Journal of Neural Transmission

, Volume 124, Issue 10, pp 1187–1195 | Cite as

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson’s disease

  • Junyi Li
  • Yongsheng Yuan
  • Min Wang
  • Jiejin Zhang
  • Li Zhang
  • Siming Jiang
  • Jian Ding
  • Kezhong ZhangEmail author
Neurology and Preclinical Neurological Studies - Original Article


Fatigue is a common complaint in patients with Parkinson’s disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.


Parkinson’s disease Resting-state fMRI Regional homogeneity Fatigue 



This work was supported by the National Natural Science Foundation of China (No. 81671258), the Science and Technology Project of Jiangsu Provincial Commission of Health and Family Planning (No. H201602), the Natural Science Foundation of Jiangsu Province (No. BK20141494), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No. 2014-WSN-013), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Science and Technology Project of Jiangsu Bureau of Traditional Chinese Medicine (No. YB2015163).

Compliance with ethical standards

Conflict of interest

None of the authors declare conflict of interests.

Ethical standards

This study has been approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University. All persons involved in this study gave their informed consent prior to their inclusion in the study.


  1. Abe K, Takanashi M, Yanagihara T (2000) Fatigue in patients with Parkinson’s disease. Behav Neurol 12(3):103–106CrossRefPubMedGoogle Scholar
  2. Alves G, Wentzel-Larsen T, Larsen JP (2004) Is fatigue an independent and persistent symptom in patients with Parkinson disease? Neurology 63(10):1908–1911CrossRefPubMedGoogle Scholar
  3. Butter CM, Trobe JD, Foster NL, Berent S (1996) Visual-spatial deficits expalin visual symptoms in Alzheimer’s disease. Am J Ophthalmol 122(1):97–105CrossRefPubMedGoogle Scholar
  4. Chaudhuri A, Behan PO (2004) Fatigue in neurological disorders. Lancet 363(9413):978–988CrossRefPubMedGoogle Scholar
  5. Choe IH, Yeo S, Chung KC, Kim SH, Lim S (2013) Decreased and increased cerebral regional homogeneity in early Parkinson’s disease. Brain Res 1527:230–237CrossRefPubMedGoogle Scholar
  6. Chou KL, Kotagal V, Bohnen NI (2016) Neuroimaging and clinical predictors of fatigue in Parkinson disease. Parkinsonism Relat Disord 23:45–49CrossRefPubMedGoogle Scholar
  7. Fereshtehnejad SM, Ghazi L, Shafieesabet M, Shahidi GA, Delbari A, Lokk J (2014) Motor, psychiatric and fatigue features associated with nutritional status and its effects on quality of life in Parkinson’s disease patients. PLoS One 9(3):e91153CrossRefPubMedPubMedCentralGoogle Scholar
  8. Friedman J, Friedman H (1993) Fatigue in Parkinson’s disease. Neurology 43(10):2016–2018CrossRefPubMedGoogle Scholar
  9. Friedman JH, Friedman H (2001) Fatigue in Parkinson’s disease: a nine-year follow-up. Mov Disord 16(6):1120–1122CrossRefPubMedGoogle Scholar
  10. Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS et al (2007) Fatigue in Parkinson’s disease: a review. Mov Disord 22(3):297–308CrossRefPubMedGoogle Scholar
  11. Hagell P, Brundin L (2009) Towards an understanding of fatigue in Parkinson disease. J Neurol Neurosurg Psychiatry 80(5):489–492CrossRefPubMedGoogle Scholar
  12. Herlofson K, Larsen JP (2002) Measuring fatigue in patients with Parkinson’s disease—the Fatigue Severity Scale. Eur J Neurol 9(6):595–600CrossRefPubMedGoogle Scholar
  13. Hogl B, Arnulf I, Comella C, Ferreira J, Iranzo A, Tilley B et al (2010) Scales to assess sleep impairment in Parkinson’s disease: critique and recommendations. Mov Disord 25(16):2704–2716CrossRefPubMedGoogle Scholar
  14. Hu XF, Zhang JQ, Jiang XM, Zhou CY, Wei LQ, Yin XT et al (2015) Amplitude of low-frequency oscillations in Parkinson’s disease: a 2-year longitudinal resting-state functional magnetic resonance imaging study. Chin Med J 128(5):593–601CrossRefPubMedPubMedCentralGoogle Scholar
  15. Karlsen K, Larsen JP, Tandberg E, Jorgensen K (1999) Fatigue in patients with Parkinson’s disease. Mov Disord 14(2):237–241CrossRefPubMedGoogle Scholar
  16. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46(10):1121–1123CrossRefPubMedGoogle Scholar
  17. Li Y, Liang P, Jia X, Li K (2016) Abnormal regional homogeneity in Parkinson’s disease: a resting state fMRI study. Clin Radiol 71(1):e28–e34CrossRefPubMedGoogle Scholar
  18. Long XY, Zuo XN, Kiviniemi V, Yang Y, Zou QH, Zhu CZ et al (2008) Default mode network as revealed with multiple methods for resting-state functional MRI analysis. J Neurosci Methods 171(2):349–355CrossRefPubMedGoogle Scholar
