Mid-Atlantic Consortium Newsletter Summer 2013

Delving Deeper into Attention-Deficit/ Hyperactivity Disorder

ChildResearchers at Kennedy Krieger Institute (KKI) have been making inroads toward better understanding of brain function in children with attention-deficit/hyperactivity disorder (ADHD).

One study directed by Stewart Mostofsky, M.D., director of the Laboratory for Neurocognitive and Imaging Research at KKI and an associate professor of neurology and psychiatry at the Johns Hopkins University School of Medicine, showed that measuring hand movements in children with ADHD could indicate the severity of the disorder. A second, related, study found that children with ADHD have significantly fewer inhibitory signals in the motor cortex than do typically developing peers, and that this measure of “unconscious” motor control was a strong predictor of the severity of impulsive, hyperactive and distractible behaviors that characterize the disorder.

When many children with ADHD deliberately move a specific part of their bodies, like their hands or fingers, they may also move another body part unintentially, a phenomenon referred to as overflow movement. Some children exhibit so-called “mirror” overflow, in which attempts to move one hand or foot leads to movement in the opposite limb.

For their research, the KKI scientists asked 50 right-handed children, ages 8 to 13, half with ADHD, to tap each finger to a thumb in sequence (index-middle-ring-little) while being videotaped. The children did the test five times with each hand. The researchers also used a device called a goniometer, taped to the children’s index and ring fingers, to record deviations in movement in the hand not doing the finger test. The investigators then measured total overflow (any change in finger positions) and phasic overflow (directed finger movements) using video recordings.

Children with ADHD had twice as much overflow movement as did typically developing children, particularly when performing finger sequencing with the left hand. This was especially pronounced in boys with ADHD. Furthermore, phasic overflow observed during the right-handed tests correlated with ADHD symptom severity as rated by the children’s parents.

Mostofsky suggests the findings could lead to new methods of diagnosing ADHD and/or could assist in monitoring responses to medical treatments for the condition.

A second study used a noninvasive procedure, transcranial magnetic stimulation (TMS) to investigate a type of motor cortex activity called short interval cortical inhibition (SICI) in children with and without ADHD. During TMS, brief magnetic pulses are used to stimulate specific areas of the brain. The effects are very temporary, and the technique allows scientists to observe how the stimulated areas of the brain function and, in this case, how that function might be involved with ADHD.

The KKI team recruited 49 right-handed children with ADHD and 49 typically-developing children, ages 8 to 12 years, to receive TMS pulses to the left motor cortex. They then measured muscle contraction in the right hand. The team also examined motor skills and measured ADHD symptom severity using parent behavioral ratings scales.

In children with ADHD, the TMS stimulation reduced SICI an average of 40 percent more than it did in typically developing children, reflecting impaired motor inhibitory function. Importantly, they also found that reduced SICI correlated with higher ADHD severity as well as impaired motor skills.

Neurons in the motor cortex that produce the neurotransmitter GABA play a key role in SICI, and these studies suggest that GABA might play a role in the development of, and treatment for, ADHD. In fact, Mostofsky and his colleagues recently published findings from their brain imaging (MRI) studies showing that GABA is reduced in the motor cortex in children with ADHD. Additionally, SICI is enhanced by the input of the neurotransmitter dopamine to these GABA-producing neurons. Stimulant medications, often used in the treatment of ADHD, have effects on dopamine, so it may be that decreased motor inhibition is the result of abnormalities in dopamine transmission. On the other hand, this study did not find an association between SICI and a history of stimulant medication use, indicating the need for further research.

Mostofsky and his team next plan to examine how SICI and overflow movements are associated with brain imaging of GABA in the motor cortex, and how these movements are modulated by experience and medications that act directly on dopamine transmission.

“Our findings suggest that motor cortex SICI may be an effective biomarker for ADHD symptom severity,” Mostofsky said. “This line of investigation holds enormous promise for providing better specificity in the diagnosis of ADHD, and for opening pathways to novel approaches for therapeutic intervention, using both medication and behavioral methods.”

The overflow and TMS studies, conducted with researchers at Cincinnati Children’s Hospital Medical Center, were published last February in the journal Neurology. The GABA imaging study was published earlier this year in the journal Archives of General Psychiatry.

 

For more information on Mostofsky’s work, see http://lnir.kennedykrieger.org/index.html

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