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Cited by 854Attention Deficit Hyperactivity DisorderFunctional Brain Connectivity StudiesNeural and Behavioral Psychology Studies

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

Open access
Castellanos, F. Xavier, Margulies, Daniel S., Kelly, Clare, Uddin, Lucina Q., Ghaffari, Manely, Kirsch, Andrew, Shaw, David, Shehzad, Zarrar +6 more·2008·Biological Psychiatry
DOI 10.1016/j.biopsych.2007.06.025PMC PMC2745053
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Abstract

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 x 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.

AI snapshot

Written from the paper’s full text.

TL;DR

Resting-state functional connectivity in adults with ADHD showed reduced negative coupling between dorsal anterior cingulate cortex and posterior default-mode regions, especially precuneus/posterior cingulate cortex. The authors propose cingulate–precuneus long-range connections as a candidate locus of dysfunction in ADHD.

Key findings

  • Healthy controls showed an antiphasic/negative relationship between dorsal anterior cingulate cortex (dACC; centered at x=8, y=7, z=38) and default-mode network components.
  • ADHD participants had significantly less negative dACC–precuneus/PCC connectivity (p<.0004, corrected; cluster = 13,436 mm³).
  • Secondary analyses found ADHD-related decreases between precuneus and other default-mode components, including ventromedial prefrontal cortex (p<3×10⁻¹¹, corrected) and portions of posterior cingulate (p<.02, corrected).
  • Regression parameter estimates for the negative dACC–PCC/precuneus relationship were −0.23 ± 0.12 in healthy controls and −0.01 ± 0.15 in ADHD (t(38)=5.10, p=9.6×10⁻⁶; d=1.61, 95% CI 0.79–2.43), and across the whole sample correlated with ADHD symptoms (Pearson r between −0.61 and −0.54, n=38, p<.001).

Methods

  • Resting-state BOLD fMRI at 3.0 Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers; 9 ADHD patients were currently treated with stimulants, discontinued for at least one day before scanning.
  • Seed-based functional connectivity analyses used three frontal ROIs (dACC, right inferior frontal gyrus, right medial frontal gyrus), GLM in FEAT, nuisance covariates, and mixed-effects group analyses in FSL/FLAME with cluster-level correction.
  • A study-specific template was created for spatial normalization; secondary analyses used the precuneus/PCC region as a seed, and exploratory correlations examined symptom severity.

Limitations

  • The paper states that no significant relationship was detected between connectivity estimates and inattention severity within the ADHD group, possibly because symptom ranges were restricted and inattentive/hyperactive symptoms were highly correlated (r=0.68).
  • The authors note that undiagnosed learning disorders in ADHD participants may have contributed, though high educational attainment diminishes this concern; they also note divergence from a prior adolescent ADHD connectivity report and suggest differences in seed ROI, anti-correlations, and age group as possible explanations.
  • Evident from the text: the sample was small (20 per group), cross-sectional, and did not directly assess attentional lapses, working memory, response variability, medication response, or effective connectivity.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2007.06.025

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 32 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Results

    In adults with ADHD compared with healthy controls, there are decreases in functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p<.0004, corrected).

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    In adults with ADHD compared with healthy controls, there are decreases in connectivity between precuneus and portions of posterior cingulate (p<.02, 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).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    In healthy controls, there is an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x=8, y=7, z=38) and default-mode network components.

    “Examination of healthy controls 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.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    In adults with ADHD compared with healthy controls, there are decreases in connectivity between precuneus and ventromedial prefrontal cortex (p<3×10−11, 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).”
    Quote in the paperSubstantial claim
  • Findingown data
    § RESULTS

    Regression parameter estimates for the negatively correlated relationship between dACC ROI and PCC/precuneus differed between groups: means ±SD −0.23 ± 0.12 for healthy controls and −0.01 ± 0.15 for ADHD; t(38)=5.10, p=9.6×10−6; d=1.61, 95% CI 0.79-2.43.

