Skip to main content
SpringerLink
Log in

Deep brain stimulation of the internal globus pallidus does not affect the limbic circuit in patients with Parkinson’s disease: a PET study

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Introduction

Internal globus pallidus (GPi) deep brain stimulation (DBS) is a safe and effective alternative treatment in Parkinson’s disease (PD) for patients with cognitive impairment. However, no study has yet investigated metabolic changes within a large series of patients undergoing GPi stimulation.

Objective

We assessed motor, cognitive and psychiatric changes, as well as modifications in brain glucose metabolism measured with FDG-PET, before and after bilateral GPi-DBS.

Methods

In the same week, 32 patients with PD underwent a motor, cognitive and psychiatric assessment and a resting-state FDG-PET scan, 4 months before and 4 months after GPi-DBS surgery. For the voxelwise metabolic change assessment, the p value was controlled for multiple comparisons using the family wise error rate.

Results

After GPi-DBS surgery, patients showed a significant overall improvement in motor status. No cognitive or psychiatric changes were observed after surgery. Nor were any clusters with significantly relative metabolic changes found in the limbic circuit after surgery. Clusters with significantly relative metabolic changes were observed in the left and right Brodmann area (BA) 6, the right BA 9, the right and left BA 39 and the left BA 17.

Conclusion

The present study confirmed that GPi-DBS is an effective treatment in patients with advanced PD, owing to metabolic changes in the areas involved in motor execution. The absence of relative metabolic decrease in the limbic circuit and the few changes affecting the associative circuit could explain why GPi-DBS is cognitively safe.

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

Similar content being viewed by others

References

  1. Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, LeBas JF, Pollak P (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 349:1925–1934

    Article  CAS  Google Scholar 

  2. Parsons TD, Rogers SA, Braaten AJ, Woods SP, Troster AI (2006) Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Lancet Neurol 5:578–588

    Article  Google Scholar 

  3. Volkmann J, Allert N, Voges J, Weiss PH, Freund HJ, Sturm V (2001) Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 56:548–551

    Article  CAS  Google Scholar 

  4. Allert N, Volkmann J, Dotse S, Hefter H, Sturm V, Freund HJ (2001) Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson’s disease. Mov Dis 16:1076–1085

    Article  CAS  Google Scholar 

  5. Drapier D, Drapier S, Sauleau P, Haegelen C, Raoul S, Biseul I, Peron J, Lallement F, Reymann JM, Edan G, Verin M, Millet B (2006) Does subthalamic nucleus stimulation induce apathy in Parkinson’s disease? J Neurol 253:1083–1091

    Article  CAS  Google Scholar 

  6. Funkiewiez A, Ardouin C, Caputo E, Krack P, Fraix V, Klinger H, Chabardes S, Foote K, Benbid AL, Pollak P (2004) Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:834–839

    Article  CAS  Google Scholar 

  7. Bonenfant J, Drapier S, Houvenaghel JF, Naudet F, Haegelen C, Sauleau P, Vérin M (2017) Pallidal stimulation in Parkinson’s patients with contraindications to subthalamic target: a 3 years follow-up. Parkinsonism Relat Disord 34:20–25

    Article  Google Scholar 

  8. Lachenmayer ML, Bettschen C, Bernasconi C, Petermann K, Debove I, Muellner J, Michelis JP, Burgunder JM, Krauss JK, Ortel MF, Pollo C, Kaelin-Lang A, Schüpbach M (2019) Stimulation of the globus pallidus internus in the treatment of Parkinson’s disease: long-term results of a monocentric cohort. Parkinsonism Relat Disord 64:118–123

    Article  CAS  Google Scholar 

  9. Lozachmeur C, Drapier S, Robert G, Dondaine T, Laviolle B, Sauleau P, Peron J, Le Jeune F, Travers D, Millet B, Vérin M, Drapier D (2014) Pallidal stimulation in Parkinson’s disease does not induce apathy. J Neuropsychiatry Clin Neurosci 26:221–226

    Article  Google Scholar 

  10. Rouaud T, Dondaine T, Drapier S, Haegelen C, Lallement F, Peron J, Raoul S, Sauleau P, Vérin M (2010) Pallidal stimulation in advanced Parkinson’s patients with contraindications for subthalamic stimulation. Mov Disord 25:1839–1846

    Article  Google Scholar 

  11. Le Jeune F, Drapier D, Bourguignon A, Peron J, Mesbah H, Drapier S, Sauleau P, Haegelen C, Travers D, Garin E, Malbert CH, Millet B, Vérin M (2009) Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study. Neurology 73:1746–1751

    Article  Google Scholar 

  12. Le Jeune F, Peron J, Biseul I, Fournier S, Sauleau P, Drapier S, Haegelen C, Drapier D, Millet B, Garin E, Herry JH, Malbert CH, Vérin M (2008) Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a PET study. Brain 131:1599–1608

    Article  Google Scholar 

  13. Le Jeune F, Peron J, Grandjean D, Drapier S, Haegelen C, Garin E, Millet B, Vérin M (2010) Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study. Eur J Nucl Med Mol Imaging 37:1512–1520

    Article  Google Scholar 

  14. Gibb WR, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51:745–752

    Article  CAS  Google Scholar 

  15. Silberstein P, Bittar RG, Boyle R, Cook R, Coyne T, O'Sullivan D, Pell M, Peppard R, Rodrigues J, Silburn P, Stell R, Watson P (2009) Deep brain stimulation for Parkinson’s disease: Australian referral guidelines. J Clin Neurosci 16:1001–1008

