We propose a novel approach to understanding the pathophysiology of Attention- Deficit/Hyperactivity Disorder (ADHD) by linking a neural circuit associated with attentional lapses to increased intra-subject response time variability. Based on our preliminary data, we hypothesize the presence of ADHD-related abnormalities in functional connectivity (regional temporal coherence) in a circuit linking dorsal anterior cingulate cortex (dACC) to the retrosplenial complex (RSC;comprising posterior cingulate cortex and precuneus). We propose to characterize this novel candidate locus of dysfunction in a sample of 50 right-handed unmedicated adults with current ADHD and a lifetime history of combined-type ADHD and 50 sex-, age-, IQ-, socioeconomic status-, and handedness-matched healthy comparisons. We will (1) use fMRI to replicate our preliminary findings of ADHD-related decreases in dACC/RSC functional connectivity strength;(2) assess group differences in the structural integrity of the dACC/RSC circuit using diffusion tensor imaging (DTI), and (3) relate functional and structural measures of circuit integrity to intra-individual response time variability during two response tasks during scanning. We will also obtain a comprehensive battery assessing nearly all putative neuropsychological deficits in ADHD in order to explore the relationships between intra-subject variability, brain circuitry abnormalities, and neuropsychological deficits in ADHD. This proposal, which combines novel methods, novel specific hypotheses, and substantial preliminary data, has the potential to delineate brain-behavior relationships that will inform translational models of pathophysiology of this common and highly impairing disorder.

Public Health Relevance

We propose to apply novel neuroimaging methods to better understand the brain mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD). Individuals with ADHD are highly inconsistent in their responses, and we will study a brain circuit that is associated with such inconsistency in 50 adults with ADHD and 50 healthy subjects. We will also measure key mental abilities that are suspected of being involved in ADHD, including alertness, working memory, ability to suppress unwanted responses, ability to shift mental set, and ability to time brief intervals. The proposed study has the potential to teach us about function and dysfunction of specific brain circuits in ADHD, a common and impairing condition. This information is needed to improve methods of diagnosis and to develop new treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH083246-03
Application #
8013937
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Friedman-Hill, Stacia
Project Start
2009-02-15
Project End
2012-12-31
Budget Start
2011-01-01
Budget End
2012-12-31
Support Year
3
Fiscal Year
2011
Total Cost
$559,142
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Koyama, Maki S; O'Connor, David; Shehzad, Zarrar et al. (2017) Differential contributions of the middle frontal gyrus functional connectivity to literacy and numeracy. Sci Rep 7:17548
Van Dam, Nicholas T; O'Connor, David; Marcelle, Enitan T et al. (2017) Data-Driven Phenotypic Categorization for Neurobiological Analyses: Beyond DSM-5 Labels. Biol Psychiatry 81:484-494
Yoncheva, Yuliya N; Somandepalli, Krishna; Reiss, Philip T et al. (2016) Mode of Anisotropy Reveals Global Diffusion Alterations in Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry 55:137-45
Cortese, Samuele; Castellanos, F Xavier; Eickhoff, Claudia R et al. (2016) Functional Decoding and Meta-analytic Connectivity Modeling in Adult Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry 80:896-904
Yang, Zhi; Zuo, Xi-Nian; McMahon, Katie L et al. (2016) Genetic and Environmental Contributions to Functional Connectivity Architecture of the Human Brain. Cereb Cortex 26:2341-2352
GarcĂ­a Murillo, Lourdes; Cortese, Samuele; Anderson, David et al. (2015) Locomotor activity measures in the diagnosis of attention deficit hyperactivity disorder: Meta-analyses and new findings. J Neurosci Methods 252:14-26
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
Zuo, Xi-Nian; Anderson, Jeffrey S; Bellec, Pierre et al. (2014) An open science resource for establishing reliability and reproducibility in functional connectomics. Sci Data 1:140049
Mennes, Maarten; Kelly, Clare; Colcombe, Stan et al. (2013) The extrinsic and intrinsic functional architectures of the human brain are not equivalent. Cereb Cortex 23:223-9

Showing the most recent 10 out of 35 publications