    “Figure 4 shows the distribution of regression parameter estimates for the negatively correlated relationship between dACC ROI and PCC/precuneus in the two groups (means ±SD −0.23 ± 0.12 and −0.01 ± 0.15 for healthy control and ADHD groups, respectively; t(38) = 5.10, p=9.6 × 10−6; d= 1.61, 95% CI 0.79 – 2.43).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 20
  • May combine two claims. 7

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data
    § RESULTS

    rIFG and rMFG ROIs were significantly negatively related to precuneus and posterior cingulate cortex (PCC) in both groups, but these relationships did not differentiate the groups significantly.

    “Although both rIFG and rMFG ROIs were significantly negatively related to precuneus and posterior cingulate cortex (PCC) in both groups (see Supplementary Figure 1), these relationships did not differentiate the groups significantly.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    The ADHD group showed significantly less negatively correlated functional activity in ACC (BA 24, 31, 32) and medial frontal gyrus (BA 6) (p<0.00002, corrected) and in superior temporal gyrus (BA 22, 41; p<0.04, corrected), including claustrum and precentral gyrus (BA 43, 44).

    “The ADHD group also showed significantly less negatively correlated functional activity in ACC (BA 24, 31, 32) and medial frontal gyrus (BA 6) (p<0.00002, corrected) and in superior temporal gyrus (BA 22, 41; p<0.04, corrected), including claustrum and precentral gyrus (BA 43, 44).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    The positively correlated regions coincided with the default-mode network in controls, but the ADHD group lacked the anterior component of that network.

    “The positively correlated regions coincided with the default-mode network in controls, but the ADHD group lacked the anterior component of that network.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusions

    Functional connectivity provides detailed spatial maps of putatively functionally related regions.

    “This method of functional connectivity (8), first applied to mapping the motor cortical system (9), provides remarkably detailed spatial maps of putatively functionally related regions (10).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [8] Friston, 1994, Functional and effective connectivity in neuroimaging: A synthesis, Hum Brain Mapp source

      Not checked in the free run.

    • cites [9] Biswal, 1995, Functional connectivity in the motor cortex of resting human brain using echo-planar MRI, Magn Reson Med source

      Not checked in the free run.

    • cites [10] Margulies, 2007, Mapping the functional connectivity of anterior cingulate cortex, Neuroimage source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusions

    Momentary lapses in attention have been associated with failure to suppress activity in the default-mode network.

    “Momentary lapses in attention have been associated with failure to suppress activity in the ‘default-mode’ network (11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Weissman, 2006, The neural bases of momentary lapses in attention, Nat Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § METHODS

    Participants with ADHD were administered the Structured Clinical Interview for DSM-IV (SCID) to rule out other Axis I comorbid diagnoses.

    “All participants with ADHD met lifetime criteria for Combined Type ADHD; they were also administered the Structured Clinical Interview for DSM-IV (SCID) to rule out other axis I comorbid diagnoses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § METHODS

    Symptom data on the ACDS 2.1 were unavailable for two subjects diagnosed with combined type ADHD by clinical interview.

    “Symptom data on this scale unavailable for two subjects diagnosed with combined type ADHD by clinical interview.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Conclusions

    The default-mode network is a large and robustly replicable network.

    “The ‘default-mode’ network, first identified by Raichle et al. (12), is a large and robustly replicable network (13, 14, 15) that comprises medial ventral prefrontal cortex (MVPFC) and posterior cingulate cortex (PCC) and precuneus in the midline and which has been linked to non-goal-directed processes (16).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [12] Raichle, 2001, A default mode of brain function, Proc Natl Acad Sci U S A source

      Not checked in the free run.

    • cites [13] Greicius, 2004, Default-mode activity during a passive sensory task: Uncoupled from deactivation but impacting activation, J Cogn Neurosci source

      Not checked in the free run.

    • cites [14] Fransson, 2005, Spontaneous low-frequency BOLD signal fluctuations: An fMRI investigation of the resting-state default mode of brain function hypothesis, Hum Brain Mapp source

      Not checked in the free run.

