Advertisement

European Child & Adolescent Psychiatry

, Volume 28, Issue 10, pp 1321–1328 | Cite as

Abnormal functional network centrality in drug-naïve boys with attention-deficit/hyperactivity disorder

  • Ming Zhou
  • Chuang Yang
  • Xuan Bu
  • Yan Liang
  • Haixi Lin
  • Xinyu Hu
  • Hong Chen
  • Meihao Wang
  • Xiaoqi HuangEmail author
Original Contribution

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder in childhood and is characterized by inattention, impulsivity, and hyperactivity. Observations of distributed functional abnormalities in ADHD suggest aberrant large-scale brain network connectivity. However, few studies have measured the voxel-wise network centrality of boys with ADHD, which captures the functional relationships of a given voxel within the entire connectivity matrix of the brain. Here, to examine the network patterns characterizing children with ADHD, we recruited 47 boys with ADHD and 21 matched control boys who underwent resting-state functional imaging scanning in a 3.0 T MRI unit. We measured voxel-wise network centrality, indexing local functional relationships across the entire brain connectome, termed degree centrality (DC). Then, we chose the brain regions with altered DC as seeds to examine the remote functional connectivity (FC) of brain regions. We found that boys with ADHD exhibited (1) decreased centrality in the left superior temporal gyrus (STG) and increased centrality in the left superior occipital lobe (SOL) and right inferior parietal lobe (IPL); (2) decreased FC between the STG and the putamen and thalamus, which belong to the cognitive cortico-striatal–thalamic–cortical (CSTC) loop, and increased FC between the STG and medial/superior frontal gyrus within the affective CSTC loop; and (3) decreased connectivity between the SOL and cuneus within the dorsal attention network. Our results demonstrated that patients with ADHD show a connectivity-based pathophysiological process in the cognitive and affective CSTC loops and attention network.

Keywords

ADHD Resting-state fMRI Degree centrality Function connectivity 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation (Grant no. 81671669) and Youth Technology Grant of Sichuan Province (no. 2017JQ0001).

Author contributions

XH and CY conceived and designed the experiments. CY, YL, HL, and HC recruited the patients and collected the data. MZ, XB, and YL performed the data analyses. MZ, CY, XB, and XH wrote the manuscript. HL, XH, and HC helped perform the analysis with constructive discussions. MZ and CY contributed to this study equally.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical statements

Approval for this study was granted by the local ethical committee of the First Hospital Affiliated to Wenzhou Medical University. All participants and their parents were fully informed about the purpose and procedures of this study and written informed consent was obtained from the parents.

Supplementary material

787_2019_1297_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)
787_2019_1297_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 18 kb)

