Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2005 Jun;76(6):775–779. doi: 10.1136/jnnp.2003.033258

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

V Czernecki 1, B Pillon 1, J Houeto 1, M Welter 1, V Mesnage 1, Y Agid 1, B Dubois 1
PMCID: PMC1739659  PMID: 15897497

Abstract

Objective: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients.

Methods: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions).

Results: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged.

Conclusions: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.

Full Text

The Full Text of this article is available as a PDF (70.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander G. E., Crutcher M. D., DeLong M. R. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. Prog Brain Res. 1990;85:119–146. [PubMed] [Google Scholar]
  2. Ardouin C., Pillon B., Peiffer E., Bejjani P., Limousin P., Damier P., Arnulf I., Benabid A. L., Agid Y., Pollak P. Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol. 1999 Aug;46(2):217–223. doi: 10.1002/1531-8249(199908)46:2<217::aid-ana11>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  3. Baron Mark S., Wichmann Thomas, Ma Demin, DeLong Mahlon R. Effects of transient focal inactivation of the basal ganglia in parkinsonian primates. J Neurosci. 2002 Jan 15;22(2):592–599. doi: 10.1523/JNEUROSCI.22-02-00592.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bechara A., Damasio H., Damasio A. R. Emotion, decision making and the orbitofrontal cortex. Cereb Cortex. 2000 Mar;10(3):295–307. doi: 10.1093/cercor/10.3.295. [DOI] [PubMed] [Google Scholar]
  5. Bechara A., Damasio H., Tranel D., Anderson S. W. Dissociation Of working memory from decision making within the human prefrontal cortex. J Neurosci. 1998 Jan 1;18(1):428–437. doi: 10.1523/JNEUROSCI.18-01-00428.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bejjani B. P., Damier P., Arnulf I., Thivard L., Bonnet A. M., Dormont D., Cornu P., Pidoux B., Samson Y., Agid Y. Transient acute depression induced by high-frequency deep-brain stimulation. N Engl J Med. 1999 May 13;340(19):1476–1480. doi: 10.1056/NEJM199905133401905. [DOI] [PubMed] [Google Scholar]
  7. Bejjani B. P., Dormont D., Pidoux B., Yelnik J., Damier P., Arnulf I., Bonnet A. M., Marsault C., Agid Y., Philippon J. Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance. J Neurosurg. 2000 Apr;92(4):615–625. doi: 10.3171/jns.2000.92.4.0615. [DOI] [PubMed] [Google Scholar]
  8. Benoit Michel, Koulibaly Pierre Malick, Migneco Octave, Darcourt Jacques, Pringuey Dominique J., Robert Philippe H. Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis. Psychiatry Res. 2002 Jun 15;114(2):103–111. doi: 10.1016/s0925-4927(02)00003-3. [DOI] [PubMed] [Google Scholar]
  9. Czernecki V., Pillon B., Houeto J. L., Pochon J. B., Levy R., Dubois B. Motivation, reward, and Parkinson's disease: influence of dopatherapy. Neuropsychologia. 2002;40(13):2257–2267. doi: 10.1016/s0028-3932(02)00108-2. [DOI] [PubMed] [Google Scholar]
  10. Defer G. L., Widner H., Marié R. M., Rémy P., Levivier M. Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord. 1999 Jul;14(4):572–584. doi: 10.1002/1531-8257(199907)14:4<572::aid-mds1005>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  11. Dias R., Robbins T. W., Roberts A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature. 1996 Mar 7;380(6569):69–72. doi: 10.1038/380069a0. [DOI] [PubMed] [Google Scholar]
  12. Funkiewiez Aurélie, Ardouin Claire, Krack Paul, Fraix Valérie, Van Blercom Nadège, Xie Jing, Moro Elena, Benabid Alim-Louis, Pollak Pierre. Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease. Mov Disord. 2003 May;18(5):524–530. doi: 10.1002/mds.10441. [DOI] [PubMed] [Google Scholar]
  13. Giménez-Roldán S., Esteban E. M., Mateo D. Switching from bromocriptine to ropinirole in patients with advanced Parkinson's disease: open label pilot responses to three different dose-ratios. Clin Neuropharmacol. 2001 Nov-Dec;24(6):346–351. doi: 10.1097/00002826-200111000-00006. [DOI] [PubMed] [Google Scholar]
  14. Goetz C. G., Blasucci L., Stebbins G. T. Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow? Neurology. 1999 Apr 12;52(6):1227–1229. doi: 10.1212/wnl.52.6.1227. [DOI] [PubMed] [Google Scholar]
  15. Houeto J. L., Mesnage V., Mallet L., Pillon B., Gargiulo M., du Moncel S. Tezenas, Bonnet A. M., Pidoux B., Dormont D., Cornu P. Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):701–707. doi: 10.1136/jnnp.72.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jahanshahi M., Ardouin C. M., Brown R. G., Rothwell J. C., Obeso J., Albanese A., Rodriguez-Oroz M. C., Moro E., Benabid A. L., Pollak P. The impact of deep brain stimulation on executive function in Parkinson's disease. Brain. 2000 Jun;123(Pt 6):1142–1154. doi: 10.1093/brain/123.6.1142. [DOI] [PubMed] [Google Scholar]
