Skip to main content
SpringerLink
Log in

Excessive Daytime Sleepiness in Parkinson’s Disease is Related to Functional Abnormalities in the Left Angular Gyrus

  • Original Article
  • Published:
Clinical Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson’s disease (PD), but its neuropathology remains elusive. Our goal is to explore the potential neural substrates of EDS in a large sample of individuals with PD.

Methods

We recruited 48 PD patients with and 87 PD patients without EDS. We used resting-state functional magnetic resonance imaging to compare amplitudes of low-frequency fluctuations (ALFF) between the two groups. We also explored functional connectivity (FC) between the entire brain and regions where ALFF differed between the two groups as well as FC between selected regions of interest. Age, Part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) score and use of dopamine receptor agonists were treated as covariates in the comparisons.

Results

EDS was associated with significantly lower ALFF in the left angular gyrus, and ALFF in this region correlated negatively with score on the Epworth Sleepiness Scale in patients with PD. EDS was also associated with significantly lower FC between the left angular gyrus and right cerebellum, based on seed-to-voxel and inter-ROI analyses.

Conclusion

Our results suggest that EDS in PD patients is associated with reduced spontaneous neural activity in the left angular gyrus and with reduced FC between the left angular gyrus and cerebellum. These findings may help understand and treat EDS in PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Knie B, Mitra MT, Logishetty K, Chaudhuri KR. Excessive daytime sleepiness in patients with Parkinson’s disease. CNS Drugs. 2011;25:203–12.

    Article  CAS  PubMed  Google Scholar 

  2. Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology. 1999;52:1908–10.

    Article  CAS  PubMed  Google Scholar 

  3. Yoo SW, Kim JS, Oh YS, Ryu DW, Lee KS. Excessive daytime sleepiness and its impact on quality of life in de novo Parkinson’s disease. Neurol Sci. 2019;40:1151–6.

    Article  PubMed  Google Scholar 

  4. Chahine LM, Amara AW, Videnovic A. A systematic review of the literature on disorders of sleep and wakefulness in Parkinson’s disease from 2005 to 2015. Sleep Med Rev. 2017;35:33–50.

    Article  PubMed  Google Scholar 

  5. Adler CH, Thorpy MJ. Sleep issues in Parkinson’s disease. Neurology. 2005;64:S12–20.

    Article  PubMed  Google Scholar 

  6. Happe S, Baier PC, Helmschmied K, Meller J, Tatsch K, Paulus W. Association of daytime sleepiness with nigrostriatal dopaminergic degeneration in early Parkinson’s disease. J Neurol. 2007;254:1037–43.

    Article  PubMed  Google Scholar 

  7. Pagano G, Molloy S, Bain PG, Rabiner EA, Chaudhuri KR, Brooks DJ, Pavese N. Sleep problems and hypothalamic dopamine D3 receptor availability in Parkinson disease. Neurology. 2016;87:2451–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yoo SW, Oh YS, Ryu DW, Lee KS, Lyoo CH, Kim JS. Low thalamic monoamine transporter availability is related to excessive daytime sleepiness in early Parkinson’s disease. Neurol Sci. 2020;41:1081–7.

    Article  PubMed  Google Scholar 

  9. Wen MC, Ng SY, Heng HS, Chao YX, Chan LL, Tan EK, Tan LC. Neural substrates of excessive daytime sleepiness in early drug naive Parkinson’s disease: a resting state functional MRI study. Parkinsonism Relat Disord. 2016;24:63–8.

    Article  PubMed  Google Scholar 

  10. Wang X, Wang M, Yuan Y, Li J, Shen Y, Zhang K. Altered amplitude of low-frequency fluctuations and functional connectivity in excessive daytime sleepiness in Parkinson disease. Front Neurosci. 2020;14:29.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zuo XN, Di Martino A, Kelly C, Shehzad ZE, Gee DG, Klein DF, Castellanos FX, Biswal BB, Milham MP. The oscillating brain: complex and reliable. Neuroimage. 2010;49:1432–45.

    Article  PubMed  Google Scholar 

  12. Gorges M, Müller HP, Lulé D, Ludolph AC, Pinkhardt EH, Kassubek J. Functional connectivity within the default mode network is associated with saccadic accuracy in Parkinson’s disease: a resting-state FMRI and videooculographic study. Brain Connect. 2013;3:265-72.

    Article  PubMed  Google Scholar 

  13. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30:1591–601.

    Article  PubMed  Google Scholar 

  14. Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993;269:2386–91.

    Article  CAS  PubMed  Google Scholar 

  15. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–5.

    Article  CAS  PubMed  Google Scholar 

  16. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23:2129–70.

    Article  PubMed  Google Scholar 

  17. Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, Huber S, Koller W, Olanow C, Shoulson I, et al. Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology. 1990;40:1529–34.

    Article  CAS  PubMed  Google Scholar 

  18. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord. 2010;25:2649–53.

