Alterations of the brain network in idiopathic rapid eye movement sleep behavior disorder: structural connectivity analysis

  • Kang Min Park
  • Ho-Joon Lee
  • Byung In Lee
  • Sung Eun KimEmail author
Neurology • Original Article



To evaluate and compare structural connectivity using graph theoretical analysis in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy subjects.


Ten consecutive patients with iRBD were recruited from a single tertiary hospital. All patients had normal brain magnetic resonance imaging results on visual inspection. They did not have any other neurological disorder. Control subjects were also enrolled. All subjects underwent three-dimensional volumetric T1-weighted imaging. Absolute structural volumes were calculated using FreeSurfer image analysis software. Structural volume and connectivity analyses were performed with Brain Analysis using Graph Theory.


Compared to healthy controls, patients with iRBD showed significant alterations in cortical and subcortical volumes, showing increased volumes of frontal cortex, thalamus, and caudate nucleus. In addition, patients with iRBD exhibited significantly different structural connectivity compared to healthy controls. In measures of global network, average degree, global efficiency, and local efficiency were decreased whereas characteristic path length was increased in iRBD patients. In measures of local network, there was significant hub reorganization in patients with iRBD. Betweenness centrality of caudate nucleus and frontal cortex was increased in patients with iRBD.


This is the first study to report that structural volume and connectivity in patients with iRBD are significantly different from those in healthy controls. iRBD patients exhibited disrupted topological disorganization of the global brain network and hub reorganization. These alterations are implicated in the pathogenesis of iRBD. They might be potential biomarkers of iRBD.


REM sleep behavior disorder Graph theory Network Magnetic resonance imaging 



This study was supported by a grant (NRF-2017R1C1B5015871) of the National Research Foundation (NRF) funded by the Ministry of Science and ICT, Republic of Korea. The funding agency had no role in the study design or conduct of this research.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Formal consent was not required for a study of this type.

Supplementary material

11325_2018_1737_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22.4 kb)
11325_2018_1737_MOESM2_ESM.docx (25 kb)
ESM 2 (DOCX 24.8 kb)


