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Neurotherapeutics logoLink to Neurotherapeutics
. 2008 Jan;5(1):14–25. doi: 10.1016/j.nurt.2007.10.067

Mechanisms of deep brain stimulation in movement disorders as revealed by changes in stimulus frequency

Merrill J Birdno 1, Warren M Grill 1,
PMCID: PMC2200868  NIHMSID: NIHMS37118  PMID: 18164480

Summary

Deep brain stimulation (DBS) is an established treatment for symptoms in movement disorders and is under investigation for symptom management in persons with psychiatric disorders and epilepsy. Nevertheless, there remains disagreement regarding the physiological mechanisms responsible for the actions of DBS, and this lack of understanding impedes both the design of DBS systems for treating novel diseases and the effective tuning of current DBS systems. Currently available data indicate that effective DBS overrides pathological bursts, low frequency oscillations, synchronization, and disrupted firing patterns present in movement disorders, and replaces them with more regularized firing. Although it is likely that the specific mechanism(s) by which DBS exerts its effects varies between diseases and target nuclei, the overriding of pathological activity appears to be ubiquitous. This review provides an overview of changes in motor symptoms with changes in DBS frequency and highlights parallels between the changes in motor symptoms and the changes in cellular activity that appear to underlic the motor symptoms.

Key Words: Electrical stimulation, high-frequency stimulation, movement disorders, basal ganglia, thalamus, midbrain

References

  • 1.Gross RE, Lozano AM. Advances in neurostimulation for movement disorders. Neurol Res. 2000;22:247–258. doi: 10.1080/01616412.2000.11740667. [DOI] [PubMed] [Google Scholar]
  • 2.Krauss JK, Yianni J, Loher TJ, Aziz TZ. Deep brain stimulation for dystonia. J Clin Neurophysiol. 2004;21:18–30. doi: 10.1097/00004691-200401000-00004. [DOI] [PubMed] [Google Scholar]
  • 3.Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337:403–406. doi: 10.1016/0140-6736(91)91175-T. [DOI] [PubMed] [Google Scholar]
  • 4.McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL. Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol. 2004;115:1239–1248. doi: 10.1016/j.clinph.2003.12.024. [DOI] [PubMed] [Google Scholar]
  • 5.Grill WM, McIntyre CC. Extracellular excitation of central neurons: implications for the mechanisms of deep brain stimulation. Thalamus Relat Syst. 2001;1:269–277. [Google Scholar]
  • 6.Kuncel AM, Grill WM. Selection of stimulus parameters for deep brain stimulation. Clin Neurophysiol. 2004;115:2431–2441. doi: 10.1016/j.clinph.2004.05.031. [DOI] [PubMed] [Google Scholar]
  • 7.Benabid AL, Koudsic A, Benazzouz A, et al. Subthalamic stimulation for Parkinson’s disease. Arch Med Res. 2000;31:282–289. doi: 10.1016/S0188-4409(00)00077-1. [DOI] [PubMed] [Google Scholar]
  • 8.Hodaic M, Wennberg RA, Dostrovsky JO, Lozano AM. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia. 2002;43:603–608. doi: 10.1046/j.1528-1157.2002.26001.x. [DOI] [PubMed] [Google Scholar]
  • 9.Gross RE. Deep brain stimulation in the treatment of neurological and psychiatric disease. Expert Rev Neurother. 2004;4:465–478. doi: 10.1586/14737175.4.3.465. [DOI] [PubMed] [Google Scholar]
  • 10.Nuttin BJ, Gabriels L, van Kuyck K, Cosyns P. Electrical stimulation of the anterior limbs of the internal capsules in patients with severe obsessive-compulsive disorder: anecdotal reports. Neurosurg Clin N Am. 2003;14:267–274. doi: 10.1016/S1042-3680(02)00117-1. [DOI] [PubMed] [Google Scholar]
  • 11.Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651–660. doi: 10.1016/j.neuron.2005.02.014. [DOI] [PubMed] [Google Scholar]