    Article  PubMed  Google Scholar 

  19. Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2012;2:125–41.

    Article  PubMed  Google Scholar 

  20. Yan CG, Wang XD, Zuo XN, Zang YF. DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging. Neuroinformatics. 2016;14:339–51.

    Article  Google Scholar 

  21. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Qin P, Wu X, Huang Z, Duncan NW, Tang W, Wolff A, Hu J, Gao L, Jin Y, Wu X, Zhang J, Lu L, Wu C, Qu X, Mao Y, Weng X, Zhang J, Northoff G. How are different neural networks related to consciousness? Ann Neurol. 2015;78:594–605.

    Article  PubMed  Google Scholar 

  23. Seghier ML. The angular gyrus: multiple functions and multiple subdivisions. Neuroscientist. 2013;19:43–61.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Binder JR, Desai RH. The neurobiology of semantic memory. Trends Cogn Sci. 2011;15:527–36.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bonner MF, Peelle JE, Cook PA, Grossman M. Heteromodal conceptual processing in the angular gyrus. Neuroimage. 2013;71:175–86.

    Article  PubMed  Google Scholar 

  26. Guo Z, Jiang Z, Jiang B, McClure MA, Mu Q. High-Frequency Repetitive Transcranial Magnetic Stimulation Could Improve Impaired Working Memory Induced by Sleep Deprivation. Neural Plast. 2019;2019:7030286.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ji T, Li X, Chen J, Ren X, Mei L, Qiu Y, Zhang J, Wang S, Xu Z, Li H, Zheng L, Peng Y, Liu Y, Ni X, Tai J, Liu J. Brain function in children with obstructive sleep apnea: a resting-state fMRI study. Sleep. 2021;44:zsab047.

    Article  PubMed  Google Scholar 

  28. Peng DC, Dai XJ, Gong HH, Li HJ, Nie X, Zhang W. Altered intrinsic regional brain activity in male patients with severe obstructive sleep apnea: a resting-state functional magnetic resonance imaging study. Neuropsychiatr Dis Treat. 2014;10:1819–26.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Song X, Roy B, Kang DW, Aysola RS, Macey PM, Woo MA, Yan-Go FL, Harper RM, Kumar R. Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea. Brain Behav. 2018;8:e00994.

    Article  PubMed  PubMed Central  Google Scholar 

  30. van Geest Q, Westerik B, van der Werf YD, Geurts JJ, Hulst HE. The role of sleep on cognition and functional connectivity in patients with multiple sclerosis. J Neurol. 2017;264:72–80.

    Article  PubMed  Google Scholar 

  31. Legostaeva L, Poydasheva A, Iazeva E, Sinitsyn D, Sergeev D, Bakulin I, Lagoda D, Kremneva E, Morozova S, Ryabinkina Y, Suponeva N, Piradov M. Stimulation of the Angular Gyrus Improves the Level of Consciousness. Brain Sci. 2019;9:103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang YS, Hsiao IT, Liu FY, Hwang FM, Lin KL, Huang WC, Guilleminault C. Neurocognition, sleep, and PET findings in type 2 vs type 1 narcolepsy. Neurology. 2018;90:e1478–87.

    Article  PubMed  Google Scholar 

  33. Huang YS, Liu FY, Lin CY, Hsiao IT, Guilleminault C. Brain imaging and cognition in young narcoleptic patients. Sleep Med. 2016;24:137–44.

    Article  PubMed  Google Scholar 

  34. DelRosso LM, Hoque R. The cerebellum and sleep. Neurol Clin. 2014;32:893–900.

    Article  PubMed  Google Scholar 

  35. Pedroso JL, Braga-Neto P, Escorcio-Bezerra ML, Abrahão A, de Albuquerque MV, Filho FM, de Souza PV, de Rezende Pinto WB, Borges FR Jr, Saraiva-Pereira ML, Jardim LB, Barsottini OG. Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2. Cerebellum. 2017;16:34–9.

    Article  CAS  PubMed  Google Scholar 

  36. Dang D, Cunnington D. Excessive daytime somnolence in spinocerebellar ataxia type 1. J Neurol Sci. 2010;290:146–7.

    Article  PubMed  Google Scholar 

  37. Yuan X, Ou R, Hou Y, Chen X, Cao B, Hu X, Shang H. Extra-Cerebellar Signs and Non-motor Features in Chinese Patients With Spinocerebellar Ataxia Type 3. Front Neurol. 2019;10:110.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Joo EY, Noh HJ, Kim JS, Koo DL, Kim D, Hwang KJ, Kim JY, Kim ST, Kim MR, Hong SB. Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia. Sleep. 2013;36:999–1007