References

  1. 1.
    Kessler RC et al (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716–723PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Polanczyk G et al (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164(6):942–948PubMedCrossRefGoogle Scholar
  3. 3.
    Schneider H, Eisenberg D (2006) Who receives a diagnosis of attention-deficit/hyperactivity disorder in the United States elementary school population? Pediatrics 117(4):e601–e609PubMedCrossRefGoogle Scholar
  4. 4.
    Singh I (2008) Beyond polemics: science and ethics of ADHD. Nat Rev Neurosci 9(12):957–964PubMedCrossRefGoogle Scholar
  5. 5.
    Castellanos FX et al (2008) Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 63(3):332–337PubMedCrossRefGoogle Scholar
  6. 6.
    Fair DA et al (2010) Atypical default network connectivity in youth with attention-deficit/hyperactivity disorder. Biol Psychiatry 68(12):1084–1091PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Gallo EF, Posner J (2016) Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms. Lancet Psychiatry 3(6):555–567PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Oldehinkel M et al (2016) Attention-deficit/hyperactivity disorder symptoms coincide with altered striatal connectivity. Biol Psychiatry Cogn Neurosci Neuroimaging 1(4):353–363PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Park BY et al (2016) Functional connectivity of child and adolescent attention deficit hyperactivity disorder patients: correlation with IQ. Front Hum Neurosci 10:565PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Zuo XN et al (2012) Network centrality in the human functional connectome. Cereb Cortex 22(8):1862–1875PubMedCrossRefGoogle Scholar
  11. 11.
    Tomasi D, Shokri-Kojori E, Volkow ND (2016) High-resolution functional connectivity density: hub locations, sensitivity, specificity, reproducibility, and reliability. Cereb Cortex 26(7):3249–3259PubMedCrossRefGoogle Scholar
  12. 12.
    Buckner RL et al (2009) Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer’s disease. J Neurosci 29(6):1860–1873PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Rubinov M et al (2009) Small-world properties of nonlinear brain activity in schizophrenia. Hum Brain Mapp 30(2):403–416PubMedCrossRefGoogle Scholar
  14. 14.
    Wang L et al (2015) The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder. Hum Brain Mapp 36(2):768–778PubMedCrossRefGoogle Scholar
  15. 15.
    Di Martino A et al (2013) Shared and distinct intrinsic functional network centrality in autism and attention-deficit/hyperactivity disorder. Biol Psychiatry 74(8):623–632PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Lai MC et al (2015) Sex/gender differences and autism: setting the scene for future research. J Am Acad Child Adolesc Psychiatry 54(1):11–24PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Chao-Gan Y, Yu-Feng Z (2010) DPARSF: a MATLAB toolbox for “Pipeline” data analysis of resting-state fMRI. Front Syst Neurosci 4:13PubMedPubMedCentralGoogle Scholar
  18. 18.
    Song XW et al (2011) REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 6(9):e25031PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Burgund ED et al (2002) The feasibility of a common stereotactic space for children and adults in fMRI studies of development. Neuroimage 17(1):184–200PubMedCrossRefGoogle Scholar
  20. 20.
    Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13(7):266–271PubMedCrossRefGoogle Scholar
  21. 21.
    Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381PubMedCrossRefGoogle Scholar
  22. 22.
    Shang CY et al (2016) Differential effects of methylphenidate and atomoxetine on intrinsic brain activity in children with attention deficit hyperactivity disorder. Psychol Med 46(15):3173–3185PubMedCrossRefGoogle Scholar
  23. 23.
    Bachmann K et al (2018) Effects of mindfulness and psychoeducation on working memory in adult ADHD: a randomised, controlled fMRI study. Behav Res Ther 106:47–56PubMedCrossRefGoogle Scholar
  24. 24.
    Beucke JC et al (2013) Abnormally high degree connectivity of the orbitofrontal cortex in obsessive–compulsive disorder. JAMA Psychiatry 70(6):619–629PubMedCrossRefGoogle Scholar
  25. 25.
    Krause J (2008) SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder. Expert Rev Neurother 8(4):611–625PubMedCrossRefGoogle Scholar
  26. 26.
    Fox MD et al (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102(27):9673–9678PubMedCrossRefGoogle Scholar
  27. 27.
