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Cited by 103Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesAutism Spectrum Disorder Research

The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study

Open access
Gehricke, Jean-G., Kruggel, Frithjof, Thampipop, Tanyaporn, Alejo, Sharina Dyan, Tatos, Erik, Fallon, James, Muftuler, L. Tugan·2017·PLOS ONE
DOI 10.1371/journal.pone.0175433PMC PMC5391018
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Abstract

BACKGROUND: This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD. METHODS: Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD) in relation to diagnosis and the number of self-reported child and adult symptoms. RESULTS: Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation) of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases. CONCLUSION: An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker.

AI snapshot

Written from the paper’s full text.

TL;DR

This MRI study examined structural and diffusion-weighted brain correlates of ADHD diagnosis and childhood/adult symptoms in young adults. It reports widespread macro- and microstructural differences, stronger associations for childhood symptoms, and morphometric prediction of ADHD diagnosis in up to 83.3% of cases.

Key findings

  • ADHD diagnosis was associated with widespread gray matter, white matter, and shape/Jacobian differences, including decreased gray matter in right middle/inferior frontal gyrus, right superior/middle temporal gyrus, left caudate head, and left parahippocampal gyrus, plus shape contractions suggesting incomplete maturation in frontal, temporal, parietal, insular, and parahippocampal regions.
  • DTI measures showed diagnosis-related differences in FA, RD, MD, and AD across regions including external capsule, optic radiation, temporal gyri, postcentral gyrus, cingulate gyrus, corpus callosum, temporal stems, internal capsule, midbrain, and pons.
  • Childhood ADHD symptoms showed stronger and more widespread microstructural associations than adult symptoms; no association was found between brain macrostructure and ADHD symptoms.
  • Morphometric data predicted ADHD diagnosis correctly in 83.3% of all cases; repeated random sub-sampling cross-validation with a 20% test set yielded 81.4% correct prediction (95% CI 0.76–0.86), and a single white matter concentration measure had an AUC of 0.917.

Methods

  • Voxel-wise linear regression models examined T1-weighted structural and diffusion-weighted MRI data in 72 participants; the text reports 31 young adults with ADHD and 41 controls, while Table 1 lists 32 ADHD and 40 controls.
  • Models included diagnosis, childhood symptoms, adult symptoms, gender, age, and intracranial volume as covariates; clusters were thresholded at voxel-level p = 0.01 and cluster-level p = 0.05, corrected using Gaussian random field theory.
  • For prediction, voxel-wise measures from significant regions were averaged per subject, logistic regression was used for a single score, and PCA plus linear discriminant analysis was used to combine six measures (GM, WM, TBM, FA, RD, MD).

Limitations

  • Stated: childhood symptoms were assessed by self-report in young adults, which may be affected by memory bias or distortion; ADHD inattentive and combined subtypes were not considered; and the morphometric findings may not be specific to ADHD.
  • Evident: the sample was modest in size, and the paper text and Table 1 disagree on group sizes (31/41 vs. 32/40).
  • Evident: controls were not entirely symptom-free—21 control participants had at least one ADHD symptom—and groups differed in employment, stimulant medication use, and subtype diagnoses, though the paper states comorbidities did not significantly differ between groups.

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Integrity signals

Registry

Crossref · 10.1371/journal.pone.0175433

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 79 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    An ADHD diagnosis is associated with regions of decreased grey matter in the right middle and inferior frontal gyrus, right superior and middle temporal gyrus, left caudate head, and left parahippocampal gyrus.

    “regions of decreased grey matter in the right middle and inferior frontal gyrus, right superior and middle temporal gyrus, left caudate head, and left parahippocampal gyrus”
    Quote in the paperSubstantial claim
  • Findingown data

    Adult ADHD symptoms are associated with decreased FA, RD, MD, and AD in the left cingulum.

    “a region of decreased FA, RD, MD, and AD in the left cingulum”
    Quote in the paperSubstantial claim
  • Findingown data

    An ADHD diagnosis is associated with decreased FA in the right superior temporal gyrus, left and right middle temporal gyrus, right postcentral gyrus, cingulate gyrus, corpus callosum, left and right temporal stem, and right midbrain.