    Article  PubMed  PubMed Central  Google Scholar 

  39. Desseilles M, Dang-Vu T, Schabus M, Sterpenich V, Maquet P, Schwartz S. Neuroimaging insights into the pathophysiology of sleep disorders. Sleep. 2008;31:777–94.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhang LB, Zhang J, Sun MJ, Chen H, Yan J, Luo FL, Yao ZX, Wu YM, Hu B. Neuronal Activity in the Cerebellum During the Sleep-Wakefulness Transition in Mice. Neurosci Bull. 2020;36:919–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Canto CB, Onuki Y, Bruinsma B, van der Werf YD, De Zeeuw CI. The Sleeping Cerebellum. Trends Neurosci. 2017;40:309–23.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang Y, Yang Y, Yang Y, Li J, Xin W, Huang Y, Shao Y, Zhang X. Alterations in Cerebellar Functional Connectivity Are Correlated With Decreased Psychomotor Vigilance Following Total Sleep Deprivation. Front Neurosci. 2019;13:134.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yang L, Lei Y, Wang L, Chen P, Cheng S, Chen S, Sun J, Li Y, Wang Y, Hu W, Yang Z. Abnormal functional connectivity density in sleep-deprived subjects. Brain Imaging Behav. 2018;12:1650–7.

    Article  PubMed  Google Scholar 

  44. Desjardins MÈ, Baril AA, Soucy JP, Dang-Vu TT, Desautels A, Petit D, Montplaisir J, Zadra A. Altered brain perfusion patterns in wakefulness and slow-wave sleep in sleepwalkers. Sleep. 2018;41:zsy039.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lim JS, Shin SA, Lee JY, Nam H, Lee JY, Kim YK. Neural substrates of rapid eye movement sleep behavior disorder in Parkinson’s disease. Parkinsonism Relat Disord. 2016;23:31–6.

    Article  PubMed  Google Scholar 

  46. Ayalon L, Ancoli-Israel S, Drummond SP. Altered brain activation during response inhibition in obstructive sleep apnea. J Sleep Res. 2009;18:204–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zhou F, Huang S, Zhuang Y, Gao L, Gong H. Frequency-dependent changes in local intrinsic oscillations in chronic primary insomnia: A study of the amplitude of low-frequency fluctuations in the resting state. Neuroimage Clin. 2016;15:458–65.

    Article  PubMed  Google Scholar 

  48. Han XH, Li XM, Tang WJ, Yu H, Wu P, Ge JJ, Wang J, Zuo CT, Shi KY. Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder. Neural Regen Res. 2019;14:868–75.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tholfsen LK, Larsen JP, Schulz J, Tysnes OB, Gjerstad MD. Development of excessive daytime sleepiness in early Parkinson disease. Neurology. 2015;85:162–8.

    Article  PubMed  Google Scholar 

  50. Johns MW. Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard. J Sleep Res. 2000;9:5–11.

    Article  CAS  PubMed  Google Scholar 

  51. Tandberg E, Larsen JP, Karlsen K. A community-based study of sleep disorders in patients with Parkinson’s disease. Mov Disord. 1998;13:895–9.

    Article  CAS  PubMed  Google Scholar 

  52. Videnovic A, Golombek D. Circadian and sleep disorders in Parkinson’s disease. Exp Neurol. 2013;243:45–56.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all the patients in this study. This study was supported by the Henan Province Science and Technology Development Plan (192102310085) and the Henan Province Medical Science and Technology Research Program (201701018).

Author information

Authors and Affiliations

  1. Department of Neurology, Henan Provincial People’s Hospital, 450003, Zhengzhou, Henan Province, China

    Jin Hua Zheng, Jian Jun Ma, Wen Hua Sun, Zhi Dong Wang, Qing Qing Chang, Lin Rui Dong, Xiao Xue Shi & Ming Jian Li

  2. Department of Neurology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

    Jin Hua Zheng, Jian Jun Ma, Wen Hua Sun, Zhi Dong Wang, Qing Qing Chang, Lin Rui Dong & Xiao Xue Shi

  3. Department of Neurology, People’s Hospital of Henan University, Henan Province, Zhengzhou, China

    Jin Hua Zheng, Jian Jun Ma & Ming Jian Li

Authors
  1. Jin Hua Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Jun Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Hua Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi Dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing Qing Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lin Rui Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao Xue Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ming Jian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Jun Ma.

Ethics declarations

Conflict of interest

J.H. Zheng, J.J. Ma, W.H. Sun, Z.D. Wang, Q.Q. Chang, L.R. Dong, X.X. Shi and M.J. Li declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Data availability

The data that support the findings of the present study are available from the corresponding authors upon reasonable request.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, J.H., Ma, J.J., Sun, W.H. et al. Excessive Daytime Sleepiness in Parkinson’s Disease is Related to Functional Abnormalities in the Left Angular Gyrus. Clin Neuroradiol 33, 121–127 (2023). https://doi.org/10.1007/s00062-022-01190-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00062-022-01190-x

Keywords

Search

Navigation