notion of ADHD as primarily a disorder of the frontal-striatal function and consider the role of the parietal attention system in the behavioral phenotype of ADHD.”

Behavioral inhibition has generally been the focus of ADHD brain research, and examining other areas of the brain and other behaviors, while not new, still needs to be encouraged, said Eve Valera, Ph.D., an instructor in the Department of Psychiatry at Harvard Medical School. “If you don't look at other regions, you won't find anything there,” said Valera, who is now studying the cerebellum in adults with ADHD.

Two other recent studies explored differences in several areas of brain activation in two groups of children with ADHD: those who took stimulant medications and those who didn't, since medication status has been suggested as a confounding factor. The first study found that underactivation in children and adolescents never treated with stimulants appeared not only in the prefrontal cortex but also in the parietal and temporal cortices.

“Despite similar task performance, medication-naïve boys with ADHD showed hypoactivation in task-specific brain regions compared with healthy subjects in two tasks: reduced activation in rostral mesial prefrontal cortex during the go/no go task and in right hemispheric inferior prefrontal, temporal, and parietal brain regions during the switch task,” wrote Anna Smith, Ph.D., of the Department of Psychiatry at the Institute of Psychiatry at King's College, London, and colleagues.

Another study found that, unlike healthy controls, subjects with ADHD did not activate the anterior cingulate cortex during unsuccessful inhibitions. The difference occurred in treatment-naïve subjects, indicating an effect not caused by past stimulant treatment. That may mean, wrote Steven Pliszka, M.D., of the Department of Psychiatry at the University of Texas Health Science Center in San Antonio, and colleagues, “that when ADHD subjects make an error or face conflict, the anterior cingulate cortex fails to adequately adjust cognitive control for the demands of the task.” They also found an increase in left ventrolateral prefrontal cortex activity on unsuccessful inhibitions, unlike ADHD subjects.

Knowing that some imaging results are not artifacts of prior treatment is a help to researchers, because, said Valera, it is hard to find child research subjects who have ADHD and are not medicated.

Besides the need to replicate current studies, Valera sees three major opportunities for imaging research in ADHD. For one thing, future studies should include more girls, she said. “Data for girls seem congruent, but we don't know for sure.”

Also, imaging the same subjects over time would improve understanding of developmental changes in children and might reveal whether there were cognitive abnormalities at some times but not at others. Finally, researchers need to look for abnormalities in the connections among brain regions by studying networks of activation, she said.

“Parietal Attentional System Aberrations During Target Detection in Adolescents With Attention Deficit Hyperactivity Disorder: Event-Related fMRI Evidence” is posted online at<http://www.ajp.psychiatryonline.org/cgi/content/full/163/6/1033>.▪