  • 12.Dostrovsky JO, Lozano AM. Mechanisms of deep brain stimulation. Mov Disord. 2002;17(suppl 3):S63–68. doi: 10.1002/mds.10143. [DOI] [PubMed] [Google Scholar]
  • 13.Moro E, Esselink RJ, Xie J, Hommel M, Benabid AL, Pollak P. The impact on Parkinson’s disease of electrical parameter settings in STN stimulation. Neurology. 2002;59:706–713. doi: 10.1212/wnl.59.5.706. [DOI] [PubMed] [Google Scholar]
  • 14.Fogelson N, Kuhn AA, Silberstein P, et al. Frequency dependent effects of subthalamic nucleus stimulation in Parkinson’s disease. Neurosci Lett. 2005;382:5–9. doi: 10.1016/j.neulet.2005.02.050. [DOI] [PubMed] [Google Scholar]
  • 15.Timmermann L, Wojtecki L, Gross J, et al. Ten-Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson’s disease. Mov Disord. 2004;19:1328–1333. doi: 10.1002/mds.20198. [DOI] [PubMed] [Google Scholar]
  • 16.Grill WM, Snyder AN, Miocinovic S. Deep brain stimulation creates an informational lesion of the stimulated nucleus. Neuroreport. 2004;15:1137–1140. doi: 10.1097/00001756-200405190-00011. [DOI] [PubMed] [Google Scholar]
  • 17.Ushe M, Mink JW, Revilla FJ, et al. Effect of stimulation frequency on tremor suppression in essential tremor. Mov Disord. 2004;19:1163–1168. doi: 10.1002/mds.20231. [DOI] [PubMed] [Google Scholar]
  • 18.Kuncel AM, Cooper SE, Wolgamuth BR, et al. Clinical response to varying the stimulus parameters in deep brain stimulation for essential tremor. Mov Disord. 2006;21:1920–1928. doi: 10.1002/mds.21087. [DOI] [PubMed] [Google Scholar]
  • 19.Welter ML, Houeto JL, Bonnet AM, et al. Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients. Arch Neurol. 2004;61:89–96. doi: 10.1001/archneur.61.1.89. [DOI] [PubMed] [Google Scholar]
  • 20.Foffani G, Ardolino G, Egidi M, Caputo E, Bossi B, Mori A. Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson’s disease. Brain Res Bull. 2006;69:123–130. doi: 10.1016/j.brainresbull.2005.11.012. [DOI] [PubMed] [Google Scholar]
  • 21.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. doi: 10.1152/jn.2000.84.1.570. [DOI] [PubMed] [Google Scholar]
  • 22.Meissner W, Leblois A, Hansel D, Bioulac B, Gross CE, Benazzouz A, et al. Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations. Brain. 2005;128:2372–2382. doi: 10.1093/brain/awh616. [DOI] [PubMed] [Google Scholar]
  • 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. doi: 10.1152/jn.00989.2003. [DOI] [PubMed] [Google Scholar]
  • 24.Anderson TR, Hu B, Iremonger K, Kiss ZH. Selective attenuation of afferent synaptic transmission as a mechanism of thalamic deep brain stimulation-induced tremor arrest. J Neurosci. 2006;26:841–850. doi: 10.1523/JNEUROSCI.3523-05.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Beurrier C, Bioulac B, Audin J, Hammond C. High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol. 2001;85:1351–1356. doi: 10.1152/jn.2001.85.4.1351. [DOI] [PubMed] [Google Scholar]
  • 26.Anderson ME, Postupna N, Ruffo M. Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J Neurophysiol. 2003;89:1150–1160. doi: 10.1152/jn.00475.2002. [DOI] [PubMed] [Google Scholar]
  • 27.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. doi: 10.1523/JNEUROSCI.23-05-01916.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Hershey T, Revilla FJ, Wemle AR, et al. Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology. 2003;61:816–821. doi: 10.1212/01.wnl.0000083991.81859.73. [DOI] [PubMed] [Google Scholar]
  • 29.Zhao YB, Sun BM, Li DY, Wang QS. Effects of bilateral subthalamic nucleus stimulation on resting-state cerebral glucose metabolism in advanced Parkinson’s disease. Chin Med J (Engl) 2004;117:1304–1308. [PubMed] [Google Scholar]
