2007 Heart-Brain summit proceedings

Deep brain stimulation:
How does it work?

Jerrold L. Vitek, MD, PhD

Director, Neuromodulation Research Center, Department of Neurosciences, Lerner Research Institute,
Cleveland Clinic,
Cleveland, OH

vitekj@ccf.org

ABSTRACT

Deep brain stimulation has significantly improved the motor symptoms in patients with Parkinson's disease (PD) and other movement disorders. The mechanisms responsible for these improvements continue to be explored. Inhibition at the site of stimulation has been the prevailing explanation for the symptom improvement observed with deep brain stimulation. Research using microelectrode recording during deep brain stimulation in the MPTP monkey model of PD has helped clarify how electrical stimulation of structures within the basal ganglia‚ Äìthalamocortical circuit improves motor symptoms, and suggests that activation of output and the resultant change in pattern of neuronal activity that permeates throughout the basal ganglia motor circuit is the mechanism responsible for symptom improvement.

CITATIONS

  1. DeLong MR.
    Primate models of movement disorders of basal ganglia origin. Trends Neurosci 1990; 13:281–285.
    http://www.ncbi.nlm.nih.gov/pubmed/1695404

  2. Filion M, Tremblay L.
    Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 1991; 547:142–151.
    http://www.ncbi.nlm.nih.gov/pubmed/1677607
  3. Miller WC, DeLong MR.
    Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A, eds. The Basal Ganglia II. Structure and Function: Current Concepts. New York, NY: Plenum; 1987:415–427.
  4. Bergman H, Wichmann T, Karmon B, DeLong MR.
    The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 1994; 72:507–520.
    http://www.ncbi.nlm.nih.gov/pubmed/7983515
  5. Nini A, Feingold A, Slovin H, Bergman H.
    Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism. J Neurophysiol 1995; 74:1800–1805.
    http://www.ncbi.nlm.nih.gov/pubmed/8989416
  6. Raz A, Vaadia E, Bergman H.
    Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism. J Neurosci 2000; 20:8559–8571.
    http://www.ncbi.nlm.nih.gov/pubmed/11069964
  7. Elder C, Vitek J.
    The motor thalamus: alteration of neuronal activity in the parkinsonian state. In: Kultas-Ilinsky K, Ilinsky IA, eds. Basal Ganglia and Thalamus in Health and Movement Disorders. New York, NY: Kluwer Academic Plenum Publishers; 2001:257–265.
  8. Fazzini E, Dogali M, Sterio D, Eidelberg D, Beric A.
    Stereotactic pallidotomy for Parkinson’s disease: a long-term follow-up of unilateral pallidotomy. Neurology 1997; 48:1273–1277.
    http://www.ncbi.nlm.nih.gov/pubmed/9153456
  9. Svennilson E, Torvik A, Lowe R, Leksell L.
    Treatment of parkinsonism by stereotactic thermolesions in the pallidal region. A clinical evaluation of 81 cases. Acta Psychiatr Scand 1960; 35:358–377.
    http://www.ncbi.nlm.nih.gov/pubmed/13835931
  10. Vitek JL, Bakay RA, Freeman A, et al.
    Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol 2003; 53:558–569.
    http://www.ncbi.nlm.nih.gov/pubmed/12730989
  11. Dogali M, Fazzini E, Kolodny E, et al.
    Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 1995; 45:753–761.
    http://www.ncbi.nlm.nih.gov/pubmed/7723966
  12. Lozano AM, Lang AF, Galvez-Jimenez N, et al.
    Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 1995; 346:1383–1387.
    http://www.ncbi.nlm.nih.gov/pubmed/7475819
  13. Baron MS, Vitek JL, Bakay RA, et al.
    Treatment of advanced Parkinson’s disease by posterior GPi pallidotomy: 1-year results of a pilot study. Ann Neurol 1996; 40:355–366.
    http://www.ncbi.nlm.nih.gov/pubmed/8797525
  14. Benazzouz A, Hallett M.
    Mechanism of action of deep brain stimulation. Neurology 2000; 55(12 Suppl 6):S13–S16.
    http://www.ncbi.nlm.nih.gov/pubmed/11188968
  15. Dostrovsky JO, Levy R, Wu JP, Hutchison WD, Tasker RR, Lozano AM.
    Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 2000; 84:570–574.
    http://www.ncbi.nlm.nih.gov/pubmed/10899228
  16. Miocinovic S, Zhang J, Xu W, et al.
    Stereotactic neurosurgical planning, recording, and visualization for deep brain stimulation in nonhuman primates. J Neurosci Methods 2007; 162:32–41.
    http://www.ncbi.nlm.nih.gov/pubmed/17275094
  17. Hashimoto T, Elder CM, Vitek JL. A template subtraction method for stimulus artifact removal in high-frequency deep brain stimulation. J Neurosci Methods 2002; 113:181–186. http://www.ncbi.nlm.nih.gov/pubmed/11772439
  18. Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL.
    Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 2003; 23:1916–1923.
    http://www.ncbi.nlm.nih.gov/pubmed/12629196
  19. Zhang J, Russo GS, Mewes K, Rye DB, Vitek JL.
    Lesions in monkey globus pallidus externus exacerbate parkinsonian symptoms. Exp Neurol 2006; 199:446–453.
    http://www.ncbi.nlm.nih.gov/pubmed/16487515
  20. Vitek JL, Hashimoto T, Peoples J, DeLong MR, Bakay RA.
    Acute stimulation in the external segment of the globus pallidus improves parkinsonian motor signs. Mov Disord 2004; 19:907–915.
    http://www.ncbi.nlm.nih.gov/pubmed/15300655
  21. Zhang J, Russo GS, Chen X, Hashimoto T, Elder CM, Vitek JL.
    Deep brain stimulation of monkey globus pallidus externus in experimental parkinsonism. Abstract presented at: 33rd Annual Meeting of the Society for Neuroscience; November 8–12, 2003; New Orleans, LA.
  22. McIntyre CC, Grill WM.
    Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol 2002; 88:1592–1604.
    http://www.ncbi.nlm.nih.gov/pubmed/12364490
  23. McIntyre CC, Grill WM, Sherman DL, Thakor NV.
    Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J Neurophysiol 2004; 91:1457–1469.
    http://www.ncbi.nlm.nih.gov/pubmed/14668299
  24. Windels F, Bruet N, Poupard A, et al.
    Influence of the frequency parameter on extracellular glutamate and gamma-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in rats. J Neurosci Res 2003; 72:259–267.
    http://www.ncbi.nlm.nih.gov/pubmed/12672001
  25. Jech R, Urgosik D, Tintera J, et al.
    Functional magnetic resonance imaging during deep brain stimulation: a pilot study in four patients with Parkinson’s disease. Mov Disord 2001; 16:1126–1132.
    http://www.ncbi.nlm.nih.gov/pubmed/11748747
  26. Perlmutter JS, Mink JW, Bastian AJ, et al.
    Blood flow responses to deep brain stimulation of thalamus. Neurology 2002; 58:1388–1394.
    http://www.ncbi.nlm.nih.gov/pubmed/12011286
  27. Hershey T, Revilla FJ, Wernle AR, et al.
    Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology 2003; 61:816–821.
    http://www.ncbi.nlm.nih.gov/pubmed/14504327