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

F. Xavier Castellanos, Daniel S. Margulies, Clare Kelly, Lucina Q. Uddin, Manely Ghaffari, Andrew Kirsch, David Shaw, Zarrar Shehzad, Adriana Di Martino, Bharat Biswal, Edmund J.S. Sonuga-Barke, John Rotrosen, Lenard A. Adler, Michael P. Milham

Research output: Contribution to journalArticle

591 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)332-337
Number of pages6
JournalBiological Psychiatry
Issue number3
StatePublished - Feb 1 2008
Externally publishedYes


  • ADHD
  • anterior cingulate cortex
  • default-mode network
  • functional magnetic resonance imaging
  • posterior cingulate cortex
  • precuneus

ASJC Scopus subject areas

  • Biological Psychiatry

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    Castellanos, F. X., Margulies, D. S., Kelly, C., Uddin, L. Q., Ghaffari, M., Kirsch, A., Shaw, D., Shehzad, Z., Di Martino, A., Biswal, B., Sonuga-Barke, E. J. S., Rotrosen, J., Adler, L. A., & Milham, M. P. (2008). Cingulate-Precuneus Interactions: A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 63(3), 332-337.