    • cites [15] Damoiseaux, 2006, Consistent resting-state networks across healthy subjects, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Conclusions

    The default-mode network has been linked to non-goal-directed processes.

    “The ‘default-mode’ network, first identified by Raichle et al. (12), is a large and robustly replicable network (13, 14, 15) that comprises medial ventral prefrontal cortex (MVPFC) and posterior cingulate cortex (PCC) and precuneus in the midline and which has been linked to non-goal-directed processes (16).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Raichle, 2007, A default mode of brain function: A brief history of an evolving idea, Neuroimage source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation
    § METHODS

    The Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2 has been validated with informant-only reports.

    “All participants were evaluated with the Adult ADHD Clinical Diagnostic Scale (ACDS) Version1.2 (26), a semi-structured interview that probes for the presence, severity and impairment associated with ADHD symptoms in childhood and adulthood, and which has been validated with informant-only reports (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Kessler, 2006, The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication, Am J Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § METHODS

    A study-specific template was created to optimize automated spatial normalization and avoid possible group differences related to registration errors.

    “In order to optimize automated spatial normalization and avoid possible group differences related to registration errors (28), we created a study specific template based upon the approach employed in optimized voxel based morphometry protocols (28).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Good, 2001, A voxel-based morphometric study of ageing in 465 normal adult human brains, Neuroimage source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusions

    The focus on executive dysfunction and the frontal lobes has left alternative hypotheses unexplored, as pointed out in a recent quantitative meta-analysis of functional imaging studies of ADHD.

    “However, as pointed out in a recent quantitative meta-analysis of functional imaging studies of ADHD (4), the focus on executive dysfunction and the frontal lobes has left alternative hypotheses unexplored.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Dickstein, 2006, The neural correlates of attention deficit hyperactivity disorder: An ALE meta-analysis, J Child Psychol Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § METHODS

    Prospective participants were screened with the Symptom Checklist-90-Revised (SCL-90 R) to exclude a broad range of psychiatric psychopathology.

    “All prospective participants were screened with the Symptom Checklist-90-Revised (SCL-90 R), to exclude a broad range of psychiatric psychopathology (25).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Deragotis, 1986

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Conclusions

    Pathophysiological models of ADHD have focused on prefrontal-striatal and mesolimbic circuits, based on findings of executive and motivational dysfunction.

    “Pathophysiological models of Attention-Deficit/Hyperactivity Disorder (ADHD) have focused on prefrontal-striatal and mesolimbic circuits (1), based on findings of executive and motivational dysfunction (2, 3).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Castellanos, 2006, Characterizing cognition in ADHD: Beyond executive dysfunction, Trends Cogn Sci source

      Not checked in the free run.

    • cites [2] Willcutt, 2005, Validity of the executive function theory of attention-deficit/hyperactivity disorder: A meta-analytic review, Biol Psychiatry source

      Not checked in the free run.

    • cites [3] Sonuga-Barke, 2005, Causal models of ADHD: from common simple deficits to multiple developmental pathways, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data
    § METHODS

    Age, sex distributions, and educational attainment did not differ significantly between the ADHD and healthy comparison groups (p>.20).

    “Age, sex distributions and educational attainment did not differ significantly (p>.20).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusions

    The default-mode network comprises medial ventral prefrontal cortex, posterior cingulate cortex, and precuneus in the midline.

    “The ‘default-mode’ network, first identified by Raichle et al. (12), is a large and robustly replicable network (13, 14, 15) that comprises medial ventral prefrontal cortex (MVPFC) and posterior cingulate cortex (PCC) and precuneus in the midline and which has been linked to non-goal-directed processes (16).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Raichle, 2001, A default mode of brain function, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § METHODS

    Repeating the analyses using the standard adult 152 brain MNI template rather than the study-specific template yielded nearly identical results.