    “regions of decreased FA in the right superior temporal gyrus, left and right middle temporal gyrus, right postcentral gyrus, cingulate gyrus, corpus callosum, left and right temporal stem, and right midbrain”
    Quote in the paperSubstantial claim
  • Findingown data

    Childhood ADHD symptoms are associated with increased FA, RD, and MD in the left sub-gyral white matter of the frontal lobe.

    “a region of increased FA, RD and MD in the left sub-gyral white matter of the frontal lobe”
    Quote in the paperSubstantial claim
  • Findingown data

    An ADHD diagnosis is associated with increased RD in the left and right postcentral gyrus, left middle temporal gyrus, cingulate gyrus, right internal capsule, and right midbrain.

    “regions of increased RD, including the left and right postcentral gyrus, left middle temporal gyrus, cingulate gyrus, right internal capsule, and right midbrain”
    Quote in the paperSubstantial claim
  • May combine two claims. 34
  • Classified as probably not a substantial claim. 28

  • May combine two claims.

    Findingown data

    An ADHD diagnosis is associated with different grey and white matter concentrations and shape differences as computed from Jacobian maps.

    “An ADHD diagnosis was associated with different grey (white) matter concentrations, and shape differences as computed from the Jacobian maps (JAC, see Table 2, S1, S2 and S3 Maps).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adult ADHD symptoms are associated with decreased FA and increased RD in the right dentate nucleus.

    “a region of decreased FA and increased RD in the right dentate nucleus”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ADHD symptoms were associated with microstructural findings, which were more prominent for childhood total symptoms compared to adult total symptoms.

    “However, ADHD symptoms were associated with microstructural findings, which were more prominent (i.e., number, size, and z-scores of significant regions) for the childhood total symptoms (see Table 4, S8, S9, S10 and S11 Maps), compared to the adult total symptoms (Table 5, S12, S13, S14 and S15 Maps).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An ADHD diagnosis is associated with shape contractions (decreased JAC suggesting incomplete maturation) in the right middle frontal gyrus, right superior temporal gyrus, left middle temporal gyrus, right postcentral gyrus, left posterior insula, and left and right parahippocampal gyrus.

    “regions with shape contractions (decreased JAC suggesting incomplete maturation) in the right middle frontal gyrus, right superior temporal gyrus, left middle temporal gyrus, right postcentral gyrus, left posterior insula, and left and right parahippocampal gyrus.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An ADHD diagnosis is associated with regions of increased white matter in the right frontal gyrus, right inferior frontal gyrus, right middle temporal gyrus, left and right external capsule, left internal capsule, and left parahippocampal gyrus.

    “regions with increased white matter in the right frontal gyrus, right inferior frontal gyrus, right middle temporal gyrus, left and right external capsule, left internal capsule, and left parahippocampal gyrus”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An ADHD diagnosis in young adults was associated with decreased grey matter concentration, increased white matter concentration, and decreased shape in widespread areas involving frontal, temporal, striatal, parietal and limbic regions.

    “An ADHD diagnosis in young adults was associated with decreased grey matter concentration, increased white matter concentration, and decreased shape in widespread areas involving frontal, temporal, striatal, parietal and limbic regions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes.

    “An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Our results show that temporal lobes are also affected in size and connectivity in young adults with ADHD.

    “Our results show that temporal lobes are also affected in size and connectivity in young adults with ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Decreased FA in the right superior temporal gyrus and both sides of the middle temporal gyrus as well as decreased AD in the occipital lobe and brainstem were associated with an ADHD diagnosis.

    “In addition, decreased FA in the right superior temporal gyrus and both sides of the middle temporal gyrus as well as decreased AD in the occipital lobe and brainstem were associated with an ADHD diagnosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Our findings revealed reduced gray matter concentrations in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, right middle temporal gyrus, left caudate head, and left parahippocampal gyrus with corresponding white matter increases associated with an ADHD diagnosis in young adults.