  • 30.Windeis F, Carcenac C, Poupard A, Savasta M. Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus. J Neurosci. 2005;25:5079–5086. doi: 10.1523/JNEUROSCI.0360-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Nowak LG, Bullier J. Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. I. Evidence from chronaxic measurements. Exp Brain Res. 1998;118:477–488. doi: 10.1007/s002210050304. [DOI] [PubMed] [Google Scholar]
  • 32.Nowak LG, Bullier J. Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments. Exp Brain Res. 1998;118:489–500. doi: 10.1007/s002210050305. [DOI] [PubMed] [Google Scholar]
  • 33.Benabid AL, Wallace B, Mitrofanis J, et al. A putative generalized model of the effects and mechanism of action of high frequency electrical stimulation of the central nervous system. Acta Neurol Belg. 2005;105:149–157. [PubMed] [Google Scholar]
  • 34.Xia R, Berger F, Piallat B, Benabid AL. Alteration of hormone and neurotransmitter production in cultured cells by high and low frequency electrical stimulation. Acta Neurochir (Wien) 2007;149:67–73. doi: 10.1007/s00701-006-1058-0. [DOI] [PubMed] [Google Scholar]
  • 35.Urbano FJ, Leznik E, Llinas RR. Cortical activation patterns evoked by afferent axons stimuli at different frequencies: an in vitro voltage-sensitive dye imaging study. Thalamus Relat Syst. 2002;1:371–371. [Google Scholar]
  • 36.Garcia L, Audin J, D’Alessandro G, Bioulac B, Hammond C. Dual effect of high-frequency stimulation on subthalamic neuron activity. J Neurosci. 2003;23:8743–8751. doi: 10.1523/JNEUROSCI.23-25-08743.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Degos B, Deniau J-M, Thierry A-M, Glowinski J, Pezard L, Maurice N. Neuroleptic-induced catalepsy: electrophysiological mechanisms of functional recovery induced by high-frequency stimulation of the subthalamic nucleus. J. Neurosci. 2005;25:7687–7696. doi: 10.1523/JNEUROSCI.1056-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.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. doi: 10.1002/mds.1217. [DOI] [PubMed] [Google Scholar]
  • 39.Phillips MD, Baker KB, Lowe MJ, et al. Parkinson disease: pattern of functional MR imaging activation during deep brain stimulation of subthalamic nucleus—initial experience. Radiology. 2006;239:209–216. doi: 10.1148/radiol.2391041990. [DOI] [PubMed] [Google Scholar]
  • 40.Windeis F, Bruet N, Poupard A, Feuerstein C, Bertrand A, Savasta M. 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. doi: 10.1002/jnr.10577. [DOI] [PubMed] [Google Scholar]
  • 41.Gale JT, Amimovin R, Williams ZM, Flaherty AW, Eskandar EN. From symphony to cacophony: Pathophysiology of the human basal ganglia in Parkinson disease. Neurosci Biobehav Rev [Epub ahead of print] Apr 25 2007. [DOI] [PubMed]
  • 42.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. doi: 10.1152/jn.1994.72.2.507. [DOI] [PubMed] [Google Scholar]
  • 43.Hammond C, Bergman H, Brown P. Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci. 2007;30:357–364. doi: 10.1016/j.tins.2007.05.004. [DOI] [PubMed] [Google Scholar]
  • 44.Brown P, Oliviero A, Mazzone P, Insola A, Tonali P, Di Lazzaro V. Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci. 2001;21:1033–1038. doi: 10.1523/JNEUROSCI.21-03-01033.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Vitek JL, Chockkan V, Zhang JY, et al. Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus. Ann Neurol. 1999;46:22–35. doi: 10.1002/1531-8249(199907)46:1<22::AID-ANA6>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  • 46.Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO. Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease. Brain. 2002;125:1196–1209. doi: 10.1093/brain/awf128. [DOI] [PubMed] [Google Scholar]
