Advertisement

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

Published:September 24, 2007DOI:https://doi.org/10.1016/j.biopsych.2007.06.025

      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 × 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.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Castellanos F.X.
        • Sonuga-Barke E.J.S.
        • Milham M.P.
        • Tannock R.
        Characterizing cognition in ADHD: Beyond executive dysfunction.
        Trends Cogn Sci. 2006; 10: 117-123
        • Willcutt E.G.
        • Doyle A.E.
        • Nigg J.T.
        • Faraone S.V.
        • Pennington B.F.
        Validity of the executive function theory of attention-deficit/hyperactivity disorder: A meta-analytic review.
        Biol Psychiatry. 2005; 57: 1336-1346
        • Sonuga-Barke E.J.S.
        Causal models of ADHD: from common simple deficits to multiple developmental pathways.
        Biol Psychiatry. 2005; 57: 1231-1238
        • Dickstein S.G.
        • Bannon K.
        • Castellanos F.X.
        • Milham M.P.
        The neural correlates of attention deficit hyperactivity disorder: An ALE meta-analysis.
        J Child Psychol Psychiatry. 2006; 47: 1051-1062
        • Barkley R.A.
        Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD.
        Psychol Bull. 1997; 121: 65-94
        • Castellanos F.X.
        • Sonuga-Barke E.J.S.
        • Scheres A.
        • Di Martino A.
        • Hyde C.
        • Walters J.R.
        Varieties of attention-deficit/hyperactivity disorder-related intra-individual variability.
        Biol Psychiatry. 2005; 57: 1416-1423
        • Sonuga-Barke E.J.
        • Castellanos F.X.
        Spontaneous attentional fluctuations in impaired states and pathological conditions: A neurobiological hypothesis.
        Neurosci Biobehav Rev. 2007; ([Epub ahead of print March 12, 2007])
        • Friston K.J.
        Functional and effective connectivity in neuroimaging: A synthesis.
        Hum Brain Mapp. 1994; 2: 56-78
        • Biswal B.
        • Yetkin F.Z.
        • Haughton V.M.
        • Hyde J.S.
        Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.
        Magn Reson Med. 1995; 34: 537-541
        • Margulies D.S.
        • Kelly A.M.C.
        • Uddin L.Q.
        • Biswal B.B.
        • Castellanos F.X.
        • Milham M.P.
        Mapping the functional connectivity of anterior cingulate cortex.
        Neuroimage. 2007; ([Epub ahead of print May 24, 2007])
        • Weissman D.H.
        • Roberts K.C.
        • Visscher K.M.
        • Woldorff M.G.
        The neural bases of momentary lapses in attention.
        Nat Neurosci. 2006; 9: 971-978
        • Raichle M.E.
        • MacLeod A.M.
        • Snyder A.Z.
        • Powers W.J.
        • Gusnard D.A.
        • Shulman G.L.
        A default mode of brain function.
        Proc Natl Acad Sci U S A. 2001; 98: 676-682
        • Greicius M.D.
        • Menon V.
        Default-mode activity during a passive sensory task: Uncoupled from deactivation but impacting activation.
        J Cogn Neurosci. 2004; 16: 1484-1492
        • Fransson P.
        Spontaneous low-frequency BOLD signal fluctuations: An fMRI investigation of the resting-state default mode of brain function hypothesis.
        Hum Brain Mapp. 2005; 26: 15-29
        • Damoiseaux J.S.
        • Rombouts S.A.
        • Barkhof F.
        • Scheltens P.
        • Stam C.J.
        • Smith S.M.
        • et al.
        Consistent resting-state networks across healthy subjects.
        Proc Natl Acad Sci U S A. 2006; 103: 13848-13854
        • Raichle M.E.
        • Snyder A.Z.
        A default mode of brain function: A brief history of an evolving idea.
        Neuroimage. 2007; ([Epub ahead of print March 3, 2007])
        • Tian L.
        • Jiang T.
        • Wang Y.
        • Zang Y.
        • He Y.
        • Liang M.
        • et al.
        Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder.
        Neurosci Lett. 2006; 400: 39-43
        • Zang Y.F.
        • Yong H.
        • Chao-Zhe Z.
        • Qing-Jiu C.
        • Man-Qiu S.
        • Meng L.
        • et al.
        Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.
        Brain Dev. 2007; 29: 83-91
        • Greicius M.D.
        • Srivastava G.
        • Reiss A.L.
        • Menon V.
        Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI.
        Proc Natl Acad Sci U S A. 2004; 101: 4637-4642
        • Buckner R.L.
        • Snyder A.Z.
        • Shannon B.J.