    “Our findings revealed reduced gray matter concentrations in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, right middle temporal gyrus, left caudate head, and left parahippocampal gyrus with corresponding white matter increases associated with an ADHD diagnosis in young adults.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Reduced grey matter in the left caudate was associated with an ADHD diagnosis, and reduced FA, as well as increased RD and MD in the left putamen, was correlated with child symptoms of ADHD, but not adult symptoms of ADHD.

    “While reduced grey matter in the left caudate was associated with an ADHD diagnosis, reduced FA, as well as increased RD and MD in the left putamen, it was also correlated with child symptoms of ADHD, but not adult symptoms of ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The strongest associations between symptoms and morphometric findings were determined by the combination of self-reported childhood symptoms and diffusion-weighted measurements, but less so for childhood symptoms and T1-weighted measures.

    “More specifically, dividing into childhood and adult symptoms, the strongest associations between symptoms and morphometric findings were determined by the combination of self-reported childhood symptoms and diffusion-weighted measurements, but less so for childhood symptoms and T1- weighted measures.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The dorsal striatum, in particular the putamen, showed regions with reduced FA on the right side and increased RD and MD on both sides including their cortico-striatal connections.

    “Similar to previous research, the dorsal striatum, in particular the putamen, showed regions with reduced FA on the right side and increased RD and MD on both sides including their cortico-striatal connections.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Subsequent meta-analyses mainly report differences in basal ganglia together with changes in total brain or gray matter volume in ADHD.

    “However, subsequent meta-analyses [8–11] mainly report differences in basal ganglia together with changes in total brain [8] or gray matter volume [11].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [8] EM Valera, 2007, Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder, Biol Psychiatry source

      Not checked in the free run.

    • cites [9] I Ellison-Wright, 2008, Structural brain change in attention deficit hyperactivity disorder identified by meta-analysis, BMC psychiatry source

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    • cites [10] T Frodl, 2012, Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects, Acta Psychiatr Scand source

      Not checked in the free run.

    • cites [11] T Nakao, 2011, Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication, Am J Psychiatry source

      Not checked in the free run.

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

    Premisecitation

    Initial brain macrostructural studies revealed that children and adolescents with ADHD show smaller brain volumes in all regions.

    “Initial brain macrostructural studies revealed that children and adolescents with ADHD show smaller brain volumes in all regions [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] FX Castellanos, 2002, Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder, J Am Med Assoc source

      Not checked in the free run.

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

    Premisecitation

    Adults with ADHD have increased MD in the orbito-medial prefrontal cortex, right anterior cingulate, and left fronto-occipital fasciculus.

    “and increased MD in the orbito-medial prefrontal cortex, right anterior cingulate, and left fronto-occipital fasciculus [19, 22].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] A Konrad, 2010, Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder, Eur J Neurosci source

      Not checked in the free run.

    • cites [22] A Konrad, 2012, White matter abnormalities and their impact on attentional performance in adult attention-deficit/hyperactivity disorder, Eur Arch Psychiatry Clin Neurosci source

      Not checked in the free run.

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

    Premisecitation

    Adults with ADHD have reduced connectivity in the orbito-medial prefrontal cortex, right anterior cingulate, right anterior corona radiata, and superior as well as inferior longitudinal fasciculus.

    “Some studies support that ADHD is associated with lifelong abnormal connectivity by showing that adults with ADHD have reduced connectivity in the orbito-medial prefrontal cortex, right anterior cingulate, right anterior corona radiata and the superior as well as inferior longitudinal fasciculus among other regions [18–21]”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [18] N Makris, 2008, Attention and executive systems abnormalities in adults with childhood ADHD: a DT-MRI study of connections, Cereb Cortex source

      Not checked in the free run.

    • cites [19] A Konrad, 2010, Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder, Eur J Neurosci source

      Not checked in the free run.

    • cites [20] N Rüsch, 2007, Inferior frontal white matter microstructure and patterns of psychopathology in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder, Neuroimage source

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    • cites [21] M Ashtari, 2005, Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study, Biol Psychiatry source

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  • Classified as probably not a substantial claim.

    Premisecitation

    ADHD primarily involves the fronto-striatal and fronto-parietal networks.

