Paradox of the Basal Ganglia Model: The Antidyskinetic Effect of Surgical Lesions in Movement Disorders

  • Jose A. Obeso
  • Fernando Alonso-Frech
  • Maria Cruz Rodriguez-Oroz
  • Lazaro Alvarez
  • Raul Macias
  • Gerardo Lopez
  • Jorge Guridi
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 58)


The revitalization of pallidotomy for Parkinson’s disease (PD) provided a new opportunity to examine the effects of focal lesion of the basal ganglia and the adequacy of current pathophysiological concepts. The accumulated data, both from early surgical experiences as well as contemporary pallidotomy, established a dual, antiparkinsonian and antidyskinetic effect of a similarly placed lesion of the globus pallidum medialis (GPm). Modern studies have shown that pallidotomy induces significant improvement of movement parameters, restores thalamocortical activity, and eliminates Levodopa-induced dyskinesias without causing any major deficit of movement control. In patients with hemichorea-ballism or dystonia, pallidotomy also induce marked amelioration of the dyskinesias. These observations pose two major paradoxes for the pathophysiological model of the basal ganglia (BG) (1) Pallidotomy improves parkinsonism and eliminates dyskinesias and (2) pallidotomy does not produce overt motor or behavioral deficits.

In this article, we review the data regarding the antidyskinetic effects of pallidotomy in PD and related movement disorders and discuss a possible solution to the first paradox of the classic basal ganglia model.