        • LaRossa G.
        • Sachs R.
        • Fotenos A.F.
        • et al.
        Molecular, structural, and functional characterization of Alzheimer’s disease: Evidence for a relationship between default activity, amyloid, and memory.
        J Neurosci. 2005; 25: 7709-7717
        • Kennedy D.P.
        • Redcay E.
        • Courchesne E.
        Failing to deactivate: Resting functional abnormalities in autism.
        Proc Natl Acad Sci U S A. 2006; 103: 8275-8280
        • Liang M.
        • Zhou Y.
        • Jiang T.
        • Liu Z.
        • Tian L.
        • Liu H.
        • et al.
        Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging.
        NeuroReport. 2006; 17: 209-213
        • Greicius M.D.
        • Flores B.H.
        • Menon V.
        • Glover G.H.
        • Solvason H.B.
        • Kenna H.
        • et al.
        Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus.
        Biol Psychiatry. 2007; ([Epub ahead of print January 8, 2007])
        • Fox M.D.
        • Snyder A.Z.
        • Vincent J.L.
        • Corbetta M.
        • Van E.
        • Raichle M.E.
        The human brain is intrinsically organized into dynamic, anticorrelated functional networks.
        Proc Natl Acad Sci U S A. 2005; 102: 9673-9678
        • Deragotis L.R.
        Symptom Checklist-90-R: Administration, Scoring, and Procedures Manual.
        3rd ed. National Computer Systems, Inc, Minneapolis1986
        • Adler L.A.
        • Cohen J.
        Diagnosis and evaluation of adult ADHD.
        Psychiatr Clin North Am. 2004; 27: 187-201
        • Kessler R.C.
        • Adler L.
        • Barkley R.
        • Biederman J.
        • Conners C.K.
        • Demler O.
        • et al.
        The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication.
        Am J Psychiatry. 2006; 163: 716-723
        • Good C.D.
        • Johnsrude I.S.
        • Ashburner J.
        • Henson R.N.
        • Friston K.J.
        • Frackowiak R.S.
        A voxel-based morphometric study of ageing in 465 normal adult human brains.
        Neuroimage. 2001; 14: 21-36
        • Sporns O.
        • Tononi G.
        • Edelman G.M.
        Connectivity and complexity: The relationship between neuroanatomy and brain dynamics.
        Neural Netw. 2000; 13: 909-922
        • Overmeyer S.
        • Bullmore E.T.
        • Suckling J.
        • Simmons A.
        • Williams S.C.R.
        • Santosh P.J.
        • et al.
        Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network.
        Psychol Med. 2001; 31: 1425-1435
        • Carmona S.
        • Vilarroya O.
        • Bielsa A.
        • Tremols V.
        • Soliva J.C.
        • Rovira M.
        • et al.
        Global and regional gray matter reductions in ADHD: A voxel-based morphometric study.
        Neurosci Lett. 2005; 389: 88-93
        • Makris N.
        • Biederman J.
        • Valera E.M.
        • Bush G.
        • Kaiser J.
        • Kennedy D.N.
        • et al.
        Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder.
        Cereb Cortex. 2007; 17: 1364-1375
        • Martinussen R.
        • Hayden J.
        • Hogg-Johnson S.
        • Tannock R.
        A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder.
        J Am Acad Child Adolesc Psychiatry. 2005; 44: 377-384
        • Hampson M.
        • Driesen N.R.
        • Skudlarski P.
        • Gore J.C.
        • Constable R.T.
        Brain connectivity related to working memory performance.
        J Neurosci. 2006; 26: 13338-13343
        • Bush G.
        • Luu P.
        • Posner M.I.
        Cognitive and emotional influences in anterior cingulate cortex.
        Trends Cogn Sci. 2000; 4: 215-222
        • Simmonds D.J.
        • Fotedar S.G.
        • Suskauer S.J.
        • Pekar J.J.
        • Denckla M.B.
        • Mostofsky S.H.
        Functional brain correlates of response time variability in children.
        Neuropsychologia. 2007; ([Epub ahead of print January 21, 2007])
        • Shaw P.
        • Lerch J.
        • Greenstein D.
        • Sharp W.
        • Clasen L.
        • Evans A.
        • et al.
        Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder.
        Arch Gen Psychiatry. 2006; 63: 540-549
        • Cavanna A.E.
        • Trimble M.R.
        The precuneus: A review of its functional anatomy and behavioural correlates.
        Brain. 2006; 129: 564-583
        • Bassett D.S.
        • Bullmore E.
        Small-world brain networks.
        Neuroscientist. 2006; 12: 512-523