  • 47.Tang JK, Moro E, Lozano AM, et al. Firing rates of pallidal neurons are similar in Huntington’s and Parkinson’s disease patients. Exp Brain Res. 2005;166:230–236. doi: 10.1007/s00221-005-2359-x. [DOI] [PubMed] [Google Scholar]
  • 48.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. doi: 10.1152/jn.1995.74.4.1800. [DOI] [PubMed] [Google Scholar]
  • 49.Bergman H, Feingold A, Nini A, et al. Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates. Trends Neurosci. 1998;21:32–38. doi: 10.1016/S0166-2236(97)01151-X. [DOI] [PubMed] [Google Scholar]
  • 50.Deuschl G, Raethjen J, Lindemann M, Krack P. The pathophysiology of tremor. Muscle Nerve. 2001;24:716–735. doi: 10.1002/mus.1063. [DOI] [PubMed] [Google Scholar]
  • 51.Silberstein P, Oliviero A, Di Lazzaro V, Insola A, Mazzone P, Brown P. Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson’s disease. Exp Neurol. 2005;194:523–529. doi: 10.1016/j.expneurol.2005.03.014. [DOI] [PubMed] [Google Scholar]
  • 52.Wichmann T, Bergman H, Starr PA, Subramanian T, Watts RL, DeLong MR. Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates. Exp Brain Res. 1999;125:397–409. doi: 10.1007/s002210050696. [DOI] [PubMed] [Google Scholar]
  • 53.Amimovin R, Williams ZM, Cosgrove GR, Eskandar EN. Visually guided movements suppress subthalamic oscillations in Parkinson’s disease patients. J Neurosci. 2004;24:11302–11306. doi: 10.1523/JNEUROSCI.3242-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Magnin M, Morel A, Jeanmonod D. Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience. 2000;96:549–564. doi: 10.1016/S0306-4522(99)00583-7. [DOI] [PubMed] [Google Scholar]
  • 55.Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–375. doi: 10.1016/0166-2236(89)90074-X. [DOI] [PubMed] [Google Scholar]
  • 56.DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 1990;13:281–285. doi: 10.1016/0166-2236(90)90110-V. [DOI] [PubMed] [Google Scholar]
  • 57.Wichmann T, DeLong MR. Pathophysiology of Parkinson’s disease: the MPTP primate model of the human disorder. Ann N Y Acad Sci. 2003;991:199–213. doi: 10.1111/j.1749-6632.2003.tb07477.x. [DOI] [PubMed] [Google Scholar]
  • 58.Rossi L, Foffani G, Marceglia S, Bracchi F, Barbieri S, Priori A. An electronic device for artefact suppression in human local field potential recordings during deep brain stimulation. J Neural Eng. 2007;4:96–106. doi: 10.1088/1741-2560/4/2/010. [DOI] [PubMed] [Google Scholar]
  • 59.Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A. 1999;96:15222–15227. doi: 10.1073/pnas.96.26.15222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Brown P, Mazzone P, Oliviero A, et al. Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson’s disease. Exp Neurol. 2004;188:480–490. doi: 10.1016/j.expneurol.2004.05.009. [DOI] [PubMed] [Google Scholar]
  • 61.Wingeier B, Tcheng T, Koop MM, Hill BC, Heit G, Bronte-Stewart HM. Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson’s disease. Exp Neurol. 2006;197:244–251. doi: 10.1016/j.expneurol.2005.09.016. [DOI] [PubMed] [Google Scholar]
  • 62.Birdno MJ, Cooper SE, Rezai AR, Grill WM. Pulse-to-pulse changes in the frequency of deep brain stimulation affect tremor and modeled neuronal activity. J Neurophysiol. 2007;98:1675–1684. doi: 10.1152/jn.00547.2007. [DOI] [PubMed] [Google Scholar]
  • 63.Garcia L, D’Alessandro G, Femagut PO, Bioulac B, Hammond C. Impact of high-frequency stimulation parameters on the pattern of discharge of subthalamic neurons. J Neurophysiol. 2005;94:3662–3669. doi: 10.1152/jn.00496.2005. [DOI] [PubMed] [Google Scholar]
  • 64.Lee DC, Grill WM. Differential effects of electric field distribution on the activation of CNS neurons. Presented at the Annual Fall Meeting of the Biomedical Engineering Society; Program No. 915; October 16, 2004; Philadelphia, Pennsylvania.