  17. Krack P., Kumar R., Ardouin C., Dowsey P. L., McVicker J. M., Benabid A. L., Pollak P. Mirthful laughter induced by subthalamic nucleus stimulation. Mov Disord. 2001 Sep;16(5):867–875. doi: 10.1002/mds.1174. [DOI] [PubMed] [Google Scholar]
  18. Limousin P., Krack P., Pollak P., Benazzouz A., Ardouin C., Hoffmann D., Benabid A. L. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med. 1998 Oct 15;339(16):1105–1111. doi: 10.1056/NEJM199810153391603. [DOI] [PubMed] [Google Scholar]
  19. Mallet Luc, Mesnage Valérie, Houeto Jean-Luc, Pelissolo Antoine, Yelnik Jérôme, Behar Cécile, Gargiulo Marcella, Welter Marie-Laure, Bonnet Anne-Marie, Pillon Bernard. Compulsions, Parkinson's disease, and stimulation. Lancet. 2002 Oct 26;360(9342):1302–1304. doi: 10.1016/S0140-6736(02)11339-0. [DOI] [PubMed] [Google Scholar]
  20. Marin RS. Apathy: Concept, Syndrome, Neural Mechanisms, and Treatment. Semin Clin Neuropsychiatry. 1996 Oct;1(4):304–314. doi: 10.1053/SCNP00100304. [DOI] [PubMed] [Google Scholar]
  21. Montgomery S. A., Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382–389. doi: 10.1192/bjp.134.4.382. [DOI] [PubMed] [Google Scholar]
  22. Nelson H. E. A modified card sorting test sensitive to frontal lobe defects. Cortex. 1976 Dec;12(4):313–324. doi: 10.1016/s0010-9452(76)80035-4. [DOI] [PubMed] [Google Scholar]
  23. Pillon B., Ardouin C., Damier P., Krack P., Houeto J. L., Klinger H., Bonnet A. M., Pollak P., Benabid A. L., Agid Y. Neuropsychological changes between "off" and "on" STN or GPi stimulation in Parkinson's disease. Neurology. 2000 Aug 8;55(3):411–418. doi: 10.1212/wnl.55.3.411. [DOI] [PubMed] [Google Scholar]
  24. Pillon B., Gouider-Khouja N., Deweer B., Vidailhet M., Malapani C., Dubois B., Agid Y. Neuropsychological pattern of striatonigral degeneration: comparison with Parkinson's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1995 Feb;58(2):174–179. doi: 10.1136/jnnp.58.2.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pillon Bernard. Neuropsychological assessment for management of patients with deep brain stimulation. Mov Disord. 2002;17 (Suppl 3):S116–S122. doi: 10.1002/mds.10152. [DOI] [PubMed] [Google Scholar]
  26. Pluck G. C., Brown R. G. Apathy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):636–642. doi: 10.1136/jnnp.73.6.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rolls E. T., Hornak J., Wade D., McGrath J. Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. J Neurol Neurosurg Psychiatry. 1994 Dec;57(12):1518–1524. doi: 10.1136/jnnp.57.12.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saint-Cyr J. A., Trépanier L. L., Kumar R., Lozano A. M., Lang A. E. Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain. 2000 Oct;123(Pt 10):2091–2108. doi: 10.1093/brain/123.10.2091. [DOI] [PubMed] [Google Scholar]
  29. Schroeder U., Kuehler A., Haslinger B., Erhard P., Fogel W., Tronnier V. M., Lange K. W., Boecker H., Ceballos-Baumann A. O. Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study. Brain. 2002 Sep;125(Pt 9):1995–2004. doi: 10.1093/brain/awf199. [DOI] [PubMed] [Google Scholar]
  30. Schultz W., Dayan P., Montague P. R. A neural substrate of prediction and reward. Science. 1997 Mar 14;275(5306):1593–1599. doi: 10.1126/science.275.5306.1593. [DOI] [PubMed] [Google Scholar]
  31. Starkstein S. E., Mayberg H. S., Preziosi T. J., Andrezejewski P., Leiguarda R., Robinson R. G. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1992 Spring;4(2):134–139. doi: 10.1176/jnp.4.2.134. [DOI] [PubMed] [Google Scholar]
  32. Swainson R., Rogers R. D., Sahakian B. J., Summers B. A., Polkey C. E., Robbins T. W. Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication. Neuropsychologia. 2000;38(5):596–612. doi: 10.1016/s0028-3932(99)00103-7. [DOI] [PubMed] [Google Scholar]
  33. Trépanier L. L., Kumar R., Lozano A. M., Lang A. E., Saint-Cyr J. A. Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease. Brain Cogn. 2000 Apr;42(3):324–347. doi: 10.1006/brcg.1999.1108. [DOI] [PubMed] [Google Scholar]
  34. Welter M. L., Houeto J. L., Tezenas du Montcel S., Mesnage V., Bonnet A. M., Pillon B., Arnulf I., Pidoux B., Dormont D., Cornu P. Clinical predictive factors of subthalamic stimulation in Parkinson's disease. Brain. 2002 Mar;125(Pt 3):575–583. doi: 10.1093/brain/awf050. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES