Cingulate-Precuneus Interactions: A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder

• Published in: Biological psychiatry (1969) Vol. 63; no. 3; pp. 332 - 337
• Main Authors: Castellanos, F. Xavier, Margulies, Daniel S., Kelly, Clare, Uddin, Lucina Q., Ghaffari, Manely, Kirsch, Andrew, Shaw, David, Shehzad, Zarrar, Di Martino, Adriana, Biswal, Bharat, Sonuga-Barke, Edmund J.S., Rotrosen, John, Adler, Lenard A., Milham, Michael P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2008; Elsevier Science
• Subjects: ADHD; Adult; anterior cingulate cortex; Attention Deficit Disorder with Hyperactivity - pathology; Attention deficit disorders. Hyperactivity; Biological and medical sciences; Brain Mapping; Case-Control Studies; Child clinical studies; default-mode network; Female; functional magnetic resonance imaging; Gyrus Cinguli - blood supply; Gyrus Cinguli - pathology; Humans; Image Processing, Computer-Assisted - methods; Magnetic Resonance Imaging - methods; Male; Medical sciences; Middle Aged; Oxygen - blood; posterior cingulate cortex; precuneus; Prefrontal Cortex - blood supply; Prefrontal Cortex - pathology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; ADHD; default-mode network; precuneus; posterior cingulate cortex; anterior cingulate cortex; functional magnetic resonance imaging; Human; Hyperactivity; Central nervous system; Nuclear magnetic resonance imaging; Encephalon; Attentional disorder; Cingulate cortex; Medical imagery; Adult; Attention disorder with hyperactivity; Functional imaging
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2007.06.025

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. 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. 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). 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.