Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder

Castellanos, F. Xavier, Margulies, Daniel S., Kelly, Clare, Uddin, Lucida Q., Ghaffari, Manley, Kirsch, Andrew, Shaw, David, Shehzad, Zarrar, Di Martino, Adriana, Biswal, Bharat, Sonuga-Barke, Edmund J.S., Rotrosen, John, Adler, Lenard A. and Milham, Michael P. (2008) Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. [in special issue: Impulse Control: Aggression, Addiction, and Attention Deficits] Biological Psychiatry, 63 (3), 332-337. (doi:10.1016/j.biopsych.2007.06.025). (PMID:17888409)

Abstract

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 x 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.

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