  1. 1.
    Ferini-Strambi L, Rinaldi F, Giora E, Marelli S, Galbiati A (2016) REM sleep behaviour disorder. Parkinsonism Relat Disord 22(Suppl 1):S69–S72. CrossRefPubMedGoogle Scholar
  2. 2.
    Paparrigopoulos TJ (2005) REM sleep behaviour disorder: clinical profiles and pathophysiology. Int Rev Psychiatry 17(4):293–300. CrossRefPubMedGoogle Scholar
  3. 3.
    Hanyu H, Inoue Y, Sakurai H, Kanetaka H, Nakamura M, Miyamoto T, Sasai T, Iwamoto T (2012) Voxel-based magnetic resonance imaging study of structural brain changes in patients with idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 18(2):136–139. CrossRefPubMedGoogle Scholar
  4. 4.
    Scherfler C, Frauscher B, Schocke M, Iranzo A, Gschliesser V, Seppi K, Santamaria J, Tolosa E, Hogl B, Poewe W, Group S (2011) White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol 69(2):400–407. CrossRefPubMedGoogle Scholar
  5. 5.
    Rahayel S, Montplaisir J, Monchi O, Bedetti C, Postuma RB, Brambati S, Carrier J, Joubert S, Latreille V, Jubault T, Gagnon JF (2015) Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder. Mov Disord 30(5):680–687. CrossRefPubMedGoogle Scholar
  6. 6.
    Unger MM, Belke M, Menzler K, Heverhagen JT, Keil B, Stiasny-Kolster K, Rosenow F, Diederich NJ, Mayer G, Moller JC, Oertel WH, Knake S (2010) Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep 33(6):767–773CrossRefGoogle Scholar
  7. 7.
    Lai YY, Siegel JM (1988) Medullary regions mediating atonia. J Neurosci 8(12):4790–4796CrossRefGoogle Scholar
  8. 8.
    Gleichgerrcht E, Kocher M, Bonilha L (2015) Connectomics and graph theory analyses: novel insights into network abnormalities in epilepsy. Epilepsia 56(11):1660–1668. CrossRefPubMedGoogle Scholar
  9. 9.
    Haneef Z, Chiang S (2014) Clinical correlates of graph theory findings in temporal lobe epilepsy. Seizure 23(10):809–818. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    van Diessen E, Diederen SJ, Braun KP, Jansen FE, Stam CJ (2013) Functional and structural brain networks in epilepsy: what have we learned? Epilepsia 54(11):1855–1865. CrossRefPubMedGoogle Scholar
  11. 11.
    American Academy of Sleep Medicine (2014) International Classification of Sleep Disorders, 3rd edn. American Academy of Sleep Medicine, Darien, pp 246–251Google Scholar
  12. 12.
    Park KM, Lee BI, Shin KJ, Ha SY, Park J, Kim TH, Mun CW, Kim SE (2018) Progressive topological disorganization of brain network in focal epilepsy. Acta Neurol Scand 137(4):425–431. CrossRefPubMedGoogle Scholar
  13. 13.
    Mijalkov M, Kakaei E, Pereira JB, Westman E, Volpe G, Alzheimer's Disease Neuroimaging I (2017) BRAPH: a graph theory software for the analysis of brain connectivity. PLoS One 12(8):e0178798. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bullmore E, Sporns O (2012) The economy of brain network organization. Nat Rev Neurosci 13(5):336–349. CrossRefPubMedGoogle Scholar
  15. 15.
    delEtoile J, Adeli H (2017) Graph theory and brain connectivity in Alzheimer's disease. Neuroscientist 23:616–626. CrossRefPubMedGoogle Scholar
  16. 16.
    Fang J, Chen H, Cao Z, Jiang Y, Ma L, Ma H, Feng T (2017) Impaired brain network architecture in newly diagnosed Parkinson's disease based on graph theoretical analysis. Neurosci Lett 657:151–158. CrossRefPubMedGoogle Scholar
  17. 17.
    Rye DB (1997) Contributions of the pedunculopontine region to normal and altered REM sleep. Sleep 20(9):757–788CrossRefGoogle Scholar
  18. 18.
    Mazza S, Soucy JP, Gravel P, Michaud M, Postuma R, Massicotte-Marquez J, Decary A, Montplaisir J (2006) Assessing whole brain perfusion changes in patients with REM sleep behavior disorder. Neurology 67(9):1618–1622. CrossRefPubMedGoogle Scholar
  19. 19.
    Albin RL, Koeppe RA, Chervin RD, Consens FB, Wernette K, Frey KA, Aldrich MS (2000) Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 55(9):1410–1412CrossRefGoogle Scholar
  20. 20.
    Rolinski M, Griffanti L, Piccini P, Roussakis AA, Szewczyk-Krolikowski K, Menke RA, Quinnell T, Zaiwalla Z, Klein JC, Mackay CE, Hu MT (2016) Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease. Brain 139(Pt 8):2224–2234. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Arnaldi D, De Carli F, Picco A, Ferrara M, Accardo J, Bossert I, Fama F, Girtler N, Morbelli S, Sambuceti G, Nobili F (2015) Nigro-caudate dopaminergic deafferentation: a marker of REM sleep behavior disorder? Neurobiol Aging 36(12):3300–3305. CrossRefPubMedGoogle Scholar
  22. 22.
    Iranzo A, Valldeoriola F, Lomena F, Molinuevo JL, Serradell M, Salamero M, Cot A, Ros D, Pavia J, Santamaria J, Tolosa E (2011) Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 10(9):797–805. CrossRefPubMedGoogle Scholar
  23. 23.
    Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13(7):266–271CrossRefGoogle Scholar
  24. 24.
    Wu P, Yu H, Peng S, Dauvilliers Y, Wang J, Ge J, Zhang H, Eidelberg D, Ma Y, Zuo C (2014) Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder. Brain 137(Pt 12):3122–3128. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Sunwoo JS, Lee S, Kim JH, Lim JA, Kim TJ, Byun JI, Jeong MH, Cha KS, Choi JW, Kim KH, Lee ST, Jung KH, Park KI, Chu K, Kim M, Lee SK, Jung KY (2017) Altered functional connectivity in idiopathic rapid eye movement sleep behavior disorder: a resting-state EEG study. Sleep 40(6).
  26. 26.
    Szewczyk-Krolikowski K, Menke RA, Rolinski M, Duff E, Salimi-Khorshidi G, Filippini N, Zamboni G, Hu MT, Mackay CE (2014) Functional connectivity in the basal ganglia network differentiates PD patients from controls. Neurology 83(3):208–214. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hawkes CH (2008) The prodromal phase of sporadic Parkinson's disease: does it exist and if so how long is it? Mov Disord 23(13):1799–1807. CrossRefPubMedGoogle Scholar
  28. 28.
    Toth B, File B, Boha R, Kardos Z, Hidasi Z, Gaal ZA, Csibri E, Salacz P, Stam CJ, Molnar M (2014) EEG network connectivity changes in mild cognitive impairment - preliminary results. Int J Psychophysiol 92(1):1–7. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Kang Min Park
    • 1
  • Ho-Joon Lee
    • 2
  • Byung In Lee
    • 1
  • Sung Eun Kim
    • 1
    Email author
  1. 1.Department of Neurology, Haeundae Paik HospitalInje University College of MedicineBusanSouth Korea
  2. 2.Department of Radiology, Haeundae Paik HospitalInje University College of MedicineBusanSouth Korea

Personalised recommendations