ADHD Linked to Impaired Motor Cortex Inhibition

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ADHD Linked to Impaired Motor Cortex Inhibition

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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 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, 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, s Hopkins

University School of Medicine, Baltimore, land.

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 & #947;-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, 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, 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.