Article

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

ABSTRACT

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.

Download full-text

Full-text

Available from: Lucina Q Uddin
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prior studies demonstrate altered organisation of functional brain networks in attentiondeficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graphtheoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organisation of structural brain networks in adults with ADHD and unaffected controls using deterministic fibre tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organisation in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.
    Full-text · Article · Oct 2015 · Clinical neuroimaging
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An important characteristic of childhood attention-deficit/hyperactivity disorder (ADHD) is a bias towards small immediate versus larger delayed rewards, but it is not known if this symptom is also a feature of adult ADHD. A delay-discounting task was administered to participants with adult ADHD and a comparison group in conjunction with functional magnetic resonance imaging. Participants responded to a series of questions that required judgments between small sums of money available immediately and larger sums obtained after a temporal delay. Question parameters were adjusted by an adaptive algorithm designed to converge on each participant’s discounting indifference point, an individual set point at which there is equal valuation of both choices. In all participants, robust task activation was observed in regions previously identified in functional imaging studies of delay discounting. However, adults with ADHD showed less task activation in a number of regions including the dorsolateral prefrontal cortex, superior frontal gyrus, anterior cingulate, caudate nucleus and declive of the cerebellum. Additionally, the degree to which a participant discounted delayed rewards was inversely related to task activation in the cerebellum. The results suggest that the bias towards immediate rewards in childhood ADHD may not persist behaviorally, but instead present in adulthood as alterations in frontostriatal and frontocerebellar networks.
    Full-text · Article · Oct 2015 · Acta neurobiologiae experimentalis
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to elucidate the dACC laterality in typically developing children and their sex/age-related differences with a sample of 84 right-handed children (6–16 years, 42 boys). We first replicated the previous finding observed in adults that gray matter density asymmetry in the dACC was region-specific: leftward (left>right) in its superior part, rightward (left<right) in its inferior part. Intrinsic connectivity analysis of these regions further revealed region-specific asymmetric connectivity profiles in dACC as well as their sex and age differences. Specifically, the superior dACC connectivity with frontoparietal network and the inferior dACC connectivity with visual network are rightward. The superior dACC connectivity with the default network (lateral temporal cortex) was more involved in the left hemisphere. In contrast, the inferior dACC connectivity with the default network (anterior medial prefrontal cortex) was more lateralized towards the right hemisphere. The superior dACC connectivity with lateral visual cortex was more distinct across two hemispheres in girls than that in boys. This connection in boys changed with age from right-prominent to left-prominent asymmetry whereas girls developed the connection from left-prominent to no asymmetry. These findings not only highlight the complexity and laterality of the dACC but also provided insights into dynamical structure–function relationships during the development.
    Full-text · Article · Oct 2015 · Developmental Cognitive Neuroscience
Show more