    “Besides these macrostructural indicators, it was suggested that ADHD primarily involves the fronto-striatal [13] as well as fronto-parietal networks [14].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] G Bush, 2005, Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions, Biol Psychiatry source

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    • cites [14] J Fan, 2004, Human attentional networks, Psychiatr Prax source

      Not checked in the free run.

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    Premisecitation

    In children and adolescents, severity of ADHD symptoms is linked to decreased frontal and temporal grey matter, caudate and cerebellar volumes, and decreased FA.

    “In children and adolescents, severity of ADHD symptoms was linked to decreased frontal and temporal grey matter, caudate and cerebellar volumes, [7] and decreased FA [15, 21, 26].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [7] FX Castellanos, 2002, Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder, J Am Med Assoc source

      Not checked in the free run.

    • cites [15] BJ Nagel, 2011, Altered white matter microstructure in children with attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

    • cites [21] M Ashtari, 2005, Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study, Biol Psychiatry source

      Not checked in the free run.

    • cites [26] CY Shang, 2013, Disturbed microstructural integrity of the frontostriatal fiber pathways and executive dysfunction in children with attention deficit hyperactivity disorder, Psychol Med source

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  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Changes in the striatum and its connections are associated with hyperactivity-impulsive symptoms in children with ADHD.

    “It was suggested that changes in the striatum and its connections are associated with hyperactivity-impulsive symptoms in children with ADHD [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] H van Ewijk, 2012, Diffusion tensor imaging in attention deficit/hyperactivity disorder: A systematic review and meta-analysis, Neurosci Biobehav Rev source

      Not checked in the free run.

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

    Premisecitation

    The lack of differences in striatal volumes in adults with ADHD may be caused by reductions in hyperactive-impulsive symptoms in adulthood.

    “This notion was corroborated by showing that the lack of differences in the striatal volumes in adults with ADHD may be caused by reductions in hyperactive-impulsive symptoms in adulthood [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] A De La Fuente, 2013, A review of attention-deficit/hyperactivity disorder from the perspective of brain networks, Front Hum Neurosci source

      Not checked in the free run.

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

    Premisecitation

    The size of basal ganglia regions may initially correlate with hyperactive-impulsive symptoms, which decline over time and may disappear during adulthood.

    “However, the size of basal ganglia regions may initially correlate with hyperactive-impulsive symptoms, which decline over time and may disappear during adulthood [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] BB Lahey, 2011, Higher-order genetic and environmental structure of prevalent forms of child and adolescent psychopathology, AMA Arch Gen Psychiatry source

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    Premisecitation

    The caudate and putamen are smaller in children but not in adults with ADHD.

    “which are smaller in children but not in adults with ADHD [7, 10].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] FX Castellanos, 2002, Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder, J Am Med Assoc source

      Not checked in the free run.

    • cites [10] T Frodl, 2012, Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects, Acta Psychiatr Scand source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    In children and adolescents with ADHD, inattention is linked to reduced brain connectivity in the frontal, anterior cingulate, temporal, and parietal regions.

    “In children and adolescents with ADHD, inattention was linked to reduced brain connectivity not only in the frontal but also in the anterior cingulate, temporal, and parietal regions [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] SB Hong, 2014, Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis, Biol Psychiatry source

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    Study design and conductcitation

    Participants were assessed according to DSM-IV-TR criteria with the Structured Clinical Interview for DSM-IV (SCID) and the QUEST method.

    “each participant was assessed according to DSM-IV-TR criteria [30] with the Structured Clinical Interview for DSM-IV (SCID), [35] and the QUEST method [36].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [30] 2000, Diagnostic and Statistical Manual of Mental Disorders

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    • cites [35] MB First, 1996, User’s guide for the structured interview for DSM-IV axis I disorders—research version (SCID-I, version 2.0, February 1996 final version), New York: Biometrics Research

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    • cites [36] T Wigal, 2007, Establishing a clinical diagnosis of ADHD in adults: the QUEST method, Advances in ADHD

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  • May combine two claims.

    Interpretationown data

    The superior longitudinal fasciculus and cortico-limbic areas are dysfunctional in individuals with ADHD.