    “Repeating our analyses using the standard adult 152 brain MNI template rather than the study specific template yielded nearly identical results.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Conclusions

    In healthy adult volunteers, decreased cue-related activation in three prefrontal regions predicted slower response times and decreased default-mode network suppression.

    “The starting point for the present study was the finding that decreased cue-related activation in three prefrontal regions predicted slower response times and decreased default-mode network suppression in healthy adult volunteers (11), suggesting potential control loci for default-mode regulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Weissman, 2006, The neural bases of momentary lapses in attention, Nat Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § METHODS

    Healthy comparison subjects were administered a semi-structured clinical interview to rule out all Axis I psychiatric disorders, including ADHD or learning disorders in childhood or adulthood.

    “A psychiatrist (AK, MG) administered a semi-structured clinical interview to healthy comparison subjects to rule out all axis I psychiatric disorders, including presence of ADHD or learning disorders in childhood or adulthood.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § DISCUSSION

    Better performance on a working memory task has been reported to be positively related to the strength of functional connectivity between anterior and posterior default-mode components (VMPFC and PCC).

    “Better performance on a working memory task has been reported to be positively related to the strength of functional connectivity between anterior and posterior default-mode components (VMPFC and PCC) (34).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Hampson, 2006, Brain connectivity related to working memory performance, J Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § DISCUSSION

    ACC is functionally and structurally complex.

    “First, ACC is functionally and structurally complex (35, 10); we ‘seeded’ an ACC subregion empirically linked to default-mode interactions, while the seed ROI used by Tian et al. comprised the entire dorsal ACC.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] Bush, 2000, Cognitive and emotional influences in anterior cingulate cortex, Trends Cogn Sci source

      Not checked in the free run.

    • cites [10] Margulies, 2007, Mapping the functional connectivity of anterior cingulate cortex, Neuroimage source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § DISCUSSION

    Tian et al. did not differentiate the anti-phase relationships (anti-correlations) that accounted for the paper's findings.

    “Second, Tian et al. did not differentiate the anti-phase relationships (“anti-correlations”) (24, 14) that accounted for our findings.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Fox, 2005, The human brain is intrinsically organized into dynamic, anticorrelated functional networks, Proc Natl Acad Sci U S A source

      Not checked in the free run.

    • cites [14] Fransson, 2005, Spontaneous low-frequency BOLD signal fluctuations: An fMRI investigation of the resting-state default mode of brain function hypothesis, Hum Brain Mapp source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § METHODS

    Multiple comparisons were corrected at the cluster level using Gaussian random field theory (min Z>2.3; cluster significance p<0.05, corrected).

    “We produced individual subject-level maps of all positively- and negatively-predicted voxels for each regressor, correcting for multiple comparisons at the cluster level using Gaussian random field theory (min Z>2.3; cluster significance: p<0.05, corrected).”
    Quote in the paperSubstantial claim
23 of 23

  • The authors state this as an assumption.

    Cortical connectivity should be reciprocal.

    “Based on the assumption that cortical connectivity should be reciprocal (29), we used the timeseries corresponding to the”
    “Based on the assumption that cortical connectivity should be reciprocal (29), we used the timeseries corresponding to the region which differed significantly between groups in our primary analyses, and derived the corresponding positively and negatively predicted networks and their significant group differences.”

  • The paper relies on this without support.

    Standard task-based functional imaging studies depend on the precise specification of underlying neuropsychological deficits.

    “Additionally, standard task-based functional imaging studies depend on the precise specification of underlying neuropsychological deficits.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The PFC is underactive in many patients with ADHD.

    “this brain region is underactive in many patients with ADHD”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Castellanos et al., 2008

    The Results and Discussion report reduced functional connectivity involving the ventromedial prefrontal cortex in the ADHD group. They do not establish that the PFC itself is underactive, or that this is true of many patients; the decreased prefrontal activation mentioned in the introductory passage concerns healthy volunteers. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • In patients with ADHD, white matter tracts linking the PFC to other brain regions appear less well organized, and functional connectivity is reduced.

