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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH085328-08
Application #
8318256
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Friedman-Hill, Stacia
Project Start
2009-08-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2012
Total Cost
$593,779
Indirect Cost
$194,958
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Carass, Aaron; Cuzzocreo, Jennifer L; Han, Shuo et al. (2018) Comparing fully automated state-of-the-art cerebellum parcellation from magnetic resonance images. Neuroimage 183:150-172
Stephens, Jaclyn A; Salorio, Cynthia F; Barber, Anita D et al. (2018) Preliminary findings of altered functional connectivity of the default mode network linked to functional outcomes one year after pediatric traumatic brain injury. Dev Neurorehabil 21:423-430
Sali, Anthony W; Anderson, Brian A; Yantis, Steven et al. (2018) Reduced Value-Driven Attentional Capture Among Children with ADHD Compared to Typically Developing Controls. J Abnorm Child Psychol 46:1187-1200
Patros, Connor H G; L Sweeney, Kristie; Mahone, E Mark et al. (2018) Greater delay discounting among girls, but not boys, with ADHD correlates with cognitive control. Child Neuropsychol 24:1026-1046
Rosch, Keri S; Crocetti, Deana; Hirabayashi, Kathryn et al. (2018) Reduced subcortical volumes among preschool-age girls and boys with ADHD. Psychiatry Res Neuroimaging 271:67-74
Seymour, Karen E; Tang, Xiaoying; Crocetti, Deana et al. (2017) Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation. Psychiatry Res Neuroimaging 261:20-28
Di Martino, Adriana; O'Connor, David; Chen, Bosi et al. (2017) Enhancing studies of the connectome in autism using the autism brain imaging data exchange II. Sci Data 4:170010
Martinelli, Mary K; Mostofsky, Stewart H; Rosch, Keri S (2017) Investigating the Impact of Cognitive Load and Motivation on Response Control in Relation to Delay Discounting in Children with ADHD. J Abnorm Child Psychol 45:1339-1353
Barber, Anita D; Caffo, Brian S; Pekar, James J et al. (2017) Decoupling of reaction time-related default mode network activity with cognitive demand. Brain Imaging Behav 11:666-676
Puts, Nicolaas A J; Harris, Ashley D; Mikkelsen, Mark et al. (2017) Altered tactile sensitivity in children with attention-deficit hyperactivity disorder. J Neurophysiol 118:2568-2578

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