Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent disorder in which impaired control of unwanted behavior affects family/social relationships and school performance. Motor response control, mediated by the basal ganglia and, at the cortical level, the supplementary motor area (SMA), is crucial for selecting to withhold unwanted responses and thereby necessary for effective inhibition of impulsive, hyperactive and off-task behavior that characterizes ADHD. Findings from the initial grant period established that ADHD is associated with abnormalities in motor response control, including impaired response inhibition and increased intrasubject response variability (ISV);additionally, the degree of impairment on these measures was found to be similar across tasks with differing cognitive demands, suggesting that impaired motor response control is a primary deficit in ADHD. Consistent with these behavioral observations, functional and anatomic MRI studies reveal children with ADHD show abnormalities in the SMA and interconnected regions of the basal ganglia. Functional MRI examination of brain-behavior correlations provided further insight, revealing that for children with ADHD, but not typically developing (TD) children, recruitment of the prefrontal cortex was associated with lower ISV, reflecting improved response control. The combined behavior and imaging findings provide the basis for a shift towards a more developmental model of ADHD in which dysfunction in neural systems critical to motor response control, established early in development, contributes to the pathophysiology of the disorder, while function of later-developing prefrontal systems facilitates compensation. The goals of the current proposal are to: use novel imaging methods to investigate the hypothesis that abnormalities in a neural circuit involving the SMA and basal ganglia contribute to ADHD-associated impairments in response control (Aim 1), investigate the hypothesis that successful motor response control in some children with ADHD depends on recruitment of prefrontal (rather than typical premotor) circuits (Aims 2 and 3), and investigate whether a presentation format that increases vigilance can also result in improved response control (Aim 4). The proposed studies will not only help to identify relevant intermediate endophenotypes of ADHD but also might point to potentially effective treatment strategies.

Public Health Relevance

Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder in childhood in which problems with response control affect social relationships and school performance. The purpose of this research is to identify differences in brain structure contributing to ADHD-associated impairments in response control and to identify mechanisms that help children with ADHD improve task performance. This work may help to improve diagnosis and treatment of ADHD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Developmental Brain Disorders Study Section (DBD)
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Friedman-Hill, Stacia
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Hugo W. Moser Research Institute Kennedy Krieger
United States
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Ament, Katarina; Mejia, Amanda; Buhlman, Rebecca et al. (2015) Evidence for specificity of motor impairments in catching and balance in children with autism. J Autism Dev Disord 45:742-51
Shou, Haochang; Eloyan, Ani; Nebel, Mary Beth et al. (2014) Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI. Neuroimage 102 Pt 2:938-44
Nebel, Mary Beth; Joel, Suresh E; Muschelli, John et al. (2014) Disruption of functional organization within the primary motor cortex in children with autism. Hum Brain Mapp 35:567-80
Puts, Nicolaas A J; Wodka, Ericka L; Tommerdahl, Mark et al. (2014) Impaired tactile processing in children with autism spectrum disorder. J Neurophysiol 111:1803-11
dos Santos Siqueira, Anderson; Biazoli Junior, Claudinei Eduardo; Comfort, William Edgar et al. (2014) Abnormal functional resting-state networks in ADHD: graph theory and pattern recognition analysis of fMRI data. Biomed Res Int 2014:380531
Elton, Amanda; Alcauter, Sarael; Gao, Wei (2014) Network connectivity abnormality profile supports a categorical-dimensional hybrid model of ADHD. Hum Brain Mapp 35:4531-43
Lin, Wei; Nielsen, Tim; Qin, Qin et al. (2014) Real-time motion correction in two-dimensional multislice imaging with through-plane navigator. Magn Reson Med 71:1995-2005
Muschelli, John; Nebel, Mary Beth; Caffo, Brian S et al. (2014) Reduction of motion-related artifacts in resting state fMRI using aCompCor. Neuroimage 96:22-35
Shiels Rosch, Keri; Dirlikov, Benjamin; Mostofsky, Stewart H (2013) Increased intrasubject variability in boys with ADHD across tests of motor and cognitive control. J Abnorm Child Psychol 41:485-95
Jacobson, Lisa A; Ryan, Matthew; Denckla, Martha B et al. (2013) Performance lapses in children with attention-deficit/hyperactivity disorder contribute to poor reading fluency. Arch Clin Neuropsychol 28:672-83

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