Deep Brain Stimulation Local Field Potential Generalize Dystonia Neuronal Firing Rate Antidyskinetic Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Albin RL, Young AB and Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12: 366–375.CrossRefPubMedGoogle Scholar
  2. Alexander GE and Crutcher MD (1990) Functional architecture of the basal ganglia circuits: Neural substrates of parallel processing. Trends Neurosci 13: 266–271.CrossRefPubMedGoogle Scholar
  3. Alkhani A and Lozano AM (2001) Pallidotomy for Parkinson’s disease: A review of contemporary literature. J Neurosurg 94: 43–49.CrossRefPubMedGoogle Scholar
  4. Alonso-Frech F, Zamarbide I, Alegre M, Rodríguez-Oroz MC, Guridi J, Manrique M, Valencia M, Arieda J and Obeso JA (2006) Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson’s disease. Brain 129: 1748–1757.CrossRefPubMedGoogle Scholar
  5. Alvarez L, Macias R, Pavon N, López G, Rodríguez-Oroz MC, Rodríguez R, Alvarez M, Pedroso I, Teijeiro J, Fernández R, Casabona E, García I, Guridi J, Juncos J, DeLong MR and Obeso JA (2009) Feb 9 Therapeutic efficacy of unilateral subthalamotomy in Parkinson’s disease: Results in 89 patients followed for up to 36 months. J Neurol Neurosurg Psychiatry.Google Scholar
  6. Andringa G, Vermeulen RJ, Drukarch B, Renier WO, Stoof JC and Cools AR (1999) The validity of the pretreated, unilaterally MPTP-treated monkeys as a model of Parkinson’s disease: A detailed behavioural analysis of the therapeutic and undesirable effects of the D2 agonist quinpirole and the D1 agonist SKF 81297. Behav Pharmacol 10: 163–173.CrossRefPubMedGoogle Scholar
  7. Bakay RAE, DeLong MR and Vitek JL (1992) Posteroventral pallidotomy for Parkinson’s disease. J Neurosurg 77: 487–488.PubMedGoogle Scholar
  8. Baron MS, Vitek JL, Bakay RA, Green J, McDonald WM, Cole SA and DeLong MR (2000) Treatment of advanced Parkinson’s disease by unilateral posterior GPi pallidotomy: 4-year results of a pilot study. Mov Disord 15: 230–237.CrossRefPubMedGoogle Scholar
  9. Bedard PJ, Blanchet PJ, Levesque D, Soghomonian JJ, Grondin R, Morissette M, Goulet M, Calon F, Falardeau P, Gomez-Mancilla B, Doucet JP, Robertson GS and DiPaolo T (1999) Pathophysiology of l-dopa-induced dyskinesias. Mov Disord 14(Suppl 1): 4–8.PubMedGoogle Scholar
  10. Brown P and Eusebio A (2008) Paradoxes of functional neurosurgery: Clues from basal ganglia recordings. Mov Disord 23: 12–20.CrossRefPubMedGoogle Scholar
  11. Brown P, Oliviero A, Mazzone P, Insola A, Tonali P and Di Lázaro V (2001) Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci 21: 1033–1038.PubMedGoogle Scholar
  12. Carbon M and Eidelberg D (2002) Modulation of regional brain function by deep brain stimulation: Studies with positron emission tomography. Curr Opin Neurol 4: 451–455.CrossRefGoogle Scholar
  13. Carbon M, Edwards C and Eidelberg D (2003) Functional brain imaging in Parkinson’s disease. Adv Neurol 91: 175–181.PubMedGoogle Scholar
  14. Carpenter MB, Whittier JR and Mettler FA (1950) Analysis of choreoid hyperkinesia in the rhesus monkey. J Comp Neurol 92: 293–322.CrossRefPubMedGoogle Scholar
  15. Ceballos-Baumann AO, Obeso JA, Vitek JL, DeLong MR, Bakay RAE, Linazasoro G and Brooks DJ (1994) Restoration of the thalamo cortical activity after posteroventral pallidotomy in Parkinson’s disease. Lancet 344: 814.CrossRefPubMedGoogle Scholar
  16. Crossman AR (1987) Primate models of dyskinesia: The experimental approach to the study of basal ganglia-related involuntary movement disorders. Neuroscience 21: 1–40.CrossRefPubMedGoogle Scholar
  17. De Bie RMA, de Haan RJ, Nijssen PCG, Rutgers WF, Beute GN, Bosch A, Haaxma R, Schmand B, Schuurman R, Staal M and Speelman J (1999) Unilateral pallidotomy in Parkinson’s disease: A randomised, single blind, multicentre trial. Lancet 354: 1665–1669.CrossRefPubMedGoogle Scholar
  18. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13: 281–285.CrossRefPubMedGoogle Scholar
  19. Dogali M. Fazzini E, Kolodny D, Eidelberg D, Sterio O, Denivinsky and Beric A (1995) Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 45: 753–761.PubMedGoogle Scholar
  20. Filion M and Tremblay L (1991) Effects of dopamine agonist on the spontaneous activity with MPTP-induced parkinsonism. Brain Res 547: 152–161.PubMedGoogle Scholar
  21. Foffani G, Ardolino G, Meda B, Egidi M, Rampini P, Caputo E, Baselli G and Priori A (2005) Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias. J Neurol Neurosurg Psychiatry 76: 426–428.CrossRefPubMedGoogle Scholar
  22. Grafton ST, Waters C, Sutton L, Lew MF and Couldwell W (1995) Pallidotomy increases activity of motor association cortex in Parkinson’s disease. A positron emission tomographic study. Ann Neurol 37: 776–783.CrossRefPubMedGoogle Scholar
  23. Guridi J and Obeso JA (2001) The subthalamic nucleus, hemiballismus and Parkinson’s disease: Reappraisal of a neurosurgical dogma. Brain 124: 5–19.CrossRefPubMedGoogle Scholar
  24. Hutchison WD, Levy R, Dostrovsky JO, Lozano AM and Lang AE (1997) Effect of apomorphine on the globus pallidus neurons in the parkinsonian patients. Ann Neurol 42: 767–775.CrossRefGoogle Scholar
  25. Israel Z and Bergman H (2008) Pathophysiology of the basal ganglia and movement disorders: From animal models to human clinical applications. Neurosci Biobehav Rev 32: 367–377.CrossRefPubMedGoogle Scholar
  26. Kimber TE, Tsa CS, Semmler J, Brophy BP and Thompson PD (1999) Voluntary movement after pallidotomy in severe Parkinson’s disease. Brain 122: 895–906.CrossRefPubMedGoogle Scholar
  27. Krack P and Vercueil L (2001) Review of the functional surgical treatment of dystonia. Eur Neurol 8: 389–399.CrossRefGoogle Scholar
  28. Laitinen LV, Bergerhein T and Hariz MI (1992) Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76: 53–61.CrossRefPubMedGoogle Scholar