  • 65.Dorval AD, Russo GS, Hashimoto T, Xu W, Vitek JL, Grill WM. Subthalamic high-frequency stimulation regularizes pallidal and thalamic neural activity. Soc Neurosci 2005; Program No. 331.7.2005 (abstract).
  • 66.Bar-Gad I, Elias S, Vaadia E, Bergman H. Complex locking rather than complete cessation of neuronal activity in the globus pallidus of a l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primate in response to pallidal microstimulation. J Neurosci. 2004;24:7410–7419. doi: 10.1523/JNEUROSCI.1691-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Zhang J, Russo GS, Mewes K, Rye DB, Vitek JL. Lesions in monkey globus pallidus extemus exacerbate parkinsonian symptoms. Exp Neurol. 2006;199:446–453. doi: 10.1016/j.expneurol.2006.01.006. [DOI] [PubMed] [Google Scholar]
  • 68.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. doi: 10.1002/mds.20137. [DOI] [PubMed] [Google Scholar]
  • 69.Meissner W, Guigoni C, Cirilli L, et al. Impact of chronic subthalamic high-frequency stimulation on metabolic basal ganglia activity: a 2-deoxyglucose uptake and cytochrome oxidase mRNA study in a macaque model of Parkinson’s disease. Eur J Neurosci. 2007;25:1492–1500. doi: 10.1111/j.1460-9568.2007.05406.x. [DOI] [PubMed] [Google Scholar]
  • 70.Kuncel AM, Cooper SE, Wolgamuth BR, Grill WM. Amplitude- and frequency-dependent changes in neuronal regularity parallel changes in tremor with thalamic deep brain stimulation. IEEE Trans Neural Syst Rehabil Eng. 2007;15:190–197. doi: 10.1109/TNSRE.2007.897004. [DOI] [PubMed] [Google Scholar]
  • 71.Babadi B. Bursting as an effective relay mode in a minimal thalamic model. J Comput Neurosci. 2005;18:229–243. doi: 10.1007/s10827-005-6560-5. [DOI] [PubMed] [Google Scholar]
  • 72.Person AL, Perkel DJ. Unitary IPSPs drive precise thalamic spiking in a circuit required for learning. Neuron. 2005;46:129–140. doi: 10.1016/j.neuron.2004.12.057. [DOI] [PubMed] [Google Scholar]
  • 73.Schlag J, Villablanca J. A quantitative study of temporal and spatial response patterns in a thalamic cell population electrically stimulated. Brain Res. 1968;8:255–270. doi: 10.1016/0006-8993(68)90046-2. [DOI] [PubMed] [Google Scholar]
  • 74.McIntyre CC, Grill WM. Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol. 2002;88:1592–1604. doi: 10.1152/jn.2002.88.4.1592. [DOI] [PubMed] [Google Scholar]
  • 75.Rubin JE, Terman D. High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model. J Comput Neurosci. 2004;16:211–235. doi: 10.1023/B:JCNS.0000025686.47117.67. [DOI] [PubMed] [Google Scholar]
  • 76.Bevan MD, Magill PJ, Hallworth NE, Bolam JP, Wilson CJ. Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs. J Neurophysiol. 2002;87:1348–1362. doi: 10.1152/jn.00582.2001. [DOI] [PubMed] [Google Scholar]