    Article  Google Scholar 

  16. Welter ML, Houeto JL, du Montcel ST, Mesnage V, Bonnet AM, Pillon B, Arnulf I, Pidoux B, Dormont D, Cornu P, Agid Y (2002) Clinical predictive factors of subthalamic stimulation in Parkinson’s disease. Brain 125:575–583

    Article  CAS  Google Scholar 

  17. Fahn S, Elton R, UPDRS Development Committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, et al. (eds) Recent developments in Parkinson’s disease. Macmillan, Florham Park, pp 153–163

    Google Scholar 

  18. Varrone A, Asenbaum S, Vander Borght T, Booij J, Nobili F, Nagren K, Darcourt J, Kapucu OL, Tatsch K, Bartenstein P, van Laere K, European Association of Nuclear Medicine Neuroimaging Committee (2009) EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2. Eur J Nucl Med Mol Imaging 36:2103–2110

    Article  Google Scholar 

  19. Meles SK, Renken RJ, Pagani M, Teune LK, Arnaldi D, Morbelli S, Nobili F, van Laar T, Obeso JA, Rodriguez-Oroz MC, Leenders KL (2020) Abnormal pattern of brain glucose metabolism in Parkinson’s disease: replication in three European cohorts. Eur J Nucl Med Mol Imaging 47:437–450

    Article  CAS  Google Scholar 

  20. Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, Kaplitt MG, Feigin A, Eidelberg D (2006) Network modulation in the treatment of Parkinson’s disease. Brain 129:2667–2678

    Article  Google Scholar 

  21. Geday J, Ostergaard K, Johnsen E, Gjedde A (2009) STN stimulation in Parkinson’s disease restores striatal inhibition of thalamocortical projection. Hum Brain Mapp 30:112–121

    Article  Google Scholar 

  22. Hershey T, Revilla FJ, Wernle AR, McGee-Minnich L, Antenor JV, Videen TO, Dowling JL, Mink JW, Perlmutter JS (2003) Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology 61:816–821

    Article  CAS  Google Scholar 

  23. Trost M, Su S, Su P, Yen RF, Tseng HM, Barnes A, Ma Y, Eidelberg D (2006) Network modulation by the subthalamic nucleus in the treatment of Parkinson’s disease. Neuroimage 31:301–307

    Article  Google Scholar 

  24. Fukuda M, Mentis MJ, Ma Y, Dhawan V, Antonini A, Lang AE, Lozano AM, Hammerstad J, Lyons K, Koller WC, Moeller JR, Eidelberg D (2001) Networks mediating the clinical effects of pallidal brain stimulation for Parkinson’s disease: a PET study of resting-state glucose metabolism. Brain 124:1601–1609

    Article  CAS  Google Scholar 

  25. Greuel A, Pauls KAM, Koy A, Sudmeyer M, Schnitzler A, Timmermann L, Fink GR, Eggers C (2020) Pallidal deep brain stimulation reduces sensorimotor cortex activation in focal/segmental dystonia. Mov Disord 35(4):629–639

    Article  CAS  Google Scholar 

  26. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128–154

    Article  CAS  Google Scholar 

  27. Yelnik J (2002) Functional anatomy of the basal ganglia. Mov Disord 17(Suppl 3):S15–21

    Article  Google Scholar 

  28. Haegelen C, Baumgarten C, Houvenaghel JF, Zhao Y, Peron J, Drapier S, Jannin P, Morandi X (2018) Functional atlases for analysis of motor and neuropsychological outcomes after medial globus pallidus and subthalamic stimulation. PLoS ONE 13:e0200262

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Elizabeth Wiles-Portier, a native speaker, for editing the manuscript for nonintellectual content.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Eugene Marquis Center, University of Rennes 1, Avenue de la bataille Flandres-Dunkerque, 35000, Rennes, France

    Xavier Palard-Novello, Antoine Girard & Florence Le Jeune

  2. UMR 1099 LTSI, INSERM, University of Rennes, Rennes, France

    Xavier Palard-Novello & Claire Haegelen

  3. Department of Neurology, University Hospital of Rennes, Rennes, France

    Sophie Drapier, Alexandre Bonnet, Jean-François Houvenaghel & Marc Vérin

  4. “Behavior and Basal Ganglia” Research Unit (EA 4712), University of Rennes 1, Rennes, France

    Sophie Drapier, Gabriel Robert, Jean-François Houvenaghel, Paul Sauleau, Marc Vérin & Florence Le Jeune

  5. Department of Psychiatry, University Hospital of Rennes, Rennes, France

    Gabriel Robert

  6. Department of Neurophysiology, Rennes University Hospital, Rennes, France

    Paul Sauleau

  7. Department of Neurosurgery, University Hospital of Rennes, Rennes, France

    Claire Haegelen

Authors
  1. Xavier Palard-Novello
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophie Drapier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandre Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antoine Girard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriel Robert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean-François Houvenaghel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Sauleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc Vérin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claire Haegelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Florence Le Jeune
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xavier Palard-Novello.

Ethics declarations

Conflicts of interest

Sophie Drapier received speech honoraria from Teva and Medtronic, and served on scientific advisory boards for Aguettant, Orkyn and Britannia. Gabriel Robert received travel support for scientific communications from Johnson & Johnson and Otsuka-Lundbeck. All other authors declare no financial conflicts of interest.

Ethical standard statement

The present study received approval from the local Ethical committee of the University Hospital of Rennes. After a complete description of the study, written informed consent was obtained from each patient.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Palard-Novello, X., Drapier, S., Bonnet, A. et al. Deep brain stimulation of the internal globus pallidus does not affect the limbic circuit in patients with Parkinson’s disease: a PET study. J Neurol 268, 701–706 (2021). https://doi.org/10.1007/s00415-020-10212-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-10212-y

Keywords

Search

Navigation