ADHD Linked to Impaired Motor Cortex Inhibition

Pauline Anderson

February 16, 2011

February 16, 2011 — Two new studies provide evidence that attention-deficit/hyperactivity disorder (ADHD), a condition characterized by lack of focus, impulsiveness, and hyperactivity, is a distinct condition characterized by impaired inhibitory function in the brain.

Both studies used the motor system as a window into brain function, and both support the hypothesis that inhibition is an important mechanism in cognition and behavior function, writes Jonathan W. Mink, MD, from the University of Rochester Medical Center in New York, in an accompanying editorial entitled "Faulty Brakes? Inhibitory Processes in Attention-Deficit/Hyperactivity Disorder."

"Although both studies used the motor system as a window into brain function in ADHD, it is likely that the motor findings reflect mechanisms shared among other frontal lobe regions involved in executive function," he writes.

The combination of quantitative behavioral methods and noninvasive physiologic methods has substantial promise for revealing more specifics about mechanisms underlying ADHD and other related disorders," Dr. Mink concludes. "This will be valuable for determining if different subtypes of ADHD arise from separate pathophysiologic processes and ultimately for guiding development and testing of new therapies."

The 2 studies and editorial were published together in the February 15 issue of Neurology.

Great Mirror Overflow

The first study quantified "mirror" movements in 25 right-handed children aged 8 to 13 years with ADHD and 25 age-matched controls. Mirror movements are unwanted or unnecessary movements in the hand or side of the body opposite to the one that is executing voluntary movements.

Researchers measured finger-tapping tasks and range of joint rotations. They used video recordings to assess phasic overflow of the index and ring fingers — that is, movements that occur when the finger moves in a similar way as the voluntary hand — in 34 children and electrogoniometer recordings to measure total overflow, defined as combined phasic overflow with tonic overflow that occurs when the muscle contracts so the finger points in the air, in 48 children.

The goniometer quantified the amount of movement in the ring and index fingers after wires and small plastic bands were secured across the metacarpophalangeal joints.

This study found that the children with ADHD had greater mirror overflow than the control children. The phasic overflow in right- and left-handed finger sequencing (RHFS and LHFS) was 65.41 in the ADHD group compared with 32.91 in controls. The variance in RHFS and LHFS total overflow was 18.87 in ADHD children and 10.73 in controls.

Mirror movements occur in childhood but lessen over time and are typically no longer seen by 13 or 14 years of age.

"Our hypothesis was that children with ADHD would persist to a greater degree than in typically developing children, and in fact we did find that this was the case," said lead author on both studies, Stewart H. Mostofsky, MD, associate professor of neurology and psychiatry, director of the Laboratory for Neurocognitive and Imaging Research, and medical director of the Center for Autism and Related Disorders, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Researchers also noted that boys with ADHS had significantly more mirror overflow than controls but that in girls the difference was not significant. "We think the gender factor is developmental," said Dr. Mostofsky. "Girls develop earlier than boys and that includes development of their motor control."

The greatest difference between the ADHD and control groups occurred during left-handed (or nondominant) finger-tapping. This, too, is probably a developmental phenomenon, said Dr. Mostofsky, adding that it takes longer to control movements in the hand that is used less often.

"I suspect that if we were to look at children in a younger age group, say 6 to 8 years, we would perhaps see there was just as much, if not more, difference when doing this test with their right hand," he said.

The findings appear to confirm previous observations that overflow movements are likely a marker of abnormal motor control development that improves with age and is more prominent in boys. But although previous research was qualitative in nature, this current study actually quantified the amount of overflow, said Dr. Mostofsky. "Here, we used 2 complementary methods — video-taped analysis and electrogoniometer — to quantify the amount of movements taking place in the hand opposite to the one executing the task."

The study shows that even at an unconscious level, children with ADHD have difficulty inhibiting unnecessary and unwanted movements, said Dr. Mostofsky.

"This suggests that many children with ADHD have a core difficulty with controlling their behavior, that they may not be under voluntary control, that they are not as efficient at doing so, and that this may contribute to broader difficulties they have with controlling voluntary impulsive hyperactive behaviors."

Magnetic Stimulation

The second study used magnetic stimulation to measure inhibitory processes in 49 children with ADHD and 49 age-matched controls aged 8 to 12 years, again all right handed.

Researchers collected data on short interval cortical inhibition (SICI), which is believed to reflect γ-aminobutyric acid–mediated inhibition within the primary motor cortex. SICI is sometimes described as one of the brain's "braking" systems.

This study found that SICI was reduced by 40% (P < .0001) in children with ADHD compared with controls. On motor development tests, those with ADHD scored 59% worse than children without ADHD.

The amount of SICI correlated significantly with the parent rating of ADHD severity, commented one of the study authors, Donald L. Gilbert, MD, director of the Tourette Syndrome and Movement Disorders Clinics and the Transcranial Magnetic Stimulation Laboratory and associate professor of child neurology at Cincinnati Children's Hospital Medical Center, Ohio.

Not only was SICI on average less efficient, but the measurement correlated with parent reports of the children's behavior, as well as with fine motor task performance evaluated with the Physical and Neurological Examination for Subtle Signs.

The study illustrates a method of using the motor system to understand the brain's behavior problems, said Dr. Gilbert.

"We're trying to understand the biology that's underneath the symptoms," he said. "These results tell us there are different ways for the brain to produce ADHD symptoms, and we've identified something that's robust enough to have a 40% average difference but is not telling the whole story."

However, Dr. Gilbert pointed out that not all patients with ADHD have the same reduced levels of SICI. There's probably a fair amount of overlap between typically developing children and those with ADHD, he said.

Although the study results may eventually provide the basis for improved treatments for ADHD, Dr. Gilbert said he doesn't think SICI will be used as a diagnostic test.

"We're not going to be dragging the magnet into clinic," he said. "I think we will use the magnet to understand groups of kids who have risk for different outcomes and as a foundation for getting deeper into understanding the chemistry of the brain, the neurotransmitters, and other kinds of problems besides the ADHD symptoms."

A 'Definable Deficit'

Asked for a comment on these findings, Michael Goldstein, MD, from Western Neurological Associates, Salt Lake City, Utah, and former vice-president of the American Academy of Neurology, said that the brain changes highlighted by this research demonstrate a physiologic basis for ADHD.

These studies go a long way toward showing that a definable deficit in brain functioning can be demonstrated in children who are chosen only as a result of their behavior.

"This is a very important point considering the attitude of many" who still believe that a child with ADHD just "isn't trying" or "needs more discipline" or even is "just being normal," Dr. Gilbert said in an email to Medscape Medical News. Many families are reluctant to seek help because of the uncertainty that the child's difficulty in the classroom, with friends, and at home is due to a brain disorder.

"These studies go a long way toward showing that a definable deficit in brain functioning can be demonstrated in children who are chosen only as a result of their behavior," said Dr. Goldstein. "In finding evidence to demonstrate what brain abnormality causes ADHD, the study authors are also demonstrating that there is a brain abnormality that causes ADHD."

Dr. Mostofsky has served on a scientific advisory for Bristol-Myers Squibb, serves on the editorial board of Neurocase, and receives research support from the National Institutes of Health (NIH). Dr. Gilbert has received honoraria from the Tourette Syndrome Association/Centers for Disease Control and Prevention, the Movement Disorder Society, the American Academy of Neurology, and the American Academy of Pediatrics, serves on the medical advisory board for the Tourette Syndrome Association, writes board review questions for PREP SA, and has received research support from the NIH. For additional conflict of interest information, please see original articles.

Neurology. 2011;76:615-621 and 622-628.

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