  19. Lorist MM, Boksem MA, Ridderinkhof KR (2005) Impaired cognitive control and reduced cingulate activity during mental fatigue. Brain Res Cogn Brain Res 24(2):199–205CrossRefPubMedGoogle Scholar
  20. Lou JS, Kearns G, Oken B, Sexton G, Nutt J (2001) Exacerbated physical fatigue and mental fatigue in Parkinson’s disease. Mov Disord 16(2):190–196CrossRefPubMedGoogle Scholar
  21. Mangun GR, Buonocore MH, Girelli M, Jha AP (1998) ERP and fMRI measures of visual spatial selective attention. Hum Brain Mapp 6(5–6):383–389CrossRefPubMedGoogle Scholar
  22. Paus T (2001) Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nat Rev Neurosci 2(6):417–424CrossRefPubMedGoogle Scholar
  23. Pavese N, Metta V, Bose SK, Chaudhuri KR, Brooks DJ (2010) Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain J Neurol 133(11):3434–3443CrossRefGoogle Scholar
  24. Pellicano C, Assogna F, Piras F, Caltagirone C, Pontieri FE, Spalletta G (2012) Regional cortical thickness and cognitive functions in non-demented Parkinson’s disease patients: a pilot study. Eur J Neurol 19(1):172–175CrossRefPubMedGoogle Scholar
  25. Pessoa L (2017) A network model of the emotional brain. Trends Cognit Sci 21(5):357–371CrossRefGoogle Scholar
  26. Prado J, Carp J, Weissman DH (2011) Variations of response time in a selective attention task are linked to variations of functional connectivity in the attentional network. NeuroImage 54(1):541–549CrossRefPubMedGoogle Scholar
  27. Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W et al (1997) Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48(6):1566–1571CrossRefPubMedGoogle Scholar
  28. Saarimaki H, Gotsopoulos A, Jaaskelainen IP, Lampinen J, Vuilleumier P, Hari R et al (2016) Discrete neural signatures of basic emotions. Cereb Cortex 26(6):2563–2573CrossRefPubMedGoogle Scholar
  29. Schiehser DM, Ayers CR, Liu L, Lessig S, Song DS, Filoteo JV (2013) Validation of the modified fatigue impact scale in Parkinson’s disease. Parkinsonism Relat Disord 19(3):335–338CrossRefPubMedGoogle Scholar
  30. Siessmeier T, Nix WA, Hardt J, Schreckenberger M, Egle UT, Bartenstein P (2003) Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 74(7):922–928CrossRefPubMedPubMedCentralGoogle Scholar
  31. Tanaka M, Ishii A, Watanabe Y (2015) Physical fatigue increases neural activation during eyes-closed state: a magnetoencephalography study. Behav Brain Funct BBF 11(1):35CrossRefPubMedGoogle Scholar
  32. Tessitore A, Giordano A, De Micco R, Caiazzo G, Russo A, Cirillo M et al (2016) Functional connectivity underpinnings of fatigue in “Drug-Naive” patients with Parkinson’s disease. Mov Disord 31(10):1497–1505CrossRefPubMedGoogle Scholar
  33. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25(15):2649–2653CrossRefPubMedGoogle Scholar
  34. Valko PO, Waldvogel D, Weller M, Bassetti CL, Held U, Baumann CR (2010) Fatigue and excessive daytime sleepiness in idiopathic Parkinson’s disease differently correlate with motor symptoms, depression and dopaminergic treatment. Eur J Neurol 17(12):1428–1436CrossRefPubMedGoogle Scholar
  35. van Hilten JJ, Weggeman M, van der Velde EA, Kerkhof GA, van Dijk JG, Roos RA (1993) Sleep, excessive daytime sleepiness and fatigue in Parkinson’s disease. J Neural Transm Parkinson’s Dis Dementia Sect 5(3):235–244CrossRefGoogle Scholar
  36. Wen MC, Ng SY, Heng HS, Chao YX, Chan LL, Tan EK et al (2016) Neural substrates of excessive daytime sleepiness in early drug naive Parkinson’s disease: a resting state functional MRI study. Parkinsonism Relat Disord 24:63–68CrossRefPubMedGoogle Scholar
  37. Wu T, Hallett M (2005) A functional MRI study of automatic movements in patients with Parkinson’s disease. Brain J Neurol 128(Pt 10):2250–2259CrossRefGoogle Scholar
  38. Wu T, Long X, Zang Y, Wang L, Hallett M, Li K et al (2009) Regional homogeneity changes in patients with Parkinson’s disease. Hum Brain Mapp 30(5):1502–1510CrossRefPubMedGoogle Scholar
  39. Zang Y, Jiang T, Lu Y, He Y, Tian L (2004) Regional homogeneity approach to fMRI data analysis. NeuroImage 22(1):394–400CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Junyi Li
    • 1
  • Yongsheng Yuan
    • 1
  • Min Wang
    • 2
  • Jiejin Zhang
    • 1
  • Li Zhang
    • 1
  • Siming Jiang
    • 1
  • Jian Ding
    • 1
  • Kezhong Zhang
    • 1
    Email author
  1. 1.Department of NeurologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Personalised recommendations