  • 77.Hallworth NE, Bevan MD. Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors. J Neurosci. 2005;25:6304–6315. doi: 10.1523/JNEUROSCI.0450-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Stefani A, Lozano AM, Peppe A, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain. 2007;130:1596–1607. doi: 10.1093/brain/awl346. [DOI] [PubMed] [Google Scholar]
  • 79.Moro E, Lang AE, Strafella AP, et al. Bilateral globus pallidus stimulation for Huntington’s disease. Ann Neurol. 2004;56:290–294. doi: 10.1002/ana.20183. [DOI] [PubMed] [Google Scholar]
  • 80.Hebb MO, Garcia R, Gaudet P, Mendez IM. Bilateral stimulation of the globus pallidus internus to treat choreathetosis in Huntington’s disease: technical case report. Neurosurgery. 2006;58:E383–E383. doi: 10.1227/01.NEU.0000195068.19801.18. [DOI] [PubMed] [Google Scholar]
  • 81.Alterman RL, Shils JL, Miravite J, Tagliati M. Lower stimulation frequency can enhance tolerability and efficacy of pallidal deep brain stimulation for dystonia. Mov Disord. 2007;22:366–368. doi: 10.1002/mds.21274. [DOI] [PubMed] [Google Scholar]
  • 82.Kumar R, Dagher A, Hutchison WD, Lang AE, Lozano AM. Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation. Neurology. 1999;53:871–874. doi: 10.1212/wnl.53.4.871. [DOI] [PubMed] [Google Scholar]
  • 83.Mazzone P, Lozano A, Stanzione P, et al. Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson’s disease. Neuroreport. 2005;16:1877–1881. doi: 10.1097/01.wnr.0000187629.38010.12. [DOI] [PubMed] [Google Scholar]
  • 84.Gomez-Gallego M, Fernandez-Villalba E, Femandez-Barreiro A, Herrero MT. Changes in the neuronal activity in the pedunculopontine nucleus in chronic MPTP-treated primates: an in situ hybridization study of cytochrome oxidase subunit I, choline acetyl transferase and substance P mRNA expression. J Neural Transm. 2007;114:319–326. doi: 10.1007/s00702-006-0547-x. [DOI] [PubMed] [Google Scholar]
  • 85.Starr PA, Rau GM, Davis V, et al. Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson’s disease and normal macaque. J Neurophysiol. 2005;93:3165–3176. doi: 10.1152/jn.00971.2004. [DOI] [PubMed] [Google Scholar]
  • 86.Tang JK, Moro E, Mahant N, et al. Neuronal firing rates and patterns in the globus pallidus internus of patients with cervical dystonia differ from those with Parkinson’s disease. J Neurophysiol. 2007;98:720–729. doi: 10.1152/jn.01107.2006. [DOI] [PubMed] [Google Scholar]
  • 87.Wei XF, Grill WM. Current density distributions, field distributions and impedance analysis of segmented deep brain stimulation electrodes. J Neural Eng. 2005;2:139–147. doi: 10.1088/1741-2560/2/4/010. [DOI] [PubMed] [Google Scholar]
  • 88.Feng XJ, Greenwald B, Rabitz H, Shea-Brown E, Kosut R. Toward closed-loop optimization of deep brain stimulation for Parkinson’s disease: concepts and lessons from a computational model. J Neural Eng. 2007;4:L14–21. doi: 10.1088/1741-2560/4/2/L03. [DOI] [PubMed] [Google Scholar]

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