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

Phyllis Green and Randolph Cōwen Institute for Pediatric Neuroscience, New York University Child Study Center, New York, NY 10016, USA.
Biological psychiatry (Impact Factor: 10.26). 02/2008; 63(3):332-7. DOI: 10.1016/j.biopsych.2007.06.025
Source: PubMed


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 x 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.

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Available from: Lucina Q Uddin
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    • "From a system's neuroscience perspective ADHD is increasingly seen as the product of disturbances in intrinsic organization of brain networks comprised of these regions (Aboitiz et al., 2014; Konrad and Eickhoff, 2010; Menon, 2011; Ray et al., 2014). Studies using functional magnetic resonance imaging (fMRI) report altered intrinsic connectivity within and between networks including the dorsal and ventral attention, salience (Mccarthy et al., 2013; Sripada et al., 2014), and default mode networks (Castellanos et al., 2008; Fair et al., 2010; Franzen et al., 2013; Mccarthy et al., 2013; Sripada et al., 2014; Uddin et al., 2008). Structural connectivity studies are less common and the extent to which these functional alterations are underpinned by deep-seated structural effects remains to be determined (Cao et al., 2014). "
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    • "Structural MRI studies of ADHD have found widespread volumetric differences, including reduced grey and white matter volume in the frontal lobes, possibly reflecting delayed or abnormal neurodevelopment (Shaw et al. 2007, Frodl and Skokauskas 2012). Studies of resting state activity in children with ADHD have found differences in inter-regional correlations within frontostriatal , frontoparietal, and frontocerebellar circuits further reinforcing the notion that abnormal brain structure produces functional differences that may ultimately affect behavior (Zang et al. 2007, Castellanos et al. 2008, Uddin et al. 2008). Persons with ADHD are frequently described as more impulsive than those without the disorder. "
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    • "To directly test our hypotheses, we employed resting-state magnetic resonance imaging (rfMRI) as the method measuring intrinsic functional connectivity (iFC) (Biswal et al., 1995, 2010), which has been used to examine the ACC circuitry in human brains (Castellanos et al., 2008; Margulies et al., 2007; Tian et al., 2006; Yan et al., 2009). This tool has been proved valuable in studying neurodevelopment processes (Fair et al., 2007; Gao et al., 2013, 2014, 2015; Kelly et al., 2009; Betzel et al., 2014). "
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