    “At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The study was approved by the Institutional Review Board of the University of California, Irvine and written consent was obtained from each participant.

    “The study was approved by the Institutional Review Board of the University of California, Irvine and written consent was obtained from each participant between July 2009 and April 2014.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    The AHA is an 18-item questionnaire based on DSM-IV criteria and was used to measure severity of both childhood and adult symptoms of ADHD.

    “The AHA [37], an 18-item questionnaire, is based on DSM-IV criteria and was used to measure severity of both childhood and adult symptoms of ADHD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] AM Mehringer, 2001, The Assessment of Hyperactivity and Attention: Development and preliminary validation of a brief self-assessment of adult ADHD, J Atten Disord source

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    Study design and conductnone given

    Only clusters passing the significance test were reported.

    “Only clusters passing the significance test were reported.”
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    Study design and conductcitation

    Severity of ADHD symptoms was evaluated using the Assessment of Hyperactivity and Attention (AHA), a quantitative measure of ADHD symptomatology.

    “Severity of ADHD symptoms was evaluated using the Assessment of Hyperactivity and Attention (AHA), which is a quantitative measure of ADHD symptomatology [37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] AM Mehringer, 2001, The Assessment of Hyperactivity and Attention: Development and preliminary validation of a brief self-assessment of adult ADHD, J Atten Disord source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Increased MD in these regions suggests reduced white matter density and potential myelin breakdown associated with an adult ADHD diagnosis.

    “More specifically, increased MD in the left middle temporal gyrus, right internal capsule, and right midbrain suggests reduced white matter density and potential myelin breakdown associated with an adult ADHD diagnosis [4], which is in agreement with in increased MD found in previous studies in children and adolescents with ADHD [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] AL Alexander, 2007, Diffusion tensor imaging of the brain, Neurotherapeutics source

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    Premisecitation

    Previous studies in children found increased FA for white matter structures connecting parietal-occipital regions and temporal lobes in children.

    “Previous studies in children found increased FA for white matter structures connecting parietal-occipital regions and temporal lobes in children [52, 53].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] TJ Silk, 2009, White‐matter abnormalities in attention deficit hyperactivity disorder: a diffusion tensor imaging study, Hum brain Mapp source

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    • cites [53] DJ Peterson, 2011, Increased regional fractional anisotropy in highly screened attention-deficit hyperactivity disorder (ADHD), J Child Neurol source

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

    Interpretationcitation

    Low FA and AD values of the white matter may reflect axonal degeneration, and/or less well-organized tracts, and may be induced by a variety of influences.

    “Low FA and AD values of the white matter may reflect axonal degeneration, and/or less well-organized tracts, and may be induced by a variety of influences [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] MG Qiu, 2011, Changes of brain structure and function in ADHD children, Brain Topogr

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The present findings may suggest that the superior longitudinal fasciculus (SLF) and the cortico-limbic associated circuitry are dysfunctional in individuals with ADHD.

    “At the brain circuitry level, the present findings may suggest that the superior longitudinal fasciculus (SLF) and the cortico-limbic associated circuitry are dysfunctional in individuals with ADHD (see Fig 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The association between microstructural findings and ADHD symptoms weakens with adult ADHD symptoms, possibly due to improved structural changes or coping skills.

    “However, microstructural differences were more strongly associated with childhood than adult symptoms, which may suggest that while microstructural findings are strongly linked to childhood symptoms, such association weakens with adult ADHD symptoms, which may be due to improved structural changes or coping skills.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The dorsal component of the SLF (SLF I) connects the dorsal and medial part of the frontal lobe with the cingulate and cingulum of the superior and medial parietal cortex.

    “More specifically, the dorsal component of the SLF (SLF I) connects the dorsal and medial part of the frontal lobe (i.e., right middle frontal gyrus in Table 2) with the cingulate (Table 3) and cingulum (Table 5) of the superior and medial parietal cortex [56, 57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] F Lacquaniti, 1995, Representing spatial information for limb movement: role of area 5 in the monkey, Cereb cortex source

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    • cites [57] VB Mountcastle, 1975, Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space, J Neurophysiol source

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    Premisecitation

    The dorsal striatum mediates aspects of decision-making, in particular predicting consequences of goal-directed actions, which are impaired in individuals with ADHD.

