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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    • "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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    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.
    Acta neurobiologiae experimentalis 10/2015; 75(3):2015. · 1.29 Impact Factor
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    • "Aberrant neural connectivity and synchrony across brain regions has emerged as a characteristic of brain differences in ADHD (Posner et al., 2014). Previous rs-fMRI studies reported reduced positive connections between the midline hub regions of the default mode network (DMN) (Fair et al., 2010) and a reduced anticorrelated relationship between the DMN and control network (Castellanos et al., 2008; Hoekzema et al., 2014) alongside dorsal attention network (Tomasi and Volkow, 2012) in ADHD. These 2 specific interactions in the DMN are dissociated in adults with and without persistent ADHD (Mattfeld et al., 2014). "
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    ABSTRACT: Background:Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder (ADHD), its treatment effects on brain resting-state functional connectivity (RSFC) remain unknown. Therefore, we aimed to investigate (1) major brain functional networks in medication-naïve adults with ADHD and (2) the efficacy of atomoxetine treatment on RSFC.Methods:After collecting baseline resting-state functional MRI scans from 24 adults with ADHD (aged 18 to 52 years) and 24 healthy controls (matched in demographic characteristics), the participants with ADHD were randomly assigned to atomoxetine (n = 12) and placebo (n = 12) arms in an 8-week double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks.Results:At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks, and hypoconnectivity within the dorsal attention and default networks in adults with ADHD. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anti-correlated relationship between the default and task-positive networks, and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults.Conclusions:Our results support the idea that atypical DMN-task positive networks interaction plays an important role in the pathophysiology of adult ADHD. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat ADHD.
    The International Journal of Neuropsychopharmacology 09/2015; DOI:10.1093/ijnp/pyv094 · 4.01 Impact Factor
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    • "In the healthy brain at rest, the DMN typically exhibits anticorrelated activity with the DAN, FPN and salience network [Chai et al., 2012; Fox et al., 2005; Keller et al., 2013; Kucyi et al., 2012]. Multiple rs-fMRI studies have demonstrated that individuals with ADHD, relative to healthy subjects, exhibit (a) decreased within-DMN FC [particularly between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC)/precuneus (PCu)] [Castellanos et al., 2008; Fair et al., 2010; Mattfeld et al., 2014] (with exceptions, however, [Barber et al., 2015]) and (b) reduced or absent anticorrelation between DMN and other association networks (DAN, FPN, salience) [Castellanos et al., 2008; Hoekzema et al., 2014; Mattfeld et al., 2014; Sun et al., 2012]. In a large rs-fMRI study of ADHD and control subjects (aged 7.2–21.8 "
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    Human Brain Mapping 06/2015; 36(9). DOI:10.1002/hbm.22850 · 5.97 Impact Factor
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