Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder.
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.
Castellanos
F Xavier
FX
Phyllis Green and Randolph Cōwen Institute for Pediatric Neuroscience, New York University Child Study Center, New York, NY 10016, USA. castef01@nyumc.org
Margulies
Daniel S
DS
Kelly
Clare
C
Uddin
Lucina Q
LQ
Ghaffari
Manely
M
Kirsch
Andrew
A
Shaw
David
D
Shehzad
Zarrar
Z
Di Martino
Adriana
A
Biswal
Bharat
B
Sonuga-Barke
Edmund J S
EJ
Rotrosen
John
J
Adler
Lenard A
LA
Milham
Michael P
MP
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000098:blood supply / Q000473:pathology*
D010100:Oxygen