    “In patients with ADHD, the white matter tracts that link the PFC to other brain regions also appear less well organized (Casey et al., 2007; Makris et al., 2008), and functional connectivity is reduced (Castellanos et al., 2008).”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Castellanos et al., 2008

  • The dorsolateral PFC has a smaller volume and reduced activity in patients with ADHD compared with controls.

    “Several imaging studies have shown that the dorsolateral PFC has a smaller volume and reduced activity in patients with ADHD compared with controls (Castellanos et al., 2002; Castellanos et al., 2008; Mostofsky et al., 2002; Rubia et al., 1999; Seidman et al., 2005).”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Castellanos et al., 2008

    The Results report reduced functional connectivity involving the dorsal anterior cingulate, precuneus, and posterior cingulate in adults with ADHD, not reduced dorsolateral PFC activity. The Discussion mentions diminished volume in the precuneus and posterior cingulate. Searches for dorsolateral PFC volume and activity found no passage in our copy addressing the claimed comparison with controls; section page numbers were not available. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • Connections to the default network were atypical in ADHD in all three subgroups.

    “Connections to the default network were atypical in ADHD in all the three subgroups, corroborating previous findings of atypical connectivity between the nucleus accumbens and regions of the default network in a group of children with ADHD combined type (which shared some participants with the current study) (Costa Dias et al., 2012), and of atypical integration of this network in ADHD (Castellano”

    From Characterizing heterogeneity in children with and without ADHD based on reward system connectivity (2015) · cites this paper as Castellanos et al., 2008

  • Systems that are positively correlated may be interpreted as integrated systems, while the ones negatively correlated may be highly segregated.

    “Previous studies suggest systems that are positively correlated may be interpreted as integrated systems, while the ones negatively correlated may be highly segregated (Castellanos et al., 2008, Fox et al., 2005, Fox et al., 2009).”

    From Characterizing heterogeneity in children with and without ADHD based on reward system connectivity (2015) · cites this paper as Castellanos et al., 2008

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Reported symptom-correlation direction conflicts with group data

    Major

    ADHD participants have much higher symptom counts in Table 1 and higher regression parameter estimates than controls. Given the reported within-group standard deviations, the stated negative correlation across the combined sample is incompatible with those group data.

  • Table 3 labels positive-network differences as negatively correlated

    Minor

    The Results describe the medial prefrontal and PCC/precuneus differences as involving positively correlated default-mode regions, but the corresponding portion of Table 3 is headed as decreases in negatively correlated connectivity.

  • Frontal seed labels are swapped in the supplement

    Minor

    The Methods assign the seed near x=34, y=45 to rIFG and the seed near x=49, y=19 to rMFG. The supplementary description assigns those locations to rMFG and rIFG, respectively.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 27

