TY - JOUR
T1 - Cingulate-Precuneus Interactions
T2 - A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder
AU - Castellanos, F. Xavier
AU - Margulies, Daniel S.
AU - Kelly, Clare
AU - Uddin, Lucina Q.
AU - Ghaffari, Manely
AU - Kirsch, Andrew
AU - Shaw, David
AU - Shehzad, Zarrar
AU - Di Martino, Adriana
AU - Biswal, Bharat
AU - Sonuga-Barke, Edmund J.S.
AU - Rotrosen, John
AU - Adler, Lenard A.
AU - Milham, Michael P.
N1 - Funding Information:
This work was supported in part by grants provided to FXC by the Stavros S. Niarchos Foundation, National Institute of Mental Health (NIMH; Grant Nos. 5R21MH066393 and 5T32MH067763), the Leon Lowenstein Foundation, NARSAD (The Mental Health Research Association), and gifts from Linda and Richard Schaps, Jill and Bob Smith, and the Taubman Foundation.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - Background: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed "default-mode" network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. Methods: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. Results: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 × 10-11, corrected) and portions of posterior cingulate (p < .02, corrected). Conclusions: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD.
AB - Background: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed "default-mode" network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. Methods: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. Results: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 × 10-11, corrected) and portions of posterior cingulate (p < .02, corrected). Conclusions: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD.
KW - ADHD
KW - anterior cingulate cortex
KW - default-mode network
KW - functional magnetic resonance imaging
KW - posterior cingulate cortex
KW - precuneus
UR - http://www.scopus.com/inward/record.url?scp=38049078773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049078773&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2007.06.025
DO - 10.1016/j.biopsych.2007.06.025
M3 - Article
C2 - 17888409
AN - SCOPUS:38049078773
VL - 63
SP - 332
EP - 337
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 3
ER -