    “The dorsal striatum mediates aspects of decision-making, in particular predicting consequences of goal-directed actions, which are impaired in individuals with ADHD [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] BW Balleine, 2007, The role of the dorsal striatum in reward and decision-making, J Neurosci source

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    Premisecitation

    As part of the dorsal attention network, the superior parietal cortex has lower connectivity in children with ADHD.

    “As part of the dorsal attention network, the superior parietal cortex has lower connectivity in children with ADHD [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] D Tomasi, 2012, Abnormal functional connectivity in children with attention-deficit/hyperactivity disorder, Biol Psychiatry source

      Not checked in the free run.

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

    Premisecitation

    The SLF II provides information on visual space and visuo-motor function, which may contribute to spatial attention.

    “The SLF II provides information on visual space and visuo-motor function, which may contribute to spatial attention [61–63].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [61] M Mesulam, 1981, A cortical network for directed attention and unilateral neglect, Ann Neurol source

      Not checked in the free run.

    • cites [62] MI Posner, 1984, Effects of parietal injury on covert orienting of attention, J Neurosci source

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    • cites [63] JW Bisley, 2003, Neuronal activity in the lateral intraparietal area and spatial attention, Science source

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  • May combine two claims.

    Interpretationreasoning

    Disturbances in connections reaching the caudate may be associated with an ADHD diagnosis in young adulthood, whereas reduced FA in the putamen may be an index of symptom severity in childhood.

    “This suggests that disturbances in connections reaching the caudate may be associated with an ADHD diagnosis in young adulthood, whereas reduced FA in the putamen may be an index of symptom severity in childhood.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The morphometric findings demonstrate sufficient sensitivity to aid in the clinical assessment and potential as a biomarker for ADHD in young adults.

    “The overall morphometric findings predict the ADHD diagnosis in 83% of cases, which demonstrates sufficient sensitivity to aid in the clinical assessment and potential as a biomarker for ADHD in young adults.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Other studies have documented the comorbidity between ADHD and depression.

    “Other studies have documented the comorbidity between ADHD and depression [76, 77].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [76] J Biederman, 2008, New insights into the comorbidity between ADHD and major depression in adolescent and young adult females, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

    • cites [77] PS Jensen, 2001, ADHD comorbidity findings from the MTA study: comparing comorbid subgroups, J Am Acad Child Adolesc Psychiatry source

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

    Premisecitation

    Atypical functional coupling in parts of the SLF II has been associated with ADHD in a functional brain imaging study.

    “Atypical functional coupling in parts of the SLF II has been associated with ADHD in a functional brain imaging study [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] JD Franzen, 2013, Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study, J Psychiatry Neurosci source

      Not checked in the free run.

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

    Premisecitation

    Such motivational deficit is in agreement with parent reports of children with ADHD who can concentrate during interesting activities but are challenged by mundane and day-to-day tasks.

    “Such motivational deficit is in agreement with parent reports of children with ADHD who can concentrate during interesting activities but are challenged by mundane and day-to-day tasks [74, 75].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [74] RA Barkley, 2011, The nature of executive function (EF) deficits in daily life activities in adults with ADHD and their relationship to performance on EF tests, J Psychopathol Behav Assess source

      Not checked in the free run.

    • cites [75] ND Volkow, 2011, Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway, Mol Psychiatry source

      Not checked in the free run.

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

    Interpretationcitation

    Such dysfunctional coupling may result in saccadic abnormalities, which have been found in children and adults with ADHD.

    “Such dysfunctional coupling may result in saccadic abnormalities, which have been found in children and adults with ADHD [65, 66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] Y Matsuo, 2015, Gap effect abnormalities during a visually guided pro-saccade task in children with attention deficit hyperactivity disorder, PloS One source

      Not checked in the free run.

    • cites [66] M Fried, 2014, ADHD subjects fail to suppress eye blinks and microsaccades while anticipating visual stimuli but recover with medication, Vision Res source

      Not checked in the free run.

