The Role of the Insula in the Non-motor Symptoms of Parkinson’s Disease

  • Braden GardnerEmail author


While Parkinson’s disease (PD) is perhaps most well-known for its effect on motor functionality, it is important to also realize that this disease has a host of non-motor symptoms (NMS) that affect patients’ day-to-day lives through neurological pathways as well. This chapter will review the literature regarding a connection between these non-motor symptoms and the insula and attempt to show that the insula has a role in facilitating these symptoms. In order to do this, this paper will first discuss what insula is and then identify non-motor symptoms of PD and some possible treatments for these symptoms, followed by discussion of the known effects of these treatments on neural tissue and, specifically, the insula. Based on reports from the literature, there is a possible link between the insula and the NMS of PD as expressed through the relationship between the treatment of these NMS and the effects these treatments have on the insula as well as the knowledge that many of the non-motor symptoms we see presented by PD fall under the category of bodily functions the insula has been shown to contribute to controlling.


Insula Parkinson’s Non-motor Treatments Connections 


  1. 1.
    Bauernfeind A, de Sousa A, Avasthi T, Dobson S, Raghanti M, Lewandowski A, Zilles K, Semendeferi K, Allman J, Craig A, Hof P, Sherwood C. A volumetric comparison of the insular cortex and its subregions in primates. J Hum Evol. 2013;64(4):263–79.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Naqvi N, Gaznick N, Tranel D, Bechara A. The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Ann N Y Acad Sci. 2014;1316:53–70.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18(7):435–50.CrossRefPubMedGoogle Scholar
  4. 4.
    Poewe W. Non-motor symptoms in Parkinson’s disease. Eur J Neurol. 2008;15(Suppl 1):14–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Pavelić A, Krbot Skorić M, Crnošija L, Habek M. Postprandial hypotension in neurological disorders: systematic review and meta-analysis. Clin Auton Res. 2017;27(4):263–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Domellöf ME, Lundin KF, Edström M, Forsgren L. Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease. Parkinsonism Relat Disord. 2017;38:41–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Rodríguez-Violante M, de Saráchaga AJ, Cervantes-Arriaga A, Davila-Avila NM, Carreón-Bautista E, Estrada-Bellmann I, Parra-López G, Cruz-Fino D, Pascasio-Astudillo F. Premotor symptoms and the risk of Parkinson's disease: a case-control study in Mexican population. Clin Neurol Neurosurg. 2017;160:46–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Schaeffer E, Berg D. Dopaminergic therapies for non-motor symptoms in Parkinson's disease. CNS Drugs. 2017;31(7):551–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Ikeda M, Kataoka H, Ueno S. Can levodopa prevent cognitive decline in patients with Parkinson’s disease? Am J Neurodegener Dis. 2017;6(2):9–14.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Nishijima H, Ueno T, Ueno S, Mori F, Miki Y, Tomiyama M. Levodopa-induced morphologic changes of prefrontal pyramidal tract-type neurons in a rat model of Parkinson's disease. Neurosci Res. 2017;115:54–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Jang W, Park J, Shin KJ, Kim JS, Kim JS, Youn J, Cho JW, Oh E, Ahn JY, Oh KW, Kim HT. Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease. J Neurol Sci. 2014;337(1–2):47–54.CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang DX, Zhang LM, Zhao XC, Sun W. Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. Biomed Pharmacother. 2017;87:332–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Curvello V, Hekierski H, Pastor P, Vavilala MS, Armstead WM. Dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of ERK MAPK in juvenile pigs. Brain Res. 2017;1670:118–24.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Setia S, Nehru B, Nath Sanyal S. Upregulation of MAPK/Erk and PI3K/Akt pathways in ulcerative colitis-associated colon cancer. Biomed Pharmacother. 2014;68(8):1023–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Yadav SK, Pandey S, Singh B. Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: a comparative study. J Chem Neuroanat. 2017;85:50–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Kimáková P, Solár S, Solárová Z, Komel R, Debeljak N. Erythropoietin and its angiogenic activity. Int J Mol Sci. 2017;18(7):1519.CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Jeong JE, Park JH, Kim CS, Lee SL, Chung HL, Kim WT, Lee EJ. Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis. Korean J Pediatr. 2017;60(6):181–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Seattle University, Seattle Science FoundationSeattleUSA

Personalised recommendations