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  2. Sonuga-Barke, 2005, Causal models of ADHD: from common simple deficits to multiple developmental pathways, Biol Psychiatry, 57, 1231, 10.1016/j.biopsych.2004.09.008 · DOI · Paper page
  3. Friston, 1994, Functional and effective connectivity in neuroimaging: A synthesis, Hum Brain Mapp, 2, 56, 10.1002/hbm.460020107 · DOI · Paper page
  4. Margulies, 2007, Mapping the functional connectivity of anterior cingulate cortex, Neuroimage, 10.1016/j.neuroimage.2007.05.019 · DOI
  5. Raichle, 2001, A default mode of brain function, Proc Natl Acad Sci U S A, 98, 676, 10.1073/pnas.98.2.676 · DOI · Paper page
  6. Fransson, 2005, Spontaneous low-frequency BOLD signal fluctuations: An fMRI investigation of the resting-state default mode of brain function hypothesis, Hum Brain Mapp, 26, 15, 10.1002/hbm.20113 · DOI · Paper page
  7. Damoiseaux, 2006, Consistent resting-state networks across healthy subjects, Proc Natl Acad Sci U S A, 103, 13848, 10.1073/pnas.0601417103 · DOI · Paper page
  8. Raichle, 2007, A default mode of brain function: A brief history of an evolving idea, Neuroimage, 10.1016/j.neuroimage.2007.02.041 · DOI · Paper page
  9. Tian, 2006, Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder, Neurosci Lett, 400, 39, 10.1016/j.neulet.2006.02.022 · DOI · Paper page
  10. Zang, 2007, Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI, Brain Dev, 29, 83, 10.1016/j.braindev.2006.07.002 · DOI · Paper page
  11. Greicius, 2004, Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI, Proc Natl Acad Sci U S A, 101, 4637, 10.1073/pnas.0308627101 · DOI · Paper page
  12. Kennedy, 2006, Failing to deactivate: Resting functional abnormalities in autism, Proc Natl Acad Sci U S A, 103, 8275, 10.1073/pnas.0600674103 · DOI · Paper page
  13. Liang, 2006, Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging, NeuroReport, 17, 209, 10.1097/01.wnr.0000198434.06518.b8 · DOI
  14. Greicius, 2007, Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus, Biol Psychiatry, 10.1016/j.biopsych.2006.09.020 · DOI · Paper page
  15. Fox, 2005, The human brain is intrinsically organized into dynamic, anticorrelated functional networks, Proc Natl Acad Sci U S A, 102, 9673, 10.1073/pnas.0504136102 · DOI · Paper page
  16. Adler, 2004, Diagnosis and evaluation of adult ADHD, Psychiatr Clin North Am, 27, 187, 10.1016/j.psc.2003.12.003 · DOI · Paper page
  17. Kessler, 2006, The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication, Am J Psychiatry, 163, 716, 10.1176/ajp.2006.163.4.716 · DOI · Paper page
  18. Sporns, 2000, Connectivity and complexity: The relationship between neuroanatomy and brain dynamics, Neural Netw, 13, 909, 10.1016/S0893-6080(00)00053-8 · DOI
  19. Overmeyer, 2001, Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network, Psychol Med, 31, 1425, 10.1017/S0033291701004706 · DOI · Paper page
  20. Carmona, 2005, Global and regional gray matter reductions in ADHD: A voxel-based morphometric study, Neurosci Lett, 389, 88, 10.1016/j.neulet.2005.07.020 · DOI · Paper page
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Cited by

Sorted by citations

Authors
Castellanos, F. X., Margulies, D. S., Kelly, C., Uddin, L. Q., Ghaffari, M., Kirsch, A., Shaw, D., Shehzad, Z., Di Martino, A., Biswal, B., Sonuga-Barke, E. J. S., Rotrosen, J., Adler, L. A., & Milham, M. P.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • New York University (US)
  • University of Medicine and Dentistry of New Jersey (US)
  • King's College London (GB)
Corresponding author
Castellanos, F. Xavier
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2008-02
Volume
63
Issue
3
Pages
332-337
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2007.06.025
PMC
PMC2745053
OpenAlex
W2023981958
Cited by
854
References
11
Citations by year
2026: 13 · 2025: 28 · 2024: 25 · 2023: 33 · 2022: 24 · 2021: 38 · 2020: 41 · 2019: 48 · 2018: 42 · 2017: 43 · 2016: 55 · 2015: 66 · 2014: 63 · 2013: 66 · 2012: 72
FWCI
26.58
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • National Institutes of Health (5r21mh066393-03, 5t32mh067763-10)
  • National Institute of Mental Health (5T32MH067763, 5R21MH066393, R01MH083246, R21-MH066393, T32MH-067763)
  • National Institute on Drug Abuse (R01DA016979)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
attention deficit hyperactivity disorder, dorsal anterior cingulate cortex, precuneus, posterior cingulate cortex, default mode network, functional connectivity, resting-state functional connectivity, ventromedial prefrontal cortex, cognitive control, adult ADHD
MeSH terms
Adult, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Female, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Case-Control Studies, Prefrontal Cortex

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