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

    Premisecitation

    The arcuate fasciculus and temporo-parietal section of the SLF connect the superior temporal gyrus with the prefrontal cortex, which modulates numerous language functions and audio-spatial information.

    “The arcuate fasciculus and temporo-parietal section of the SLF connect the superior temporal gyrus (Tables 2, 3 and 4) with the prefrontal cortex, which modulates numerous language functions and audio-spatial information [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] M Petrides, 2002, Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey, Eur J Neurosci source

      Not checked in the free run.

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

    Premisecitation

    The SLF III has been associated with language articulation and connects the rostral part of the inferior parietal lobule with the middle frontal gyrus, the inferior frontal gyrus, and the frontal lobe.

    “The SLF III has been associated with language articulation and connects the rostral part of the inferior parietal lobule with the middle frontal gyrus, the inferior frontal gyrus (Table 2), and the frontal lobe (Table 5) [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] M Petrides, 2002, Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey, Eur J Neurosci source

      Not checked in the free run.

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

    Study design and conductreasoning

    The findings have to be interpreted with caution because childhood symptoms were assessed via self-report by young adults, which may be problematic due to memory bias or distortion.

    “The findings have to be interpreted with caution because childhood symptoms were assessed via self-report by young adults, which may be problematic due to memory bias or distortion.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    The study did not take into consideration that ADHD inattentive and combined subtypes may be different disorders based on unique WM microstructure.

    “In addition, emerging evidence suggests that the ADHD inattentive and ADHD combined subtypes in children may be different disorders based on their unique WM microstructure [78], which was not taken into consideration in this study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    At the brain circuitry level, the involvement of the SLF and cortico-limbic areas may suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults.

    “At the brain circuitry level, the involvement of the SLF and cortico-limbic areas may suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults, which could be investigated in future studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Previous morphometric and DTI studies on white/gray matter integrity in adults with ADHD revealed deficits in structural connectivity, but they may be not unique to ADHD.

    “Furthermore, while previous morphometric and DTI studies on white/gray matter integrity in adults with ADHD revealed deficits in structural connectivity, they may be not unique to ADHD [79].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] ND Davenport, 2010, Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia, Psychiatry Res source

      Not checked in the free run.

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

    Premisecitation

    Emerging evidence suggests that the ADHD inattentive and ADHD combined subtypes in children may be different disorders based on their unique WM microstructure.

    “In addition, emerging evidence suggests that the ADHD inattentive and ADHD combined subtypes in children may be different disorders based on their unique WM microstructure [78], which was not taken into consideration in this study.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] A Svatkova, 2016, Unique white matter microstructural patterns in ADHD presentations—a diffusion tensor imaging study, Hum Brain Mapp source

      Not checked in the free run.

52 of 52

  • The paper relies on this without support.

    There are no studies that directly examine brain anatomical correlates of ADHD diagnosis as well as child and adult ADHD symptoms in young adults with ADHD.

    “However, there are no studies that directly examine brain anatomical correlates of ADHD diagnosis as well as child and adult ADHD symptoms in young adults with ADHD.”

  • The paper relies on this without support.

    The extent of dysfunctional connectivity has yet to be determined in young adults with ADHD.

    “However, the extent of dysfunctional connectivity has yet to be determined in young adults with ADHD.”

  • The paper relies on this without support.

    The corpus callosum is central for communicating between different brain areas.

    “The corpus callosum is central for communicating between different brain areas.”

  • The paper relies on this without support.

    The SLF are longitudinal, intra-hemispheric, cortico-cortical bundles of myelinated axons that link the posterior and anterior cortices, including the frontal lobe to the anterior occipital as well as parietal and posterior temporal lobes.

    “The SLF are longitudinal, intra-hemispheric, cortico-cortical bundles of myelinated axons that link the posterior and anterior cortices, including the frontal lobe to the anterior occipital as well as parietal and posterior temporal lobes.”

  • The paper relies on this without support.

    The SLF is primarily responsible for the visual and motor coordination, as well as spatial sense, language, and mirror neuron systems.