    Fassbender C et al (2009) A lack of default network suppression is linked to increased distractibility in ADHD. Brain Res 1273:114–128PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Wang S et al (2013) Altered neural circuits related to sustained attention and executive control in children with ADHD: an event-related fMRI study. Clin Neurophysiol 124(11):2181–2190PubMedCrossRefGoogle Scholar
  29. 29.
    Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3(3):201–215PubMedCrossRefGoogle Scholar
  30. 30.
    Hopfinger JB, Buonocore MH, Mangun GR (2000) The neural mechanisms of top-down attentional control. Nat Neurosci 3(3):284–291PubMedCrossRefGoogle Scholar
  31. 31.
    Maia TV, Cooney RE, Peterson BS (2008) The neural bases of obsessive–compulsive disorder in children and adults. Dev Psychopathol 20(4):1251–1283PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Wang Z et al (2011) The neural circuits that generate tics in Tourette’s syndrome. Am J Psychiatry 168(12):1326–1337PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Di Martino A et al (2008) Functional connectivity of human striatum: a resting state FMRI study. Cereb Cortex 18(12):2735–2747PubMedCrossRefGoogle Scholar
  34. 34.
    Lehericy S et al (2004) Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol 55(4):522–529PubMedCrossRefGoogle Scholar
  35. 35.
    Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nat Rev Neurosci 7(6):464–476PubMedCrossRefGoogle Scholar
  36. 36.
    Cardinal RN et al (2004) Limbic corticostriatal systems and delayed reinforcement. Ann N Y Acad Sci 1021:33–50PubMedCrossRefGoogle Scholar
  37. 37.
    Marsh R, Maia TV, Peterson BS (2009) Functional disturbances within frontostriatal circuits across multiple childhood psychopathologies. Am J Psychiatry 166(6):664–674PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Sonuga-Barke EJ et al (2008) Executive dysfunction and delay aversion in attention deficit hyperactivity disorder: nosologic and diagnostic implications. Child Adolesc Psychiatr Clin N Am 17(2):367–384, ixPubMedCrossRefGoogle Scholar
  39. 39.
    Turner BM et al (2007) The cerebellum and emotional experience. Neuropsychologia 45(6):1331–1341PubMedCrossRefGoogle Scholar
  40. 40.
    Castellanos FX, Proal E (2012) Large-scale brain systems in ADHD: beyond the prefrontal-striatal model. Trends Cogn Sci 16(1):17–26PubMedCrossRefGoogle Scholar
  41. 41.
    Chelaru MI, Dragoi V (2008) Asymmetric synaptic depression in cortical networks. Cereb Cortex 18(4):771–788PubMedCrossRefGoogle Scholar
  42. 42.
    Lee JS et al (2005) Regional cerebral blood flow in children with attention deficit hyperactivity disorder: comparison before and after methylphenidate treatment. Hum Brain Mapp 24(3):157–164PubMedCrossRefGoogle Scholar
  43. 43.
    Yang Z et al (2018) Altered patterns of resting-state functional connectivity between the caudate and other brain regions in medication-naive children with attention deficit hyperactivity disorder. Clin Imaging 47:47–51PubMedCrossRefGoogle Scholar
  44. 44.
    Mazaheri A et al (2010) Functional disconnection of frontal cortex and visual cortex in attention-deficit/hyperactivity disorder. Biol Psychiatry 67(7):617–623PubMedCrossRefGoogle Scholar
  45. 45.
    Cho SC et al (2007) The relationship between regional cerebral blood flow and response to methylphenidate in children with attention-deficit hyperactivity disorder: comparison between non-responders to methylphenidate and responders. J Psychiatr Res 41(6):459–465PubMedCrossRefGoogle Scholar
  46. 46.
    Villemonteix T et al (2015) Grey matter volume differences associated with gender in children with attention-deficit/hyperactivity disorder: a voxel-based morphometry study. Dev Cogn Neurosci 14:32–37PubMedCrossRefGoogle Scholar
  47. 47.
    Dirlikov B et al (2015) Distinct frontal lobe morphology in girls and boys with ADHD. Neuroimage Clin 7:222–229PubMedCrossRefGoogle Scholar
  48. 48.
    Valera EM et al (2010) Sex differences in the functional neuroanatomy of working memory in adults with ADHD. Am J Psychiatry 167:86–94PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Huaxi MR Research Center (HMRRC), Department of RadiologyWest China Hospital of Sichuan UniversityChengduPeople’s Republic of China
  2. 2.Department of RadiologyThe Third Hospital of Mianyang/Sichuan Mental Health CenterMianyangPeople’s Republic of China
  3. 3.Center of Psychoradiology, The Third Hospital of Mianyang/Sichuan Mental Health CenterMianyangPeople’s Republic of China
  4. 4.Department of PsychiatryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China

Personalised recommendations