  29. Limousin P, Brown RG, Jahanshahi M, Asselman P, Quinn NP, Thomas D, Obeso JA and Rothwell JC (1999) The effects of posteroventral pallidotomy on the preparation and execution of voluntary hand and arm movements in Parkinson’s disease. Brain 122: 315–327.CrossRefPubMedGoogle Scholar
  30. Lozano AM, Lang AE, Galvez-Jimenez N, Miyasaki J, Duff J, Hutchison WD and Dostrovski J (1995) Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 346: 1383–1387.CrossRefPubMedGoogle Scholar
  31. Lozano AM, Lang AE, Levy R, Hutchison W and Dostrovsky J (2000) Neuronal recordings in patients with Parkinson’s disease with dyskinesias induced by apomorphine. Ann Neurol 47: S141–S146.CrossRefPubMedGoogle Scholar
  32. Marsden CD and Obeso JA (1994) The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson’s disease. Brain 117: 877–897.CrossRefPubMedGoogle Scholar
  33. Meissner W, Ravenscroft P, Reese R, Harnack D, Morgenstern R, Kupsch A, Klitgaard H, Bioulac B, Gross CE, Bezard E and Boraud T (2006) Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracellular striatal dopamine. Neurobiol Dis 22: 586–598.CrossRefPubMedGoogle Scholar
  34. Merello M, Nouzeilles MI, Cammarota A, Betti O and Leiguarda R (1999a) Comparison of 1-year follow-up evaluations of patients with indication for pallidotomy who did not undergo surgery versus patients with Parkinson’s disease who did undergo pallidotomy: A case control study. Neurosurgery 44: 461–468.CrossRefPubMedGoogle Scholar
  35. Merello M, Balej J, Delfino M, Cammarota A, Betti O and Leiguarda R (1999b) Apomorphine induces changes in GPi spontaneous outflow in patients with Parkinson’s disease. Mov Disord 14: 45–49.CrossRefPubMedGoogle Scholar
  36. Merello M, Cerquetti D, Cammarota A, Tenca E, Artes C, Antico J and Leiguarda R (2004) Neuronal globus pallidus activity in patients with generalised dystonia. Mov Disord 19: 548–554.CrossRefPubMedGoogle Scholar
  37. Meyers R (1942) The modification of alternating tremors, rigidity and festination by surgery of the basal ganglia. Res Nerv Ment Dis Proc 21: 602–665.Google Scholar
  38. Modesti LM and Van Buren JM (1979) Hemiballismus complicating stereotactic thalamotomy. Appl Neurophysiol 42: 267–283.PubMedGoogle Scholar
  39. Narabayashi H (1997) Pallidotomy revisited. Analysis of posteroventral pallidotomy. Stereotact Funct Neurosurg 69: 54–61.CrossRefPubMedGoogle Scholar
  40. Obeso JA, Linazasoro G and Rothwell JC (1996) Assessing the effects of pallidotomy in Parkinson’s disease. Lancet 347: 1490.CrossRefPubMedGoogle Scholar
  41. Obeso JA, Guridi J and DeLong MR (1997) Surgery for Parkinson’s disease. J Neurol Neurosurg Psychiatry 62: 2–8.CrossRefPubMedGoogle Scholar
  42. Ondo WG, Desalloms M, Jankovic J and Grossman RG (1998) Pallidotomy for generalized dystonia. Mov Disord 13: 693–698.CrossRefPubMedGoogle Scholar
  43. Papa SM, Desimone R, Fiorani M and Oldfield EH (1999) Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias. Ann Neurol 46: 732–738.CrossRefPubMedGoogle Scholar
  44. Pfann KD, Penn RD, Shannon KM and Corcos DM (1998) Pallidotomy and bradykinesia. Implications for basal ganglia function. Neurology 51: 796–803.PubMedGoogle Scholar
  45. Priori A, Foffani G, Pesenti A, Tamma F, Bianchi AM, Pellegrini M, Locatelli M, Moxon KA and Villani RM (2004) Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson’s disease. Exp Neurol 189: 369–379.CrossRefPubMedGoogle Scholar
  46. Samuel M, Ceballos-Baumann AU, Turjanski N, Boecker H, Gorospe A, Linazasoro G, Holmes AP, DeLong MR, Vitek JL, Thomas DGT, Quinn NP, Obeso JA and Brooks DJ (1997) Pallidotomy in Parkinson’s disease increases supplementary motor area and prefrontal activation during performance of volitional movements: An H2 O15 PET study. Brain 120: 1301–1313.CrossRefPubMedGoogle Scholar
  47. Silberstein P, Kühn AA, Kupsch A, Trottenberg T, Krauss JK, Wöhrle JC, Mazzone P, Insola A, Di Lazzaro V, Oliviero A, Aziz T and Brown P (2003) Patterning of globus pallidus local field potentials differs between Parkinson’s disease and dystonia. Brain 126: 2597–2608.CrossRefPubMedGoogle Scholar
  48. Strafella A, Ashby P, Lozano A and Lang AE (1997) Pallidotomy increases cortical inhibition in Parkinson’s disease. Can J Neurol Sci 24: 133–136.PubMedGoogle Scholar
  49. Suarez JI, Matman LV, Reich SG, Dougherty PM, Hallett M and Lenz FA (1997) Pallidotomy for hemiballismus: Efficacy and characteristics of neuronal activity. Ann Neurol 42: 807–811.CrossRefPubMedGoogle Scholar
  50. Vitek JL, Bakay RAE, Hashimoto T, Kaneoke Y, Mewes K, Zhang JY, Rye D, Starr P, Baron M, Turner R and DeLong MR (1998) Microelectrode-guided pallidotomy: Technical approach and application for medically intractable Parkinson’s disease. J Neurosurg 88: 1027–1043.CrossRefPubMedGoogle Scholar
  51. Vitek JL, Chockkan V, Zhang J-Y, Kaneoke Y, Evatt M, DeLong MR, Triche S, Mewes K, Hashimoto T and Bakay RAE (1999) Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus. Ann Neurol 46: 22–35.CrossRefPubMedGoogle Scholar
  52. Vitek JL, and Giroux M (2000) Physiology of hypokinetic and hyperkinetic movement disorders: model for dyskinesia. Ann Neurol 47: S131–140.PubMedGoogle Scholar
  53. Vitek JL, Bakay RAE, Freeman A, Evatt M, Green J, McDonald W, Haber M, Barnhart H, Walay N, Triche S, Mewes K, Chockkan V, Zhang JY and DeLong MR (2003) Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol 53: 558–5569.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jose A. Obeso
    • 1
  • Fernando Alonso-Frech
    • 1
  • Maria Cruz Rodriguez-Oroz
    • 1
  • Lazaro Alvarez
    • 1
  • Raul Macias
    • 1
  • Gerardo Lopez
    • 1
  • Jorge Guridi
    • 1
  1. 1.Neurologia-Neurociencias, Clinica Universitaria, Universidad de NavarraPamplonaSpain

Personalised recommendations