    “The SLF is primarily responsible for the visual and motor coordination, as well as spatial sense, language, and mirror neuron systems.”

  • The paper relies on this without support.

    The cortico-limbic associated circuitry connects the amygdala with the thalamus and orbital frontal cortex.

    “The cortico-limbic associated circuitry connects the amygdala with the thalamus and orbital frontal cortex.”

  • The paper relies on this without support.

    The cortico-limbic associated circuitry is primarily responsible for emotional learning and behavioral regulation.

    “It is primarily responsible for emotional learning and behavioral regulation.”

  • The paper relies on this without support.

    The SLF II connects the middle frontal gyrus with the post central gyrus of the parietal lobe.

    “The SLF II connects the middle frontal gyrus (Table 2) with the post central gyrus (Table 4) of the parietal lobe.”

  • The paper relies on this without support.

    The SLF I codes primarily for location of body parts in a body-centered coordinate system and regulates higher aspects of motor behavior.

    “However, the SLF I codes primarily for location of body parts in a body-centered coordinate system and regulates higher aspects of motor behavior.”
9 of 9

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?

  • Although reduced frontal lobe volume has been frequently reported in ADHD, studies are discrepant about whether the anomaly is unilateral or bilateral, which subregions are involved, whether it comprises white matter, gray matter, or both, and whether it reflects overall smaller brain volume.

    “Although reduced frontal lobe volume has been frequently reported, there are discrepancies as to whether the anomaly: (1) was unilateral (Li et al., 2007; Ambrosino et al., 2017) or bilateral (Gehricke et al., 2017);”

    From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Gehricke et al., 2017

    Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

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.

  • ADHD and control group sizes disagree

    Major

    The abstract and Participants section state that there were 31 participants with ADHD and 41 controls, but Table 1 labels the groups as 32 and 40. This changes the reported group composition, although both versions total 72.

  • Childhood-symptom frontal FA direction is reversed

    Major

    The discussion says childhood symptoms were associated with reduced frontal-lobe FA, whereas all three frontal-lobe FA clusters in Table 4 have positive z-scores. The table therefore reports increased, not reduced, FA in those regions.

  • Adult-symptom cingulum RD and AD directions are reversed

    Minor

    The discussion describes increased RD and AD in the left cingulum, but Table 5 reports negative z-scores for both measures there. The results paragraph also describes the left cingulum's RD and AD as decreased.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. MB First, 1996, User’s guide for the structured interview for DSM-IV axis I disorders—research version (SCID-I, version 2.0, February 1996 final version), New York: Biometrics Research
  2. T Wigal, 2007, Establishing a clinical diagnosis of ADHD in adults: the QUEST method, Advances in ADHD, 2, 17

Cited by

Sorted by citations

Related

Authors
Gehricke, J.-G., Kruggel, F., Thampipop, T., Alejo, S. D., Tatos, E., Fallon, J., & Muftuler, L. T.
Affiliations
  • University of California, Irvine (US)
  • Medical College of Wisconsin (US)
Corresponding author
Gehricke, Jean-G.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-04-13
Volume
12
Issue
4
Pages
e0175433
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0175433
PMC
PMC5391018
OpenAlex
W2607276191
Semantic Scholar
b003cc3f73682834d8289afda1c7abdb20aa0867
Cited by
103
References
79
Citations by year
2026: 5 · 2025: 12 · 2024: 13 · 2023: 20 · 2022: 12 · 2021: 16 · 2020: 9 · 2019: 11 · 2018: 4 · 2017: 1
FWCI
5.61
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
Funders
National Institute on Drug Abuse (DA25131)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
attention deficit hyperactivity disorder, adult ADHD, childhood ADHD symptoms, structural brain connectivity, white matter maturation, gray matter density, superior longitudinal fasciculus, temporal lobe, frontal lobe, diffusion-weighted imaging
MeSH terms
Adult, Attention Deficit Disorder with Hyperactivity, Female, Frontal Lobe, Humans, Male, Diffusion Magnetic Resonance Imaging, Young Adult, Gray Matter

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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