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.

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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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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 06/2015; 36(9). DOI:10.1002/hbm.22850 · 5.97 Impact Factor
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    • "They also display reduced task-induced attenuation of VLF oscillations in regions linked to DMN (Castellanos et al., 2008; Fair et al., 2010; Fassbender et al., 2009; Liddle et al., 2011; Tian et al., 2008). In line with neuroimaging findings, studies with DC-EEG have found reduced resting state VLF EEG power in adolescents with ADHD, along with decreased rest-to-task attenuation of VLF EEG power compared to healthy agematched volunteers (Helps et al., 2010). "
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    • "<0.1 Hz) blood-oxygen-level dependent (BOLD) signals, in ADHD patients during wakeful rest when no specific task externally oriented is being undertaken (Castellanos et al., 2008; Sripada et al., 2014; Tian et al., 2008). Much of the focus of this work has been on a set of widely distributed, but functionally connected, brain regions including the posterior cingulate cortex (PCC), precuneus (PrC), medial prefrontal cortex (mPFC) and inferior parietal lobes (IPL) – termed the Default Mode Network (DMN) (Cao et al., 2009; Castellanos et al., 2008; Fair et al., 2010; Uddin et al., 2008). Functionally, DMN activity is a " double edged sword " ; on the one hand, it is a neural substrate for important introspective cognitive processes such as meditation (Hasenkamp et al., 2012) and self-related thoughts about the personal past and future (Buckner and Carroll, 2007; Spreng et al., 2009): Dysfunction during rest, seen in ADHD, may disrupt processes of prospection and undermine effective decision making (Sonuga-Barke and Fairchild, 2012). "
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